greenmedinfo--2020-10-12--Glycyrrhizin alleviates Con A-induced hepatitis.

Glycyrrhizin , a triterpenoid compound , has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis .
However , the mechanism by which glycyrrhizin inhibits inflammation is unclear .
Using a Con A-induced hepatitis model in mice , we found that administration of glycyrrhizin ameliorates Con A-induced liver injury , which manifests as reduction in the production of inflammatory cytokines IFN-γ , IL-6 and IL-17 , as well as serum alanine aminotransferase ( ALT ) .
Blockade of IL-17 dramatically mitigates liver injury resulting from Con A challenge .
Interestingly , @ @ @ @ @ @ @ , the endogenous alarmin inflammatory molecule high-mobility group box 1 ( HMGB1 ) is significantly decreased in mice injected with glycyrrhizin combined with Con A compared to those injected with Con A alone .
In contrast , the administration of glycyrrhizin with Con A challenge up-regulates the production of IL-25 .
Furthermore , an increase in the proportion of protective lymphocyte subset , Gr-1CD11b ( Myeloid-Derived Suppressor Cell , MDSCs ) , could be induced by increased IL-25 to restrain immune cell activation and favor the resolution of detrimental immune reactions caused by @ @ @ @ @ @ @ that glycyrrhizin plays a protective role in Con A-induced hepatitis .
This protective role is particularly associated with reducing the production of IL-17 and enhancing the expression of IL-25 .
The present study may provide a new strategy for the treatment of acute hepatitis in the clinical setting .

Glycyrrhizin, a triterpenoid compound, has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis. However, the mechanism by which glycyrrhizin inhibits inflammation is unclear. Using a Con A-induced hepatitis model in mice, we found that administration of glycyrrhizin ameliorates Con A-induced liver injury, which manifests as reduction in the production of inflammatory cytokines IFN-γ, IL-6 and IL-17, as well as serum alanine aminotransferase (ALT). Blockade of IL-17 dramatically mitigates liver injury resulting from Con A challenge. Interestingly, at both the mRNA and protein levels, the endogenous alarmin inflammatory molecule high-mobility group box 1 (HMGB1) is significantly decreased in mice injected with glycyrrhizin combined with Con A compared to those injected with Con A alone. In contrast, the administration of glycyrrhizin with Con A challenge up-regulates the production of IL-25. Furthermore, an increase in the proportion of protective lymphocyte subset, Gr-1CD11b(Myeloid-Derived Suppressor Cell, MDSCs), could be induced by increased IL-25 to restrain immune cell activation and favor the resolution of detrimental immune reactions caused by Con A challenge. The results indicate that glycyrrhizin plays a protective role in Con A-induced hepatitis. This protective role is particularly associated with reducing the production of IL-17 and enhancing the expression of IL-25. The present study may provide a new strategy for the treatment of acute hepatitis in the clinical setting.


greenmedinfo--2020-10-12--Glycyrrhizin attenuates hepatic ischemia-reperfusion injury.

Gasdermin D ( GSDMD ) , a genetic substrate for inflammatory caspases , plays a central role in pyroptosis of macrophages and release of interleukin‑1β ( IL-1β ) , but was mainly referred to microbial infection .
High mobility group box-1 ( HMGB1 ) , served as an alarm molecule during various pathological process , has been widely recognized to be involved in liver ischemia-reperfusion ( I/R ) .
Glycyrrhizin , a natural anti-inflammatory and antiviraltriterpene in clinical use , was recently referred to have ability to prevent I/R induced liver injury by inhibiting HMGB1 expression and activity .
However @ @ @ @ @ @ @ subsequently to HMGB1 inhibition during liver I/R remain enigmatic .
This study was designed to explore the functional role and molecular mechanism of glycyrrhizin in the regulation of I/R induced liver injury .
We found that liver I/R promotes GSDMD-mediated pyroptotic cell death of Kupffer cells , which was inhibited by glycyrrhizin .
Interestingly , endogenous HMGB1 , not exogenous one , was involved in hypoxia-reoxygenation ( H/R ) induced pyroptosis .
Moreover , GSDMD knockdown protects kupffer cells against H/R induced pyroptosis in vitro .
Here , we report , for the @ @ @ @ @ @ @ damage and kupffer cells pyroptosis during liver ischemia-reperfusion injury ( LIRI ) and identify a previously unrecognized HMGB1- dependent GSDMD- mediated signaling pathway in the mechanism of kupffer cells pyroptosis induced by H/R .
Our findings provide the first demonstration of GSDMD-determined pyroptotic cell death responsible for I/R induced release of IL-1β and this would provide a mandate to better understand the unconventional mechanisms of cytokine release in the sterile innate immune system .

Gasdermin D (GSDMD), a genetic substrate for inflammatory caspases, plays a central role in pyroptosis of macrophages and release of interleukin‑1β (IL-1β), but was mainly referred to microbial infection. High mobility group box-1 (HMGB1), served as an alarm molecule during various pathological process, has been widely recognized to be involved in liver ischemia-reperfusion (I/R). Glycyrrhizin, a natural anti-inflammatory and antiviraltriterpene in clinical use, was recently referred to have ability to prevent I/R induced liver injury by inhibiting HMGB1 expression and activity. However, the mechanisms responsible for damage amelioration subsequently to HMGB1 inhibition during liver I/R remain enigmatic. This study was designed to explore the functional role and molecular mechanism of glycyrrhizin in the regulation of I/R induced liver injury. We found that liver I/R promotes GSDMD-mediated pyroptotic cell death of Kupffer cells, which was inhibited by glycyrrhizin. Interestingly, endogenous HMGB1, not exogenous one, was involved in hypoxia-reoxygenation (H/R) induced pyroptosis. Moreover, GSDMD knockdown protects kupffer cells against H/R induced pyroptosis in vitro. Here, we report, for the first time, that glycyrrhizin attenuated tissue damage and kupffer cells pyroptosis during liver ischemia-reperfusion injury (LIRI) and identify a previously unrecognized HMGB1- dependent GSDMD- mediated signaling pathway in the mechanism of kupffer cells pyroptosis induced by H/R. Our findings provide the first demonstration of GSDMD-determined pyroptotic cell death responsible for I/R induced release of IL-1β and this would provide a mandate to better understand the unconventional mechanisms of cytokine release in the sterile innate immune system.


greenmedinfo--2020-10-12--Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respira

Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?

Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed .
In this context , we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid ( GLR ) , a drug used to treat liver diseases ( including viral hepatitis ) and specific cutaneous inflammation ( such as atopic dermatitis ) in some countries .
The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed .
GLR has shown activities against different viruses , including SARS-associated Human and animal coronaviruses .
GLR is a non-hemolytic saponin and a potent immuno-active @ @ @ @ @ @ @ membrane effects .
At the membrane level , GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells .
At the intracellular and circulating levels , GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1 .
We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR .
The membrane and cytoplasmic effects of GLR , coupled with its long-established medical use as a relatively safe drug , make GLR @ @ @ @ @ @ @ the SARS-CoV-2 coronavirus , alone and in combination with other drugs .
The rational supporting combinations with ( hydroxy ) chloroquine and tenofovir ( two drugs active against SARS-CoV-2 ) is also discussed .
Based on this analysis , we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19 .

Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.


greenmedinfo--2020-10-12--Compound glycyrrhizin plus conventional therapy for psoriasis vulgaris.

BACKGROUND : Psoriasis vulgaris is a chronic skin condition affecting patients ' quality of life .
Long-term use of conventional therapy increases risk of unwanted side effects .
Compound glycyrrhizin in conjunction with conventional therapy has been used in clinical practice , but the evidence for such practice has not been evaluated systematically .
OBJECTIVE : This review aims to evaluate the efficacy and safety of compound glycyrrhizin in combination with conventional therapy for psoriasis vulgaris .
METHODS : PubMed , Excerpta Medica dataBASE ( Embase ) , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , @ @ @ @ @ @ @ Allied and Complementary Medicine Database ( AMED ) , CiNii , Chinese Biomedical Literature , China National Knowledge Infrastructure , Chinese Scientific Journals Full Text Database and Wanfang Data were searched from their respective inceptions to July 2015 .
Randomized controlled trials comparing compound glycyrrhizin plus conventional therapy to conventional therapy alone for psoriasis vulgaris were included .
Data analysis was performed using Review Manager 5.3 .
RESULTS : Eleven randomized controlled trials were included in this review .
Meta-analysis of the 11 randomized controlled trials indicated that the addition of compound glycyrrhizin @ @ @ @ @ @ @ Area and Severity Index ( PASI ) 60 ( RR : 1.30 [ 1.21 , 1.40 ] , I= 6 % ) , when compared with conventional therapy alone .
Comparable numbers of patients experienced adverse events in the two groups .
CONCLUSIONS : Compound glycyrrhizin in conjunction with conventional therapy enhances clinical response , and compound glycyrrhizin as add-on therapy does not appear to pose any additional risk in the treatment of psoriasis vulgaris .
However , the findings should be interpreted with caution of methodological flaws in the included studies .
@ @ @ @ @ @

BACKGROUND: Psoriasis vulgaris is a chronic skin condition affecting patients' quality of life. Long-term use of conventional therapy increases risk of unwanted side effects. Compound glycyrrhizin in conjunction with conventional therapy has been used in clinical practice, but the evidence for such practice has not been evaluated systematically.
OBJECTIVE: This review aims to evaluate the efficacy and safety of compound glycyrrhizin in combination with conventional therapy for psoriasis vulgaris.
METHODS: PubMed, Excerpta Medica dataBASE (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database (AMED), CiNii, Chinese Biomedical Literature, China National Knowledge Infrastructure, Chinese Scientific Journals Full Text Database and Wanfang Data were searched from their respective inceptions to July 2015. Randomized controlled trials comparing compound glycyrrhizin plus conventional therapy to conventional therapy alone for psoriasis vulgaris were included. Data analysis was performed using Review Manager 5.3.
RESULTS: Eleven randomized controlled trials were included in this review. Meta-analysis of the 11 randomized controlled trials indicated that the addition of compound glycyrrhizin increased the number of patients achieving Psoriasis Area and Severity Index (PASI) 60 (RR: 1.30 [1.21, 1.40], I= 6%), when compared with conventional therapy alone. Comparable numbers of patients experienced adverse events in the two groups.
CONCLUSIONS: Compound glycyrrhizin in conjunction with conventional therapy enhances clinical response, and compound glycyrrhizin as add-on therapy does not appear to pose any additional risk in the treatment of psoriasis vulgaris. However, the findings should be interpreted with caution of methodological flaws in the included studies. PROSPERO registration number: CRD42015027763.


greenmedinfo--2020-10-12--Glycyrrhizin, a potential drug for autoimmune encephalomyelitis by inhibiting high-mobility group bo

Glycyrrhizin, a potential drug for autoimmune encephalomyelitis by inhibiting high-mobility group box 1.

Autoimmune encephalomyelitis is a chronic autoimmune disease caused by immune-mediated sterile inflammatory response and demyelination in the central nervous system @ @ @ @ @ group box protein 1 ( HMGB1 ) is a ubiquitous nuclear protein , which can @ @ @ @ @ and induce proinflammatory responses in autoimmune encephalomyelitis .
Glycyrrhizin ( GL ) , a major @ @ @ @ @ can inhibit the proinflammatory bioactivities of HMGB1 .
In this article , we bring some @ @ @ @ @ GL on CNS inflammatory diseases and discuss the therapeutic potential of GL in autoimmune encephalomyelitis @ @ @ @

Autoimmune encephalomyelitis is a chronic autoimmune disease caused by immune-mediated sterile inflammatory response and demyelination in the central nervous system (CNS). High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein, which can be released from damaged cells and induce proinflammatory responses in autoimmune encephalomyelitis. Glycyrrhizin (GL), a major constituent of licorice root, can inhibit the proinflammatory bioactivities of HMGB1. In this article, we bring some insight into the effects of GL on CNS inflammatory diseases and discuss the therapeutic potential of GL in autoimmune encephalomyelitis in the future.


greenmedinfo--2020-10-12--Antidepressant effect of paeoniflorin Is through inhibiting pyroptosis CASP-11/GSDMD pathway.

Nod-like receptor protein 3 ( NLRP3 ) -associated neuroinflammation mediated by activated microglia is involved in the pathogenesis of depression .
The role of the pore-forming protein gasdermin D ( GSDMD ) , a newly identified pyroptosis executioner downstream of NLRP3 inflammasome mediating inflammatory programmed cell death , in depression has not been well defined .
Here , we provide evidence that paeoniflorin ( PF ) , a monoterpene glycoside compound derived from Paeonia lactiflora , ameliorated reserpine-induced mouse depression-like behaviors , characterized as increased mobility time in tail suspension test and forced swimming test , as well as the @ @ @ @ @ @ @ depressive hippocampus .
The molecular docking simulation predicted that PF would interact with C-terminus of GSDMD .
We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia , along with the proteins involved in pyroptosis signaling transduction including caspase ( CASP ) -11 , CASP-1 , NLRP3 , and interleukin ( IL ) -1β in the hippocampus of mice treated with reserpine .
And also , PF prevented lipopolysaccharide ( LPS ) and adenosine triphosphate ( ATP ) -induced pyroptosis in murine N9 microglia in vitro @ @ @ @ @ @ @ CASP-11 , NLRP3 , CASP-1 cleavage , as well as IL-1β .
Furthermore , VX-765 , an effective and selective inhibitor for CASP-1 activation , reduced the expression of inflammasome and pyroptosis-associated proteins in over-activated N9 and also facilitated PF-mediated inhibition of pyroptosis synergistically .
Collectively , the data indicated that PF exerted antidepressant effects , alleviating neuroinflammation through inhibiting CASP-11-dependent pyroptosis signaling transduction induced by over-activated microglia in the hippocampus of mice treated with reserpine .
Thus , GSDMD-mediated pyroptosis in activated microglia is a previously unrecognized inflammatory mechanismof depression and represents @ @ @ @ @ @ @ given PF administration .

Nod-like receptor protein 3 (NLRP3)-associated neuroinflammation mediated by activated microglia is involved in the pathogenesis of depression. The role of the pore-forming protein gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome mediating inflammatory programmed cell death, in depression has not been well defined. Here, we provide evidence that paeoniflorin (PF), a monoterpene glycoside compound derived from Paeonia lactiflora, ameliorated reserpine-induced mouse depression-like behaviors, characterized as increased mobility time in tail suspension test and forced swimming test, as well as the abnormal alteration of synaptic plasticity in the depressive hippocampus. The molecular docking simulation predicted that PF would interact with C-terminus of GSDMD. We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia, along with the proteins involved in pyroptosis signaling transduction including caspase (CASP)-11, CASP-1, NLRP3, and interleukin (IL)-1β in the hippocampus of mice treated with reserpine. And also, PF prevented lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced pyroptosis in murine N9 microglia in vitro, evidenced by inhibiting the expression of CASP-11, NLRP3, CASP-1 cleavage, as well as IL-1β. Furthermore, VX-765, an effective and selective inhibitor for CASP-1 activation, reduced the expression of inflammasome and pyroptosis-associated proteins in over-activated N9 and also facilitated PF-mediated inhibition of pyroptosis synergistically. Collectively, the data indicated that PF exerted antidepressant effects, alleviating neuroinflammation through inhibiting CASP-11-dependent pyroptosis signaling transduction induced by over-activated microglia in the hippocampus of mice treated with reserpine. Thus, GSDMD-mediated pyroptosis in activated microglia is a previously unrecognized inflammatory mechanismof depression and represents a unique therapeutic opportunity for mitigating depression given PF administration.


greenmedinfo--2020-10-12--Paeoniflorin affects hepatocellular carcinoma progression by inhibiting Wnt/β-catenin pathway.

BACKGROUND : Hepatocellular carcinoma ( HCC ) is a primary liver cancer with high mortality .
Paeoniflorin is a pinane monoterpene picroside with anti-tumor effect isolated from Chinese peony root and white peony root .
OBJECTIVE : To investigate the underlying mechanism of paeoniflorin ( PF ) regulating hepatocellular carcinoma ( HCC ) progression via 5-hydroxytryptamine receptor 1D ( 5-HT1D ) .
METHODS : HepG2 and SMMC-7721 hepatoma cells were treated with different concentrations of PF ( 0 , 5 , 10 , 20μM ) .
Cell proliferation , apoptosis , migration , and invasion were examined by CCK-8 and @ @ @ @ @ @ @ wound healing assay , and transwell assay , respectively .
RT-qPCR assay was used to detect the expression level of 5-HT1D , and Western blot assay was used to detect the expressions of 5-HT1D and Wnt/β-catenin pathway-related proteins .
RESULTS : With the increase of PF concentration , the mRNA level of 5-HT1D in HepG2 and SMMC-7721 hepatoma cells were decreased in a dose-dependent manner , and the proliferation , colony formation , migration and invasion ability of cells were gradually weakened , while the apoptosis rate was gradually increased .
Overexpression of @ @ @ @ @ @ @ formation , migration and invasion of HepG2 and SMMC-7721 cells , and increased the expression of Wnt/β-catenin pathway-related proteins β-actenin , survivin , C-myc , and Cyclin D1 .
Furthermore , 5-HT1D overexpression could reverse the effect of PF on hepatoma cells and inhibit the expressions of Wnt/β-catenin pathway-related proteins .
CONCLUSION : PF may inhibit the progression of HCC by blocking Wnt/β-catenin pathway expression through downregulating 5-HT1D .

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality. Paeoniflorin is a pinane monoterpene picroside with anti-tumor effect isolated from Chinese peony root and white peony root.
OBJECTIVE: To investigate the underlying mechanism of paeoniflorin (PF) regulating hepatocellular carcinoma (HCC) progression via 5-hydroxytryptamine receptor 1D (5-HT1D).
METHODS: HepG2 and SMMC-7721 hepatoma cells were treated with different concentrations of PF (0, 5, 10, 20μM). Cell proliferation, apoptosis, migration, and invasion were examined by CCK-8 and colony formation assays, flow cytometry, wound healing assay, and transwell assay, respectively. RT-qPCR assay was used to detect the expression level of 5-HT1D, and Western blot assay was used to detect the expressions of 5-HT1D and Wnt/β-catenin pathway-related proteins.
RESULTS: With the increase of PF concentration, the mRNA level of 5-HT1D in HepG2 and SMMC-7721 hepatoma cells were decreased in a dose-dependent manner, and the proliferation, colony formation, migration and invasion ability of cells were gradually weakened, while the apoptosis rate was gradually increased. Overexpression of 5-HT1D significantly promoted the proliferation, colony formation, migration and invasion of HepG2 and SMMC-7721 cells, and increased the expression of Wnt/β-catenin pathway-related proteins β-actenin, survivin, C-myc, and Cyclin D1. Furthermore, 5-HT1D overexpression could reverse the effect of PF on hepatoma cells and inhibit the expressions of Wnt/β-catenin pathway-related proteins.
CONCLUSION: PF may inhibit the progression of HCC by blocking Wnt/β-catenin pathway expression through downregulating 5-HT1D.


greenmedinfo--2020-10-12--Multiple functions of policosanol in elderly patients with dyslipidemia.

OBJECTIVE : To determine the multiple functions of policosanol in elderly dyslipidemia patients.There were 294 elderly dyslipidemia patients enrolled into this clinical study .
They were randomly divided into four groups , as follows : 20 mg policosanol ( group A , n = 64 ) ; 10 mg policosanol ( group B , n = 72 ) ; 20 mg atorvastatin ( group C , n = 91 ) ; and 10 mg policosanol + 20 mg atorvastatin ( group D , n = 62 ) .
Plasma platelet count , platelet aggregation rate , circulating endothelial cell ( @ @ @ @ @ @ @ protein ( hs-CRP ) , and carotid intima-media thickness ( IMT ) were measured before the study ( week 0 ) and at weeks 12 , 24 , and 52 .
RESULTS : In group A , the platelet aggregation rate caused by adenosine diphosphate ( ADP ) after treatment was significantly decreased compared with before treatment ( 48.79 % ± 20.29 % vs. 40.37 % ± 23.56 % ) , but the arachidonic acid ( AA ) -induced platelet aggregation rates were similar .
The platelet aggregation rates induced by AA and @ @ @ @ @ @ @ and D did not change significantly .
CEC counts and hs-CRP and homocysteine levels in all groups after treatment were significantly lower compared with before treatment , but carotid IMTs were similar .
CONCLUSION : Policosanol regulates blood lipid levels and improves endothelial cell function , and it could delay the progress of atherosclerosis.ChiCTR-RRC-17013396 ( retrospectively registered ) .

OBJECTIVE: To determine the multiple functions of policosanol in elderly dyslipidemia patients.There were 294 elderly dyslipidemia patients enrolled into this clinical study. They were randomly divided into four groups, as follows: 20 mg policosanol (group A, n = 64); 10 mg policosanol (group B, n = 72); 20 mg atorvastatin (group C, n = 91); and 10 mg policosanol + 20 mg atorvastatin (group D, n = 62). Plasma platelet count, platelet aggregation rate, circulating endothelial cell (CEC) count, high sensitivity C-reactive protein (hs-CRP), and carotid intima-media thickness (IMT) were measured before the study (week 0) and at weeks 12, 24, and 52.
RESULTS: In group A, the platelet aggregation rate caused by adenosine diphosphate (ADP) after treatment was significantly decreased compared with before treatment (48.79% ± 20.29% vs. 40.37% ± 23.56%), but the arachidonic acid (AA)-induced platelet aggregation rates were similar. The platelet aggregation rates induced by AA and ADP in groups B, C, and D did not change significantly. CEC counts and hs-CRP and homocysteine levels in all groups after treatment were significantly lower compared with before treatment, but carotid IMTs were similar.
CONCLUSION: Policosanol regulates blood lipid levels and improves endothelial cell function, and it could delay the progress of atherosclerosis.ChiCTR-RRC-17013396 (retrospectively registered).


greenmedinfo--2020-10-12--Nanoemulsification of rice bran wax policosanol enhances its cardio-protective effects.

Policosanol , a mixture of long-chain alcohols found in animal and plant waxes , has several biological effects including lipid-lowering that have been extensively studied .
However , its bioavailability is low .
To investigate the effect of nanoemulsified rice bran wax policosanol ( NPOL ) on plasma homocysteine , heart and liver histology in hyperlipidemic rats , high-fat diet containing 2.5 % cholesterol was used to induce hyperlipidemia in Sprague Dawley rats .
The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol ( POL ) in comparison with normal diet ( ND ) , high-cholesterol diet @ @ @ @ @ @ @ Plasma homocysteine , heart and liver histology , and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma ( PPARG ) were evaluated .
The NPOL group , similar to the simvastatin group , showed reduced plasma homocysteine , preserved heart and liver histology , and down-regulated hepatic PPARG mRNA in comparison to the control group , and was better than the POL group .
The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background @ @ @ @ @ @ @ policosanol .

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.


Is Coronavirus Contagious?

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This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-10-12--[VIDEO] Crimes Against Humanity

[VIDEO] Crimes Against Humanity


greenmedinfo--2020-10-12--Glycyrrhetinic acid ameliorates imiquimod-induced psoriasis-like skin lesions in mice.

BACKGROUND : Psoriasis is a chronic inflammatory skin disease affecting 2-3 % of the population worldwide .
Hyperproliferative keratinocytes were thought to be an amplifier of inflammatory response , thereby sustaining persistence of psoriasis lesions .
Agents with the ability to inhibit keratinocyte proliferation or induce apoptosis are potentially useful for psoriasis treatment .
18β-Glycyrrhetinic acid ( GA ) , an active metabolite of glycyrrhizin , exhibits diverse pharmacological activities , including anti-inflammatory , anti-bacteria and anti-proliferation .
The current study aims to evaluate the effects of GA on the proliferation and apoptosis of human HaCaT keratinocytes in vitro and @ @ @ @ @ @ @ skin lesions of imiquimod ( IMQ ) -induced psoriasis-like mouse model in vivo .
METHODS : Cell viability was assayed by CCK-8 .
Flow cytometry was performed to measure apoptosis and reactive oxygen species ( ROS ) , with Annexin V-FITC/PI detection kit and DCFH-DA probe respectively .
Caspase 9/3 activities were measured using caspase activity assay kits .
The protein levels of Akt and p-Akt were determined using Western blotting .
IMQ was applied to induce psoriasis-like skin lesions in mice .
The histological change in mouse skin lesions was detected using @ @ @ @ @ @ @ ) staining .
The severity of skin lesions was scored based on Psoriasis Area Severity Index ( PASI ) .
RT-PCR was employed to examine the relative expression of TNF-α , IL-22 and IL-17A in mouse skin lesions .
RESULTS : GA decreased HaCaT keratinocytes viability and induced cell apoptosis in a dose-dependent manner .
In the presence of GA , intracellular ROS levels were significantly elevated .
NAC , a ROS inhibitor , attenuated GA-mediated HaCaT keratinocytes growth inhibition and apoptosis .
In addition , GA treatment remarkably decreased p-Akt protein level @ @ @ @ @ @ @ cells were co-treated with GA and NAC .
LY294002 ( a PI3K inhibitor ) treatment significantly enhanced GA-mediated cytotoxicity .
Moreover , GA ameliorated IMQ-induced psoriasis-like skin lesions in mice .
CONCLUSIONS : GA inhibits proliferation and induces apoptosis in HaCaT keratinocytes through ROS-mediated inhibition of PI3K-Akt signaling pathway , and ameliorates IMQ-induced psoriasis-like skin lesions in mice .

BACKGROUND: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population worldwide. Hyperproliferative keratinocytes were thought to be an amplifier of inflammatory response, thereby sustaining persistence of psoriasis lesions. Agents with the ability to inhibit keratinocyte proliferation or induce apoptosis are potentially useful for psoriasis treatment. 18β-Glycyrrhetinic acid (GA), an active metabolite of glycyrrhizin, exhibits diverse pharmacological activities, including anti-inflammatory, anti-bacteria and anti-proliferation. The current study aims to evaluate the effects of GA on the proliferation and apoptosis of human HaCaT keratinocytes in vitro and investigate the effects of GA on the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model in vivo.
METHODS: Cell viability was assayed by CCK-8. Flow cytometry was performed to measure apoptosis and reactive oxygen species (ROS), with Annexin V-FITC/PI detection kit and DCFH-DA probe respectively. Caspase 9/3 activities were measured using caspase activity assay kits. The protein levels of Akt and p-Akt were determined using Western blotting. IMQ was applied to induce psoriasis-like skin lesions in mice. The histological change in mouse skin lesions was detected using hematoxylin and eosin (H&E) staining. The severity of skin lesions was scored based on Psoriasis Area Severity Index (PASI). RT-PCR was employed to examine the relative expression of TNF-α, IL-22 and IL-17A in mouse skin lesions.
RESULTS: GA decreased HaCaT keratinocytes viability and induced cell apoptosis in a dose-dependent manner. In the presence of GA, intracellular ROS levels were significantly elevated. NAC, a ROS inhibitor, attenuated GA-mediated HaCaT keratinocytes growth inhibition and apoptosis. In addition, GA treatment remarkably decreased p-Akt protein level, which could be restored partially when cells were co-treated with GA and NAC. LY294002 (a PI3K inhibitor) treatment significantly enhanced GA-mediated cytotoxicity. Moreover, GA ameliorated IMQ-induced psoriasis-like skin lesions in mice.
CONCLUSIONS: GA inhibits proliferation and induces apoptosis in HaCaT keratinocytes through ROS-mediated inhibition of PI3K-Akt signaling pathway, and ameliorates IMQ-induced psoriasis-like skin lesions in mice.


greenmedinfo--2020-10-12--The protective effects of 18 β-glycyrrhetinic acid on imiquimod-induced psoriasis.

Psoriasis is recognized as an autoimmune and inflammatory dermatosis , which is estimated to affect 2-3 % of the population worldwide .
18-Glycyrrhetinic acid ( GA ) , one of the main ingredients of Licorice ( GlycyrrhizaL . )
, has been shown to have numerous pharmacological effects such as antioxidative , antitumor , and anti-inflammatory activities .
However , it remains to be explored whether GA has antipsoriatic effect on psoriasis .
In this study , we evaluated the protective effect of GA on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse model .
Results indicated that @ @ @ @ @ @ @ psoriasis area and severity index scores .
GA also suppressed the mRNA levels of IL-6 , TNF- , IL-17 , IL-23 , and IL-1in the skin and increased the proportion of CD4+ Foxp3+ regulatory T cells ( Tregs ) in both lymph nodes and spleens .
Its anti-inflammatory and immunomodulatory activities may be related to its suppression of the STAT3 and mTOR signaling .
In conclusion , GA ameliorated the symptoms of psoriasis , at least in part , through inhibition of inflammatory cytokines and STAT3/mTOR signaling and activation of Tregs in both @ @ @ @ @ @ @ are expected to be beneficial in the treatment and prevention of psoriasis .

Psoriasis is recognized as an autoimmune and inflammatory dermatosis, which is estimated to affect 2-3% of the population worldwide. 18-Glycyrrhetinic acid (GA), one of the main ingredients of Licorice (GlycyrrhizaL.), has been shown to have numerous pharmacological effects such as antioxidative, antitumor, and anti-inflammatory activities. However, it remains to be explored whether GA has antipsoriatic effect on psoriasis. In this study, we evaluated the protective effect of GA on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse model. Results indicated that GA dramatically improved psoriatic lesions and reduced psoriasis area and severity index scores. GA also suppressed the mRNA levels of IL-6, TNF-, IL-17, IL-23, and IL-1in the skin and increased the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens. Its anti-inflammatory and immunomodulatory activities may be related to its suppression of the STAT3 and mTOR signaling. In conclusion, GA ameliorated the symptoms of psoriasis, at least in part, through inhibition of inflammatory cytokines and STAT3/mTOR signaling and activation of Tregs in both lymph nodes and spleens. These effects are expected to be beneficial in the treatment and prevention of psoriasis.


greenmedinfo--2020-10-12--18β-glycyrrhetinic acid improves cardiac diastolic function by attenuating intracellular calcium ove

18β-glycyrrhetinic acid improves cardiac diastolic function by attenuating intracellular calcium overload.

Ranolazine , a late sodium current inhibitor , has been demonstrated to be effective on heart failure .
18β-glycyrrhetinic acid ( 18β-GA ) has the similar inhibitory effect on late sodium currents .
However , its effect on diastolic function is still unknown .
This study aimed to determine whether 18β-GA can improve the diastolic function and to explore the underlying mechanisms .
Eighty male Sprague Dawley ( SD ) rats of Langendorff model were randomly divided into the following groups : group A , normal cardiac perfusion group ; group B , ischemia-reperfusion group ; group C , ischemia-reperfusion @ @ @ @ @ @ @ ; group D , ranolazine group ; and group E , 18β-GA group with four different concentrations .
Furthermore , a pressure-overloaded rat model induced by trans-aortic constriction ( TAC ) was established .
Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC .
Changes of free intracellular calcium ( Ca ) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents .
With the intervention of ATX-II on ischemia reperfusion injury group , 5µmol/L ranolazine , and 5 , 10 @ @ @ @ @ @ @ improve ATX-II-induced cardiac diastolic dysfunction .
630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats .
18β-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes .
The study demonstrates that 18β-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats .
The mechanism may be attributed to the inhibition of enhanced late sodium currents .

Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18β-glycyrrhetinic acid (18β-GA) has the similar inhibitory effect on late sodium currents. However, its effect on diastolic function is still unknown. This study aimed to determine whether 18β-GA can improve the diastolic function and to explore the underlying mechanisms. Eighty male Sprague Dawley (SD) rats of Langendorff model were randomly divided into the following groups: group A, normal cardiac perfusion group; group B, ischemia-reperfusion group; group C, ischemia-reperfusion with anemoniasulcata toxin II (ATX-II); group D, ranolazine group; and group E, 18β-GA group with four different concentrations. Furthermore, a pressure-overloaded rat model induced by trans-aortic constriction (TAC) was established. Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC. Changes of free intracellular calcium (Ca) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents. With the intervention of ATX-II on ischemia reperfusion injury group, 5µmol/L ranolazine, and 5, 10, 20, 40 µmol/L 18β-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18β-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18β-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats. The mechanism may be attributed to the inhibition of enhanced late sodium currents.


greenmedinfo--2020-10-12--Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary art

Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage.

Hypoxia/reoxygenation ( H/R ) is one of the main causes of coronary artery disease ( CAD ) , which is primarily induced by damage to coronary artery endothelial cells ( CAECs ) .
Glycyrrhizic acid ( GA ) is a natural and abundant pentacyclic triterpenoid glycoside of the licorice root extract , and it has been reported to elicit protective effects against hypoxia , inflammation and apoptosis in ischemic myocardium ; therefore , GA may serve as a promising therapeutic agent for ischemia-associated CAD .
In the present study , the protective effects of GA against H/R-induced injury in CAECs @ @ @ @ @ @ @ H/R maintained cell viability and decreased H/R-induced cell apoptosis in human CAECs .
In addition , H/R-mediated induction of intracellular and mitochondrial reactive oxygen species ( ROS ) was significantly decreased by GA exposure .
Similar to ROS scavengers , GA treatment not only exhibited protective effects , but also maintained the mitochondrial membrane potential after H/R and inhibited H/R-induced mitochondrial dysfunction , including deficits in ATP synthesis , mitochondrial DNA copy number and mitochondrial transcriptional activity .
Furthermore , GA decreased autophagy/mitophagy , and its protective effect against H/R was abolished by @ @ @ @ @ @ @ suggested that GA exhibited protective effects against H/R-induced CAEC injury by decreasing ROS accumulation and maintaining mitochondrial homeostasis .
Further investigation into the precise mechanisms underlying the decrease in ROS accumulation induced by GA is required .

Hypoxia/reoxygenation (H/R) is one of the main causes of coronary artery disease (CAD), which is primarily induced by damage to coronary artery endothelial cells (CAECs). Glycyrrhizic acid (GA) is a natural and abundant pentacyclic triterpenoid glycoside of the licorice root extract, and it has been reported to elicit protective effects against hypoxia, inflammation and apoptosis in ischemic myocardium; therefore, GA may serve as a promising therapeutic agent for ischemia-associated CAD. In the present study, the protective effects of GA against H/R-induced injury in CAECs were investigated. Treatment with GA during H/R maintained cell viability and decreased H/R-induced cell apoptosis in human CAECs. In addition, H/R-mediated induction of intracellular and mitochondrial reactive oxygen species (ROS) was significantly decreased by GA exposure. Similar to ROS scavengers, GA treatment not only exhibited protective effects, but also maintained the mitochondrial membrane potential after H/R and inhibited H/R-induced mitochondrial dysfunction, including deficits in ATP synthesis, mitochondrial DNA copy number and mitochondrial transcriptional activity. Furthermore, GA decreased autophagy/mitophagy, and its protective effect against H/R was abolished by autophagy promotion. Collectively, the results suggested that GA exhibited protective effects against H/R-induced CAEC injury by decreasing ROS accumulation and maintaining mitochondrial homeostasis. Further investigation into the precise mechanisms underlying the decrease in ROS accumulation induced by GA is required.


greenmedinfo--2020-10-12--Glycyrrhizin could be a potential candidate for the prevention of doxorubicin induced cardiotoxicity

Glycyrrhizin could be a potential candidate for the prevention of doxorubicin induced cardiotoxicity.

Doxorubicin ( DOX ) is one of the most effective and irreplaceable chemotherapeutic agents but its clinical use is limited due to its cardiotoxicity .
Glycyrrhizin ( GL ) has been applied to liver disorders for long .
However , little is known that if GL could be meaningful in attenuating cardiotoxicity .
The aim of this study is to investigate the cardioprotective effects of GL in DOX-induced cardiotoxicity ( DIC ) and the underlying mechanism .
Here , H9c2 cardiomyoblasts , Neonatal rat cardiomyocytes ( NRCMs ) , and Rats were introduced as test models .
A single dose @ @ @ @ @ @ @ ) was applied to induce acute cardiotoxicity in vivo , as reflected by growth inhibition , increased levels of AST and CK-MB , and reduction of SOD activity , while GL ( 25 or 50 mg/kg/d , 14 d , i.p . )
could counteract these effects .
Moreover , pre-incubation with GL ( 0.8 mM for 12 h ) in H9c2 cells protected against DOX-induced cytotoxicity , oxidative stress and depolarization of mitochondrial membrane potential ( MMP ) .
Besides , Western blot analysis showed that DOX upregulated the expression of LC3 @ @ @ @ @ @ @ both in vitro and in vivo and improved the obstructed autophagy flux in DOX-treated H9c2 cells with an autophagy inhibitor Bafilomycin A1 ( Baf A1 , 50 nM , 2 h ) .
It has been previously documented that High-mobility group box 1 ( HMGB1 ) was involved in DIC .
In our work , knockdown of HMGB1 significantly increased cell viability and LC3 II level in H9c2 , suggesting HMGB1 was crucial in DOX-induced autophagy-triggering cell death .
Intriguingly , GL is a direct inhibitor of HMGB1 .
We found that GL @ @ @ @ @ @ @ H9c2 cells .
More importantly , in non-silencing H9c2 cells ( transfected with negative control siRNA ) cells , the expression of phospho-Akt , phospho-mTOR , p62 , and LC3 II was significantly decreased with GL pretreament compared to DOX alone .
However , in H9c2/HMGB1 ( transfected with HMGB1 siRNA ) cells exposed to DOX , the expression of p-Akt , p-mTOR , p62 , LC3 II had no statistical difference with or without GL , revealing that HMGB1 mediated the cardioprotective action of GL in DIC .
Taken together , our @ @ @ @ @ @ @ HMGB1-dependent Akt/mTOR signaling pathway might contribute to attenuate DIC and go a novel insight into the underlying mechanisms of GL 's cardioprotective action .
GL could be a potential candidate for the prevention of DIC .

Doxorubicin (DOX) is one of the most effective and irreplaceable chemotherapeutic agents but its clinical use is limited due to its cardiotoxicity. Glycyrrhizin(GL) has been applied to liver disorders for long. However, little is known that if GL could be meaningful in attenuating cardiotoxicity. The aim of this study is to investigate the cardioprotective effects of GL in DOX-induced cardiotoxicity (DIC) and the underlying mechanism. Here, H9c2 cardiomyoblasts, Neonatal rat cardiomyocytes (NRCMs), and Rats were introduced as test models. A single dose of 20 mg/kg DOX (i.p.) was applied to induce acute cardiotoxicity in vivo, as reflected by growth inhibition, increased levels of AST and CK-MB, and reduction of SOD activity, while GL (25 or 50 mg/kg/d, 14 d, i.p.) could counteract these effects. Moreover, pre-incubation with GL (0.8 mM for 12 h) in H9c2 cells protected against DOX-induced cytotoxicity, oxidative stress and depolarization of mitochondrial membrane potential (MMP). Besides, Western blot analysis showed that DOX upregulated the expression of LC3 II and p62 whereas GL reversed that both in vitro and in vivo and improved the obstructed autophagy flux in DOX-treated H9c2 cells with an autophagy inhibitor Bafilomycin A1 (Baf A1, 50 nM, 2 h). It has been previously documented that High-mobility group box 1 (HMGB1) was involved in DIC. In our work, knockdown of HMGB1 significantly increased cell viability and LC3 II level in H9c2, suggesting HMGB1 was crucial in DOX-induced autophagy-triggering cell death. Intriguingly, GL is a direct inhibitor of HMGB1. We found that GL downregulated Akt/mTOR autophagy signaling pathway in DOX-treated H9c2 cells. More importantly, in non-silencing H9c2 cells (transfected with negative control siRNA) cells, the expression of phospho-Akt, phospho-mTOR, p62, and LC3 II was significantly decreased with GL pretreament compared to DOX alone. However, in H9c2/HMGB1(transfected with HMGB1 siRNA) cells exposed to DOX, the expression of p-Akt, p-mTOR, p62, LC3 II had no statistical difference with or without GL, revealing that HMGB1 mediated the cardioprotective action of GL in DIC. Taken together, our findings demonstrate that improved autophagy flux via HMGB1-dependent Akt/mTOR signaling pathway might contribute to attenuate DIC and go a novel insight into the underlying mechanisms of GL's cardioprotective action. GL could be a potential candidate for the prevention of DIC.


greenmedinfo--2020-10-12--Glycyrrhizin may reduce the severity of an infection with COVID-19 at the two stages of the COVID-19

Glycyrrhizin may reduce the severity of an infection with COVID-19 at the two stages of the COVID-19 induced disease process.

The role of the ACE2 enzyme in the COVID-19 infection is 2-fold , with opposing implications for the disease development .
1 .
The membrane bound angiotensin converting enzyme 2 ( ACE2 ) serves as the entry point of COVID-19 2 .
Conversely , it supports an anti-inflammatory pathway .
This led to the controversy of the impact of medications , which influence its expression .
ACE2 is part of the wider renin-angiotensin-aldosterone system ( RAAS ) and is upregulated via compounds , which inhibits the classical ACE , thereby plasma aldosterone and aldosterone receptor ( MR ) activation .
@ @ @ @ @ @ @ binding the COVID-19 by reducing ACE2 expression .
Glycyrrhizin ( GL ) is a frequent component in traditional Chinese medicines , which have been used to control COVID-19 infections .
Its systemically active metabolite glycyrrhetinic acid ( GA ) inhibits 11beta hydroxysteroid dehydrogenase ( 11betaHSD2 ) and activates MR in organs , which express this enzyme , including the lungs .
Does this affect the protective effect of ACE2 ?
Importantly , GL has anti-inflammatory properties by itself via toll like receptor 4 ( TLR4 ) antagonism and therefore compensates for the reduced @ @ @ @ @ @ @ , a direct effect of GL or GA to reduce virus transmission exists , which may involve reduced expression of type 2 transmembrane serine protease ( TMPRSS2 ) , which is required for virus uptake .
Glycyrrhizin may reduce the severity of an infection with COVID-19 at the two stages of the COVID-19 induced disease process , 1 .
To block the number of entry points and 2. provide an ACE2 independent anti-inflammatory mechanism .

The role of the ACE2 enzyme in the COVID-19 infection is 2-fold, with opposing implications for the disease development. 1. The membrane bound angiotensin converting enzyme 2 (ACE2) serves as the entry point of COVID-19 2. Conversely, it supports an anti-inflammatory pathway. This led to the controversy of the impact of medications, which influence its expression. ACE2 is part of the wider renin-angiotensin-aldosterone system (RAAS) and is upregulated via compounds, which inhibits the classical ACE, thereby plasma aldosterone and aldosterone receptor (MR) activation. MR activation may therefore protect organs from binding the COVID-19 by reducing ACE2 expression. Glycyrrhizin (GL) is a frequent component in traditional Chinese medicines, which have been used to control COVID-19 infections. Its systemically active metabolite glycyrrhetinic acid (GA) inhibits 11beta hydroxysteroid dehydrogenase(11betaHSD2) and activates MR in organs, which express this enzyme, including the lungs. Does this affect the protective effect of ACE2? Importantly, GL has anti-inflammatory properties by itself via toll like receptor 4 (TLR4) antagonism and therefore compensates for the reduced protection of the downregulated ACE2. Finally, a direct effect of GL or GA to reduce virus transmission exists, which may involve reduced expression of type 2 transmembrane serine protease (TMPRSS2), which is required for virus uptake. Glycyrrhizin may reduce the severity of an infection with COVID-19 at the two stages of the COVID-19 induced disease process, 1. To block the number of entry points and 2. provide an ACE2 independent anti-inflammatory mechanism.


greenmedinfo--2020-10-12--Glycyrrhizin ameliorates radiation induced enteritis.

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies , which can lead to a decrease in patients ' tolerance to radiotherapy and the quality of life .
It has been demonstrated that glycyrrhizin ( GL ) possesses significant anti-inflammatory activity .
However , little is known about its anti-inflammatory effect in radiation enteritis .
In the present study , we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved .
The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish @ @ @ @ @ @ @ and eosin staining was performed to analyze the pathological changes in the jejunum .
The expression of TNF-in the jejunum was analyzed by immunochemistry .
The levels of inflammatory cytokines , such as TNF- , IL-6 , IL-1 , and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay .
The intestinal absorption capacity was tested using the D-xylose absorption assay .
The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining .
We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory @ @ @ @ @ @ @ , IL-1 , and HMGB1 levels .
Furthermore , the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment .
In conclusion , these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses , as well as the HMGB1/TLR4 signaling pathway .
Thereby , GL might be a potential therapeutic agent for the treatment of radiation enteritis .

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-, IL-6, IL-1, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-, IL-6, IL-1, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.


greenmedinfo--2020-10-12--A licorice roots extract induces apoptosis and cell cycle arrest and improves metabolism via regulat

A licorice roots extract induces apoptosis and cell cycle arrest and improves metabolism via regulating MiRNAs in liver cancer cells.

Targeting altered metabolism in cancer provides a promising preventive and therapeutic approach .
Natural products interplay between gene expression and metabolism either by targeting altered metabolic enzymes and/or affecting the regulating miRNAs .
Licorice is a widely known product used as flavoring agent .
Glycyrrhizin and other metabolites were reported to exert several metabolic benefits .
Here , we investigated the effect of licorice roots extract on some metabolic pathways and their regulating miRNAs in hepatocellular carcinoma cells .
Our data showed various beneficial effects of licorice roots extract including induction of apoptosis and cell cycle arrest .
Second , @ @ @ @ @ @ @ miR-34c-5p , miR-122-5p , miR-126-3p , miR195-5p , miR-199a-5p , miR-206 , and miR-326-5p .
Third , inhibiting HIF1α , PI3K and C-Myc and activating AMPK and p53 .
Fourth , inhibiting enzymes of glycolysis ; HK-2 , LDH-A and PK-M2 ; pentose phosphate pathway ; G6PD and glutaminolysis ; glutaminase .
However , such an extract upregulated oncogenic miRNAs ; miR-21 , miR-221 , and miR-222 .
Although the present data highlightsthe ability of licorice roots extract to enhance apoptosis and cell cycle arrest and correct altered metabolism , it warns against @ @ @ @ @ @ @ use for prevention and therapy should proceed with caution .
Further experiments are required to investigate whether a specific bioactive ingredient is responsible for upregulating the oncogenic miRNAs .

Targeting altered metabolism in cancer provides a promising preventive and therapeutic approach. Natural products interplay between gene expression and metabolism either by targeting altered metabolic enzymes and/or affecting the regulating miRNAs. Licorice is a widely known product used as flavoring agent. Glycyrrhizin and other metabolites were reported to exert several metabolic benefits. Here, we investigated the effect of licorice roots extract on some metabolic pathways and their regulating miRNAs in hepatocellular carcinoma cells. Our data showed various beneficial effects of licorice roots extract including induction of apoptosis and cell cycle arrest. Second, upregulating tumor suppressor miRNAs; let7a-3p, miR-34c-5p, miR-122-5p, miR-126-3p, miR195-5p, miR-199a-5p, miR-206, and miR-326-5p. Third, inhibiting HIF1α, PI3K and C-Myc and activating AMPK and p53. Fourth, inhibiting enzymes of glycolysis; HK-2, LDH-A and PK-M2; pentose phosphate pathway; G6PD and glutaminolysis; glutaminase. However, such an extract upregulated oncogenic miRNAs; miR-21, miR-221, and miR-222. Although the present data highlightsthe ability of licorice roots extract to enhance apoptosis and cell cycle arrest and correct altered metabolism, it warns against its unfavorable effects, hence, its use for prevention and therapy should proceed with caution. Further experiments are required to investigate whether a specific bioactive ingredient is responsible for upregulating the oncogenic miRNAs.


greenmedinfo--2020-10-12--Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19.

OBJECTIVE : Coronavirus disease 2019 ( COVID-19 ) is a fatal and fast-spreading viral infection .
To date , the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths ( according to the data from World Health Organization ; updated on 2 June 2020 ) .
Although COVID-19 can be rapidly diagnosed , efficient clinical treatment of COVID-19 remains unavailable , resulting in high fatality .
Some clinical trials have identified vitamin C ( VC ) as a potent compound pneumonia management .
In addition , glycyrrhizic acid ( GA ) @ @ @ @ @ @ @ pneumonia-induced inflammatory stress .
We hypothesized that the combination of VC and GA is a potential option for treating COVID-19 .
METHODS : The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19 , using bioinformational network pharmacology .
RESULTS : We uncovered optimal targets , biological processes and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathways of VC + GA against COVID-19 .
Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity @ @ @ @ @ @ @ activation of the T cell receptor signaling pathway , regulation of Fc gamma R-mediated phagocytosis , ErbBsignaling pathway and vascular endothelial growth factor signaling pathway .
We also identified 17 core targets of VC + GA , which suggest as antimicrobial function .
CONCLUSIONS : For the first time , our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19 .
These results should benefit efforts to address the most pressing problem currently facing the world .

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19.
METHODS: The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology.
RESULTS: We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbBsignaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function.
CONCLUSIONS: For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.


greenmedinfo--2020-10-12--Glycyrrhizin improves inflammation and apoptosis via suppressing HMGB1 and PI3K/mTOR pathway in lipo

Glycyrrhizin improves inflammation and apoptosis via suppressing HMGB1 and PI3K/mTOR pathway in lipopolysaccharide-induced acute liver injury.

OBJECTIVE : Acute liver injury ( ALI ) is mainly characterized by the symptom of metabolic disorders , homeostasis unbalance , and loss of liver function .
There are no effective treatment methods at present stage except the liver transplantation .
Effective treatment for early ALI is of great significance for the treatment of liver injury thereof .
Glycyrrhizin ( GL ) is a promising inhibitor of the high-mobility group box-1 gene ( HMGB1 ) which is expressed much higher in an inflammatory injury .
However , it is not clear whether GL improves ALI via the inhibition of HMGB1 @ @ @ @ @ @ @ the function and mechanism of glycyrrhizin on acute liver injury .
MATERIALS AND METHODS : The expression of HMGB1 and inflammation in liver macrophages were analyzed .
Lipopolysaccharide ( LPS ) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1 .
Then , LPS injection was utilized to induce ALI in mice , and then we evaluated GL treatment in ALI model .
RESULTS : The results showed that the @ @ @ @ @ @ @ markedly increased in LPS-activated liver macrophages .
GL inhibited the progress of macrophages inflammation by restraining HMGB1 , and the administration of GL could reverse the effects of LPS-induced ALI in mice .
Moreover , PI3K/mTOR pathway was significantly suppressed by GL application .
CONCLUSIONS : These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1 .
GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI .
GL may become a novel drug for the therapy of ALI in the future .

OBJECTIVE: Acute liver injury (ALI) is mainly characterized by the symptom of metabolic disorders, homeostasis unbalance, and loss of liver function. There are no effective treatment methods at present stage except the liver transplantation. Effective treatment for early ALI is of great significance for the treatment of liver injury thereof. Glycyrrhizin (GL) is a promising inhibitor of the high-mobility group box-1 gene (HMGB1) which is expressed much higher in an inflammatory injury. However, it is not clear whether GL improves ALI via the inhibition of HMGB1. The present study is to probe the function and mechanism of glycyrrhizin on acute liver injury.
MATERIALS AND METHODS: The expression of HMGB1 and inflammation in liver macrophages were analyzed. Lipopolysaccharide (LPS) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1. Then, LPS injection was utilized to induce ALI in mice, and then we evaluated GL treatment in ALI model.
RESULTS: The results showed that the expressions of HMGB1 and inflammatory factors were markedly increased in LPS-activated liver macrophages. GL inhibited the progress of macrophages inflammation by restraining HMGB1, and the administration of GL could reverse the effects of LPS-induced ALI in mice. Moreover, PI3K/mTOR pathway was significantly suppressed by GL application.
CONCLUSIONS: These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1. GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI. GL may become a novel drug for the therapy of ALI in the future.


greenmedinfo--2020-10-12--Glycyrrhizic acid facilitates anti-tumor immunity by attenuating Tregs and MDSCs: An immunotherapeut

Glycyrrhizic acid facilitates anti-tumor immunity by attenuating Tregs and MDSCs: An immunotherapeutic approach.

Melanoma is one of the most aggressive malignancies and its treatment remains challenging due to its highly metastatic property and availability of limited effective drugs .
In addition , immunosuppresive tumor microenvironment ( TME ) has been identified as major barrier to evoke anti-tumor response in melanoma .
Recent studies revealed that immunosuppressive TME is directly correlated with heightened activations of T regulatory cells ( Tregs ) and Myeloid derived suppressor cells ( MDSCs ) functions .
In this study , we investigated the anti-cancer effect of a triterpenoid , glycyrrhizic acid ( GA ) on melanoma .
Our study @ @ @ @ @ @ @ effects on melanoma cells it significantly restricted progression of melanoma tumor .
However , the therapeutic efficacy of GA in impressive regression of tumor was found to be directly correlated with induction of apoptosis and modulation of cytokines from Th2 to Th1 type .
To unravel the mechanism of anti-melanoma effect of GA , it has been delineated that GA inhibits pSTAT3 to evade anti-tumor suppressive function of Tregs and MDSCs .
Downregulation of FOXP3 , GITR and CTLA4 in tumor-infiltrating Tregs and inhibition of Cox2 , PGE2 and Arginase 1 in intra-tumoral @ @ @ @ @ @ @ key events during therapeutic intervention of GA in melanoma management .
Moreover , GA effectively restricted advanced stage solid tumor while used in combination with Mycobacterium indicus pranii , a known immunomodulator , which alone is reported to be ineffective to restrict advanced stage solid tumor .
Thus , our findings may open up a novel insight of GA as a promising agent in cancer immunotherapy or adjuvant therapy in future .

Melanoma is one of the most aggressive malignancies and its treatment remains challenging due to its highly metastatic property and availability of limited effective drugs. In addition, immunosuppresive tumor microenvironment (TME) has been identified as major barrier to evoke anti-tumor response in melanoma. Recent studies revealed that immunosuppressive TME is directly correlated with heightened activations of T regulatory cells (Tregs) and Myeloid derived suppressor cells (MDSCs) functions. In this study, we investigated the anti-cancer effect of a triterpenoid, glycyrrhizic acid (GA) on melanoma. Our study revealed that GA not only exhibited anti-proliferative effects on melanoma cells it significantly restricted progression of melanoma tumor. However, the therapeutic efficacy of GA in impressive regression of tumor was found to be directly correlated with induction of apoptosis and modulation of cytokines from Th2 to Th1 type. To unravel the mechanism of anti-melanoma effect of GA, it has been delineated that GA inhibits pSTAT3 to evade anti-tumor suppressive function of Tregs and MDSCs. Downregulation of FOXP3, GITR and CTLA4 in tumor-infiltrating Tregs and inhibition of Cox2, PGE2 and Arginase 1 in intra-tumoral MDSC were evidenced as some of the key events during therapeutic intervention of GA in melanoma management. Moreover, GA effectively restricted advanced stage solid tumor while used in combination with Mycobacterium indicus pranii, a known immunomodulator, which alone is reported to be ineffective to restrict advanced stage solid tumor. Thus, our findings may open up a novel insight of GA as a promising agent in cancer immunotherapy or adjuvant therapy in future.


greenmedinfo--2020-10-12--Glycyrrhizin: An old weapon against a novel coronavirus.

Currently , over 100 countries are fighting against a common enemy , the severe acute respiratory syndrome coronavirus ( SARS-CoV ) -2 , which causes COVID-19 .
This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario .
Glycyrrhizin ( GZ ) is a promising agent against SARS-CoV-2 as its antiviral activity against SARS-CoV has already been confirmed .
It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS-CoV and SARS-CoV-2 .
There are many possible mechanisms through which @ @ @ @ @ @ @ oxide production in macrophages , affecting transcription factors and cellular signalling pathways , directly altering the viral lipid-bilayer membrane , and binding to the ACE2 receptor .
In this review , we discuss the possible use of GZ in the COVID-19 setting , where topical administration appears to be promising , with the nasal and oral cavity notably being the potent location in terms of viral load .
The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor , as well @ @ @ @ @ @ @ GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2 .

Currently, over 100 countries are fighting against a common enemy, the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes COVID-19. This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario. Glycyrrhizin (GZ) is a promising agent against SARS-CoV-2 as its antiviral activity against SARS-CoV has already been confirmed. It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS-CoV and SARS-CoV-2. There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid-bilayer membrane, and binding to the ACE2 receptor. In this review, we discuss the possible use of GZ in the COVID-19 setting, where topical administration appears to be promising, with the nasal and oral cavity notably being the potent location in terms of viral load. The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2.


greenmedinfo--2020-10-12--Effects of glycyrrhizin on multi-drug tesistant Pseudomonas aeruginosa.

The effects of glycyrrhizin ( GLY ) on multi-drug resistant ( MDR ) systemic ( MDR9 ) vs. ocular ( B1045 ) clinical isolates were determined .
Proteomes of each isolate with/without GLY treatment were profiled using liquid chromatography mass spectrometry ( LC-MS/MS ) .
The effect of GLY on adherence of MDR isolates to immortalized human ( HCET ) and mouse ( MCEC ) corneal epithelial cells , and biofilm and dispersal was tested .
Both isolates were treated with GLY ( 0.25 minimum inhibitory concentration ( MIC ) , 10 mg/mL for MDR9 and 3.75 mg/mL for B1045 @ @ @ @ @ @ @ MDR9 had a greater response to GLY ( 51 % of identified proteins affected vs. < 1 % in B1045 ) .
In MDR9 vs. controls , GLY decreased the abundance of proteins for : antibiotic resistance , biofilm formation , and type III secretion .
Further , antibiotic resistance and type III secretion proteins had higher control abundances in MDR9 vs. B1045 .
GLY ( 5 and 10 mg/mL ) significantly reduced binding of both isolates to MCEC , and B1045 to HCET .
MDR9 binding to HCET was only reduced at @ @ @ @ @ @ @ and 10 mg/mL ) enhanced dispersal for both isolates , at early ( 6.5 h ) but not later times ( 24-72 h ) .
This study provides evidence that GLY has a greater effect on the proteome of MDR9 vs. B1045 , yet it was equally effective at disrupting adherence and early biofilm dispersal .

The effects of glycyrrhizin (GLY) on multi-drug resistant (MDR) systemic (MDR9) vs. ocular (B1045)clinical isolates were determined. Proteomes of each isolate with/without GLY treatment were profiled using liquid chromatography mass spectrometry (LC-MS/MS). The effect of GLY on adherence of MDR isolates to immortalized human (HCET) and mouse (MCEC) corneal epithelial cells, and biofilm and dispersal was tested. Both isolates were treated with GLY (0.25 minimum inhibitory concentration (MIC), 10 mg/mL for MDR9 and 3.75 mg/mL for B1045) and subjected to proteomic analysis. MDR9 had a greater response to GLY (51% of identified proteins affected vs.<1% in B1045). In MDR9 vs. controls, GLY decreased the abundance of proteins for: antibiotic resistance, biofilm formation, and type III secretion. Further, antibiotic resistance and type III secretion proteins had higher control abundances in MDR9 vs. B1045. GLY (5 and 10 mg/mL) significantly reduced binding of both isolates to MCEC, and B1045 to HCET. MDR9 binding to HCET was only reduced at 10 mg/mL GLY. GLY (5 and 10 mg/mL) enhanced dispersal for both isolates, at early (6.5 h) but not later times (24-72 h). This study provides evidence that GLY has a greater effect on the proteome of MDR9 vs. B1045, yet it was equally effective at disrupting adherence and early biofilm dispersal.


greenmedinfo--2020-10-12--Beneficial effects of glycyrrhizin in chronic periodontitis through the inhibition of inflammatory r

Beneficial effects of glycyrrhizin in chronic periodontitis through the inhibition of inflammatory response.

Elevated inflammatory cytokines and high mobility group box 1 ( HMGB1 ) production are associated with chronic periodontitis ( CP ) .
Glycyrrhizin is the major constituent of ( Fabaceae ) root with anti-inflammation activities .
This study evaluated the effects of glycyrrhizin on CP .
TNF-α-treated human periodontal ligament stem cell ( hPDLSC ) model was established , and was administrated with 1 , 2 or 5 mM glycyrrhizin for 24 h. After treatment , the expression of HMGB1and inflammatory cytokines was monitored .
Significantly increased HMGB1 ( median : 5646.4 , range : 1918.2-8233.7 vs median : 204.5 @ @ @ @ @ @ @ , TNF-α ( median : 345.5 , range : 161.0-567.9 vs median : 93.5 , range : 58.1-159.3 , pg/mL ) , IL-1β ( median : 2014.6 , range : 209.5-4308.1 vs median : 224.5 , range : 48.8-335.8 , pg/mL ) and IL-6 ( median : 1223.6 , range : 398.2-2183.8 vs median : 240.4 , range : 105.2-400.5 , pg/mL ) were detected in gingival crevicular fluid from CP patients .
Glycyrrhizin significantly prevented TNF-α-induced expression of HMGB1 ( 691.5 ± 136.4 vs 142.8 ± 57.3 pg/mL ) , IL-6 ( @ @ @ @ @ @ @ pg/mL ) and IL-1β ( 176.3 ± 47.2 vs 53.9 ± 25.7 pg/mL ) in hPDLSC .
In CP rats , glycyrrhizin significantly decreased HMGB1 ( 5795.6 ± 1121.5 vs 586.4 ± 436.8 pg/mL ) , TNF-α ( 421.8 ± 93.7 vs 87.9 ± 21.6 pg/mL ) , IL-6 ( 1423.8 ± 235.2 vs 622.6 ± 176.1 pg/mL ) and IL-1β ( 1562.8 ± 334.3 vs 733.5 ± 265.1 pg/mL ) in gingival crevicular fluid .
Glycyrrhizin suppresses inflammatory activities in CP rats and represents a promising molecule for controlling CP .

Elevated inflammatory cytokines and high mobility group box 1 (HMGB1) production are associated with chronic periodontitis (CP). Glycyrrhizin is the major constituent of(Fabaceae) root with anti-inflammation activities. This study evaluated the effects of glycyrrhizin on CP. TNF-α-treated human periodontal ligament stem cell (hPDLSC) model was established, and was administrated with 1, 2 or 5 mM glycyrrhizin for 24 h. After treatment, the expression of HMGB1and inflammatory cytokines was monitored. Significantly increased HMGB1 (median: 5646.4, range: 1918.2-8233.7 vs median: 204.5, range: 98.7-283.6, pg/mL), TNF-α (median: 345.5, range: 161.0-567.9 vs median: 93.5, range: 58.1-159.3, pg/mL), IL-1β (median: 2014.6, range: 209.5-4308.1 vs median: 224.5, range: 48.8-335.8, pg/mL) and IL-6 (median: 1223.6, range: 398.2-2183.8 vs median: 240.4, range: 105.2-400.5, pg/mL) were detected in gingival crevicular fluid from CP patients. Glycyrrhizin significantly prevented TNF-α-induced expression of HMGB1 (691.5 ± 136.4 vs 142.8 ± 57.3 pg/mL), IL-6 (388.1 ± 85.2 vs 189.4 ± 61.2 pg/mL) and IL-1β (176.3 ± 47.2 vs 53.9 ± 25.7 pg/mL) in hPDLSC. In CP rats, glycyrrhizin significantly decreased HMGB1 (5795.6 ± 1121.5 vs 586.4 ± 436.8 pg/mL), TNF-α (421.8 ± 93.7 vs 87.9 ± 21.6 pg/mL), IL-6 (1423.8 ± 235.2 vs 622.6 ± 176.1 pg/mL) and IL-1β (1562.8 ± 334.3 vs 733.5 ± 265.1 pg/mL) in gingival crevicular fluid. Glycyrrhizin suppresses inflammatory activities in CP rats and represents a promising molecule for controlling CP.


greenmedinfo--2020-10-12--The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible re

The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible related signal pathway.

Objectives : To investigate the protective effect of glycyrrhizin ( GL ) on hepatic ischemia-reperfusion injury ( HIRI ) .
Materials and Methods : Forty SD rats were randomly divided into sham group , HIRI group , GL 100 mg/kg group , and GL 200 mg/kg group .
The pathological alterations of liver tissue in each group were observed .
The levels of alanine transaminase ( ALT ) , aspartate aminotransferase ( AST ) , endothelin-1 ( ET-l ) , nitric oxide ( NO ) , tumor necrosis factor-α ( TNF-α ) , interleukin-1β ( IL-1β ) , interleukin-6 ( @ @ @ @ @ @ @ ) , malondialdehyde ( MDA ) , and glutathione peroxidase ( GSH-Px ) were detected .
Western blot was used to detect the expression levels of cytoplasmic protein caspase-3 , Bax , Bcl-2 , heme oxygenase-1 ( HO-1 ) , nuclear factor erythroid 2-related factor 2 ( Nrf2 ) , and nuclear protein Nrf2 .
Results : Compared with the HIRI group , the levels of AST , ALT , ET-1 , TNF-α , IL-1β , and IL-6 in GL groups were lower , serum NO content was higher , MDA content was @ @ @ @ @ @ @ significantly increased , apoptosis index was lower ( 0.05 ) , which was more obvious in high-dose GL ( 200 mg/kg ) group .
The LC3-II/LC3-I ratio and Beclin-1 protein expression levels in the GL group were significantly lower than the HIRI group , but the expression levels of cytoplasmic protein HO-1 and nuclear protein Nrf2 were significantly higher than those of the HIRI group , which was more obvious in the high-dose GL group ( 0.05 ) .
Conclusion : GL has a protective effect on the liver of HIRI rats , @ @ @ @ @ @ @ activation of the Nrf2/HO-1 signaling pathway , inhibition of oxidative stress , inflammation , autophagy , and apoptosis .

Objectives: To investigate the protective effect of glycyrrhizin (GL) on hepatic ischemia-reperfusion injury (HIRI).
Materials and Methods: Forty SD rats were randomly divided into sham group, HIRI group, GL 100 mg/kg group, and GL 200 mg/kg group. The pathological alterations of liver tissue in each group were observed. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), endothelin-1 (ET-l), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected. Western blot was used to detect the expression levels of cytoplasmic protein caspase-3, Bax, Bcl-2, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear protein Nrf2.
Results: Compared with the HIRI group, the levels of AST, ALT, ET-1, TNF-α, IL-1β, and IL-6 in GL groups were lower, serum NO content was higher, MDA content was lower, SOD and GSH-Px activities were significantly increased, apoptosis index was lower (0.05), which was more obvious in high-dose GL (200 mg/kg) group. The LC3-II/LC3-I ratio and Beclin-1 protein expression levels in the GL group were significantly lower than the HIRI group, but the expression levels of cytoplasmic protein HO-1 and nuclear protein Nrf2 were significantly higher than those of the HIRI group, which was more obvious in the high-dose GL group (0.05).
Conclusion: GL has a protective effect on the liver of HIRI rats, and its mechanism may be related to activation of the Nrf2/HO-1 signaling pathway, inhibition of oxidative stress, inflammation, autophagy, and apoptosis.


greenmedinfo--2020-10-12--Ability of post-treatment glycyrrhizic acid to mitigate cerebral ischemia/reperfusion injury.

BACKGROUND Diabetes aggravates cerebral ischemia/reperfusion ( I/R ) injury by increasing inflammatory reactions , but its specific mechanism is currently unclear .
MATERIAL AND METHODS Diabetes was induced in mice with a high-fat diet combined with streptozotocin .
These mice were subjected to transient middle cerebral artery occlusion ( tMCAO ) for 60 min , followed by reperfusion for 24-72 h and post-treatment glycyrrhizic acid ( GA ) .
Control and diabetic mice were randomly allocated to 8 groups of 18 mice each .
Blood glucose , brain infarction , brain edema , and neurological function were monitored .
Necrosis @ @ @ @ @ @ @ of neurons by immunofluorescent ( IF ) staining for NeuN , and activation of inflammatory microglia by IF staining for Iba-1 .
Levels of HMGB1 , TLR4 , Myd88 , and NF-kappaB mRNA and protein in ischemic brain were determined by qRT-PCR and western blotting , respectively , and serum concentrations of IL-1ß , IL-6 , and TNF-alpha by ELISA .
RESULTS Infarction volume , brain edema , and neurological function after tMCAO were significantly aggravated in diabetes , but ameliorated by post-treatment GA. GA also reduced neuronal loss and microglial activation .
@ @ @ @ @ @ @ neurological scores .
GA suppressed the expression of Myd88 and a proinflammatory pathway that included Myd88 , HMGB1 , TLR4 , and NF-kappaB , as well as reducing serum concentrations of IL-1ß , IL-6 , and TNF-alpha .
CONCLUSIONS Post-treatment inhibited inflammatory responses and provided therapeutic benefits in diabetic mice with cerebral I/R injury , suggesting that GA may be a candidate drug to suppress cerebral I/R in diabetic patients .

BACKGROUND Diabetes aggravates cerebral ischemia/reperfusion (I/R) injury by increasing inflammatory reactions, but its specific mechanism is currently unclear. MATERIAL AND METHODS Diabetes was induced in mice with a high-fat diet combined with streptozotocin. These mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, followed by reperfusion for 24-72 h and post-treatment glycyrrhizic acid (GA). Control and diabetic mice were randomly allocated to 8 groups of 18 mice each. Blood glucose, brain infarction, brain edema, and neurological function were monitored. Necrosis was determined by Nissl staining, loss of neurons by immunofluorescent (IF) staining for NeuN, and activation of inflammatory microglia by IF staining for Iba-1. Levels of HMGB1, TLR4, Myd88, and NF-kappaB mRNA and protein in ischemic brain were determined by qRT-PCR and western blotting, respectively, and serum concentrations of IL-1ß, IL-6, and TNF-alpha by ELISA. RESULTS Infarction volume, brain edema, and neurological function after tMCAO were significantly aggravated in diabetes, but ameliorated by post-treatment GA. GA also reduced neuronal loss and microglial activation. Cerebral Myd88 level showed a positive correlationwith neurological scores. GA suppressed the expression of Myd88 and a proinflammatory pathway that included Myd88, HMGB1, TLR4, and NF-kappaB, as well as reducing serum concentrations of IL-1ß, IL-6, and TNF-alpha. CONCLUSIONS Post-treatment inhibited inflammatory responses and provided therapeutic benefits in diabetic mice with cerebral I/R injury, suggesting that GA may be a candidate drug to suppress cerebral I/R in diabetic patients.


greenmedinfo--2020-10-13--Apigenin-7-O-glucoside had similar effect as trolox to inhibit hydrogen peroxide-induced ROS product

Apigenin-7-O-glucoside had similar effect as trolox to inhibit hydrogen peroxide-induced ROS production in RAW264.7 cells.

OBJECTIVES : Chamomile has long been used as a medicinal plant due to its antioxidative and anti-inflammatory activity .
Apigenin-7-O-glucoside ( AG ) is one of the major ethanol extract components from chamomile ; however , the underlying mechanism remains unclear .
METHODS : In this study , the antioxidant potential and the anti-inflammatory activities of AG were analysed and compared with those of trolox .
We demonstrate the protective effects of AG on free radical-induced oxidative damage of DNA , proteins and erythrocytes .
Flow cytometry assay was used to detect ROS production .
Additionally , the expression of @ @ @ @ @ @ @ ELISA and Western blotting , respectively .
KEY FINDINGS : AG and trolox showed different efficiency as antioxidant in different experimental systems .
AG had similar effect as trolox to inhibit HO-induced ROS production in RAW264.7 cells , while exerted stronger inhibition against free radical-induced oxidative damage on erythrocytes than trolox .
Interestingly , compared with trolox , AG also had stronger inhibitory effect on LPS-induced NF-κB/NLRP3/caspase-1 signalling in RAW246.7 cells .
CONCLUSIONS : These results suggest the potential of AG as a pharmaceutical drug for anti-oxidation and anti-inflammation , and the combined @ @ @ @ @ @ @ its efficacy .
Our findings will provide new insights into the development of new drugs with antioxidative and anti-inflammatory functions .

OBJECTIVES: Chamomile has long been used as a medicinal plant due to its antioxidative and anti-inflammatory activity. Apigenin-7-O-glucoside (AG) is one of the major ethanol extract components from chamomile; however, the underlying mechanism remains unclear.
METHODS: In this study, the antioxidant potential and the anti-inflammatory activities of AG were analysed and compared with those of trolox. We demonstrate the protective effects of AG on free radical-induced oxidative damage of DNA, proteins and erythrocytes. Flow cytometry assay was used to detect ROS production. Additionally, the expression of anti-oxidation-related and inflammation-related factors was detected by ELISA and Western blotting, respectively.
KEY FINDINGS: AG and trolox showed different efficiency as antioxidant in different experimental systems. AG had similar effect as trolox to inhibit HO-induced ROS production in RAW264.7 cells, while exerted stronger inhibition against free radical-induced oxidative damage on erythrocytes than trolox. Interestingly, compared with trolox, AG also had stronger inhibitory effect on LPS-induced NF-κB/NLRP3/caspase-1 signalling in RAW246.7 cells.
CONCLUSIONS: These results suggest the potential of AG as a pharmaceutical drug for anti-oxidation and anti-inflammation, and the combined usage of AG and trolox might promote its efficacy. Our findings will provide new insights into the development of new drugs with antioxidative and anti-inflammatory functions.


greenmedinfo--2020-10-13--Apigenin enhanced antitumor effect of cisplatin in lung cancer via inhibition of cancer stem cells.

Cancer stem cell theory has been proposed to explain tumor heterogeneity and the carcinogenesis process .
Highly tumorigenic lung cancer stem cells develop resistance to cisplatin ( CDDP ) , a common chemotherapy drug .
Herein , we attempted to clarify whether apigenin ( API ) can improve the antitumor efficiency of CDDP in lung cancer using cancer stem cells .
Lung cancer stem cells were identified as CD 133 positive cancer cells in non-small cell lung cancer ( NSCLC ) A549 , H1299 cells and CDDP-resistant NSCLC A549R cells .
The cytotoxic effect of API was measured in CDDP-treated @ @ @ @ @ @ @ .
API repressed CD 133 positive cells and enhanced the antitumor effect of CDDP in A549 , H1299 , and A549R cells .
The synergistic antitumor effect of API and CDDP was blocked by addition of the p53 inhibitor Pifithrin-α , and siRNA targeting thegene in A549R cells .
Furthermore , API eliminates CDDP-induced CSC via p53 , since A549R cells lacking p53 and Pifithrin-α addition derepressed the decrease in CD 133 positive cells after API treatment in CDDP-treated A549 and A549R cells .
The findings indicate that API might eliminate cancer stem @ @ @ @ @ @ @ CDDP in NSCLC via p53 .

Cancer stem cell theory has been proposed to explain tumor heterogeneity and the carcinogenesis process. Highly tumorigenic lung cancer stem cells develop resistance to cisplatin (CDDP), a common chemotherapy drug. Herein, we attempted to clarify whether apigenin (API) can improve the antitumor efficiency of CDDP in lung cancer using cancer stem cells. Lung cancer stem cells were identified as CD 133 positive cancer cells in non-small cell lung cancer (NSCLC) A549, H1299 cells and CDDP-resistant NSCLC A549R cells. The cytotoxic effect of API was measured in CDDP-treated A549, H1299, and A549R cells. API repressed CD 133 positive cells and enhanced the antitumor effect of CDDP in A549, H1299, and A549R cells. The synergistic antitumor effect of API and CDDP was blocked by addition of the p53 inhibitor Pifithrin-α, and siRNA targeting thegene in A549R cells. Furthermore, API eliminates CDDP-induced CSC via p53, since A549R cells lacking p53 and Pifithrin-α addition derepressed the decrease in CD 133 positive cells after API treatment in CDDP-treated A549 and A549R cells. The findings indicate that API might eliminate cancer stem cells and enhance the antitumor effects of CDDP in NSCLC via p53.


greenmedinfo--2020-10-13--Apigenin effect against Leishmania tropica amastigotes in vitro.

Cutaneous Leishmaniasis is a current public health problem in Syria .
It causes different skin lesions that vary in their @ @ @ @ @ to permanent deformity ones .
However , the used treatments have many disadvantages as their @ @ @ @ @ effects .
Flavonoids including Apigenin reported to have many anti parasitic properties .
As well @ @ @ @ @ therapeutic alternatives in the treatment of Leishmaniasis due to its low side effects and toxicity @ @ @ @ @ evaluate the efficacy of Apigenin against L.tropica amastigotes in vitro using Leishmania-Macrophage Interaction Assay .
@ @ @ @ @ of efficacy of Apigenin against L.tropica amastigotes since Apigenin reduced the infection index at IC60.44µM @ @ @ @ @ in humans and using Apigenin as a candidate for the chemotherapeutic treatment against Leishmaniasis .

Cutaneous Leishmaniasis is a current public health problem in Syria. It causes different skin lesions that vary in their severity from spontaneously heal lesions to permanent deformity ones. However, the used treatments have many disadvantages as their high toxicity and many side effects. Flavonoids including Apigenin reported to have many anti parasitic properties. As well as their preference as potential therapeutic alternatives in the treatment of Leishmaniasis due to its low side effects and toxicity. This study aims to evaluate the efficacy of Apigenin against L.tropica amastigotes in vitro using Leishmania-Macrophage Interaction Assay. Our study demonstrated the possibility of efficacy of Apigenin against L.tropica amastigotes since Apigenin reduced the infection index at IC60.44µM and this requires subsequent studies in humans and using Apigenin as a candidate for the chemotherapeutic treatment against Leishmaniasis.


greenmedinfo--2020-10-13--Apigenin promotes antibacterial activity via regulation of nitric oxide and superoxide anion product

Apigenin promotes antibacterial activity via regulation of nitric oxide and superoxide anion production.

Apigenin is a naturally occurring flavone isolated from the medicinal herb , Aster yomena .
The present study was designed @ @ @ @ @ mechanism of apigenin in Escherichia coli .
Administration of apigenin resulted in a rapid increase @ @ @ @ @ an increase in reactive nitrogen species ( RNS ) and nitric oxide ( NO ) @ @ @ @ @ increases reactive oxygen species ( ROS ) , superoxide anion ( O ) which left @ @ @ @ @ to activate superoxide dismutase .
Finally , we found that perturbance of the membrane lipid @ @ @ @ @ and formation 8-hydroxy-2'-deoxyguanosine occurred during the process and apoptosis-like death hallmarks were further observed .
@ @ @ @ @ NO synthase inhibitor ( l-NAME ) and the Oscavenger ( Tiron ) and observed attenuation @ @ @ @ @ presence .
Taken together , these results suggest that apigenin induces bacterial apoptosis via activation @ @ @ @ @ on the production and accumulation of RNS/ROS .

Apigenin is a naturally occurring flavone isolated from the medicinal herb, Aster yomena. The present study was designed to elucidate the apoptosis-like antibacterial mechanism of apigenin in Escherichia coli. Administration of apigenin resulted in a rapid increase in intracellular calcium accompanied by an increase in reactive nitrogen species (RNS) and nitric oxide (NO) levels. Furthermore, apigenin increases reactive oxygen species (ROS), superoxide anion (O) which left E. coli with no ability to activate superoxide dismutase. Finally, we found that perturbance of the membrane lipid bilayer leading to glutathione oxidation and formation 8-hydroxy-2'-deoxyguanosine occurred during the process and apoptosis-like death hallmarks were further observed. Furthermore, we applied the NO synthase inhibitor ( l-NAME) and the Oscavenger (Tiron) and observed attenuation in apoptotic markers under their presence. Taken together, these results suggest that apigenin induces bacterial apoptosis via activation of cellular oxidative pathways dependent on the production and accumulation of RNS/ROS.


greenmedinfo--2020-10-13--Antioxidant apigenin relieves age-related muscle atrophy.

Skeletal muscle atrophy in the elderly causes loss in muscle mass and functions .
Naturally-occurring antioxidant flavonoid apigenin is able to ameliorate obesity-and denervation-induced muscle atrophies , but its effects on age-related muscle atrophy remains unknown .
We hypothesized that apigenin can relieve muscle atrophy in aged mice , probably through special effects on reactive oxygen species and enzymes with antioxidant functions .
For the male mice of the study , apigenin showed significant dose-dependent effects in relieving aging-related muscle atrophy according to results of frailty index as indicator of frailty associated with ageing , grip strength and running distance @ @ @ @ @ @ @ morphological features and increased mitochondria number and volume , as manifested by succinate dehydrogenase staining and transmission electron microscopy .
Our tests also suggested that apigenin promoted activities of enzymes such as superoxide dismutase and glutathione peroxidase for antioxidation and those for aerobic respiration such as mitochondrial respiratory enzyme complexes I , II and IV , increased ATP , and enhanced expression of genes such as peroxisome proliferator-activated receptor-γ coactivator 1α , mitochondrial transcription factor A , nuclear respiratory factor-1 , and ATP5B involved in mitochondrial biogenesis .
The data also suggested that @ @ @ @ @ @ @ and DNA fragmentation as indicators of mitophagy and apoptosis in aged mice with skeletal muscle atrophy .
Together , the results suggest that apigenin relieves age-related skeletal muscle atrophy through reducing oxidative stress and inhibiting hyperactive autophagy and apoptosis .

Skeletal muscle atrophy in the elderly causes loss in muscle mass and functions. Naturally-occurring antioxidant flavonoid apigenin is able to ameliorate obesity-and denervation-induced muscle atrophies, but its effects on age-related muscle atrophy remains unknown. We hypothesized that apigenin can relieve muscle atrophy in aged mice, probably through special effects on reactive oxygen species and enzymes with antioxidant functions. For the male mice of the study, apigenin showed significant dose-dependent effects in relieving aging-related muscle atrophy according to results of frailty index as indicator of frailty associated with ageing, grip strength and running distance. Apigenin also improved myofiber size and morphological features and increased mitochondria number and volume, as manifested by succinate dehydrogenase staining and transmission electron microscopy. Our tests also suggested that apigenin promoted activities of enzymes such as superoxide dismutase and glutathione peroxidase for antioxidation and those for aerobic respiration such as mitochondrial respiratory enzyme complexes I, II and IV, increased ATP, and enhanced expression of genes such as peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, nuclear respiratory factor-1, and ATP5B involved in mitochondrial biogenesis. The data also suggested that apigenin inhibited Bcl-2/adenovirus E1B 19kD-interacting protein 3 and DNA fragmentation as indicators of mitophagy and apoptosis in aged mice with skeletal muscle atrophy. Together, the results suggest that apigenin relieves age-related skeletal muscle atrophy through reducing oxidative stress and inhibiting hyperactive autophagy and apoptosis.