greenmedinfo--2020-09-03--A topical ointment formulation containing leaves' powder of Lawsonia inermis accelerate excision wou

A topical ointment formulation containing leaves' powder of Lawsonia inermis accelerate excision wound healing.

Aim : ( LI ) , a naturally grown or cultivated shrub in Northeast of Africa and India , has been traditionally used as a strong remedy for several injuries .
However , few studies have reported its use as a cicatrizing agent .
The aim of this study was to evaluate the effect of daily application of an ointment prepared with LI leaves ' powder on wound healing in Wistar rats .
Materials and Methods : Twenty female Wistar rats were used in this study .
Excisional wound model was realized by removing skin from the dorsal part of @ @ @ @ @ @ @ have been then treated by a daily application of LI ointment prepared by mixing leaves ' powder to petroleum jelly in test group and by simple application of petroleum jelly in control group .
Evaluation of wound healing activity was then based on calculating the percentage of wound contraction , period of epithelialization , and wound index every 3 days for a period of 24 days , then , a histological study of the healed excised wound was performed .
Results : Treatment with LI has shown excellent wound healing activity , since @ @ @ @ @ @ @ , and reduced period of epithelialization and wound index as compared to control ( p < 0.05 ) .
These results have been supported by the histological findings that revealed better epithelialization , dermal differentiation , collagen fiber orientation , and angiogenesis in LI treated rats compared to control ( p < 0.05 ) .
Conclusion : We can conclude that LI leaves ' can be used as a potential wound healing agent .

Aim: (LI), a naturally grown or cultivated shrub in Northeast of Africa and India, has been traditionally used as a strong remedy for several injuries. However, few studies have reported its use as a cicatrizing agent. The aim of this study was to evaluate the effect of daily application of an ointment prepared with LI leaves' powder on wound healing in Wistar rats.
Materials and Methods: Twenty female Wistar rats were used in this study. Excisional wound model was realized by removing skin from the dorsal part of the neck of each animal. Wounds have been then treated by a daily application of LI ointment prepared by mixing leaves' powder to petroleum jelly in test group and by simple application of petroleum jelly in control group. Evaluation of wound healing activity was then based on calculating the percentage of wound contraction, period of epithelialization, and wound index every 3 days for a period of 24 days, then, a histological study of the healed excised wound was performed.
Results: Treatment with LI has shown excellent wound healing activity, since it has increased percent of wound contraction, and reduced period of epithelialization and wound index as compared to control (p<0.05). These results have been supported by the histological findings that revealed better epithelialization, dermal differentiation, collagen fiber orientation, and angiogenesis in LI treated rats compared to control (p<0.05).
Conclusion: We can conclude that LI leaves' can be used as a potential wound healing agent.


greenmedinfo--2020-09-03--Herbal extracts with antifungal activity against Candida albicans.

BACKGROUND : In the era of antimicrobial resistance , fungal pathogens are not an exception .
Several strategies , including antimicrobial stewardship programs and high throughput screening of new drugs are being implemented .
Several recent studies have demonstrated effectiveness of plant compounds with antifungal activity .
OBJECTIVE : In this systematic review we examine the use of natural compounds as a possible avenue to fight fungal infections produced by Candida albicans , the most common human fungal pathogen .
METHOD : Electronic literature searches were conducted through PubMed/MEDLINE , Cochrane , and Science Direct limited to the 5 years @ @ @ @ @ @ @ included with 186 plants extracts evaluated .
RESULTS : Although the majority of the natural extracts exhibited antifungal activities against C. albicans ( both in vivo and in vitro ) , the strongest antifungal activity was obtained from Lawsonia inermis , Pelargonium graveolens , Camellia sinensis , Mentha piperita , and Citrus latifolia .
CONCLUSION : The main components with proven antifungal activities were phenolic compounds such as gallic acid , thymol , and flavonoids ( specially catechin ) , polyphenols such as tannins , terpenoids and saponins .
The incorporation of nanotechnology @ @ @ @ @ @ @ natural compounds .
Further research is needed to fully characterize the composition of all herbal extracts with antifungal activity as well as the mechanisms of action of the active compounds .

BACKGROUND: In the era of antimicrobial resistance, fungal pathogens are not an exception. Several strategies, including antimicrobial stewardship programs and high throughput screening of new drugs are being implemented. Several recent studies have demonstrated effectiveness of plant compounds with antifungal activity.
OBJECTIVE: In this systematic review we examine the use of natural compounds as a possible avenue to fight fungal infections produced by Candida albicans, the most common human fungal pathogen.
METHOD: Electronic literature searches were conducted through PubMed/MEDLINE, Cochrane, and Science Direct limited to the 5 years. A total of 131 articles were included with 186 plants extracts evaluated.
RESULTS: Although the majority of the natural extracts exhibited antifungal activities against C. albicans (both in vivo and in vitro), the strongest antifungal activity was obtained from Lawsonia inermis, Pelargonium graveolens, Camellia sinensis, Mentha piperita, and Citrus latifolia.
CONCLUSION: The main components with proven antifungal activities were phenolic compounds such as gallic acid, thymol, and flavonoids (specially catechin), polyphenols such as tannins, terpenoids and saponins. The incorporation of nanotechnology enhances greatly the antifungal properties of these natural compounds. Further research is needed to fully characterize the composition of all herbal extracts with antifungal activity as well as the mechanisms of action of the active compounds.


greenmedinfo--2020-09-03--Effects of Moro orange juice on some metabolic and morphological parameters in obese and diabetes.

BACKGROUND : Nutritional intervention with the use of phytochemicals is an important method for the treatment and prevention of a metabolic syndrome .
The objective of this study was to chemically characterize Moro orange juice .
The influence of juice intake on metabolic parameters of rats that were obese , diabetic or both by means of body mass management after the activation of anthocyanins during refrigerated storage was also assessed .
RESULTS : Juice intake reversed most of the metabolic abnormalities exhibited by obese rats , including reduction of body mass and improvement of the biochemical profile .
The loss @ @ @ @ @ @ @ obese and diabetic animals was not attributed to juice intake , but to type I diabetes mellitus .
In these animals , no improvement was observed in the biochemical profile , liver enzymes and glycemia , so this treatment model was deemed unfeasible .
CONCLUSION : The beneficial effects can not be explained only by the anthocyanin C3G present in the juice , but rather , by the synergism between all the components .
Studies in humans are needed to determine whether the ingestion of this orange can be recommended as an effective @ @ @ @ @ @ @ obesity.© 2020 Society of Chemical Industry .

BACKGROUND: Nutritional intervention with the use of phytochemicals is an important method for the treatment and prevention of a metabolic syndrome. The objective of this study was to chemically characterize Moro orange juice. The influence of juice intake on metabolic parameters of rats that were obese, diabetic or both by means of body mass management after the activation of anthocyanins during refrigerated storage was also assessed.
RESULTS: Juice intake reversed most of the metabolic abnormalities exhibited by obese rats, including reduction of body mass and improvement of the biochemical profile. The loss of body mass by diabetic animals and obese and diabetic animals was not attributed to juice intake, but to type I diabetes mellitus. In these animals, no improvement was observed in the biochemical profile, liver enzymes and glycemia, so this treatment model was deemed unfeasible.
CONCLUSION: The beneficial effects cannot be explained only by the anthocyanin C3G present in the juice, but rather, by the synergism between all the components. Studies in humans are needed to determine whether the ingestion of this orange can be recommended as an effective strategy to prevent or ameliorate complications of obesity.© 2020 Society of Chemical Industry.


greenmedinfo--2020-09-04--The effects of NAC on amending TNF-α and IL-6 levels were significant after sensitivity analysis.

Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders , type two diabetes @ @ @ @ @ ( NAC ) is considered an antioxidant .
The present meta-analysis aims to determine the @ @ @ @ @ inflammation and oxidative stress .
PubMed-Medline , SCOPUS , Web of Science and Embase databases @ @ @ @ @ up to Nov 2019 .
Random effect analysis was used to perform meta-analysis .
Subgroup @ @ @ @ @ find heterogeneity sources .
Meta-regression analysis was used to explore linear relationship between effect size @ @ @ @ @ fill analysis were performed in case of the presence of publication bias .
Quality assessment @ @ @ @ @ 's tool .
A total of 28 studies were included in meta-analysis .
NAC significantly @ @ @ @ @ ( SMD = -1.44 μmol/L ; 95 % CI : -2.05 , -0.84 ; P

Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders, type two diabetes, and obesity. N-acetylcysteine (NAC) is considered an antioxidant. The present meta-analysis aims to determine the efficacy of NAC in alleviating inflammation and oxidative stress. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to Nov 2019. Random effect analysis was used to perform meta-analysis. Subgroup analyses were carried out to find heterogeneity sources. Meta-regression analysis was used to explore linear relationship between effect size and variables. Trim and fill analysis were performed in case of the presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. A total of 28 studies were included in meta-analysis. NAC significantly decreased malondialdehyde (MDA) (SMD = -1.44 μmol/L; 95% CI: -2.05, -0.84; P < 0.001), IL-8 (WMD = -2.56 pg/ml; 95% CI: -3.89, -1.23; P < 0.001) and homocysteine (WMD = -1.45 pg/ml; 95% CI: -2.74, -0.17; P = 0.027) levels. There were no significant effects of NAC supplementation on CRP (SMD = -0.1 g/L; 95% CI: -0.52, 0.32; P = 0.647), TNF- α (WMD = -0.2 pg/ml; 95% CI: -0.65, 0.25; P = 0.378) and IL-6 (WMD = -0.41 pg/ml; 95% CI: -1.15, 0.32; P = 0.270) levels. However, NAC effects were significant in ameliorating TNF-α and IL-6 using sensitivity analysis. NAC significantly decreased MDA, IL-8, and homocysteine levels. The effects of NAC on amending TNF-α and IL-6 levels were significant after sensitivityanalysis. No significant change was observed on CRP levels.


greenmedinfo--2020-09-04--Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf

Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf2.

AIMS : Obesity-related glomerulopathy ( ORG ) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions .
Isothiocyanate sulforaphane ( SFN ) can protect kidneys from ORG-related damages .
In this study , we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action .
MAIN METHODS : We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months .
Thereafter , we used nuclear factor erythroid 2-related factor 2-deficient ( Nrf2 ) and wild type mice in our ORG model with SFN treatment @ @ @ @ @ @ @ mouse podocyte model in vitro .
The body weight , wet weight of perirenal-and peritesticular fat , and urinary albumin/creatinine ratio were assessed .
We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes .
In addition , we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting .
KEY FINDINGS : Treatment with SFN reduced body weight , organ-associated fat weight , and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens .
SFN treated mice exhibited higher expression levels @ @ @ @ @ @ @ .
However , treatment with SFN did not affect these parameters in obese Nrf2mice .
Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2mice .
SIGNIFICANCE : Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2 .

AIMS: Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action.
MAIN METHODS: We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting.
KEY FINDINGS: Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2mice.
SIGNIFICANCE: Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.


greenmedinfo--2020-09-04--N-acetycysteine: A potential therapeutic agent in COVID-19 infection.

COVID-19 is an overwhelming pandemic which has shattered the whole world .
Lung injury being the main clinical manifestation , @ @ @ @ @ COPD ( chronic obstructive pulmonary disease ) and ARDS ( acute respiratory distress syndrome ) @ @ @ @ @ this might be redox imbalance due to viral infection .
Elevation in Glutathione ( GSH @ @ @ @ @ its promolecule might be effective .
N-acetylcysteine is one such drug with potency to scavenge @ @ @ @ @ side effects , and an effective precursor of glutathione .
Consequently we hypothesize that N-acetylcysteine @ @ @ @ @ may be treated as a potential therapeutic solution in cases of COVID-19 patients .

COVID-19 is an overwhelming pandemic which has shattered the whole world. Lung injury being the main clinical manifestation, it is likely to cause COPD (chronic obstructive pulmonary disease) and ARDS (acute respiratory distress syndrome). The possible cause behind this might be redox imbalance due to viral infection. Elevation in Glutathione (GSH) levels by administration of its promolecule might be effective. N-acetylcysteine is one such drug with potency to scavenge Reactive Oxygen Species, least side effects, and an effective precursor of glutathione. Consequently we hypothesize that N-acetylcysteine along with the conventional treatment may be treated as a potential therapeutic solution in cases of COVID-19 patients.


greenmedinfo--2020-09-04--N-acetylcysteine promotes oral absorption of curcumin.

To solve the low oral bioavailability of curcumin ( CUR ) due to the limits imposed by gastrointestinal ( GI @ @ @ @ @ a nano delivery system to evaluate the effect of N-acetyl-L-cysteine ( NAC ) on intestinal @ @ @ @ @ CUR .
CUR was first encapsulated in bovine serum albumin nanoparticles ( CUR-BSA-NPs ) , @ @ @ @ @ by NAC ( CUR-NBSA-NPs ) .
In situ single-pass intestinal perfusion assay demonstrated that CUR-NBSA-NPs @ @ @ @ @ rates in GI tract .
Additionally , the distribution study in GI tract revealed that @ @ @ @ @ intestinal segments compared to the BSA nanoparticles .
Plasma concentration-time curves in rats showed that @ @ @ @ @ CUR after oral administration of CUR-NBSA-NPs were increased to 3.25- , 4.42- , and 1.43-fold @ @ @ @ @ suspension .
In conclusion , NAC promotes oral absorption of CUR , thereby improving its @ @ @

To solve the low oral bioavailability of curcumin (CUR) due to the limits imposed by gastrointestinal (GI) barrier, we constructed a nano delivery system to evaluate the effect of N-acetyl-L-cysteine (NAC) on intestinal absorption and oral bioavailability of CUR. CUR was first encapsulated in bovine serum albumin nanoparticles (CUR-BSA-NPs), and then was further modified by NAC (CUR-NBSA-NPs). In situ single-pass intestinal perfusion assay demonstrated that CUR-NBSA-NPs displayed excellent permeation and absorption rates in GI tract. Additionally, the distribution study in GI tract revealed that more NBSA-NPs were absorbed by intestinal segments compared to the BSA nanoparticles. Plasma concentration-time curves in rats showed that AUC, Cand MRTvalues of CUR after oral administration of CUR-NBSA-NPs were increased to 3.25-, 4.42-, and 1.43-fold compared with that of CUR suspension. In conclusion, NAC promotes oral absorption of CUR, thereby improving its oral bioavailability.


greenmedinfo--2020-09-04--Combination therapy with cinnamaldehyde and hyperthermia induces apoptosis of A549 non-small cell lu

Combination therapy with cinnamaldehyde and hyperthermia induces apoptosis of A549 non-small cell lung carcinoma cells.

Lung cancer is the largest cause of cancer-induced deaths .
Non-small cell lung cancer ( NSCLC ) is the most frequently observed subtype of lung cancer .
Although recent studies have provided many therapeutic options , there is still a need for effective and safe treatments .
This paper reports the combined effects of cinnamaldehyde ( CNM ) , a flavonoid from cinnamon , together with hyperthermia , a therapeutic option for cancer treatment , on the A549 NSCLC cell line .
A hyperthermia treatment of 43°C potentiated the cytotoxicity of CNM in A549 cells .
This was attributed to @ @ @ @ @ @ @ suppression of the survival/protective factors , as confirmed by Western blot assays .
Flow cytometry supported this result because the apoptotic profile , cell health profile , and cell cycle profile were regulated by CNM and hyperthermia combination therapy .
The changes in reactive oxygen species ( ROS ) and its downstream target pathway , mitogen-activated protein kinases ( MAPK ) , were evaluated .
The CNM and hyperthermia combination increased the generation of ROS and MAPK phosphorylation .
N-acetylcysteine ( NAC ) , a ROS inhibitor , abolished the apoptotic events caused @ @ @ @ @ @ @ that the cytotoxic effect was dependent of ROS signaling .
Therefore , we suggest CNM and hyperthermia combination as an effective therapeutic option for the NSCLC treatment .

Lung cancer is the largest cause of cancer-induced deaths. Non-small cell lung cancer (NSCLC) is the most frequently observed subtype of lung cancer. Although recent studies have provided many therapeutic options, there is still a need for effective and safe treatments. This paper reports the combined effects of cinnamaldehyde (CNM), a flavonoid from cinnamon, together with hyperthermia, a therapeutic option for cancer treatment, on the A549 NSCLC cell line. A hyperthermia treatment of 43°C potentiated the cytotoxicity of CNM in A549 cells. This was attributed to an increase in the apoptosis markers and suppression of the survival/protective factors, as confirmed by Western blot assays. Flow cytometry supported this result because the apoptotic profile, cell health profile, and cell cycle profile were regulated by CNM and hyperthermia combination therapy. The changes in reactive oxygen species (ROS) and its downstream target pathway, mitogen-activated protein kinases (MAPK), were evaluated. The CNM and hyperthermia combination increased the generation of ROS and MAPK phosphorylation. N-acetylcysteine (NAC), a ROS inhibitor, abolished the apoptotic events caused by CNM and hyperthermia co-treatment, suggesting that the cytotoxic effect was dependent of ROS signaling. Therefore, we suggest CNM and hyperthermia combination as an effective therapeutic option for the NSCLC treatment.


greenmedinfo--2020-09-04--Clinical efficacy of acetylcysteine combined with tetrandrine tablets on patients with silicosis.

Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis was investigated to observe the exercise tolerance and pulmonary function of the patients .
The clinical data of 248 cases of silicosis patients treated in Branch of Tai'an City Central Hospital were retrospectively analyzed in this study , including 116 cases with conventional therapy ( control group ) , and 132 cases treated with acetylcysteine and tetrandrine tablets on the basis of conventional therapy ( observation group ) .
The chest tightness , chest pain , cough and sputum production were evaluated by the St. George Respiratory @ @ @ @ @ @ @ effects after treatment were recorded .
Exercise tolerance was measured by 6-min walk test ( 6MWT ) and pulmonary function was measured by pulmonary function instrument .
The symptoms of chest tightness , chest pain , cough and sputum production in the observation group and the control group after 8 months of treatment were significantly lower than those before treatment ( P < 0.05 ) , and that in the observation group after treatment was significantly higher than that in the control group ( P < 0.05 ) .
The incidence of side @ @ @ @ @ @ @ group was significantly lower than that in the control group ( P < 0.05 ) .
The 6MWT , forced vital capacity ( FVC ) and forced expiratory volume in 1 sec ( FEV1 ) in the observation group and the control group after treatment were significantly higher than those before treatment ( P < 0.001 ) ; the 6MWT in the observation group after treatment was significantly higher than that in the control group ( P < 0.001 ) .
In conclusion , acetylcysteine combined with tetrandrine tablets on the basis of @ @ @ @ @ @ @ more effective than conventional therapy alone , which can also improve exercise tolerance , pulmonary function and clinical symptoms such as chest tightness , chest pain , cough , sputum production of silicosis patients , and is helpful for clinical application .

Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis was investigated to observe the exercise tolerance and pulmonary function of the patients. The clinical data of 248 cases of silicosis patients treated in Branch of Tai'an City Central Hospital were retrospectively analyzed in this study, including 116 cases with conventional therapy (control group), and 132 cases treated with acetylcysteine and tetrandrine tablets on the basis of conventional therapy (observation group). The chest tightness, chest pain, cough and sputum production were evaluated by the St. George Respiratory questionnaire (SGRQ); and side effects after treatment were recorded. Exercise tolerance was measured by 6-min walk test (6MWT) and pulmonary function was measured by pulmonary function instrument. The symptoms of chest tightness, chest pain, cough and sputum production in the observation group and the control group after 8 months of treatment were significantly lower than those before treatment (P<0.05), and that in the observation group after treatment was significantly higher than that in the control group (P<0.05). The incidence of side effects of the drug in the observation group was significantly lower than that in the control group (P<0.05). The 6MWT, forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) in the observation group and the control group after treatment were significantly higher than those before treatment (P<0.001); the 6MWT in the observation group after treatment was significantly higher than that in the control group (P<0.001). In conclusion, acetylcysteine combined with tetrandrine tablets on the basis of conventional therapy in treatment of silicosis is more effective than conventional therapy alone, which can also improve exercise tolerance, pulmonary function and clinical symptoms such as chest tightness, chest pain, cough, sputum production of silicosis patients, and is helpful for clinical application.


greenmedinfo--2020-09-04--Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

COVID-19 may cause pneumonia , acute respiratory distress syndrome , cardiovascular alterations , and multiple organ failure , which have been ascribed to a cytokine storm , a systemic inflammatory response , and an attack by the immune system .
Moreover , an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients .
N- Acetyl-L-cysteine ( NAC ) is a precursor of reduced glutathione ( GSH ) .
Due to its tolerability , this pleiotropic drug has been proposed not only as a mucolytic agent , but also as a preventive/therapeutic agent in a variety of disorders involving @ @ @ @ @ @ @ very high doses , NAC is also used as an antidote against paracetamol intoxication .
Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells .
Based on a broad range of antioxidant and anti-inflammatory mechanisms , which are herein reviewed , the oral administration of NAC is likely to attenuate the risk of developing COVID-19 , as it was previously demonstrated for influenza and influenza-like illnesses .
Moreover , high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in @ @ @ @ @ @ @ also including pulmonary and cardiovascular adverse events .

COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.


greenmedinfo--2020-09-04--Myricetin may represent a potential candidate and strategy for S. aureus infection.

, an important agent for lethal bacterial infections , can cause a broad spectrum of diseases in various host species @ @ @ @ @ and highly virulent strains has raised increasing concerns about the novel therapeutic strategies or agents @ @ @ @ @ critical role of Hla , an essential virulence determinant , in the pathogenicity ofrenders this @ @ @ @ @ effective therapeutic applications .
Here , we have identified myricetin as an effective inhibitor of @ @ @ @ @ production and neutralizes Hla activity without affecting bacterial growth .
Myricetin treatment reduced the oligomerization @ @ @ @ @ formation .
The addition of myricetin to the coinfection system of host cells andsignificantly decreased @ @ @ @ @ inflammatory response in cells .
Furthermore , -infected mice that received myricetin showed alleviated tissue @ @ @ @ @ Our results indicated that myricetin inhibitsvirulence by targeting Hla and downregulates the inflammatory response in @ @ @ @ @ in addition to traditional antibiotics with antibacterial activity , myricetin may represent a potential candidate @ @ @ @ @

, an important agent for lethal bacterial infections, can cause a broad spectrum of diseases in various host species. The emergence of multidrug-resistant and highly virulent strains has raised increasing concerns about the novel therapeutic strategies or agents available for treatinginfection. The critical role of Hla, an essential virulence determinant, in the pathogenicity ofrenders this toxin an attractive target for effective therapeutic applications. Here, we have identified myricetin as an effective inhibitor of Hla that simultaneously inhibits Hla production and neutralizes Hla activity without affecting bacterial growth. Myricetin treatment reduced the oligomerization of Hla and Hla-mediated biofilm formation. The addition of myricetin to the coinfection system of host cells andsignificantly decreased cell injury and downregulated the inflammatory response in cells. Furthermore,-infected mice that received myricetin showed alleviated tissue damage in the lung. Our results indicated that myricetin inhibitsvirulence by targeting Hla and downregulates the inflammatory response in host cells. Overall, in addition to traditional antibiotics with antibacterial activity, myricetin may represent a potential candidate, and strategy forinfection.


greenmedinfo--2020-09-04--Myricetin protects against H2O2-induced oxidative damage and apoptosis in bovine mammary epithelial

Myricetin protects against H2O2-induced oxidative damage and apoptosis in bovine mammary epithelial cells.

High-producing dairy cows are prone to oxidative stress due to their high secretion and strong metabolism , and excessive oxidative stress may cause the apoptosis of bovine mammary epithelial cells ( bMECs ) .
Myricetin ( Myr ) has been shown to have a wide range of pharmaceutical activities .
The aim of this study was to evaluate the effect of Myr on hydrogen peroxide ( HO ) -induced oxidative stress and apoptosis in bMECs and to clarify the underlying mechanism .
bMECs were pretreated with or without Myr and then stimulated with HO .
The results showed that Myr @ @ @ @ @ @ @ superoxide dismutase levels and decreased the malondialdehyde ( MDA ) and reactive oxygen species ( ROS ) levels in a model of oxidative stress induced by HOin bMECs .
Mechanistic studies found that Myr inhibited HO-induced oxidative stress in bMECs through the adenosine monophosphate-activated protein kinase/nuclear factor erythroid-2 related factor 2 ( AMPK/NRF2 ) signaling pathway .
Additional research found that Myr could also inhibit HO-induced apoptosis in bMECs through NRF2 .
These data suggest that Myr effectively alleviated oxidative stress and apoptosis in HO-induced bMECs through the activation of the AMPK/NRF2 signaling @ @

High-producing dairy cows are prone to oxidative stress due to their high secretion and strong metabolism, and excessive oxidative stress may cause the apoptosis of bovine mammary epithelial cells (bMECs). Myricetin (Myr) has been shown to have a wide range of pharmaceutical activities. The aim of this study was to evaluate the effect of Myr on hydrogen peroxide (HO)-induced oxidative stress and apoptosis in bMECs and to clarify the underlying mechanism. bMECs were pretreated with or without Myr and then stimulated with HO. The results showed that Myr significantly increased the total antioxidant capacity and superoxide dismutase levels and decreased the malondialdehyde (MDA) and reactive oxygen species (ROS) levels in a model of oxidative stress induced by HOin bMECs. Mechanistic studies found that Myr inhibited HO-induced oxidative stress in bMECs through the adenosine monophosphate-activated protein kinase/nuclear factor erythroid-2 related factor 2 (AMPK/NRF2) signaling pathway. Additional research found that Myr could also inhibit HO-induced apoptosis in bMECs through NRF2. These data suggest that Myr effectively alleviated oxidative stress and apoptosis in HO-induced bMECs through the activation of the AMPK/NRF2 signaling pathway.


greenmedinfo--2020-09-04--Piperlongumine increases the apoptotic effect of doxorubicin and paclitaxel in a cervical cancer cel

Piperlongumine increases the apoptotic effect of doxorubicin and paclitaxel in a cervical cancer cell line.

Objective : Piperlongumine ( PL ) is an alkaloid derived from the edible pepper ( Piper longum L ) and @ @ @ @ @ have various biologic activities including anticancer effects .
Our aim in this study was to @ @ @ @ @ PL on a cervical cancer cell line ( HeLa ) and to evaluate the effects @ @ @ @ @ therapies on apoptotic cancer cell death .
Material and Methods : The cytotoxicity , IC50 @ @ @ @ @ by fluorescent imaging , and apoptotic cell rates by Annexin V staining using flow cytometry @ @ @ @ @ doxorubicin , paclitaxel , and for their combinations .
Results : It was shown that @ @ @ @ @ the apoptosis in HeLa cells .
PL in combination with doxorubicin and paclitaxel increased apoptotic @ @ @ @ @ chemotherapeutic agent alone .
Conclusion : We conclude that the PL inhibits cancer cell growth @ @ @ @ @ a potential anticancer activity in cervical cancer , especially when combined with doxorubicin and paclitaxel @

Objective: Piperlongumine (PL) is an alkaloid derived from the edible pepper (Piper longum L) and it has been described to have various biologic activities including anticancer effects. Our aim in this study was to assess the cytotoxic role of PL on a cervical cancer cell line (HeLa) and to evaluate the effects of PL/doxorubicin and PL/paclitaxel combination therapies on apoptotic cancer cell death.
Material and Methods: The cytotoxicity, IC50 doses by MTT assay confirmed by fluorescent imaging, and apoptotic cell rates by Annexin V staining using flow cytometry were determined for PL, doxorubicin, paclitaxel, and for their combinations.
Results: It was shown that the PL by itself induced the apoptosis in HeLa cells. PL in combination with doxorubicin and paclitaxel increased apoptotic cell death compared to either chemotherapeutic agent alone.
Conclusion: We conclude that the PL inhibits cancer cell growth by inducing apoptosis and has a potential anticancer activity in cervical cancer, especially when combined with doxorubicin and paclitaxel.


greenmedinfo--2020-09-04--The current review highlights anticancer studies on piperlongumine.

Piperlongumine , a white to beige biologically active alkaloid/amide phytochemical , has high pharmacological relevance as an anticancer agent .
Piperlongumine has several biological activities , including selective cytotoxicity against multiple cancer cells of different origins at a preclinical level .
Several preclinical studies have documented the anticancer potential of piperlongumine through its targeting of multiple molecular mechanisms , such as cell cycle arrest , anti-angiogenesis , anti- invasive and anti-metastasis pathways , autophagy pathways , and intrinsic apoptotic pathways in vitro and in vivo .
Mechanistically , piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive @ @ @ @ @ @ @ damage , or modulating key regulatory proteins , including PI3K , AKT , mTOR , NF-kβ , STATs , and cyclin D1 .
Furthermore , combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy .
Nanoformulation of piperlongumine has been associated with increased aqueous solubility and bioavailability and lower toxicity , thus enhancing therapeutic efficacy in both preclinical and clinical settings .
The current review highlights anticancer studies on the occurrence , chemical properties , chemopreventive mechanisms , toxicity , bioavailability , and @ @ @ @ @ @ @ vivo .

Piperlongumine, a white to beige biologically active alkaloid/amide phytochemical, has high pharmacological relevance as an anticancer agent. Piperlongumine has several biological activities, including selective cytotoxicity against multiple cancer cells of different origins at a preclinical level. Several preclinical studies have documented the anticancer potential of piperlongumine through its targeting of multiple molecular mechanisms, such as cell cycle arrest, anti-angiogenesis, anti- invasive and anti-metastasis pathways, autophagy pathways, and intrinsic apoptotic pathways in vitro and in vivo. Mechanistically, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cyclin D1. Furthermore, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy. Nanoformulation of piperlongumine has been associated with increased aqueous solubility and bioavailability and lower toxicity, thus enhancing therapeutic efficacy in both preclinical and clinical settings. The current review highlights anticancer studies on the occurrence, chemical properties, chemopreventive mechanisms, toxicity, bioavailability, and pharmaceutical relevance of piperlonguminein vitro and in vivo.


greenmedinfo--2020-09-04--Increased expression of FosB through reactive oxygen species accumulation functions as pro-apoptotic

Increased expression of FosB through reactive oxygen species accumulation functions as pro-apoptotic protein in piperlongumine treated MCF7 breast cancer cells.

Piperlongumine ( PL ) , a natural alkaloid compound isolated from long pepper ( ) , can selectively kill cancer cells , but not normal cells , by accumulation of reactive oxygen species ( ROS ) .
The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells .
PL downregulates SETDB1 expression , and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death .
PL treatment generated ROS .
ROS inhibitor NAC ( N-acetyl cysteine ) recovered SETDB1 expression decreased by PL .
@ @ @ @ @ @ @ FosB during PL treatment .
PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection , implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells .
PL induced cell death in A549 lung cancer cells , but molecular changes involved in the induction of these cell deaths might be different .
These results suggest that SETDB1 mediated FosB expression may induce cell @ @ @ @ @ @ @ .

Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.


greenmedinfo--2020-09-04--Survivin promotes piperlongumine resistance in ovarian cancer.

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients @ @ @ @ @ regarded as the most robust anti-apoptosis protein , and its overexpression in ovarian cancer is @ @ @ @ @ apoptosis resistance .
Piperlongumine ( PL ) extracted from peppers is defined as an active @ @ @ @ @ spectrum of antitumor effects .
Here , we demonstrate that PL induces the rapid depletion @ @ @ @ @ reactive oxygen species ( ROS ) -mediated proteasome-dependent pathway , while exerting a remarkable inhibitory @ @ @ @ @ ovarian cancer cells .
Overexpression of survivin raises the survival rate of ovarian cancer cells @ @ @ @ @ PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin .
Our findings reveal @ @ @ @ @ PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer @ @ @ @ @ pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin .

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.


greenmedinfo--2020-09-04--Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer

Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells.

Piperlongumine ( PL ) , a herbal drug extracted from long pepper ( Piper longum L ) , is known @ @ @ @ @ properties .
Although , its anti-cancer potential has been evaluated in cancer models like breast @ @ @ @ @ hepatocellular and lung carcinoma , there is no report on its bio-activity evaluation in intestinal @ @ @ @ @ report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms @ @ @ @ @ demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and @ @ @ @ @ PL elevated the levels of intracellular reactive oxygen species , which may lead to lethal @ @ @ @ @ , and nuclear fragmentation .
Remarkably , P53 , P21 , BAX , and SMAD4 @ @ @ @ @ treatment whereas ; BCL2 and SURVIVIN were down-regulated .
Moreover , the combination study also @ @ @ @ @ PL with the current chemotherapeutic drug paclitaxel .
These findings suggest that PL possesses anti-neoplastic @ @ @ @ @ .

Piperlongumine (PL), a herbal drug extracted from long pepper (Piper longum L), is known for its anti-inflammatory and anti-cancer properties. Although, its anti-cancer potential has been evaluated in cancer models like breast, pancreatic, gastric, hepatocellular and lung carcinoma, there is no report on its bio-activity evaluation in intestinal cancers. Here, we report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms of action. Cytotoxicity studies demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and time-dependent manner. Also, PL elevated the levels of intracellular reactive oxygen species, which may lead to lethal oxidative stress, mitochondrial dysfunction, and nuclear fragmentation. Remarkably, P53, P21, BAX, and SMAD4 were significantly upregulated after PL treatment whereas; BCL2 and SURVIVIN were down-regulated. Moreover, the combination study also shows the synergistic effect of PL with the current chemotherapeutic drug paclitaxel. These findings suggest that PL possesses anti-neoplastic properties in intestinal cancer cells.


greenmedinfo--2020-09-04--Synergistic effects of piperlongumine and gemcitabine against KRAS mutant lung cancer.

OBJECTIVE : To determine the combined efficacy of piperlongumine and gemcitabine for treatment ofmutant lung cancer .
METHODS : The cell growth inhibition of piperlongumine , gemcitabine , and piperlongumine plus gemcitabine was measured by Cell Counting Kit‑8 assay and the combination index was calculated .
In addition , the combined effects of piperlongumine and gemcitabine on cell apoptosis , reactive oxygen species ( ROS ) contents , and microtubule-associated protein 1 light chain 3B ( LC3B ) expression were examined .
RESULTS : Piperlongumine increased ROS contents and LC3B-II expression .
Following the combined treatment with piperlongumine and 10 @ @ @ @ @ @ @ ROS and cell viability returned to normal levels , and the expression of LC3B-II decreased to the predose level .
Gemcitabine also induced cell apoptosis , increased ROS contents , and LC3B-II expression .
The combination of piperlongumine with gemcitabine exhibited a synergetic anticancer activity with the combination index < 1 .
The combined application of gemcitabine and piperlongumine yielded synergistic effects on cell apoptosis , but failed to synergistically increase ROS levels and LC3B-II expression .
CONCLUSION : Combination therapy with piperlongumine and gemcitabine is a promising treatment option formutant lung cancer @

OBJECTIVE: To determine the combined efficacy of piperlongumine and gemcitabine for treatment ofmutant lung cancer.
METHODS: The cell growth inhibition of piperlongumine, gemcitabine, and piperlongumine plus gemcitabine was measured by Cell Counting Kit‑8 assay and the combination index was calculated. In addition, the combined effects of piperlongumine and gemcitabine on cell apoptosis, reactive oxygen species (ROS) contents, and microtubule-associated protein 1 light chain 3B (LC3B) expression were examined.
RESULTS: Piperlongumine increased ROS contents and LC3B-II expression. Following the combined treatment with piperlongumine and 10 mM N-acetyl-L-cysteine (NAC), intracellular ROS and cell viability returned to normal levels, and the expression of LC3B-II decreased to the predose level. Gemcitabine also induced cell apoptosis, increased ROS contents, and LC3B-II expression. The combination of piperlongumine with gemcitabine exhibited a synergetic anticancer activity with the combination index<1. The combined application of gemcitabine and piperlongumine yielded synergistic effects on cell apoptosis, but failed to synergistically increase ROS levels and LC3B-II expression.
CONCLUSION: Combination therapy with piperlongumine and gemcitabine is a promising treatment option formutant lung cancer.


greenmedinfo--2020-09-04--Piperlongumine is a promising antitumor agent that deserves further study for colorectal cancer trea

Piperlongumine is a promising antitumor agent that deserves further study for colorectal cancer treatment.

Background : Deregulation of Cyclin D1 and cell cycle progression plays a critical role in tumorigenesis .
The natural compound piperlongumine ( PL ) exhibits potential anticancer effects in various cancer models , but the underlying mechanism needs further elucidation .
Methods : The inhibitory effect of PL on colorectal cancer ( CRC ) cells was determined by anchorage-dependent and -independent assays .
The protein level of Cyclin D1 was examined by immunoblot ( IB ) and immunohistochemical staining ( IHC ) .
The mRNA level was determined by qRT-PCR .
Phosphorylation of histone H3 was analyzed by immunofluorescence ( @ @ @ @ @ @ @ examined by flow cytometry .
The in vivo antitumor effect was validated by the xenograft mouse model .
Results : Cyclin D1 was overexpressed in CRC tissues and cells , and was required for maintaining cell growth , colony formation , and in vivo tumorigenesis .
PL decreased the protein level of c-Fos , which eventually reduced the transcriptional activity of AP-1 and the mRNA level of Cyclin D1 .
Mechanism study showed that PL impaired EGF-induced activation of ERK1/2 and Akt signalings , which resulted in a reduction of c-Fos transcription .
@ @ @ @ @ @ @ c-Fos and caused the ubiquitination-dependent degradation of c-Fos .
Finally , the in vivo antitumor effect of PL on CRC cells was examined using a xenograft mouse model .
Conclusion : Our data indicate that PL is a promising antitumor agent that deserves further study for CRC treatment .

Background: Deregulation of Cyclin D1 and cell cycle progression plays a critical role in tumorigenesis. The natural compound piperlongumine (PL) exhibits potential anticancer effects in various cancer models, but the underlying mechanism needs further elucidation.
Methods: The inhibitory effect of PL on colorectal cancer (CRC) cells was determined by anchorage-dependent and -independent assays. The protein level of Cyclin D1 was examined by immunoblot (IB) and immunohistochemical staining (IHC). The mRNA level was determined by qRT-PCR. Phosphorylation of histone H3 was analyzed by immunofluorescence (IF). The cell cycle was examined by flow cytometry. The in vivo antitumor effect was validated by the xenograft mouse model.
Results: Cyclin D1 was overexpressed in CRC tissues and cells, and was required for maintaining cell growth, colony formation, and in vivo tumorigenesis. PL decreased the protein level of c-Fos, which eventually reduced the transcriptional activity of AP-1 and the mRNA level of Cyclin D1. Mechanism study showed that PL impaired EGF-induced activation of ERK1/2 and Akt signalings, which resulted in a reduction of c-Fos transcription. Furthermore, PL reduced the half-life of c-Fos and caused the ubiquitination-dependent degradation of c-Fos. Finally, the in vivo antitumor effect of PL on CRC cells was examined using a xenograft mouse model.
Conclusion: Our data indicate that PL is a promising antitumor agent that deserves further study for CRC treatment.


greenmedinfo--2020-09-04--Piperlongumine may act as a promising agent for therapeutic immunosuppression.

Piperlongumine ( PL ) , a natural small molecule derived from theLinn plant , has received growing interest as a prooxidative drug with promising anticancer properties .
Yet , the influence of PL on primary human T cells remained elusive .
Knowledge of this is of crucial importance , however , since T cells in particular play a critical role in tumor control .
Therefore , we investigated the effects of PL on the survival and function of primary human peripheral blood T cells ( PBTs ) .
While PL was not cytotoxic to PBTs , it interfered with several @ @ @ @ @ @ @ inhibited T cell/APC immune synapse formation , co-stimulation-induced upregulation of CD69 and CD25 , T cell proliferation and the secretion of proinflammatory cytokines .
PL-induced immune suppression was prevented in the presence of thiol-containing antioxidants .
In line with this finding , PL increased the levels of intracellular reactive oxygen species and decreased glutathione in PBTs .
Diminished intracellular glutathione was accompanied by a decrease in S-glutathionylation on actin suggesting a global alteration of the antioxidant response .
Gene expression analysis demonstrated that T17-related genes were predominantly inhibited by PL .
Consistently , @ @ @ @ @ @ @ cells into T17 subsets was significantly diminished while differentiation into Tcells was substantially increased upon PL treatment .
This opposed consequence for T17 and Tcells was again abolished by thiol-containing antioxidants .
Taken together , PL may act as a promising agent for therapeutic immunosuppression by exerting prooxidative effects in human T cells resulting in a diminished T17 but enhanced Tcell differentiation .

Piperlongumine (PL), a natural small molecule derived from theLinn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in particular play a critical role in tumor control. Therefore, we investigated the effects of PL on the survival and function of primary human peripheral blood T cells (PBTs). While PL was not cytotoxic to PBTs, it interfered with several stages of T cell activation as it inhibited T cell/APC immune synapse formation, co-stimulation-induced upregulation of CD69 and CD25, T cell proliferation and the secretion of proinflammatory cytokines. PL-induced immune suppression was prevented in the presence of thiol-containing antioxidants. In line with this finding, PL increased the levels of intracellular reactive oxygen species and decreased glutathione in PBTs. Diminished intracellular glutathione was accompanied by a decrease in S-glutathionylation on actin suggesting a global alteration of the antioxidant response. Gene expression analysis demonstrated that T17-related genes were predominantly inhibited by PL. Consistently, the polarization of primary human naïve CD4T cells into T17 subsets was significantly diminished while differentiation into Tcells was substantially increased upon PL treatment. This opposed consequence for T17 and Tcells was again abolished by thiol-containing antioxidants. Taken together, PL may act as a promising agent for therapeutic immunosuppression by exerting prooxidative effects in human T cells resulting in a diminished T17 but enhanced Tcell differentiation.


greenmedinfo--2020-09-04--Selected alkaloids exhibit a cytotoxic effect on A549 cells.

BACKGROUND : Cancers are one of the leading causes of deaths nowadays .
The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine .
Therefore , the evaluation of the influence of two alkaloids-piperlongumine ( PL ) , sanguinarine ( SAN ) and their combination-on the basic life processes of the A549 cell line was considered reasonable .
METHODS : The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death , changes in the distribution of cell @ @ @ @ @ @ @ metastatic potential of A549 cells .
The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines : MCF-7 , H1299 and HepG2 .
RESULTS : The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells .
Additionally , the compounds and their combination did not exhibit a cytotoxic effect against normal cells .
The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition .
CONCLUSION : Selected alkaloids exhibit a cytotoxic effect @ @ @ @ @ @ @ treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species ( ROS ) .

BACKGROUND: Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids-piperlongumine (PL), sanguinarine (SAN) and their combination-on the basic life processes of the A549 cell line was considered reasonable.
METHODS: The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2.
RESULTS: The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition.
CONCLUSION: Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).


greenmedinfo--2020-09-04--Piperlonguminine a new mitochondrial aldehyde dehydrogenase activator protects the heart from ischem

Piperlonguminine a new mitochondrial aldehyde dehydrogenase activator protects the heart from ischemia/reperfusion injury.

BACKGROUND : Detoxification of aldehydes by aldehyde dehydrogenases ( ALDHs ) is crucial to maintain cell function .
In cardiovascular diseases , reactive oxygen species generated during ischemia/reperfusion events trigger lipoperoxidation , promoting cell accumulation of highly toxic lipid aldehydes compromising cardiac function .
In this context , activation of ALDH2 , may contribute to preservation of cell integrity by diminishing aldehydes content more efficiently .
METHODS : The theoretic interaction of piperlonguminine ( PPLG ) with ALDH2 was evaluated by docking analysis .
Recombinant human ALDH2 was used to evaluate the effects of PPLG on the kinetics of the @ @ @ @ @ @ @ further investigated in a myocardial infarction model in rats , evaluating ALDHs activity , antioxidant enzymes , oxidative stress markers and mitochondrial function .
RESULTS : PPLG increased the activity of recombinant human ALDH2 and protected the enzyme from inactivation by lipid aldehydes .
Additionally , administration of this drug prevented the damage induced by ischemia/reperfusion in rats , restoring heart rate and blood pressure , which correlated with protection of ALDHs activity in the tissue , a lower content of lipid aldehydes , and the preservation of mitochondrial function .
CONCLUSION : @ @ @ @ @ @ @ damage generated in heart ischemia/reperfusion events , by decreasing lipid aldehydes concentration promoting cardioprotection .

BACKGROUND: Detoxification of aldehydes by aldehyde dehydrogenases (ALDHs) is crucial to maintain cell function. In cardiovascular diseases, reactive oxygen species generated during ischemia/reperfusion events trigger lipoperoxidation, promoting cell accumulation of highly toxic lipid aldehydes compromising cardiac function. In this context, activation of ALDH2, may contribute to preservation of cell integrity by diminishing aldehydes content more efficiently.
METHODS: The theoretic interaction of piperlonguminine (PPLG) with ALDH2 was evaluated by docking analysis. Recombinant human ALDH2 was used to evaluate the effects of PPLG on the kinetics of the enzyme. The effects of PPLG were further investigated in a myocardial infarction model in rats, evaluating ALDHs activity, antioxidant enzymes, oxidative stress markers and mitochondrial function.
RESULTS: PPLG increased the activity of recombinant human ALDH2 and protected the enzyme from inactivation by lipid aldehydes. Additionally, administration of this drug prevented the damage induced by ischemia/reperfusion in rats, restoring heart rate and blood pressure, which correlated with protection of ALDHs activity in the tissue, a lower content of lipid aldehydes, and the preservation of mitochondrial function.
CONCLUSION: Activation of ALDH2 by piperlonguminine ameliorates cell damage generated in heart ischemia/reperfusion events, by decreasing lipid aldehydes concentration promoting cardioprotection.


greenmedinfo--2020-09-04--Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase-1 expression in cholangio

Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase-1 expression in cholangiocarcinoma cell lines.

Piperlongumine ( PL ) produces reactive oxygen species ( ROS ) and induces G2/M-phase arrest in cholangiocarcinoma ( CCA ) cells via the JNK/ERK pathway .
A differential response to PL was observed among all CCA cell lines However , the underlying mechanisms have remained to be fully elucidated .
The aim of the present study was to investigate the molecular mechanisms of PL-induced heme oxygenase-1 ( HO-1 ) expression in CCA cell lines .
The anti-proliferative action of PL in the CCA cell lines KKU-100 and KKU-213A was analyzed using sulforhodamine B assays .
Reverse transcription-quantitative PCR and western @ @ @ @ @ @ @ and protein expression .
HO-1 inhibition was achieved using the chemical inhibitor zinc protophoryn or specific small interfering RNA to HO-1 .
Intracellular ROS was detected using a 2,7-dichlorodihydrofluorescein diacetate fluorescence assay .
High expression of phase-II detoxification enzymes , including NADPH quinone oxidoreductase-1 , heme oxygenase-1 , superoxide dismutases and aldo-keto reductase 1 subunits C-1 and 3 , were detected in the KKU-100 cell line .
Of the CCA cell lines tested , KKU-100 was the least sensitive to PL .
Dose-dependent upregulation of HO-1 expression via PI3K/Akt activation was detected in @ @ @ @ @ @ @ eliminated the antioxidant defense mechanisms , leading to increased anti-cancer activity of PL in the CCA cell lines via an increase in intracellular ROS levels and apoptotic protein expression .
These observations indicated that HO-1 inhibition had a chemosensitizing effect on CCA to PL .

Piperlongumine (PL) produces reactive oxygen species (ROS) and induces G2/M-phase arrest in cholangiocarcinoma (CCA) cells via the JNK/ERK pathway. A differential response to PL was observed among all CCA cell lines However, the underlying mechanisms have remained to be fully elucidated. The aim of the present study was to investigate the molecular mechanisms of PL-induced heme oxygenase-1 (HO-1) expression in CCA cell lines. The anti-proliferative action of PL in the CCA cell lines KKU-100 and KKU-213A was analyzed using sulforhodamine B assays. Reverse transcription-quantitative PCR and western blot analyses were used to examine mRNA and protein expression. HO-1 inhibition was achieved using the chemical inhibitor zinc protophoryn or specific small interfering RNA to HO-1. Intracellular ROS was detected using a 2,7-dichlorodihydrofluorescein diacetate fluorescence assay. High expression of phase-II detoxification enzymes, including NADPH quinone oxidoreductase-1, heme oxygenase-1, superoxide dismutases and aldo-keto reductase 1 subunits C-1 and 3, were detected in the KKU-100 cell line. Of the CCA cell lines tested, KKU-100 was the least sensitive to PL. Dose-dependent upregulation of HO-1 expression via PI3K/Akt activation was detected in PL-treated CCA cells. Inhibition of HO-1 eliminated the antioxidant defense mechanisms, leading to increased anti-cancer activity of PL in the CCA cell lines via an increase in intracellular ROS levels and apoptotic protein expression. These observations indicated that HO-1 inhibition had a chemosensitizing effect on CCA to PL.


greenmedinfo--2020-09-04--Piperlongumine inhibits head and neck squamous cell carcinoma proliferation by docking to Akt.

Piperlongumine ( PL ) is a biologically active alkaloid isolated from the long pepper roots and widely used as a traditional medicine in Ayurvedic medicine .
However , the mechanism of PL 's effect on head and neck squamous cell carcinoma ( HNSCC ) is not well understood .
We performed cell experiments to confirm PL 's inhibitory effect on HNSCC and employing cisplatin as positive control .
Next , we conducted bioinformatics to predict PL 's potential targets and verified by western blotting .
Molecular docking , Biacore experiment and kinase activity assays were applied to elucidate the mechanism @ @ @ @ @ @ @ In vivo efficacy was verified by xenotransplantation and immunohistochemistry .
PL inhibited proliferation , promoted late apoptosis , arrested cell cycle and inhibited DNA replication of the HEp-2 and FaDu cell lines .
Employing bioinformatics , we found that PL 's target was Akt and PL attenuated Akt phosphorylation .
We found from molecular docking , Biacore experiment and kinase activity assay that PL inhibited Akt activation by docking to Akt to restrain its activity .
In addition , PL significantly inhibited the growth of xenograft tumors by down regulating the expression of @ @ @ @ @ @ @ new insights into the molecular functions of PL and indicate its potential as a therapeutic agent for HNSCC .

Piperlongumine (PL) is a biologically active alkaloid isolated from the long pepper roots and widely used as a traditional medicine in Ayurvedic medicine. However, the mechanism of PL's effect on head and neck squamous cell carcinoma (HNSCC) is not well understood. We performed cell experiments to confirm PL's inhibitory effect on HNSCC and employing cisplatin as positive control. Next, we conducted bioinformatics to predict PL's potential targets and verified by western blotting. Molecular docking, Biacore experiment and kinase activity assays were applied to elucidate the mechanism by which PL inhibited target activity. In vivo efficacy was verified by xenotransplantation and immunohistochemistry. PL inhibited proliferation, promoted late apoptosis, arrested cell cycle and inhibited DNA replication of the HEp-2 and FaDu cell lines. Employing bioinformatics, we found that PL's target was Akt and PL attenuated Akt phosphorylation. We found from molecular docking, Biacore experiment and kinase activity assay that PL inhibited Akt activation by docking to Akt to restrain its activity. In addition, PL significantly inhibited the growth of xenograft tumors by down regulating the expression of p-Akt in vivo. This study provides new insights into the molecular functions of PL and indicate its potential as a therapeutic agent for HNSCC.


greenmedinfo--2020-09-04--Dichloromethane extraction from Piper nigrum L. and P. longum L. to mitigate ischemic stroke.

Dichloromethane fraction ( DF ) of Piper nigrum L. and P. longum L. ( PnL and PlL ) , has @ @ @ @ @ protective effect against ischemic stroke in rats .
However , the regulatory mechanism exerted by @ @ @ @ @ been fully elucidated .
In this study , we found that DF greatly ameliorated cerebral @ @ @ @ @ model of permanent middle cerebral artery occlusion ( pMCAO ) .
The neurological score , @ @ @ @ @ volume , phosphorylation of AKT ( p-AKT ) , phosphorylation mTOR ( p-mTOR ) , @ @ @ @ @ determined .
Additionally , we discovered that DF pretreatment reduced infarct volume , neurological score @ @ @ @ @ Furthermore , DF therapy caused the downregulation of Atg7 and p-AKT expression , as well @ @ @ @ @ expression .
In conclusion , our findings indicated that DF treatment can reduce brain damage @ @ @ @ @ by activating the Akt-mTOR signaling pathway in ischemic stroke .

Dichloromethane fraction (DF) of Piper nigrum L. and P. longum L. (PnL and PlL), has been found to exert a protective effect against ischemic stroke in rats. However, the regulatory mechanism exerted by PnL and PIL have not been fully elucidated. In this study, we found that DF greatly ameliorated cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion (pMCAO). The neurological score, behavioral assessment, brain infarct volume, phosphorylation of AKT (p-AKT), phosphorylation mTOR (p-mTOR), and Atg7 protein levels were determined. Additionally, we discovered that DF pretreatment reduced infarct volume, neurological score, and brain damage. Furthermore, DF therapy caused the downregulation of Atg7 and p-AKT expression, as well as the upregulation of p-mTOR expression. In conclusion, our findings indicated that DF treatment can reduce brain damage and inhibit apoptosis and autophagy by activating the Akt-mTOR signaling pathway in ischemic stroke.


greenmedinfo--2020-09-04--An anti-inflammatory composition of Boswellia serrata resin extracts alleviates pain and protects ca

An anti-inflammatory composition of Boswellia serrata resin extracts alleviates pain and protects cartilage in monoiodoacetate-induced osteoarthritis in rats.

The boswellic acids , the active compounds ingum resin extract , are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase ( 5-LOX ) .
Here , we present the anti-osteoarthritis ( OA ) efficacy of LI13019F1 ( also known as Serratrin® ) , a unique composition containing the acidic and nonacidic fractions ofgum resin .
This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration ( IC ) of 43.35 ± 4.90 g/mL .
Also , LI13019F1 strongly inhibited the leukotriene B ( IC , 7.80 ± 2.40 g/mL ) and prostaglandin E ( IC , 6.19 @ @ @ @ @ @ @ blood-derived cells .
Besides , LI13019F1 reduced TNF-production with the ICof 12.38 ± 0.423 g/mL .
On average , 1 , 2.5 , and 5 g/mL doses of LI13019F1 protected 34.62 , 47.66 , and 62.29 % SW1353 human chondrosarcoma cells from IL-1induced SOX-9 depletion , respectively .
Further , a 28-day preclinical proof-of-concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate- ( MIA- ) inducedrats .
At the end of the study , 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements ( 55.17 ± 5.81 g @ @ @ @ @ @ @ ± 6.30 g ( < 0.05 ) , respectively , vs. MIA : 31.22 ± 7.15 g ) in body-weight-bearing capacities .
Concurrently , LI13019F1-150 and LI13019F1-300 rats substantially ( < 0.05 ) increased the threshold of pain sensitivity to pressure ( 26.98 ± 2.36 and 28.06 ± 2.72-gram force , respectively ; vs. 18.63 ± 5.82 in MIA ) and increased ( < 0.05 ) the latent time to withdraw the paw after a thermal stimulus ( 23.61 ± 2.73 and 28.18 ± 1.90 sec , respectively ; vs. 16.56 ± 1.22 @ @ @ @ @ @ @ , the histological observations on Safranin-O green stained articular cartilage revealed that LI13019F1 also prevented the MIA-induced structural damage of the cartilage and reduced the loss of the extracellular matrix ( ECM ) components in the experimental rats .
In conclusion , the present observations suggest that LI13019F1 , a new composition ofgum resin extracts , reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model .

The boswellic acids, the active compounds ingum resin extract, are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase (5-LOX). Here, we present the anti-osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions ofgum resin. This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration (IC) of 43.35 ± 4.90 g/mL. Also, LI13019F1 strongly inhibited the leukotriene B(IC, 7.80 ± 2.40 g/mL) and prostaglandin E(IC, 6.19 ± 0.52 g/mL) productions in human blood-derived cells. Besides, LI13019F1 reduced TNF-production with the ICof 12.38 ± 0.423 g/mL. On average, 1, 2.5, and 5 g/mL doses of LI13019F1 protected 34.62, 47.66, and 62.29% SW1353 human chondrosarcoma cells from IL-1induced SOX-9 depletion, respectively. Further, a 28-day preclinical proof-of-concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate- (MIA-) inducedrats. At the end of the study, 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements (55.17 ± 5.81 g (<0.05), and 66.22 ± 6.30 g (<0.05), respectively, vs. MIA: 31.22 ± 7.15 g) in body-weight-bearing capacities. Concurrently, LI13019F1-150 and LI13019F1-300 rats substantially (<0.05) increased the threshold of pain sensitivity to pressure (26.98 ± 2.36 and 28.06 ± 2.72-gram force, respectively; vs. 18.63 ± 5.82 in MIA) and increased (<0.05) the latent time to withdraw the paw after a thermal stimulus (23.61 ± 2.73 and 28.18 ± 1.90 sec, respectively; vs. 16.56 ± 1.22 sec. in MIA). Besides, the histological observations on Safranin-O green stained articular cartilage revealed that LI13019F1 also prevented the MIA-induced structural damage of the cartilage and reduced the loss of the extracellular matrix (ECM) components in the experimental rats. In conclusion, the present observations suggest that LI13019F1, a new composition ofgum resin extracts, reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model.


greenmedinfo--2020-09-04--Effect of extract from Boswellia serrata gum resin on decrease of GAD65 autoantibodies in a patient

Effect of extract from Boswellia serrata gum resin on decrease of GAD65 autoantibodies in a patient with latent autoimmune diabetes in adults.

Background : Extracts from Boswellia serrata gum resin have anti-inflammatory effect and are used for treatment of a variety of chronic inflammatory diseases .
It was previously demonstrated that the treatment with Boswellia serrata gum resin of LADA ( Latent Autoimmune Diabetes in Adults ) patients decreased blood levels of IA2 antibodies , one of the markers associated with LADA autoimmune diabetes .
Primary Study Objective : The purpose of this study was to test whether Boswellia serrata gum resin also influences GAD65 autoantibodies as the other marker associated with LADA .
Methods/Design : We report a case study of @ @ @ @ @ @ @ GAD65 autoantibodies who was treated with extract from Boswellia serrata gum resin , during 9 months .
Blood levels of GAD65 autoantibodies , fasting blood glucose levels and HbA1c were measured before the treatment and periodically during the treatment .
Results : Over the observed period , the blood levels of GAD65 autoantibodies linearly decreased about 25 % .
Conclusion : The study confirms that extract of Boswellia serrata gum resin seems to prevent insulitis in patients with LADA , as indicated by its action on both markers of autoimmune diabetes , i.e.
@ @ @ @ @ @ @ possibility that the treatment with boswellic acids of LADA patients with positive autoantibodies could be beneficial on the course of the disease , calls for further investigation and a clinical study .

Background: Extracts from Boswellia serrata gum resin have anti-inflammatory effect and are used for treatment of a variety of chronic inflammatory diseases. It was previously demonstrated that the treatment with Boswellia serrata gum resin of LADA (Latent Autoimmune Diabetes in Adults) patients decreased blood levels of IA2 antibodies, one of the markers associated with LADA autoimmune diabetes.
Primary Study Objective: The purpose of this study was to test whether Boswellia serrata gum resin also influences GAD65 autoantibodies as the other marker associated with LADA.
Methods/Design: We report a case study of male patient diagnosed with LADA with positive GAD65 autoantibodies who was treated with extract from Boswellia serrata gum resin, during 9 months. Blood levels of GAD65 autoantibodies, fasting blood glucose levels and HbA1c were measured before the treatment and periodically during the treatment.
Results: Over the observed period, the blood levels of GAD65 autoantibodies linearly decreased about 25%.
Conclusion: The study confirms that extract of Boswellia serrata gum resin seems to prevent insulitis in patients with LADA, as indicated by its action on both markers of autoimmune diabetes, i.e., GAD65 and IA2 autoantibodies. The possibility that the treatment with boswellic acids of LADA patients with positive autoantibodies could be beneficial on the course of the disease, calls for further investigation and a clinical study.


greenmedinfo--2020-09-04--Boswellia and its extract may be an effective and safe treatment option for patient with osteoarthri

Boswellia and its extract may be an effective and safe treatment option for patient with osteoarthritis.

BACKGROUND : Osteoarthritis ( OA ) is the commonest form of inflammatory joint disease .
Unfortunately , to date , there is no appropriate treatment for OA .
Boswellia serrata was considered as a potent anti-inflammatory , anti-arthritic and analgesic agent that may be a drug for OA .
METHODS : In this meta-analysis , data from randomized controlled trials were obtained to assess the effects of Boswellia or its extract versus placebo or western medicine in patients with OA .
The primary outcomes included visual analogue score ( VAS ) , WOMAC pain , WOMAC stiffness , WOMAC function @ @ @ @ @ @ @ trials involving 545 patients were included .
Compared with the control group , Boswellia and its extract may relieve the pain [ VAS : ( WMD -8.33 ; 95 % CI -11.19 , - 5.46 ; P < 0.00001 ) ; WOMAC pain : ( WMD -14.22 ; 95 % CI -22.34 , - 6.09 ; P = 0 .
0006 ) ] and stiffness [ WOMAC stiffness : ( WMD -10.04 ; 95 % CI -15.86 , - 4.22 ; P = 0 .
0007 ) ] , and improve the joint @ @ @ @ @ @ @ WMD -10.75 ; 95 % CI -15.06 , - 6.43 ; P < 0 .
00001 ) ; lequesne index : ( WMD -2.27 ; 95 % CI -3.08 , - 1.45 ; P < 0 .
00001 ) ] .
CONCLUSION : Based on current evidence , Boswellia and its extract may be an effective and safe treatment option for patient with OA , and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks .

BACKGROUND: Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was considered as a potent anti-inflammatory, anti-arthritic and analgesic agent that may be a drug for OA.
METHODS: In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of Boswellia or its extract versus placebo or western medicine in patients with OA. The primary outcomes included visual analogue score (VAS), WOMAC pain, WOMAC stiffness, WOMAC function and lequesne index.
RESULT: Seven trials involving 545 patients were included. Compared with the control group, Boswellia and its extract may relieve the pain [VAS: (WMD -8.33; 95% CI -11.19, - 5.46; P<0.00001); WOMAC pain: (WMD -14.22; 95% CI -22.34, - 6.09; P = 0. 0006)] and stiffness [WOMAC stiffness: (WMD -10.04; 95% CI -15.86, - 4.22; P = 0. 0007)], and improve the joint's function [WOMAC function: (WMD -10.75; 95% CI -15.06, - 6.43; P<0. 00001); lequesne index: (WMD -2.27; 95% CI -3.08, - 1.45; P<0. 00001)].
CONCLUSION: Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks.


greenmedinfo--2020-09-04--Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine.

Glucose 6-phosphate dehydrogenase ( G6PD ) deficiency facilitates human coronavirus infection due to glutathione depletion .
G6PD deficiency may especially @ @ @ @ @ disease-2019 ( COVID-19 ) infection when employing pro-oxidant therapy .
However , glutathione depletion is @ @ @ @ @ ) administration .
We describe a severe case of COVID-19 infection in a G6PD-deficient patient @ @ @ @ @ from intravenous ( IV ) NAC beyond reversal of hemolysis .
NAC blocked hemolysis and @ @ @ @ @ C-reactive protein ( CRP ) , and ferritin and allowed removal from respirator and veno-venous @ @ @ @ @ recovery of the G6PD-deficient patient .
NAC was also administered to 9 additional respirator-dependent COVID-19-infected @ @ @ @ @ NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 @ @ @ @ @ action may involve the blockade of viral infection and the ensuing cytokine storm that warrant @ @ @ @ @ setting of controlled clinical trials .

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.


greenmedinfo--2020-09-04--Plant based foods play a vital role to enhance the immunity of people to control of COVID-19.

This review focused on the use of plant based foods for enhancing the immunity of all aged groups against COVID-19 .
In humans , coronaviruses are included in the spectrum of viruses that cause the common cold and , recently , severe acute respiratory syndrome ( SARS ) .
Emerging infectious diseases , such as SARS present a major threat to public health .
The novel coronavirus has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization .
COVID-19 is usually caused a virus to which most probably the people with low immunity @ @ @ @ @ @ @ foods increased the intestinal beneficial bacteria which are helpful and makes up of 85 % of the immune system .
By the use of plenty of water , minerals like magnesium and Zinc , micronutrients , herbs , food rich in vitamins C , D & E and better life style one can promote the health and can overcome this infection .
Various studies investigated that a powerful antioxidant Glutathione and a bioflavonoid Quercetin may prevent various infections including COVID-19 .
In conclusion , the plant based foods play a vital role to @ @ @ @ @ @ @ of COVID-19 .

This review focused on the use of plant based foods for enhancing the immunity of all aged groups against COVID-19. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and, recently, severe acute respiratory syndrome (SARS). Emerging infectious diseases, such as SARS present a major threat to public health. The novel coronavirus has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. COVID-19 is usually caused a virus to which most probably the people with low immunity response are being effected. Plant based foods increased the intestinal beneficial bacteria which are helpful and makes up of 85% of the immune system. By the use of plenty of water, minerals like magnesium and Zinc, micronutrients, herbs, food rich in vitamins C, D&E and better life style one can promote the health and can overcome this infection. Various studies investigated that a powerful antioxidant Glutathione and a bioflavonoid Quercetin may prevent various infections including COVID-19. In conclusion, the plant based foods play a vital role to enhance the immunity of people to control of COVID-19.


greenmedinfo--2020-09-04--These results indicated a possible important therapeutic role for hydroxytyrosol in the prevention o

These results indicated a possible important therapeutic role for hydroxytyrosol in the prevention or management of bovine mastitis.

BACKGROUND : Bovine mastitis is a growing health problem , affecting both welfare of dairy cattle and milk production .
It often leads to chronic infections , disturbing the quality of milk and resulting in cow death .
Thus , it has a great economic impact for breeders .
METHODS : In this study , we evaluated the protective effect of hydroxytyrosol-a natural molecule which is the major constituent of many phyto-complexes-in an in vitro model of mastitis induced by LPS ( 1μg/mL ) .
RESULTS : Our results showed that hydroxytyrosol ( 10 and 25μM ) was able to @ @ @ @ @ @ @ ( intracellular ROS , GSH and NOX-1 ) and the consequently inflammatory response ( TNF-α , IL-1β and IL-6 ) .
The protective effect of hydroxytyrosol is also related to the enhancement of endogenous antioxidant systems ( Nrf2 , HO-1 , NQO-1 and Txnrd1 ) .
Moreover , hydroxytyrosol showed an important protective effect on cell functionality ( α-casein S1 , α-casein S2 and β-casein ) .
CONCLUSIONS : Taken together , our results showed a significant protective effect of hydroxytyrosol on oxidative stress and inflammatory response in MAC-T cells .
Thus , @ @ @ @ @ @ @ for hydroxytyrosol in the prevention or management of bovine mastitis .

BACKGROUND: Bovine mastitis is a growing health problem, affecting both welfare of dairy cattle and milk production. It often leads to chronic infections, disturbing the quality of milk and resulting in cow death. Thus, it has a great economic impact for breeders.
METHODS: In this study, we evaluated the protective effect of hydroxytyrosol-a natural molecule which is the major constituent of many phyto-complexes-in an in vitro model of mastitis induced by LPS (1μg/mL).
RESULTS: Our results showed that hydroxytyrosol (10 and 25μM) was able to prevent the oxidative stress induced by LPS (intracellular ROS, GSH and NOX-1) and the consequently inflammatory response (TNF-α, IL-1β and IL-6). The protective effect of hydroxytyrosol is also related to the enhancement of endogenous antioxidant systems (Nrf2, HO-1, NQO-1 and Txnrd1). Moreover, hydroxytyrosol showed an important protective effect on cell functionality (α-casein S1, α-casein S2 and β-casein).
CONCLUSIONS: Taken together, our results showed a significant protective effect of hydroxytyrosol on oxidative stress and inflammatory response in MAC-T cells. Thus, we indicated a possible important therapeutic role for hydroxytyrosol in the prevention or management of bovine mastitis.


greenmedinfo--2020-09-04--Hydroxytyrosol as a promising ally in the treatment of fibromyalgia.

Fibromyalgia ( FM ) is a chronic and highly disabling syndrome , which is still underdiagnosed , with controversial treatment .
Although its aetiology is unknown , a number of studies have pointed to the involvement of altered mitochondrial metabolism , increased oxidative stress and inflammation .
The intake of extra virgin olive oil , and particularly of one of its phenolic compounds , hydroxytyrosol ( HT ) , has proven to be protective in terms of redox homeostatic balance and the reduction of inflammation .
In this context , using a proteomic approach with nanoscale liquid chromatography coupled to @ @ @ @ @ @ @ analysed : ( i ) Changes in the proteome of dermal fibroblasts from a patient with FM versus a healthy control , and ( ii ) the effect of the treatment with a nutritional relevant dose of HT .
Our results unveiled that fibroblast from FM show a differential expression in proteins involved in the turnover of extracellular matrix and oxidative metabolism that could explain the inflammatory status of these patients .
Moreover , a number of these proteins results normalized by the treatment with HT .
In conclusion , our results support @ @ @ @ @ @ @ beneficial in the management of FM .

Fibromyalgia (FM) is a chronic and highly disabling syndrome, which is still underdiagnosed, with controversial treatment. Although its aetiology is unknown, a number of studies have pointed to the involvement of altered mitochondrial metabolism, increased oxidative stress and inflammation. The intake of extra virgin olive oil, and particularly of one of its phenolic compounds, hydroxytyrosol (HT), has proven to be protective in terms of redox homeostatic balance and the reduction of inflammation. In this context, using a proteomic approach with nanoscale liquid chromatography coupled to tandem mass spectrometry, the present study analysed: (i) Changes in the proteome of dermal fibroblasts from a patient with FM versus a healthy control, and (ii) the effect of the treatment with a nutritional relevant dose of HT. Our results unveiled that fibroblast from FM show a differential expression in proteins involved in the turnover of extracellular matrix and oxidative metabolism that could explain the inflammatory status of these patients. Moreover, a number of these proteins results normalized by the treatment with HT. In conclusion, our results support that an HT-enriched diet could be highly beneficial in the management of FM.


greenmedinfo--2020-09-04--Hydroxytyrosol attenuates hepatic fat accumulation.

Two experiments were carried out to examine the impacts of hydroxytyrosol ( HT ) on lipid metabolism and mitochondrial function in .
Triplicate groups of fish were fed four test diets : ( 1 ) low-fat diet ( LFD , 5 % fat ) , ( 2 ) high-fat diet ( HFD , 15 % fat ) , ( 3 ) LFD + 100 mg/kg HT ( LFD + HT ) , and ( 4 ) HFD + 100 mg/kg HT ( HFD + HT ) ( in vivo ) .
Hepatocytes from the same batch were exposed to three @ @ @ @ @ @ @ , oleic acid ( OA ) medium [ L15 + 400μM OA ] , and OA + HT medium [ L15 + 400 μM OA + 10 μM HT ] to explore the roles of HT in mitochondrial function ( in vitro ) .
Fish fed HFD had excessive fat deposition in the liver , and HT inclusion in the HFD decreased hepatic fat deposition .
Transmission electron microscopy revealed that the HFD triggers loss of cristae and metrical density and hydropic changes in mitochondria and that HT supplementation attenuates the ultrastructural alterations @ @ @ @ @ @ @ showed that HT decreases fat deposition in hepatocytes , suppresses the reactive oxygen species formation , and facilitates the expression of phospho-AMPK protein and the genes involved in mitochondria biogenesis ( , , ) and autophagy ( , , ) .
These findings suggest the lipid-lowering effect of HT mediated by activation of mitochondrial biogenesis and autophagy through the AMPK pathway .

Two experiments were carried out to examine the impacts of hydroxytyrosol (HT) on lipid metabolism and mitochondrial function in. Triplicate groups of fish were fed four test diets: (1) low-fat diet (LFD, 5% fat), (2) high-fat diet (HFD, 15% fat), (3) LFD + 100 mg/kg HT (LFD + HT), and (4) HFD + 100 mg/kg HT (HFD + HT) (in vivo). Hepatocytes from the same batch were exposed to three media including L-15 medium (L15), oleic acid (OA) medium [L15 + 400μM OA], and OA + HT medium [L15 + 400 μM OA + 10 μM HT] to explore the roles of HT in mitochondrial function (in vitro). Fish fed HFD had excessive fat deposition in the liver, and HT inclusion in the HFD decreased hepatic fat deposition. Transmission electron microscopy revealed that the HFD triggers loss of cristae and metrical density and hydropic changes in mitochondria and that HT supplementation attenuates the ultrastructural alterations of mitochondria. The in vitro test showed that HT decreases fat deposition in hepatocytes, suppresses the reactive oxygen species formation, and facilitates the expression of phospho-AMPK protein and the genes involved in mitochondria biogenesis (,,) and autophagy (,,). These findings suggest the lipid-lowering effect of HT mediated by activation of mitochondrial biogenesis and autophagy through the AMPK pathway.


greenmedinfo--2020-09-04--Olive fruit and almond skin extract seems to protect LDL from oxidation and to prevent inflammatory

Olive fruit and almond skin extract seems to protect LDL from oxidation and to prevent inflammatory status in moderately hypercholesterolemic subjects.

Hydroxytyrosol ( HT ) from olives and polyphenols from almond skin ( ASPs ) possess cardioprotective properties .
This pilot @ @ @ @ @ supplementation with a combination of olive fruit and almond skin extracts on low-density lipoprotein ( @ @ @ @ @ lipid homeostasis , and inflammatory parameters in adults with moderate hypercholesterolemia .
A randomized , @ @ @ @ @ pilot study of 8 weeks was performed .
The extract group ( EG ) received @ @ @ @ @ HT +210 mg ASPs , and the control group ( CG ) received a placebo @ @ @ @ @ LDL ( oxLDL ) levels and the oxLDL/LDL ratio were lower in the EG than @ @ @ @ @ weeks of treatment ( 18.76 ± 3.91 vs. 10.34 ± 4.22 ,

Hydroxytyrosol (HT) from olives and polyphenols from almond skin (ASPs) possess cardioprotective properties. This pilot study evaluates the effect of supplementation with a combination of olive fruit and almond skin extracts on low-density lipoprotein (LDL) cholesterol oxidation, lipid homeostasis, and inflammatory parameters in adults with moderate hypercholesterolemia. A randomized, parallel, double-blind, placebo-controlled pilot study of 8 weeks was performed. The extract group (EG) received the supplement with 7.5 mg HT +210 mg ASPs, and the control group (CG) received a placebo composed of maltodextrin. Oxidized LDL (oxLDL) levels and the oxLDL/LDL ratio were lower in the EG than in the CG after 8 weeks of treatment (18.76 ± 3.91 vs. 10.34 ± 4.22, < .001 and 0.151 ± 0.025 vs. 0.08 ± 0.023, < .001, respectively). Interleukin-1β levels were significantly higher in the CG than in the EG at week 4 ( = .004), IL-6 was significantly higher in the CG than in the EG at week 4 ( = .049), and IL-10 was significantly increased at week 4 in both groups ( = .002 for CG and = .001 for EG). In conclusion, daily consumption of a combination of an olive fruit extract and an almond skin extract for 8 weeks seems to protect LDL from oxidation and to prevent inflammatory status in moderately hypercholesterolemic subjects.


greenmedinfo--2020-09-04--Wide biological role of hydroxytyrosol: possible therapeutic and preventive properties in cardiovasc

Wide biological role of hydroxytyrosol: possible therapeutic and preventive properties in cardiovascular diseases.

The growing incidence of cardiovascular disease ( CVD ) has promoted investigations of natural molecules that could prevent and treat @ @ @ @ @ hydroxytyrosol , a polyphenolic compound of olive oil , is well known for its antioxidant @ @ @ @ @ effects .
Its strong antioxidant properties are due to the scavenging of radicals and the @ @ @ @ @ of antioxidant enzymes ( SOD , CAT , HO-1 , NOS , COX-2 , GSH @ @ @ @ @ the lipid peroxidation of low-density lipoprotein ( LDL ) cholesterol , a hallmark of atherosclerosis @ @ @ @ @ stress and an improved lipid profile were also demonstrated in healthy subjects as well as @ @ @ @ @ hydroxytyrosol ( HT ) supplementation .
These results might open a new therapeutic scenario through @ @ @ @ @ CVDs .
This review is the first attempt to collect together scientific literature on HT @ @ @ @ @ in vivo models , as well as in human clinical studies , describing its potential @ @ @ @ @ .

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.