greenmedinfo--2020-06-03--Citrus peel flavonoids as potential cancer prevention agents.

Citrus fruit and in particular flavonoid compounds from citrus peel have been identified as agents with utility in the treatment @ @ @ @ @ provides a background and overview regarding the compounds found within citrus peel with putative anticancer @ @ @ @ @ associated in vitro and in vivo studies .
Historical studies have identified a number of @ @ @ @ @ modulated by citrus peel flavonoids including cell proliferation , cell cycle regulation , apoptosis , @ @ @ @ @ More recently , molecular studies have started to elucidate the underlying cell signaling pathways that @ @ @ @ @ ' mechanism of action .
These growing data support further research into the chemopreventative potential @ @ @ @ @ and purified flavonoids in particular .
This critical review highlights new research in the field @ @ @ @ @ by flavonoids and other polyphenolic compounds into a generalized schema .

Citrus fruit and in particular flavonoid compounds from citrus peel have been identified as agents with utility in the treatment of cancer. This review provides a background and overview regarding the compounds found within citrus peel with putative anticancer potential as well as the associated in vitro and in vivo studies. Historical studies have identified a number of cellular processes that can be modulated by citrus peel flavonoids including cell proliferation, cell cycle regulation, apoptosis, metastasis, and angiogenesis. More recently, molecular studies have started to elucidate the underlying cell signaling pathways that are responsible for the flavonoids' mechanism of action. These growing data support further research into the chemopreventative potential of citrus peel extracts, and purified flavonoids in particular. This critical review highlights new research in the field and synthesizes the pathways modulated by flavonoids and other polyphenolic compounds into a generalized schema.


greenmedinfo--2020-06-03--Anti-tumorigenic efficacy of tangeretin in liver cancer - an in-silico approach.

BACKGROUND : Liver cancer is otherwise known as Hepatic cancer which originated from the liver .
Hepatocellular carcinoma ( HCC ) is the common primary Liver cancer and is one of the emerging problems worldwide .
Very few treatments are available to treat HCC , because the molecular mechanism and other HCC mechanisms are still unclear .
Cyclooxygenase 2 ( COX-2 ) , one of the most promising targets for Hepatocellular Carcinoma and it is one of the dimeric enzymes which convert Arachidonic acid into Prostaglandin H2 in the step of Prostaglandin biosynthesis .
Several , natural bioactive compounds involved @ @ @ @ @ @ @ cancer .
Tangeretin , one of the natural polymethoxyflavone which is present in the peel of citrus fruits and it also acts as an Anti-oxidant modulator and Anti-cancerous .
METHODS : Computational approaches like Molecular docking and Molecular dynamics was performed to identify the potential inhibitor for Hepatocellular Carcinoma .
OBJECTIVES : The main objective of this study is to find a suitable inhibitor for Hepatocellular Carcinoma .
RESULTS : In this study , COX-2 considered as the potential target for Hepatocellular Carcinoma which was examined with Tangeretin .
CONCLUSION : Tangeretin was @ @ @ @ @ @ @ , DFT analysis , ADMET prediction , and Molecular Dynamics simulation .
Tangeretin had good docking scores , fulfill the pharmacological properties through ADMET prediction , and the Protein-Ligand complex had good stability in Molecular Dynamics simulation .

BACKGROUND: Liver cancer is otherwise known as Hepatic cancer which originated from the liver. Hepatocellular carcinoma (HCC) is the common primary Liver cancer and is one of the emerging problems worldwide. Very few treatments are available to treat HCC, because the molecular mechanism and other HCC mechanisms are still unclear. Cyclooxygenase 2 (COX-2), one of the most promising targets for Hepatocellular Carcinoma and it is one of the dimeric enzymes which convert Arachidonic acid into Prostaglandin H2 in the step of Prostaglandin biosynthesis. Several, natural bioactive compounds involved in the treatment of various types of cancer. Tangeretin, one of the natural polymethoxyflavone which is present in the peel of citrus fruits and it also acts as an Anti-oxidant modulator and Anti-cancerous.
METHODS: Computational approaches like Molecular docking and Molecular dynamics was performed to identify the potential inhibitor for Hepatocellular Carcinoma.
OBJECTIVES: The main objective of this study is to find a suitable inhibitor for Hepatocellular Carcinoma.
RESULTS: In this study, COX-2 considered as the potential target for Hepatocellular Carcinoma which was examined with Tangeretin.
CONCLUSION: Tangeretin was screened against C0X-2 which includes Molecular Docking, DFT analysis, ADMET prediction, and Molecular Dynamics simulation. Tangeretin had good docking scores, fulfill the pharmacological properties through ADMET prediction, and the Protein-Ligand complex had good stability in Molecular Dynamics simulation.


greenmedinfo--2020-06-03--Nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. p

Nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.

Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer .
Consequently , meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans .
Nobiletin , an important dietary polymethoxylated flavonoid in citrus fruits , possesses multidimensional pharmaceutical properties , including its ability to act as an anticancer , anti-inflammatory , antioxidative , cardiovascularly defensive , neuroprotective , and antimetabolic agent .
Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial ( GES ) -1 cell line .
@ @ @ @ @ @ @ of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species ( ROS ) , mediating DNA injury and augmenting nuclear fragmentations .
Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells .
Phosphatidylinositol-3 kinase ( PI3K ) /protein kinase B ( AKT ) /phosphatase and tensin homolog signaling have been implicated to affect cell endurance , inflammation , proliferation , and carcinogenic activity in gastric GES-1 cells .
We find that nobiletin strongly @ @ @ @ @ @ @ cyclooxygenase-2 , PI3K , AKT , and mitogen-activated protein kinase molecules , including p38 , extracellular receptor kinase 1 , and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells .
We conclude that nobiletin potentially impedes H. pylori infection and its related activation , likely preventing H. pylori infection-mediated gastric cancer .

Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer. Consequently, meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans. Nobiletin, an important dietary polymethoxylated flavonoid in citrus fruits, possesses multidimensional pharmaceutical properties, including its ability to act as an anticancer, anti-inflammatory, antioxidative, cardiovascularly defensive, neuroprotective, and antimetabolic agent. Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial (GES)-1 cell line. Our results show that the culture system of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species (ROS), mediating DNA injury and augmenting nuclear fragmentations. Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/phosphatase and tensin homolog signaling have been implicated to affect cell endurance, inflammation, proliferation, and carcinogenic activity in gastric GES-1 cells. We find that nobiletin strongly impedes tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, PI3K, AKT, and mitogen-activated protein kinase molecules, including p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. We conclude that nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.


greenmedinfo--2020-06-03--Tangeretin: a mechanistic review of its pharmacological and therapeutic effects.

To date , a large number of synthetic drugs have been developed for the treatment and prevention of different disorders @ @ @ @ @ , diabetes mellitus , and cancer .
However , these drugs suffer from a variety @ @ @ @ @ and low efficacy .
In response to this problem , researchers have focused on the @ @ @ @ @ their valuable biological activities and low side effects .
Flavonoids consist of a wide range @ @ @ @ @ found in fruits and vegetables and demonstrate a number of pharmacological and therapeutic effects .
@ @ @ @ @ a key member of flavonoids that is extensively found in citrus peels .
It has @ @ @ @ @ as antioxidant , anti-inflammatory , antitumor , hepatoprotective , and neuroprotective effects .
In the @ @ @ @ @ the various pharmacological and therapeutic effects of TGN and then , demonstrate how this naturally @ @ @ @ @ to exert its impacts .

To date, a large number of synthetic drugs have been developed for the treatment and prevention of different disorders, such as neurodegenerative diseases, diabetes mellitus, and cancer. However, these drugs suffer from a variety of drawbacks including side effects and low efficacy. In response to this problem, researchers have focused on the plant-derived natural products due to their valuable biological activities and low side effects. Flavonoids consist of a wide range of naturally occurring compounds exclusively found in fruits and vegetables and demonstrate a number of pharmacological and therapeutic effects. Tangeretin (TGN) is a key member of flavonoids that is extensively found in citrus peels. It has different favorable biological activities such as antioxidant, anti-inflammatory, antitumor, hepatoprotective, and neuroprotective effects. In the present review, we discuss the various pharmacological and therapeutic effects of TGN and then, demonstrate how this naturally occurring compound affects signaling pathways to exert its impacts.


greenmedinfo--2020-06-03--These findings indicated that the modulation of lipid homeostasis might be the key pathways for the

These findings indicated that the modulation of lipid homeostasis might be the key pathways for the mechanisms of tangeretin in the antiobesity.

Tangeretin ( TAN ) exhibited antilipogenic , antidiabetic , and lipid-lowering effects .
However , the lipid biomarkers and the @ @ @ @ @ cholesterol-lowering effects of TAN have not been sufficiently investigated .
Herein , we integrated biochemical @ @ @ @ @ its efficacy and mechanisms in high-fat diet-fed rats .
TAN at supplementation levels of 0.04 @ @ @ @ @ significantly decreased body weight gain , serum total cholesterol , and low-density lipoprotein cholesterol levels @ @ @ @ @ .
These beneficial effects were associated with the declining levels of fatty acids , diacylglycerols @ @ @ @ @ , ceramides , and cholesteryl esters by hepatic lipidomics analysis , which were attributed to @ @ @ @ @ lipid oxidation- and bile acid biosynthesis-related genes .
Additionally , 21 lipids were identified as @ @ @ @ @ as DGs and phosphatidylethanolamines .
These findings indicated that the modulation of lipid homeostasis might @ @ @ @ @ the mechanisms of TAN in the antiobesity and cholesterol-lowering effects .

Tangeretin (TAN) exhibited antilipogenic, antidiabetic, and lipid-lowering effects. However, the lipid biomarkers and the underlying mechanisms for antiobesity and cholesterol-lowering effects of TAN have not been sufficiently investigated. Herein, we integrated biochemical analysis with lipidomics to elucidate its efficacy and mechanisms in high-fat diet-fed rats. TAN at supplementation levels of 0.04 and 0.08% not only significantly decreased body weight gain, serum total cholesterol, and low-density lipoprotein cholesterol levels but also ameliorated hepatic steatosis. These beneficial effects were associated with the declining levels of fatty acids, diacylglycerols (DGs), triacylglycerols, ceramides, and cholesteryl esters by hepatic lipidomics analysis, which were attributed to downregulating lipogenesis-related genes and upregulating lipid oxidation- and bile acid biosynthesis-related genes. Additionally, 21 lipids were identified as potential lipid biomarkers, such as DGs and phosphatidylethanolamines. These findings indicated that the modulation of lipid homeostasis might be the key pathways for the mechanisms of TAN in the antiobesity and cholesterol-lowering effects.


greenmedinfo--2020-06-03--Tangeretin ameliorates erectile and testicular dysfunction.

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities .
This study examined whether tangeretin improved @ @ @ @ @ ester hydrochloride ( L-NAME ) -induced hypertensive rats .
Male Sprague-Dawley rats received L-NAME to @ @ @ @ @ for 5 w and were treated with tangeretin ( 15 or 30 mg/kg ) or @ @ @ @ @ ) for the final two weeks .
Mean arterial pressure ( MAP ) , intracavernosal @ @ @ @ @ to cavernous nerve stimulation , endothelial nitric oxide synthase ( eNOS ) , Angiotensin II @ @ @ @ @ ) and gp91protein expressions and malondialdehyde ( MDA ) level in penile tissues were measured @ @ @ @ @ , seminiferous tubule morphology , serum testosterone , testicular eNOS and steroidogenic acute regulatory protein @ @ @ @ @ evaluated .
Aortic superoxide generation , plasma and testicular MDA and plasma nitrate/nitrite levels were @ @ @ @ @ pressure and increased the maximum ICP/MAP associated with suppression of ATR/gp91phox and upregulation of eNOS @ @ @ @ @ P

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in N-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (ATR) and gp91protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of ATR/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and ATR/gp91expressions and testicular eNOS and StAR expression.


greenmedinfo--2020-06-03--Bioactivity-guided identification of anti-adipogenic isothiocyanates in the Moringa oleifera.

Due to the side effects of obesity medications , many studies have focused on the natural products used in the @ @ @ @ @ .
Moringa seed pods and leaves are widely used as vegetables or diet supplements due @ @ @ @ @ .
However , no bioactivity-guided anti-adipogenic study was previously conducted .
Therefore , a preadipocyte @ @ @ @ @ the bioactivity assay to identify the anti-adipogenic compounds in the peeled Moringa seed .
Two @ @ @ @ @ ) were isolated and identified .
Compound , 4- ( α-l-rhamnosyloxy ) benzyl isothiocyanateshowed a @ @ @ @ @ ICvalue of 9.2μg/mL .
The isothiocyanate ( ITC ) group in compoundcould be responsible for @ @ @ @ @ addition , a series of compounds with the ITC group were used to further investigate @ @ @ @ @ foods containing ITC derivatives have the potential of being used to control weight .

Due to the side effects of obesity medications, many studies have focused on the natural products used in the daily diet to control weight. Moringa seed pods and leaves are widely used as vegetables or diet supplements due to the high nutrition value. However, no bioactivity-guided anti-adipogenic study was previously conducted. Therefore, a preadipocyte cell line was adopted as the bioactivity assay to identify the anti-adipogenic compounds in the peeled Moringa seed. Two known sulphur-containing compounds (and) were isolated and identified. Compound, 4-(α-l-rhamnosyloxy) benzyl isothiocyanateshowed a great anti-adipogneic effect with an ICvalue of 9.2μg/mL. The isothiocyanate (ITC) group in compoundcould be responsible for the inhibitory activity. In addition, a series of compounds with the ITC group were used to further investigate the structure-activity relationship, indicating foods containing ITC derivatives have the potential of being used to control weight.


greenmedinfo--2020-06-03--Anti-hyperalgesic properties of ethanolic crude extract from the peels of Citrus reticulate.

The therapeutic effects from Citrus reticulata on painful inflammatory ailments are associated to its flavonoids constituent and phytochemical studies with Citrus genus affirm that the peels have important amounts of it .
These bioactive compounds have been a considerable therapeutic source and evaluate potential application of the peel extract is significant .
This research aims to investigate the influence of ethanolic crude extract from the peels of Citrus reticulata and its possible mechanism of action in different animal models of pain .
The extract reduced hyperalgesia in the second phase of formalin test ( vehicle : 501.5± 40.0 s ; @ @ @ @ @ @ @ ± 41.1 s ) , in the carrageenan model ( vehicle at 4th h : 82.5 ± 9.6 % ; C. reticulata extract 300 mg/kg at 4th h : 47.5 ± 6.5 % ) and in Complete Freund 's Adjuvant model ( vehicle : 501.5 ± 40.0 s ; C. reticulata extract 300 mg/kg : 161.8 ± 41.1 s ) .
Thepossible contribution of opioidergic and adenosinergic systems in the anti-hyperalgesic effect of C. reticulata extract was observed after treatment , with non-selective antagonists for both systems , which produced reversal effects .
@ @ @ @ @ @ @ reticulata extract suggest a potential therapeutic benefit in treating painful conditions .

The therapeutic effects from Citrus reticulata on painful inflammatory ailments are associated to its flavonoids constituent and phytochemical studies with Citrus genus affirm that the peels have important amounts of it. These bioactive compounds have been a considerable therapeutic source and evaluate potential application of the peel extract is significant. This research aims to investigate the influence of ethanolic crude extract from the peels of Citrus reticulata and its possible mechanism of action in different animal models of pain. The extract reduced hyperalgesia in the second phase of formalin test (vehicle: 501.5± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s), in the carrageenan model (vehicle at 4th h: 82.5 ± 9.6 %; C. reticulata extract 300 mg/kg at 4th h: 47.5 ± 6.5 %) and in Complete Freund's Adjuvant model (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s). Thepossible contribution of opioidergic and adenosinergic systems in the anti-hyperalgesic effect of C. reticulata extract was observed after treatment, with non-selective antagonists for both systems, which produced reversal effects. In conclusion, these properties of C. reticulata extract suggest a potential therapeutic benefit in treating painful conditions.


greenmedinfo--2020-06-04--Anti-inflammatory and wound healing potential of a clove oil emulsion.

Emulsion formulations of essential oils are of major interest due to their relative biosafety , biocompatibility and good pharmacological potential .
Their structural constituents ( oil and water phase ) facilitate ready solubilization of incorporated hydrophilic/lipophilic actives for their targeted delivery .
In the present study , m5S cells were tested for their viability at various concentrations of clove oil and an alkyl polyglucoside emulsifier , viz.
, Montanov 202™ .
Thereafter , good cell viable concentrations of oil ( 10 % ) and emulsifier ( 4 % ) were used at their optimised ratio ( 1:0.4 ) to formulate @ @ @ @ @ @ @ inversion technique followed by ultrasonication for particle size reduction .
Gas chromatography-mass spectrometry ( GC-MS ) analysis of clove oil revealed eugenol ( 76.11 % ) and eugenyl acetate ( 12.41 % ) as major constituents .
The formulated clove oil emulsion was then characterised with respect to its size , zeta potential , microscopic and thermal analysis and the presence of liquid crystals were observed in the same .
It was further studied for its anti-inflammatory potential in female Wistar rats wherein topical treatment with the emulsion inhibited paw swelling induced by @ @ @ @ @ @ @ min compared to untreated animals .
Similarly , the emulsion 's wound healing potential was also significant with respect to wounds induced by both incision ( wound breaking strength of 338.91 ± 5.02 g ) and excision ( 95 % wound contraction by 16th day ) model in these animals , with a re-epithelization period of 10.67 ± 1.67 days and results being comparable with diclofenac gel and neomycin cream ( positive controls ) .
Histopathology of the skin sections showed accelerated healing with early granular tissue and collagen formation in emulsion treated @ @ @ @ @ @ @ this clove oil emulsion can substitute chemical based topical products for anti-inflammatory and wound healing applications due to its biological constituents as well as because of the presence of liquid crystals in its formulation .

Emulsion formulations of essential oils are of major interest due to their relative biosafety, biocompatibility and good pharmacological potential. Their structural constituents (oil and water phase) facilitate ready solubilization of incorporated hydrophilic/lipophilic actives for their targeted delivery. In the present study, m5S cells were tested for their viability at various concentrations of clove oil and an alkyl polyglucoside emulsifier, viz., Montanov 202™. Thereafter, good cell viable concentrations of oil (10 %) and emulsifier (4%) were used at their optimised ratio (1:0.4) to formulate an oil in water emulsion using phase inversion technique followed by ultrasonication for particle size reduction. Gas chromatography-mass spectrometry (GC-MS) analysis of clove oil revealed eugenol (76.11 %) and eugenyl acetate (12.41 %) as major constituents. The formulated clove oil emulsion was then characterised with respect to its size, zeta potential, microscopic and thermal analysis and the presence of liquid crystals were observed in the same. It was further studied for its anti-inflammatory potential in female Wistar rats wherein topical treatment with the emulsion inhibited paw swelling induced by carrageenan model by 40-60% over 30-180 min compared to untreated animals. Similarly, the emulsion's wound healing potential was also significant with respect to wounds induced by both incision (wound breaking strength of 338.91 ± 5.02 g) and excision (95 % wound contraction by 16th day) model in these animals, with a re-epithelization period of 10.67 ± 1.67 days and results being comparable with diclofenac gel and neomycin cream (positive controls). Histopathology of the skin sections showed accelerated healing with early granular tissue and collagen formation in emulsion treated animals. It is hence envisaged that this clove oil emulsion can substitute chemical based topical products for anti-inflammatory and wound healing applications due to its biological constituents as well as because of the presence of liquid crystals in its formulation.


greenmedinfo--2020-06-04--Evaluation of encapsulated eugenol by chitosan nanoparticles on the aggressive model of rheumatoid a

Evaluation of encapsulated eugenol by chitosan nanoparticles on the aggressive model of rheumatoid arthritis.

Chitosan Nanoparticles Eugenol recognizes as a potent antioxidant that can use the first therapeutic chemical to treat rheumatoid arthritis ( RA ) instead of Methotrexate .
The purpose of this study was to investigate the effects of Chitosan Nanoparticles Eugenol as a potent Nano-herbal agent in the healing process of experimental neonatal RA compared to Methotrexate .
The neonatal Wistar rats induced rheumatoid arthritis in both genders were divided into sham , control , the treatment receiving Methotrexate , and the second treatment receiving encapsulated Eugenol by Chitosan Nanoparticles groups .
Afterward , Malondialdehyde , for assessment of lipid peroxidation @ @ @ @ @ @ @ kit , FOXO3 protein as an antioxidant up-regulating by western blotting and expression of the TGF-β and CCL2/MCP-1 genes by real-time PCR evaluation , supported by a cartilage histopathology analysis .
Based on these results , Methotrexate and Eugenol encapsulated by Chitosan Nanoparticles , a significant decrease is observed in the serum level of MDA and FOXO3 protein expression in comparison to the control group .
Additionally , Nanoparticle herbal agent and Methotrexate has a decreasing effect on the expression of TGF-β and MCP-1 genes and a significant positive correlation was observed between @ @ @ @ @ @ @ hyperplasia , and pannus formation were extreme in the Collagen Induced Arthritis rats .
It can be concluded that Encapsulated Eugenol by Chitosan Nanoparticles and Methotrexate , probably by dint of their immunomodulatory , anti-inflammatory , and antioxidant potential has a protective effect against RA .
Nano Eugenol is capable of delivering promising linesresults to treat autoimmune diseases such as RA can also be suggested .

Chitosan Nanoparticles Eugenol recognizes as a potent antioxidant that can use the first therapeutic chemical to treat rheumatoid arthritis (RA) instead of Methotrexate. The purpose of this study was to investigate the effects of Chitosan Nanoparticles Eugenol as a potent Nano-herbal agent in the healing process of experimental neonatal RA compared to Methotrexate. The neonatal Wistar rats induced rheumatoid arthritis in both genders were divided into sham, control, the treatment receiving Methotrexate, and the second treatment receiving encapsulated Eugenol by Chitosan Nanoparticles groups. Afterward, Malondialdehyde, for assessment of lipid peroxidation as an oxidative stress biomarker by assay kit, FOXO3 protein as an antioxidant up-regulating by western blotting and expression of the TGF-β and CCL2/MCP-1 genes by real-time PCR evaluation, supported by a cartilage histopathology analysis. Based on these results, Methotrexate and Eugenol encapsulated by Chitosan Nanoparticles, a significant decrease is observed in the serum level of MDA and FOXO3 protein expression in comparison to the control group. Additionally, Nanoparticle herbal agent and Methotrexate has a decreasing effect on the expression of TGF-β and MCP-1 genes and a significant positive correlation was observed between MCP-1 and TGF-β. Inflammation, synovial hyperplasia, and pannus formation were extreme in the Collagen Induced Arthritis rats. It can be concluded that Encapsulated Eugenol by Chitosan Nanoparticles and Methotrexate, probably by dint of their immunomodulatory, anti-inflammatory, and antioxidant potential has a protective effect against RA. Nano Eugenol is capable of delivering promising linesresults to treat autoimmune diseases such as RA can also be suggested.


greenmedinfo--2020-06-03--Synergistic effect of eugenol and probiotic Lactobacillus plantarum Zs2058 against salmonella infect

Synergistic effect of eugenol and probiotic Lactobacillus plantarum Zs2058 against salmonella infection.

Previously , we showed the preventive effects ofZS2058 ( ZS2058 ) oninfection in murine models .
In this work , we found that eugenol has a selective antibacterial effect , which inhibitedmore than probiotics ZS2058 in vitro .
It suggested a synergistic effect of them beyond their individual anti-activity .
We verified the conjecture in murine models .
The results showed that the combination of ZS2058 and eugenol ( CLPZE ) significantly increased ( = 0.026 ) the survival rate of-infected mice from 60 % to 80 % and the effect of CLPZE on preventing-infection was 2-fold that of ZS2058 @ @ @ @ @ @ @ .
CLPZE had a synergistic effect on inhibiting ST growth ( the coefficient drug interaction ( ( CDI ) = 0.829 ) , reducing its invasiveness ( CDI = 0.373 ) and downregulating virulence genes ' expression in vitro .
CLPZE helped the host form a healthier gut ecosystem .
CLPZE also elicited a stronger and earlier immune response to systemic infection .
In conclusion , these obtained results suggest that ZS2058 and eugenol have a synergistic effect on preventinginfection and open new perspectives in the strategies of controlling the prevalence ofby combination @ @ @ @ @ @ @

Previously, we showed the preventive effects ofZS2058 (ZS2058) oninfection in murine models. In this work, we found that eugenol has a selective antibacterial effect, which inhibitedmore than probiotics ZS2058 in vitro. It suggested a synergistic effect of them beyond their individual anti-activity. We verified the conjecture in murine models. The results showed that the combination of ZS2058 and eugenol (CLPZE) significantly increased (= 0.026) the survival rate of-infected mice from 60% to 80% and the effect of CLPZE on preventing-infection was 2-fold that of ZS2058 alone and 6-fold that of eugenol alone. CLPZE had a synergistic effect on inhibiting ST growth (the coefficient drug interaction ((CDI) = 0.829), reducing its invasiveness (CDI = 0.373) and downregulating virulence genes' expression in vitro. CLPZE helped the host form a healthier gut ecosystem. CLPZE also elicited a stronger and earlier immune response to systemic infection. In conclusion, these obtained results suggest that ZS2058 and eugenol have a synergistic effect on preventinginfection and open new perspectives in the strategies of controlling the prevalence ofby combination of probiotics and functional food components.


greenmedinfo--2020-06-03--Docosahexaenoic acid-rich fish oil supplementation reduces kinase associated with insulin resistance

Docosahexaenoic acid-rich fish oil supplementation reduces kinase associated with insulin resistance in overweight and obese midlife adults.

Targeting kinases linked to insulin resistance ( IR ) and inflammation may help in reducing the risk of type 2 diabetes ( T2D ) and Alzheimer 's disease ( AD ) in its early stages .
This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase ( GSK-3 ) , which is linked to both IR and AD .
Baseline and post-intervention plasma samples from 58 adults with abdominal obesity ( Age : 51.7± 1.7 years , BMI : 31.9 ± 0.8 kg/m ) were analysed for outcome measures .
Participants were allocated to 2 g @ @ @ @ @ @ @ DHA + 120 mg EPA ) ( n = 31 ) or placebo capsules ( n = 27 ) per day for 12 weeks .
Compared to placebo , DHA-rich fish oil significantly reduced GSK-3β by -2.3 ± 0.3 ng/mL .
An inverse correlation ( < 0.05 ) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L .
DHA-rich fish oil reduces GSK-3 and IR , suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids ( LCn-3PUFA ) @ @ @ @ @

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer's disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7± 1.7 years, BMI: 31.9 ± 0.8 kg/m) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3β by -2.3 ± 0.3 ng/mL. An inverse correlation (<0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk.


greenmedinfo--2020-06-03--Unique triterpenoid of jujube root protects cisplatin-induced damage in kidney epithelial LLC-PK1 ce

Unique triterpenoid of jujube root protects cisplatin-induced damage in kidney epithelial LLC-PK1 cells.

Chronic exposure to cisplatin is associated with irreversible kidney impairment .
In this present study , we explored the protective @ @ @ @ @ ester ( 3DC2ME ) isolated from roots of jujube ( , Rhamnaceae ) against cisplatin-induced @ @ @ @ @ kidney epithelial LLC-PK1 cells , western blotting and staining with specific autophagy epifluorescent dye CytoID @ @ @ @ @ molecular pathways involving autophagy .
Treatment with 3DC2ME reduced the increased Cyto-ID-stained autophagic vesicles and @ @ @ @ @ 5 ' AMP-activated protein kinase subunitβ-1 ( AMPK ) /mammalian target of rapamycin ( mTOR @ @ @ @ @ cisplatin-induced cell death .
Additionally , treatment with autophagy inhibitor 3-methyladenine ( 3-MA ) and @ @ @ @ @ the cisplatin-induced apoptosis .
Although further research is necessary to substantiate the effects , we @ @ @ @ @ action of 3DC2ME as an adjuvant for cancer patients .

Chronic exposure to cisplatin is associated with irreversible kidney impairment. In this present study, we explored the protective effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from roots of jujube (, Rhamnaceae) against cisplatin-induced damage in vitro. In kidney epithelial LLC-PK1 cells, western blotting and staining with specific autophagy epifluorescent dye CytoID were used to determine the molecular pathways involving autophagy. Treatment with 3DC2ME reduced the increased Cyto-ID-stained autophagic vesicles and reversed the protein expressions of 5' AMP-activated protein kinase subunitβ-1 (AMPK)/mammalian target of rapamycin (mTOR)-dependent signaling pathway in cisplatin-induced cell death. Additionally, treatment with autophagy inhibitor 3-methyladenine (3-MA) and with or without 3DC2ME attenuated the cisplatin-induced apoptosis. Although further research is necessary to substantiate the effects, we evaluated the potential mechanism of action of 3DC2ME as an adjuvant for cancer patients.


greenmedinfo--2020-06-04--Red orange and lemon extract could prevent the renal damage induced by diabetic nephropathy.

Diabetic nephropathy ( DN ) is the primary cause of end-stage renal disease , worldwide , and oxidative stress has been recognized as a key factor in the pathogenesis and progression of DN .
Nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidase has the most important contribution to reactive oxygen species generation during the development of DN .
Bioactive compound use has emerged as a potential approach to reduce chronic renal failure .
Therefore , a red orange and lemon extract ( RLE ) rich in anthocyanins was chosen in our study , to reduce the toxic renal effects during @ @ @ @ @ @ @ fatty rat ( ZDF ) .
RLE effects were examined daily for 24 weeks , through gavage , in ZDF rats treated with RLE ( 90 mg/kg ) .
At the end of the experiment , ZDF rats treated with RLE showed a reduction of the diabetes-associated up-regulation of both NOX4 and the p47-phox and p22-phox subunits , and restored the BAX/BCL-2 ratio respect to ZDF rats .
Furthermore , RLE was able to reduce the oxidative DNA damage measured in urine samples in ZDF rats .
This study showed that RLE could @ @ @ @ @ @ @ through its capacity to inhibit NOX4 and apoptosis mechanisms .

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, worldwide, and oxidative stress has been recognized as a key factor in the pathogenesis and progression of DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has the most important contribution to reactive oxygen species generation during the development of DN. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, a red orange and lemon extract (RLE) rich in anthocyanins was chosen in our study, to reduce the toxic renal effects during the development of DN in Zucker diabetic fatty rat (ZDF). RLE effects were examined daily for 24 weeks, through gavage, in ZDF rats treated with RLE (90 mg/kg). At the end of the experiment, ZDF rats treated with RLE showed a reduction of the diabetes-associated up-regulation of both NOX4 and the p47-phox and p22-phox subunits, and restored the BAX/BCL-2 ratio respect to ZDF rats. Furthermore, RLE was able to reduce the oxidative DNA damage measured in urine samples in ZDF rats. This study showed that RLE could prevent the renal damage induced by DN through its capacity to inhibit NOX4 and apoptosis mechanisms.


greenmedinfo--2020-06-04--The Power and Mystery of Melanin Explained [Excerpt from Sayer Ji's REGENERATE]

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greenmedinfo--2020-06-04--The results suggest that curcumin synergizes with either flavocoxid or β-caryophyllene, exerting an

The results suggest that curcumin synergizes with either flavocoxid or β-caryophyllene, exerting an anti-inflammatory activity.

Drug combination is widely used to treat chronic inflammatory diseases .
A similar strategy might be worth of interest to design plant-derived natural products to treat inflammatory conditions .
Curcumin is a natural phenolic compound which shares anti-inflammatory activity with both flavocoxid , a flavonoid mixture of baicalin and catechin , andβ-caryophyllene , a bicyclic sesquiterpene .
The aim of this study was to investigate the synergy potential of curcumin with both flavocoxid and β-caryophyllene in human articular chondrocytes triggered with lipopolysaccharide ( LPS ) , in an experimentalmodel of osteoarthritis.Human articular chondrocytes were stimulated with LPS alone or in @ @ @ @ @ @ @ was extracted 4 h after treatment to study interleukin 1β ( IL-1β ) , NF-κB , and STAT3 mRNA expression .
A drug combination study was designed choosing 5 doses to demonstrate a synergistic effect of compounds , according to Chou and Talalay method .
A median-effect equation was applied and finally , the combination index ( CI ) was used to clarify the nature of the compounds interaction ( synergistic versus additive versus antagonistic inhibitory effects ) ; CI < 1 , CI = 1 , and CI > 1 indicated synergistic @ @ @ @ @ @ @ respectively.LPS prompted IL-1β expression .
Curcumin , flavocoxid and β-caryophyllene suppressed IL-1β expression with different IC .
A synergistic action for the reduction of the inflammatory phenotype in human chondrocytes was observed for the combination curcumin-flavocoxid with a percentage from 10 % to 90 % , and for the combination curcumin-β-caryophyllene from 50 % to 90 % .
ICdoses of either flavocoxid , β-caryophyllene and curcumin alone or in combination were safe and did not affect cell vitality .
Moreover , the same ICdoses reduced the transcription factors NF-κB and STAT3 mRNA expression @ @ @ @ @ @ @ were greater than the natural products alone , thus suggesting that the site where the synergy takes place could be at the signal transduction level.The results suggest that curcumin synergizes with either flavocoxid orβ-caryophyllene , exerting an anti-inflammatory activity and thus strongly suggesting the potential of a dual combination of these compounds for the management of osteoarthritis and unmasking a new feature of these natural products .

Drug combination is widely used to treat chronic inflammatory diseases. A similar strategy might be worth of interest to design plant-derived natural products to treat inflammatory conditions. Curcumin is a natural phenolic compound which shares anti-inflammatory activity with both flavocoxid, a flavonoid mixture of baicalin and catechin, andβ-caryophyllene, a bicyclic sesquiterpene. The aim of this study was to investigate the synergy potential of curcumin with both flavocoxid and β-caryophyllene in human articular chondrocytes triggered with lipopolysaccharide (LPS), in an experimentalmodel of osteoarthritis.Human articular chondrocytes were stimulated with LPS alone or in combination with different treatments. Total RNA was extracted 4 h after treatment to study interleukin 1β (IL-1β), NF-κB, and STAT3 mRNA expression. A drug combination study was designed choosing 5 doses to demonstrate a synergistic effect of compounds, according to Chou and Talalay method. A median-effect equation was applied and finally, the combination index (CI) was used to clarify the nature of the compounds interaction (synergistic versus additive versus antagonistic inhibitory effects); CI<1, CI = 1, and CI>1 indicated synergistic, additive, and antagonistic effects, respectively.LPS prompted IL-1β expression. Curcumin, flavocoxid and β-caryophyllene suppressed IL-1β expression with different IC. A synergistic action for the reduction of the inflammatory phenotype in human chondrocytes was observed for the combination curcumin-flavocoxid with a percentage from 10% to 90%, and for the combination curcumin-β-caryophyllene from 50% to 90%. ICdoses of either flavocoxid,β-caryophyllene and curcumin alone or in combination were safe and did not affect cell vitality. Moreover, the same ICdoses reduced the transcription factors NF-κB and STAT3 mRNA expression and interestingly the effects of the combinations were greater than the natural products alone, thus suggesting that the site where the synergy takes place could be at the signal transduction level.The results suggest that curcumin synergizes with either flavocoxid orβ-caryophyllene, exerting an anti-inflammatory activity and thus strongly suggesting the potential of a dual combination of these compounds for the management of osteoarthritis and unmasking a new feature of these natural products.


greenmedinfo--2020-06-04--Citrus aurantium dry extracts ameliorate adipocyte differentiation of 3T3-L1 cells exposed to TNFα b

Citrus aurantium dry extracts ameliorate adipocyte differentiation of 3T3-L1 cells exposed to TNFα by down-regulating miR-155 expression.

L. dry extracts ( de ) improve adipogenesis in vitro .
These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta ( ) expression and cyclic Adenosine Monophosphate ( cAMP ) response element-binding protein ( ) activation.andare also targets of .
This study investigated whetherde regulatesexpression in the early stages of adipogenesis and whether it ameliorates adipocyte differentiation of cells exposed to tumor necrosis factor-alpha ( TNFα ) .
Adipogenic stimuli ( AS ) were performed in 3T3-L1 pre-adipocytes treated withde , TNFα , or both .
Gene and miRNA expression were determined by quantitative real-time PCR .
@ @ @ @ @ @ @ treatment enhanced AS effects during the early adipogenesis phases by further down-regulatingexpression and increasing bothandmRNA and protein levels .
At variance , TNFα inhibited 3T3-L1 adipogenesis and abolished AS effects on , , andexpression .
However , in cells exposed to TNFα , de improved adipocyte differentiation and restored the AS effects on miRNA and gene expression at early time points .
In conclusion , this study identifieddown-regulation as part of the mechanism through whichde enhances adipogenesis of pre-adipocytes in vitro .
Furthermore , it provides evidence ofde efficacy against TNFα negative effects @ @ @

L. dry extracts (de) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta () expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein () activation.andare also targets of. This study investigated whetherde regulatesexpression in the early stages of adipogenesis and whether it ameliorates adipocyte differentiation of cells exposed to tumor necrosis factor-alpha (TNFα). Adipogenic stimuli (AS) were performed in 3T3-L1 pre-adipocytes treated withde, TNFα, or both. Gene and miRNA expression were determined by quantitative real-time PCR. Adipogenesis was evaluated by Oil-Red O staining.de treatment enhanced AS effects during the early adipogenesis phases by further down-regulatingexpression and increasing bothandmRNA and protein levels. At variance, TNFα inhibited 3T3-L1 adipogenesis and abolished AS effects on,, andexpression. However, in cells exposed to TNFα,de improved adipocyte differentiation and restored the AS effects on miRNA and gene expression at early time points. In conclusion, this study identifieddown-regulation as part of the mechanism through whichde enhances adipogenesis of pre-adipocytes in vitro. Furthermore, it provides evidence ofde efficacy against TNFα negative effects on adipogenesis.


greenmedinfo--2020-06-04--Beta-caryophyllene enhances wound healing through multiple routes.

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices .
Recently , it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 ( CB2 ) .
Activation of CB2 will decrease pain , a major signal for inflammatory responses .
We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation .
Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization .
The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration , suggesting that the higher re-epithelialization is due to enhanced cell @ @ @ @ @ @ @ tissues also had up-regulated gene expression for hair follicle bulge stem cells .
Olfactory receptors were not involved in the enhanced wound healing .
Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene .
Interestingly , there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene .
Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing , an effect generated by synergetic impacts of multiple @ @

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.


greenmedinfo--2020-06-04--Top Five Natural Antiviral Agents

Top Five Natural Antiviral Agents


greenmedinfo--2020-06-04--The present findings suggest that β-Caryophyllene has significant anti-nicotine effects.

BACKGROUND AND PURPOSE : β-Caryophyllene ( BCP ) is a plant-derived terpenoid used as a food additive for many decades .
Recent studies indicate that BCP is a cannabinoid CBreceptor agonist with medical benefits for a number of human diseases .
However , little is known about its therapeutic potential for drug abuse and addiction .
EXPERIMENT APPROACH : We used pharmacological , transgenic , and optogenetic approaches to systematically evaluate the effects of BCP on nicotine-taking and nicotine-seeking behaviour in animal models of drug self-administration , electrical , and optical brain-stimulation reward .
KEY RESULTS : Systemic administration of @ @ @ @ @ @ @ for nicotine seeking in rats and mice .
The reduction in nicotine self-administration was blocked by AM630 , a selective CBreceptor antagonist , but not by AM251 , a selective CBreceptor antagonist , suggesting involvement of a CBreceptor mechanism .
Genetic deletion of CBreceptors in mice blocked the reduction in nicotine self-administration produced only by low doses , but not by high doses , of BCP , suggesting involvement of both CBand non-CBreceptor mechanisms .
Furthermore , in the intracranial self-stimulation paradigm , BCP attenuated electrical brain-stimulation reward and nicotine-enhanced brain-stimulation reward in @ @ @ @ @ @ @ brain-stimulation reward maintained by optogenetic stimulation of dopaminergic neurons in the ventral tegmental area in DAT-cre mice , suggesting the involvement of a dopamine-dependent mechanism in BCP 's action .
CONCLUSIONS AND IMPLICATIONS : The present findings suggest that BCP has significant anti-nicotine effects via both CBand non-CBreceptor mechanisms and , therefore , deserves further study as a potential new pharmacotherapy for cigarette smoking cessation .

BACKGROUND AND PURPOSE: β-Caryophyllene (BCP) is a plant-derived terpenoid used as a food additive for many decades. Recent studies indicate that BCP is a cannabinoid CBreceptor agonist with medical benefits for a number of human diseases. However, little is known about its therapeutic potential for drug abuse and addiction.
EXPERIMENT APPROACH: We used pharmacological, transgenic, and optogenetic approaches to systematically evaluate the effects of BCP on nicotine-taking and nicotine-seeking behaviour in animal models of drug self-administration, electrical, and optical brain-stimulation reward.
KEY RESULTS: Systemic administration of BCP dose-dependently inhibited nicotine self-administration and motivation for nicotine seeking in rats and mice. The reduction in nicotine self-administration was blocked by AM630, a selective CBreceptor antagonist, but not by AM251, a selective CBreceptor antagonist, suggesting involvement of a CBreceptor mechanism. Genetic deletion of CBreceptors in mice blocked the reduction in nicotine self-administration produced only by low doses, but not by high doses, of BCP, suggesting involvement of both CBand non-CBreceptor mechanisms. Furthermore, in the intracranial self-stimulation paradigm, BCP attenuated electrical brain-stimulation reward and nicotine-enhanced brain-stimulation reward in rats. Lastly, BCP also attenuated brain-stimulation reward maintained by optogenetic stimulation of dopaminergic neurons in the ventral tegmental area in DAT-cre mice, suggesting the involvement of a dopamine-dependent mechanism in BCP's action.
CONCLUSIONS AND IMPLICATIONS: The present findings suggest that BCP has significant anti-nicotine effects via both CBand non-CBreceptor mechanisms and, therefore, deserves further study as a potential new pharmacotherapy for cigarette smoking cessation.


greenmedinfo--2020-06-04--Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression.

Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism .
The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors.β-Caryophyllene ( BCP ) is a CB2 agonist that exhibited anti-inflammatory , analgesic effects but minimal psychoactive effects .
To test if BCP exhibits antidepressant-like action , animals were chronically restrained with additional stressors for 28 days , and BCP ( 25 , 50 , 100 mg/kg ) was intraperitoneally injected once a day during the stress inflicting period .
Then despair related behaviors and hippocampal expression of neurotrophic , @ @ @ @ @ @ @ .
To test the effect of BCP on long-term depression , field potentials were measured during the application of lipopolysaccharide and low frequency stimulation .
In the tail suspension test and forced swim test , chronic stress-induced despair behaviors were reduced by BCP .
Also BCP improved the stress-related changes in the hippocampal expression of COX-2 , BDNF , and CB2 receptor expression .
In organotypic hippocampal slices , BCP reduced the lipopolysaccharide-induced intensification of the long-term depression .
In conclusion , BCP improved chronic stress related behavioral and biochemical changes .
These @ @ @ @ @ @ @ in treating depression and stress related mental illnesses .

Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism. The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors.β-Caryophyllene (BCP) is a CB2 agonist that exhibited anti-inflammatory, analgesic effects but minimal psychoactive effects. To test if BCP exhibits antidepressant-like action, animals were chronically restrained with additional stressors for 28 days, and BCP (25, 50, 100 mg/kg) was intraperitoneally injected once a day during the stress inflicting period. Then despair related behaviors and hippocampal expression of neurotrophic, inflammatory and cannabinoid receptor levels were measured. To test the effect of BCP on long-term depression, field potentials were measured during the application of lipopolysaccharide and low frequency stimulation. In the tail suspension test and forced swim test, chronic stress-induced despair behaviors were reduced by BCP. Also BCP improved the stress-related changes in the hippocampal expression of COX-2, BDNF, and CB2 receptor expression. In organotypic hippocampal slices, BCP reduced the lipopolysaccharide-induced intensification of the long-term depression. In conclusion, BCP improved chronic stress related behavioral and biochemical changes. These results suggest that BCP may be effective in treating depression and stress related mental illnesses.


greenmedinfo--2020-06-04--The study indicates a therapeutic approach to treat T2DM by Beta-caryophyllene and l-arginine combin

The study indicates a therapeutic approach to treat T2DM by Beta-caryophyllene and l-arginine combination as food and dietary supplement.

Beta-caryophyllene ( BCP ) is a flavoring agent , whereas l-arginine ( LA ) is used as a food supplement .
They possess insulinotropic andβ cell regeneration activities , respectively .
We assessed the antidiabetic potential of BCP , LA , and its combination in RIN-5F cell lines and diabetic rats .
Ex vivo studies were carried out for glucose uptake and absorption of the combination of BCP with LA .
The results indicated that the combination of BCP with LA showed a significant decrease in glucose absorption and an increase in its uptake in tissues and also an increase @ @ @ @ @ @ @ The combination treatment of BCP with LA showed a significant reduction in glucose , lipid levels , and oxidative stress in pancreatic tissue when compared with the diabetic group .
Furthermore , the combination of BCP with LA normalized glucose tolerance and pancreatic cell damage in diabetic rats .
In conclusion , the combinational treatment showed significant potentials in the treatment of type 2 diabetes mellitus .
PRACTICAL APPLICATIONS : Type 2 diabetes mellitus is the most prevalent chronic metabolic disorder affecting a large population .
Beta-caryophyllene is a CBreceptor agonist shown to @ @ @ @ @ @ @ food supplement that possesses beta-cell regeneration property .
The combination of BCP with LA could work as a potential therapeutic intervention , considering the individual pharmacological activities of each .
We evaluated the antidiabetic activity of the combination of BCP with LA in diabetic rats using ex vivo and in vitro experimentations .
Results from the study revealed that the combination of BCP with LA showed a significant ( p

Beta-caryophyllene (BCP) is a flavoring agent, whereas l-arginine (LA) is used as a food supplement. They possess insulinotropic andβ cell regeneration activities, respectively. We assessed the antidiabetic potential of BCP, LA, and its combination in RIN-5F cell lines and diabetic rats. Ex vivo studies were carried out for glucose uptake and absorption of the combination of BCP with LA. The results indicated that the combination of BCP with LA showed a significant decrease in glucose absorption and an increase in its uptake in tissues and also an increase in insulin secretion in RIN-5F cells. The combination treatment of BCP with LA showed a significant reduction in glucose, lipid levels, and oxidative stress in pancreatic tissue when compared with the diabetic group. Furthermore, the combination of BCP with LA normalized glucose tolerance and pancreatic cell damage in diabetic rats. In conclusion, the combinational treatment showed significant potentials in the treatment of type 2 diabetes mellitus. PRACTICAL APPLICATIONS: Type 2 diabetes mellitus is the most prevalent chronic metabolic disorder affecting a large population. Beta-caryophyllene is a CBreceptor agonist shown to have insulinotropic activity. l-Arginine is a food supplement that possesses beta-cell regeneration property. The combination of BCP with LA could work as a potential therapeutic intervention, considering the individual pharmacological activities of each. We evaluated the antidiabetic activity of the combination of BCP with LA in diabetic rats using ex vivo and in vitro experimentations. Results from the study revealed that the combination of BCP with LA showed a significant (p < .001) reduction in glucose and lipid levels as compared to individual treatment. In vitro study also supports the diabetic potential of the combination of BCP with LA in the glucose-induced insulin secretion in RIN-5F cell lines. The study indicates a therapeutic approach to treat T2DM by BCP andLA combination as food and dietary supplement.


greenmedinfo--2020-06-04--This review examines the phytochemical composition and biological activities of clove extracts.

Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases .
Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides , saponins , flavonoids , steroids , tannins , alkaloids , terpenes , etc .
Syzygium aromaticum ( clove ) is a traditional spice that has been used for food preservation and possesses various pharmacological activities .
S. aromaticum is rich in many phytochemicals as follows : sesquiterpenes , monoterpenes , hydrocarbon , and phenolic compounds .
Eugenyl acetate @ @ @ @ @ @ @ significant phytochemicals in clove oil .
Pharmacologically , S. aromaticum has been examined toward various pathogenic parasites and microorganisms , including pathogenic bacteria , Plasmodium , Babesia , Theileria parasites , Herpes simplex , and hepatitis C viruses .
Severalreports documented the analgesic , antioxidant , anticancer , antiseptic , anti-depressant , antispasmodic , anti-inflammatory , antiviral , antifungal , and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistantand .
Moreover , eugenol was found to protect against CClinduced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various @ @ @ @ @ @ @ examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound , eugenol , and implicates new findings from gas chromatography-mass spectroscopy ( GC-MS ) analysis .

Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, andβ-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Severalreports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistantand. Moreover, eugenol was found to protect against CClinduced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including,,and. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis.


greenmedinfo--2020-06-04--In vitro anticandidal potency of clove extracts against vaginal candidiasis.

BACKGROUND : Candida vaginitis is a global health hazard that increases morbidity among women of childbearing age .
Recent studies have revealed a high incidence of drug-resistant Candida strains .
Additionally , treating Candida vulvovaginitis during pregnancy is challenging as antifungal therapy is associated with fetal abnormalities .
Hence , it is important to develop novel therapeutic strategies to treat vulvovaginal candidiasis .
METHODS : In this study , we used the disc diffusion method to evaluate the anticandidal activity of different Syzygium aromaticum extracts ( methanol , ethyl acetate , n-hexane , and diethyl ether ) against C. albicans @ @ @ @ @ @ @ .
Furthermore , gas chromatography-mass spectrometry ( GC-MS ) analysis of different S. aromaticum extracts was performed to determine active components exhibiting anticandidal activity .
Cytotoxicity of different clove extracts against the HUH7 cell line was evaluated .
RESULTS : The ethyl acetate extract exhibited the highest antifungal activity against C. albicans , C. glabrata , and C. tropicalis with inhibition zone diameters of 20.9 , 14.9 , and 30.7 mm , respectively .
The minimum inhibitory concentration of the S. aromaticum ethyl acetate extract was 250 μg/disc against C. tropicalis , and @ @ @ @ @ @ @ glabrata , while the minimum fungicidal concentration was 0.5 mg/disc against C. tropicalis and 1 mg/disc against the C. albicans and C. glabrata .
GC-MS analysis of the ethyl acetate extract revealed the main bioactive compound as eugenol ( 58.88 % ) , followed by eugenyl acetate ( 23.86 % ) , trans-caryophyllene ( 14.44 % ) , and α-humulene ( 1.88 % ) .
The cytotoxicity assay indicated that the diethyl ether extract demonstrated the lowest toxicological effect against the HUH7 cell line , with a relative ICof 62.43 μg/ml ; the @ @ @ @ @ @ @ IC , 24.17 μg/ml ) .
CONCLUSION : As the S. aromaticum extract exhibited high antifungal activity at low concentrations , it can be a potential source of natural antifungal drugs .

BACKGROUND: Candida vaginitis is a global health hazard that increases morbidity among women of childbearing age. Recent studies have revealed a high incidence of drug-resistant Candida strains. Additionally, treating Candida vulvovaginitis during pregnancy is challenging as antifungal therapy is associated with fetal abnormalities. Hence, it is important to develop novel therapeutic strategies to treat vulvovaginal candidiasis.
METHODS: In this study, we used the disc diffusion method to evaluate the anticandidal activity of different Syzygium aromaticum extracts (methanol, ethyl acetate, n-hexane, and diethyl ether) against C. albicans, C. glabrata, and C. tropicalis. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of different S. aromaticum extracts was performed to determine active components exhibiting anticandidal activity. Cytotoxicity of different clove extracts against the HUH7 cell line was evaluated.
RESULTS: The ethyl acetate extract exhibited the highest antifungal activity against C. albicans, C. glabrata, and C. tropicalis with inhibition zone diameters of 20.9, 14.9, and 30.7 mm, respectively. The minimum inhibitory concentration of the S. aromaticum ethyl acetate extract was 250 μg/disc against C. tropicalis, and 500 μg/disc against C. albicans and C. glabrata, while the minimum fungicidal concentration was 0.5 mg/disc against C. tropicalis and 1 mg/disc against the C. albicans and C. glabrata. GC-MS analysis of the ethyl acetate extract revealed the main bioactive compound as eugenol (58.88%), followed by eugenyl acetate (23.86%), trans-caryophyllene (14.44%), and α-humulene (1.88%). The cytotoxicity assay indicated that the diethyl ether extract demonstrated the lowest toxicological effect against the HUH7 cell line, with a relative ICof 62.43 μg/ml; the methanolic extract demonstrated a higher toxicity (IC, 24.17 μg/ml).
CONCLUSION: As the S. aromaticum extract exhibited high antifungal activity at low concentrations, it can be a potential source of natural antifungal drugs.


greenmedinfo--2020-06-04--Inhibitory effects of β-caryophyllene on Helicobacter pylori infection in vitro and in vivo.

The human specific bacterial pathogen ( ) is associated with severe gastric diseases , including gastric cancer .
Recently , the increasing resistance makes the usage of antibiotics less effectively .
Therefore , development of a new antimicrobial agent is required to controlinfection .
In the current study , the inhibitory effect ofβ-caryophyllene ongrowth , as well as the antibacterial therapeutic effect , has been demonstrated.β-caryophyllene inhibitedgrowth via the downregulation ofE , N , B , andA and also downregulated virulence factors such as CagA , VacA , and SecA proteins.β-caryophyllene inhibited expression of several T4SS components , so that @ @ @ @ @ @ @ was decreased byβ-caryophyllene treatment .
β-caryophyllene also inhibited VacA entry through the downregulation of T5SS .
Afterβ-caryophyllene administration on Mongolian gerbils , the immunohistochemistry ( IHC ) and Hematoxylin & Eosin stains showed therapeutic effects in the treated groups .
Hematological data , which was consistent with histological data , support the therapeutic effect ofβ-caryophyllene administration .
Such a positive effect of β-caryophyllene oninfection potently substantiates the natural compound as being capable of being used as a new antimicrobial agent or functional health food to help patients who are suffering from gastroduodenal diseases @ @ @

The human specific bacterial pathogen() is associated with severe gastric diseases, including gastric cancer. Recently, the increasing resistance makes the usage of antibiotics less effectively. Therefore, development of a new antimicrobial agent is required to controlinfection. In the current study, the inhibitory effect ofβ-caryophyllene ongrowth, as well as the antibacterial therapeutic effect, has been demonstrated.β-caryophyllene inhibitedgrowth via the downregulation ofE,N,B, andA and also downregulated virulence factors such as CagA, VacA, and SecA proteins.β-caryophyllene inhibited expression of several T4SS components, so that CagA translocation into-infected AGS gastric cancer cells was decreased byβ-caryophyllene treatment. β-caryophyllene also inhibited VacA entry through the downregulation of T5SS. Afterβ-caryophyllene administration on Mongolian gerbils, the immunohistochemistry (IHC) and Hematoxylin&Eosin stains showed therapeutic effects in the treated groups. Hematological data, which was consistent with histological data, support the therapeutic effect ofβ-caryophyllene administration. Such a positive effect of β-caryophyllene oninfection potently substantiates the natural compound as being capable of being used as a new antimicrobial agent or functional health food to help patients who are suffering from gastroduodenal diseases due toinfection.


greenmedinfo--2020-06-04--Role of β-caryophyllene in the antinociceptive and anti-inflammatory effects of Tagetes lucida essen

Role of β-caryophyllene in the antinociceptive and anti-inflammatory effects of Tagetes lucida essential oil.

Cav .
( Asteraceae ) is an ancient medicinal plant commonly used to alleviate pain .
Nevertheless , scientific studies validating this property are lacking in the literature .
Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities ofessential oil ( TLEO ) and a bioactive metabolite .
The chemical constitution and possible toxicity of the extract and the mechanism of action ofβ-caryophyllene were also explored .
Temporal course curves and dose-response graphics were generated using TLEO ( 0.1-10 mg/kg or 3.16-31.62 mg/kg ) and β-caryophyllene ( 3.16-10 mg/kg ) .
Metamizole ( 80 mg/kg ) @ @ @ @ @ @ @ used as reference drugs in the formalin assay and writhingtest in rats and mice , respectively .
The β-caryophyllene mechanism of action was explored in the presence of naloxone ( 1 mg/kg ) , flumazenil ( 10 mg/kg ) , WAY100635 ( 0.16 mg/kg ) , or nitro-l-arginine methyl ester ( L-NAME ) ( 20 mg/kg ) in the formalin test in rats .
GC/MS analysis demonstrated the presenceof geranyl acetate ( 49.89 % ) , geraniol ( 7.92 % ) , and β-caryophyllene ( 6.27 % ) .
Significant and dose-dependent antinociceptive @ @ @ @ @ @ @ without the presence of gastric damage .
In conclusion , β-caryophyllene was confirmed as a bioactive compound in theanalgesic properties by involving the participation of receptors like opioids , benzodiazepines , and Serotonin 1A receptor ( 5-HT ) , as well as nitric oxide .

Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities ofessential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action ofβ-caryophyllene were also explored. Temporal course curves and dose-response graphics were generated using TLEO (0.1-10 mg/kg or 3.16-31.62 mg/kg) and β-caryophyllene (3.16-10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhingtest in rats and mice, respectively. The β-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presenceof geranyl acetate (49.89%), geraniol (7.92%), and β-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and β-caryophyllene without the presence of gastric damage. In conclusion, β-caryophyllene was confirmed as a bioactive compound in theanalgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT), as well as nitric oxide.


greenmedinfo--2020-06-04--Metaxalone has synergistic effect with β-caryophyllene production of inflammatory cytokines.

: Backgrounds and Objective : Inflammation is implicated in the pathogenesis of many diseases .
Inflammatory cytokines with painful conditions are well known as biomarkers in human muscle pain , and they are produced by macrophages .
Metaxalone is used as a skeletal muscle relaxant , but the mechanism by which metaxalone acts is unknown .
This study was undertaken to investigate whether or not metaxalone exhibits an inhibitory effect on the activity of inflammatory macrophages in vitro .
METHODS : Mouse macrophage RAW264.7 cells were cultured in Dulbecco 's Modification of Eagle 's Medium containing 10 % fetal bovine @ @ @ @ @ @ @ Cell growth was assayed by counting number of cells attached on culture dishes .
Inflammatory cytokines released into culture medium were analyzed with the ELISA kit .
RESULTS : Metaxalone ( 1-100µM ) was found to decrease the number of macrophages by inhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro .
The combination of metaxalone ( 0.1 or 1 µM ) and β-caryophyllene ( 10 or 50 µM ) , which their alone did not have a significant effect on cell number , caused potential effects on the growth @ @ @ @ @ @ @ mechanistically , levels of mitogen-activated protein kinase were decreased by treatment with metaxalone or β-caryophyllene , and each effect was enhanced by their combination .
Furthermore , levels of caspase-3 were increased by metaxalone or β-caryophyllene and enhanced by their combination .
Notably , productions of inflammatory cytokines , including tumor necrosis factor-α , interleukin-6 or prostaglandin E2 , which were enhanced by lipopolysaccharide ( LPS ) , were repressed by culturing with metaxalone .
Levels of cyclooxygenase ( COX ) -1 , COX-2 and nuclear factor kappa B , which were increased @ @ @ @ @ @ @ metaxalone .
CONCLUSION : Metaxalone was found to suppress the activity of inflammatory macrophages in vitro .

: Backgrounds and Objective: Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines with painful conditions are well known as biomarkers in human muscle pain, and they are produced by macrophages. Metaxalone is used as a skeletal muscle relaxant, but the mechanism by which metaxalone acts is unknown. This study was undertaken to investigate whether or not metaxalone exhibits an inhibitory effect on the activity of inflammatory macrophages in vitro.
METHODS: Mouse macrophage RAW264.7 cells were cultured in Dulbecco's Modification of Eagle's Medium containing 10% fetal bovine serum in the presence of metaxalone. Cell growth was assayed by counting number of cells attached on culture dishes. Inflammatory cytokines released into culture medium were analyzed with the ELISA kit.
RESULTS: Metaxalone (1-100µM) was found to decrease the number of macrophages by inhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro. The combination of metaxalone (0.1 or 1 µM) and β-caryophyllene (10 or 50 µM), which their alone did not have a significant effect on cell number, caused potential effects on the growth and death of RAW264.7 cells. Molecular mechanistically, levels of mitogen-activated protein kinase were decreased by treatment with metaxalone or β-caryophyllene, and each effect was enhanced by their combination. Furthermore, levels of caspase-3 were increased by metaxalone or β-caryophyllene and enhanced by their combination. Notably, productions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 or prostaglandin E2, which were enhanced by lipopolysaccharide (LPS), were repressed by culturing with metaxalone. Levels of cyclooxygenase (COX)-1, COX-2 and nuclear factor kappa B, which were increased by LPS treatment, were reduced by metaxalone.
CONCLUSION: Metaxalone was found to suppress the activity of inflammatory macrophages in vitro.


greenmedinfo--2020-06-04--Beta-caryophyllene suppresses ovarian cancer proliferation by inducing cell cycle arrest and apoptos

Beta-caryophyllene suppresses ovarian cancer proliferation by inducing cell cycle arrest and apoptosis.

BACKGROUND : Ovarian cancer is the fifth most common cause of cancer deaths among women with lesser prognostics .
Current treatment options are chemotherapy with platinum and taxane based chemotherapy , post cytoreductive surgery.β-Caryophyllene ( BCP ) an essential oil found in many plant species are known to possess an anti-proliferative effect .
OBJECTIVE : We aimed to investigate the antiproliferative , cytotoxic , and apoptotic role of BCP against ovarian cancer cells PA-1 and OAW 42 .
METHODS : The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue exclusion assay .
Cell @ @ @ @ @ @ @ performed by flow cytometry to determine cell cycle distribution and apoptosis respectively .
RESULTS : Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner on ovarian cancer cells .
Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells .
Results of apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells .
The apoptosis is mediated by caspase-3 activation .
CONCLUSION : The results of our present study prove that BCP exerts its action partly by inducing cell @ @ @ @ @ @ @ .
We conclude that BCP is a potential anti-cancer agent .

BACKGROUND: Ovarian cancer is the fifth most common cause of cancer deaths among women with lesser prognostics. Current treatment options are chemotherapy with platinum and taxane based chemotherapy, post cytoreductive surgery.β-Caryophyllene (BCP) an essential oil found in many plant species are known to possess an anti-proliferative effect.
OBJECTIVE: We aimed to investigate the antiproliferative, cytotoxic, and apoptotic role of BCP against ovarian cancer cells PA-1 and OAW 42.
METHODS: The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue exclusion assay. Cell cycle and live dead cell analyses were performed by flow cytometry to determine cell cycle distribution and apoptosis respectively.
RESULTS: Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner on ovarian cancer cells. Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells. Results of apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells. The apoptosis is mediated by caspase-3 activation.
CONCLUSION: The results of our present study prove that BCP exerts its action partly by inducing cell cycle arrest and apoptosis in ovarian cancer. We conclude that BCP is a potential anti-cancer agent.


greenmedinfo--2020-06-04--Antibacterial activity and mode of action of β-caryophyllene on Bacillus cereus.

: Natural products such as essential oils ( EOs ) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms .
Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents .
This study investigates the antibacterial activity and mechanism ofβ-caryophyllene , a compound that can be found in various EOs , against .
The minimum inhibitory concentration ofβ-caryophyllene againstwas 2.5 % ( v/v ) , whereas killing kinetics ofβ-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours .
Zeta-potential measurement in the cells @ @ @ @ @ @ @ of β-caryophyllene at 1.25 % ( v/v ) showed an increase in the membrane permeability surface charge to -3.98 mV , compared to untreated cells ( -5.46 mV ) .
Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene .
Additionally , β-caryophyllene does not interfere with the efflux activity ofvia the ethidium bromide influx/efflux activity .
The results revealed thatβ-caryophyllene was able to alter membrane permeability and integrity of , leading to membrane damage and intracellular content leakage , which eventually caused cell death .
: Natural @ @ @ @ @ @ @ ) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms .
Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents .
This study investigates the antibacterial activity and mechanism ofβ-caryophyllene , a compound that can be found in various EOs , against .
The minimum inhibitory concentration ofβ-caryophyllene againstwas 2.5 % ( v/v ) , whereas killing kinetics ofβ-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours .
Zeta-potential measurement in the cells treated with @ @ @ @ @ @ @ at 1.25 % ( v/v ) showed an increase in the membrane permeability surface charge to –3.98 mV , compared to untreated cells ( –5.46 mV ) .
Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene .
Additionally , β-caryophyllene does not interfere with the efflux activity ofvia the ethidium bromide influx/efflux activity .
The results revealed thatβ-caryophyllene was able to alter membrane permeability and integrity of , leading to membrane damage and intracellular content leakage , which eventually caused cell death .

: Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism ofβ-caryophyllene, a compound that can be found in various EOs, against. The minimum inhibitory concentration ofβ-caryophyllene againstwas 2.5% (v/v), whereas killing kinetics ofβ-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to -3.98 mV, compared to untreated cells (-5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity ofvia the ethidium bromide influx/efflux activity. The results revealed thatβ-caryophyllene was able to alter membrane permeability and integrity of, leading to membrane damage and intracellular content leakage, which eventually caused cell death.
: Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism ofβ-caryophyllene, a compound that can be found in various EOs, against. The minimum inhibitory concentration ofβ-caryophyllene againstwas 2.5% (v/v), whereas killing kinetics ofβ-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to –3.98 mV, compared to untreated cells (–5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity ofvia the ethidium bromide influx/efflux activity. The results revealed thatβ-caryophyllene was able to alter membrane permeability and integrity of, leading to membrane damage and intracellular content leakage, which eventually caused cell death.


greenmedinfo--2020-06-04--Healing activity of hydrogel containing nanoemulsified β-caryophyllene.

β-caryophyllene is a sesquiterpene present in the oil of many plant species , such as Copaifera sp.
, which has been shown to possesses potent anti-inflammatory action ; however , its healing activity remains under study .
The objectives of the present study were to produce a nanoemulsion containing β-caryophyllene followed by a hydrogel containing nanoemulsified β-caryophyllene , to evaluate the permeation profile in vitro , and to assess the in vivo healing activity , which is so far unexplored in the literature for pure β-caryophyllene and in pharmaceutical formulation .
The nanoemulsion was obtained through high-pressure homogenization and the @ @ @ @ @ @ @ Both formulations were characterized according to droplet size , polydispersity index , volume-weighted mean diameters , particle distribution , droplets diameters tracking , zeta potential , viscosity and bioadhesion behavior .
β-caryophyllene content was determined by gas chromatography coupled with mass spectrometry ( GC/MS ) .
Both formulations presented a nanometric droplet size , negative zeta potential , high β-caryophyllene content , and were stable for 60 days .
In agreement with the viscosity results , the hydrogel containing the β-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion .
The skin permeation study @ @ @ @ @ @ @ was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation .
On the other hand , in the simulated deeply wounded skin ( dermis ) , no significant differences were observed between the formulations and isolated β-caryophyllene with respect to the amount of marker retention in the dermis , suggesting saturation of this skin layer .
For the study of healingactivity , the dorsal wound model was performed with an evaluation of the lesion size , anti-inflammatory markers , and antioxidant activity .
The initial closure of the wound @ @ @ @ @ @ @ with the hydrogel containing the β-caryophyllene nanoemulsion , indicating its anti-inflammatory effect .
The histological analysis indicated that on day 12 day of the lesion , the hydrogel presented similar results to those of the positive control group ( Dersani® oil ) , proving effectiveness in cutaneous tissue repair .

β-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing β-caryophyllene followed by a hydrogel containing nanoemulsified β-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure β-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. β-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high β-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the β-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated β-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated β-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healingactivity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the β-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair.


greenmedinfo--2020-06-04--β-caryophyllene alleviates cerebral ischemia/reperfusion injury.

Cerebral ischemia-reperfusion ( I/R ) injury is an important cause of acute ischemic stroke .
Timely elimination of damaged proteins and organelles by regulating autophagy during cerebral ischemia-reperfusion plays an important role in relieving brain damage .
In order to investigate whetherβ-caryophyllene ( BCP ) could protect neurons from cerebral I/R injury by regulating auto-phagy , C57 BL/6 J male mice were randomly divided into sham operation group , model group , and drug-administered group .
After intra-gastric administration was given for 5 days , the middle cerebral artery occlusion ( MCAO ) model was established by suture method .
@ @ @ @ @ @ @ infarct volume and neurological function were assessed ; the pathological changes of cortical tissue were observed by HE staining ; Western blot was used to detect the expression of autophagy-related proteins beclin1 , p62 , LC3 B and apoptosis-related protein Bcl-2 ; immunofluorescence was used to observe the expression of LC3 B in the ischemic cortex .
The autophagy of cortical tissue in the ischemic area was observed by transmission electron microscopy .
The experimental results showed that as compared with the model group , the BCP pretreatment significantly reduced the neurological deficit @ @ @ @ @ @ @ volume , reduced the death of brain tissue cells in the ischemic area , up-regulated the expression of beclin1 , LC3 B and Bcl-2 protein , down-regulated p62 protein expression , and significantly increased the number of autophagosomes in the cortical tissue of the ischemic area .
It was finally determined that BCP could protect neurons from cerebral ischemia-reperfusion injury by activating autophagy .

Cerebral ischemia-reperfusion(I/R) injury is an important cause of acute ischemic stroke. Timely elimination of damaged proteins and organelles by regulating autophagy during cerebral ischemia-reperfusion plays an important role in relieving brain damage. In order to investigate whetherβ-caryophyllene(BCP) could protect neurons from cerebral I/R injury by regulating auto-phagy, C57 BL/6 J male mice were randomly divided into sham operation group, model group, and drug-administered group. After intra-gastric administration was given for 5 days, the middle cerebral artery occlusion(MCAO) model was established by suture method. Twenty four hours after surgery, the infarct volume and neurological function were assessed; the pathological changes of cortical tissue were observed by HE staining; Western blot was used to detect the expression of autophagy-related proteins beclin1,p62, LC3 B and apoptosis-related protein Bcl-2; immunofluorescence was used to observe the expression of LC3 B in the ischemic cortex. The autophagy of cortical tissue in the ischemic area was observed by transmission electron microscopy. The experimental results showed that as compared with the model group, the BCP pretreatment significantly reduced the neurological deficit, decreased the percentage of cerebral infarction volume, reduced the death of brain tissue cells in the ischemic area, up-regulated the expression of beclin1, LC3 B and Bcl-2 protein, down-regulated p62 protein expression,and significantly increased the number of autophagosomes in the cortical tissue of the ischemic area. It was finally determined that BCP could protect neurons from cerebral ischemia-reperfusion injury by activating autophagy.


greenmedinfo--2020-06-04--β-caryophyllene inhibits cell proliferation through a direct modulation of CB2 receptors in glioblas

β-caryophyllene inhibits cell proliferation through a direct modulation of CB2 receptors in glioblastoma cells.

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation .
b-caryophyllene ( BCP ) is a cannabinoid receptor 2 ( CB2 ) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma ( PPARg ) receptors .
BCP effects were investigated in an in vitro model of glioblastoma .
U-373 and U87 , derived from a human glioblastoma , and human glioma stem-like cells ( GSCs ) were treated with BCP at different doses and time-points .
AM360 , a specific CB2 antagonist , was added 2 h before BCP treatment .
@ @ @ @ @ @ @ reducing cell viability , inhibiting cell cycle , and increasing apoptosis , as demonstrated by Tunel assay , caspase-3 and caspase -9 activation .
In addition , the pro-apoptotic BAX expression was increased , whereas the anti-apoptotic Bcl-2 expression was reduced .
Treatment with BCP decreased Beclin-1 , LC3 and p62/SQSTM1 expression , indicating a possible switch of autophagy to apoptosis .
BCP 's anti-inflammatory effect was demonstrated by NF-κB reduction , PPARg activation and TNF-a decrease ; BCP significantly reduced Jun N-Terminal Kinase ( JNK ) expression as a consequence of TNF-α @ @ @ @ @ @ @ thus demonstrating the BCP mechanism of action through the CB2 receptor .
These findings let us hypothesize that BCPmay act as a tumor suppressor in glioblastoma , acting on CB2 receptor and modulating JNK .

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP's anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCPmay act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK.