PMID: 

Oxid Med Cell Longev. 2019 ;2019:3643715. Epub 2019 Dec 13. PMID: 31915505

Abstract Title: 

The Antioxidant Alpha-Lipoic Acid Inhibits Proliferation and Invasion of Human Gastric Cancer Cells via Suppression of STAT3-Mediated MUC4 Gene Expression.

Abstract: 

Background: Metastasis and invasion are the main causes of mortality in gastric cancer. To improve the treatment of gastric cancer, the development of effective and innovative antitumor agents toward invasion and proliferation is needed. Alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, showed antiproliferative and cytotoxic effects on several cancers. So it is feasible to explore whether ALA can be used to inhibit proliferation and invasion in human gastric cancer.Methods: The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performedcell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3.Results: We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region.Conclusion: ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

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PMID: 

Pak J Biol Sci. 2019 Jan ;22(8):361-371. PMID: 31930824

Abstract Title: 

Potential Protective Role of Rutin and Alpha-lipoic Acid Against Cisplatin-induced Nephrotoxicity in Rats.

Abstract: 

BACKGROUND AND OBJECTIVE: Cisplatin-induced nephrotoxicity is a serious complication that restricts its utilization in cancer treatment. Rutin and alpha-lipoic acid have antioxidant effectiveness, anti-inflammatory efficacy and prevent oxidative stress. Therefore, the current study planned to investigate the potential defensive impacts of rutin and alpha-lipoic acid on cisplatin-induced renal damage in rats.MATERIALS AND METHODS: Fifty-six adult male Wistar albino rats were randomly divided into seven groups. Rats of group 1: Treated with saline as the control. Group 2: Orally received rutin daily for 2 weeks. Group 3: Rats were orally administered with alpha-lipoic acid (ALA) daily for 2 weeks. Group 4: Rats were intraperitoneal (i.p.) injected with cisplatin to develop the acute renal injury. Group 5: Rats injected with cisplatin then treated orally with RT. Group 6: Rats were injected i.p., with cisplatin then treated orally with ALA. Group 7: Rats injected with cisplatin then treated orally with RT and ALA daily for 2 weeks.RESULTS: The cisplatin administration to rats induced nephrotoxicity associated with a significant increase in serum urea, creatinine, albumin and significantly reduce haemoglobin and red blood cells count. The animal treated with cisplatin showed a significant increase in the level of renal malondialdehyde associated with reduction in the levels of glutathione-s-transferase, glutathione reductase and catalase compared to control group. Moreover, cisplatin treated group recorded significant increase in nuclear factor kappa B, IL-6 and p53 levels compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate and acute tubular injury. In correlation with the cisplatin group, Rutin and alpha-lipoic acid ameliorated cisplatin-induction increase in serum urea, creatinine, albumin, oxidative stress and inflammation were observed. Moreover, rutin and alpha-lipoic acid showed an enhancement in haematological and histopathological structures.CONCLUSION: These results indicated that rutin and alpha-lipoic acid showed a protective effect against cisplatin-induced nephrotoxicity in rats.

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PMID: 

Environ Toxicol Pharmacol. 2020 Jan 7 ;75:103323. Epub 2020 Jan 7. PMID: 31935550

Abstract Title: 

Effect ofα-lipoic acid on spatial memory and structural integrity of developing hippocampal neurons in rats subjected to sodium arsenite exposure.

Abstract: 

BACKGROUND: Exposure to arsenic has been reported to affect the nervous system in a number of ways. Various epidemiological studies suggest cognitive impairment in subjects following exposure to environmental arsenic. The goal of the present study was to determine if supplementation of exogenousα-lipoic acid (ALA) could ameliorate sodium arsenite (NaAsO) induced adverse effects on learning and memory and synaptic connectivity in rat hippocampus.METHODS: Accordingly, NaAsOalone (1.5/2.0 mg/kg bw) or NaAsOalong with ALA (70 mg/kg bw) was administered by intraperitoneal (i.p.) route from postnatal day (PND) 4-17 to Wistar rat pups (experimental groups) and the Control groups received either distilled water or no treatment at all. After carrying out Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test, the fresh brain tissues were collected on PND 18 and processed for Golgi Cox staining.RESULTS: Observations of MWM test revealed impaired learning and memory in iAs alone treated animals as against those co-exposed to iAs and ALA. In Golgi stained hippocampal sections of iAs alone treated animals, decreased dendritic arborization and reduced number of spines in pyramidal neurons (CA1) and granule cells (DG) was observed whereas neuronal morphology was preserved in the controls and ALA supplemented groups CONCLUSIONS: These observations are suggestive of beneficial effects of ALA on iAs induced effects on learning and memory as well as on hippocampal neuronal morphology.

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PMID: 

J Cell Commun Signal. 2019 Dec 16. Epub 2019 Dec 16. PMID: 31820335

Abstract Title: 

Lutein reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases in retinal pigment epithelial (ARPE-19) cells.

Abstract: 

Diabetic retinopathy (DR) is a major cause of acquired blindness among working adults. The retinal pigment epithelium (RPE), constitutes an outer blood-retinal barrier, is vastly affected in diabetic humans and animals. Lower levels of lutein in the serum and retina of diabetic population, and beneficial effects of carotenoids supplementation in diabetic retinopathy patients created an interest to examine the protective effect of lutein on hyperglycemia-mediated changes in oxidative stress and antioxidant defense system in ARPE-19 cells. The WST-1 assay was performed to analyze the impact of glucose, and lutein on the viability of ARPE-19. The intracellular oxidative stress was measured by a DCF (dichlorofluorescein) assay, mitochondrial membrane potential (MMP) was monitored using a JC-10 MMP assay kit and GSH level was examined using GSH/GSSG ratio detection kit. The oxidative stress markers, protein carbonyl and malondialdehyde were spectrophotometrically measured using 2,4-dinitrophenylhydrazine and 2-thiobarbituric acid, respectively. The expression of endogenous antioxidant enzymes and regulatory proteins in ARPE-19 was quantified by western blotting. The localization of Nrf2 protein was examined by immunofluorescent staining. The results show that lutein (up to 1.0 μM) did not affect the viability of ARPE-19 grown in both normal and high-glucose conditions. Lutein treatment blocked high glucose-mediated elevation of intracellular ROS, protein carbonyl and malondialdehyde content in ARPE-19 cells. The decreased MMP and GSH levels observed in ARPE-19 grown under high-glucose condition were rescued by lutein treatment. Further, lutein protected high glucose-mediated down-regulation of a redox-sensitive transcription factor, Nrf2, and antioxidant enzymes, SOD2, HO-1, and catalase. This protective effect of lutein was linked with activated nuclear translocation of Nrf2, which was associated with increased activation of regulatory proteins such as Erk and AKT. Our study indicates that improving the concentration of lutein in the retina could protect RPE from diabetes-associated damage.

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PMID: 

J Ethnopharmacol. 2020 Jan 10 ;251:112564. Epub 2020 Jan 10. PMID: 31926987

Abstract Title: 

Ginsenoside metabolite 20(S)-protopanaxatriol from Panax ginseng attenuates inflammation-mediated NLRP3 inflammasome activation.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Meyer (Araliaceae), has been used in traditional medicine for preventive and therapeutic purposes in Asian countries. One of the active ginsenoside metabolites, 20(S)-Protopanaxatriol (PPT), has been associated with diverse pharmacological effects, including anti-inflammatory properties.AIM OF THE STUDY: Although the capacity of PPT as an anti-inflammatory agent has been studied, this study aimed to explore the intrinsic mechanism of PPT in regulating inflammasome activation-mediated inflammatory responses in experimental models.MATERIALS AND METHODS: Lipopolysaccharide (LPS)-primed peritoneal macrophages in vitro was used to study the role of PPT on inflammasome activation. LPS-induced septic shock and monosodium urate (MSU)-induced murine peritonitis models were employed for in vivo evaluations.RESULTS: PPT attenuated NLRP3 inflammasome activation and also reduced ASC oligomerization, leading to attenuation of interleukin (IL)-1β secretion. Further, PPT inhibited IL-1β secretion in both LPS-induced septic shock and MSU-induced mouse peritonitis models.CONCLUSIONS: This study revealed that ginsenoside metabolite PPT, inhibits inflammation-mediated inflammasome activation and supported the traditional use of ginseng in treating various inflammatory disorders.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:2417418. Epub 2019 Dec 17. PMID: 31929811

Abstract Title: 

Ginsenoside Rg3 (Shenyi Capsule) Combined with Chemotherapy for Digestive System Cancer in China: A Meta-Analysis and Systematic Review.

Abstract: 

Objective: In China, ginsenoside Rg3 is often used in combination with chemotherapy to treat digestive system cancer. We here performed a meta-analysis and systematic review to provide a much needed high-quality evaluation of the efficacy and safety of ginsenoside Rg3 combined with chemotherapy in these cancers.Materials and Methods: The PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu (VIP) databases were searched. All randomized controlled trials (RCTs) concerning ginsenoside Rg3 combined with chemotherapy for digestive system cancer were selected. Dichotomous data were expressed as odds ratios (ORs) with 95% confidence intervals (CI). The methodological quality of the included studies was evaluated according to the Cochrane evidence-based medicine system, and the statistical analyses were performed with Review Manager 5.3 and STATA 12.0 software. In addition, the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of the evidence. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits.Results: A total of 18 trials comprising 1531 patients were included in this study. The results revealed that the trials were of sufficient standard to draw reliable conclusions that ginsenoside Rg3 combined with chemotherapy could improve the objective response rate (ORR; OR 2.17, 95% CI 1.72-2.73), disease control rate (DCR; OR 2.83, 95% CI 2.02-3.96), 1-year survival rate (SR; OR = 2.33, 95% CI = 1.24-4.37), Karnofsky Performance Scale (KPS; OR 2.67, 95% CI 1.76-4.03), gastrointestinal dysfunction (OR 0.44, 95% CI 0.31-0.61), and the decline of leucocyte count (OR 0.28, 95% CI 0.21-0.38).Conclusion: Ginsenoside Rg3 combined with chemotherapy can improve the clinical efficacy and alleviate treatment-induced side effects for digestive system cancer.

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PMID: 

Biomolecules. 2020 Jan 10 ;10(1). Epub 2020 Jan 10. PMID: 31936879

Abstract Title: 

A Critical Regulation of Th17 Cell Responses and Autoimmune Neuro-Inflammation by Ginsenoside Rg3.

Abstract: 

Among diverse helper T-cell subsets, Th17 cells appear to be pathogenic in diverse autoimmune diseases, and thus, targeting Th17 cells could be beneficial for the treatment of the diseases in humans. Ginsenoside Rg3 is one of the most potent components in Korean Red Ginseng (KRG;Meyer) in ameliorating inflammatory responses. However, the role of Rg3 in Th17 cells and Th17-mediated autoimmunity is unclear. We found that Rg3 significantly inhibited the differentiation of Th17 cells from naïve precursors in a dendritic cell (DC)-T co-culture system. While Rg3 minimally affected the secretion of IL-6, TNFα, and IL-12p40 from DCs, it significantly hampered the expression of IL-17A and RORγt in T cells in a T-cell-intrinsic manner. Moreover, Rg3 alleviated the onset and severity of experimental autoimmune encephalomyelitis (EAE), induced by transferring myelin oligodendrocyte glycoprotein (MOG)-reactive T cells. Our findings demonstrate that Rg3 inhibited Th17 differentiation and Th17-mediated neuro-inflammation, suggesting Rg3 as a potential candidate for resolving Th17-relatedautoimmune diseases.

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PMID: 

FEMS Microbiol Lett. 2020 Jan 17. Epub 2020 Jan 17. PMID: 31950993

Abstract Title: 

Improving Alzheimer's disease by altering Gut Microbiota in tree shrews with ginsenoside Rg1.

Abstract: 

Ginsenoside Rg1 (GRg1) has neuroprotective effects on Alzheimer's disease (AD). The occurrence and progression of AD are closely related to gut microbiota. Few studies have learned the direct relationship between GRg1 and gut microbiota. In this study, we found an original way by using GRg1 in the AD model of tree shrews to research this relationship. Morris Water Maze and Immunohistochemistry were performed to test the cognition repairing function of GRg1 by tree shrews, 16S ribosomal RNA sequencing to explore the composition and abundance of gut microbiota. After GRg1 treatment, the result of Morris Water Maze showed the improvement of cognitive function, and Immunohistochemistry revealed the decrease of tau protein. Moreover, 16SrRNA sequencing results showed the abundance of Proteobacteria and Verrucomicrobia were significantly different, and Lactobacillaceae was significantly increased in GRg1 treatment group. It also showed the gut microbiome with middle and high dose of GRg1 was close to the normal group. In conclusion, this study suggests that GRg1 with middle and high dose may change the abundance of gut microbiota to improve AD, Proteobacteria and Verrucomicrobia are key microbiota. This is the first report that has ever studied the relationship between GRg1 and gut microbiota on tree shrews.

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PMID: 

Int J Mol Med. 2020 Jan 15. Epub 2020 Jan 15. PMID: 31985021

Abstract Title: 

Ginsenoside protects against AKI via activation of HIF‑1α and VEGF‑A in the kidney‑brain axis.

Abstract: 

Acute kidney injury (AKI) is characterized by abrupt kidney dysfunction. It results in remote organ dysfunction, including the brain. The underlying mechanism of the kidney‑brain axis in AKI and effective protective approaches remain unknown. The present study aimed to investigate the potential protective effect of ginsenoside (GS) on AKI induced by glycerol in rats. Kidney function was initially assessed by blood urea nitrogen (BUN) and creatinine (Cre) tests, andwas identified to be severely impaired following glycerol treatment, based on significant increases in BUN and Cre levels observed. Severe extensive necrosis of the majority of the renal tubules was observed by hematoxylin and eosin staining, additionally confirming that glycerol induced AKI. GS wasidentified to ameliorate the impairment of kidney function in the context of AKI. Further investigation of the mechanism revealed that GS may induce protection against oxidative stress via a kidney‑brain axis. Furthermore, GS improved the activation of hypoxia‑inducible factor 1α (HIF‑1α) and vascular endothelial growth factor A (VEGF‑A) in the hypothalamus response to AKI, and in the kidney tissues. The protective effect of GS in AKI may be associated with the interaction between the kidney and the brain. Taken together, these results suggested that GS was involved in the protective effects against AKI by decreasing oxidative damage to the kidney and brain, and by upregulating HIF‑1α and VEGF‑A levels in the kidney‑brain axis.

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PMID: 

Biomed Pharmacother. 2020 Jan 28 ;125:109913. Epub 2020 Jan 28. PMID: 32006902

Abstract Title: 

Ginsenoside Rb1 attenuates cardiomyocyte apoptosis induced by myocardial ischemia reperfusion injury through mTOR signal pathway.

Abstract: 

OBJECTIVE: Ginsenoside Rb1 (GRb1) is known to play an effective protection on myocardial infarction, yet its therapeutic mechanism on myocardial ischemia/reperfusion (I/R) injury has remained obscure. Here we sought to investigate the protective mechanism of GRb1 preconditioning on myocardial I/R injury in rats.METHODS AND RESULTS: We report here that GRb1 preconditioning could improve myocardial I/R injury induced-cardiac functions including LVDP, -dp/dt min and + dp/dt max; however, the heart rate (HR) was maintained at a level comparable to the I/R group. Additionally, in I/R injury group given GRb1 preconditioning, release of myocardial enzymes (CK-MB and Trop l) and CtsB was decreased. Moreover, GRb1 decreased the expression of apoptotic related proteins e.g. cleaved-caspase 3; however, the ratio of Bcl-2/Bax related to anti-apoptosis was decreased. The study was extended by injecting rapamycin intraperitoneally before GRb1 pretreatment. Thus, mTOR pathway was significantly upregulated after GRb1 pretreatment when compared with I/R. Remarkably, the anti-apoptosis protection of GRb1 pretreatment was attenuated by rapamycin. Furthermore, GRb1 effectively reduced the infarct size thus supporting its role in anti-myocardial I/R injury.CONCLUSIONS: It is concluded that GRb1 preconditioning can ameliorate myocardial I/R injury as manifested by the improvement of cardiac function indices; moreover, release of myocardial enzymes, namely, CK-MB, Trop l and CtsB was reduced. More importantly, we have shown that the protective effect of GRb1 against I/R injury induced cardiomyocyte apoptosis is associated with the activation of mTOR signal pathway as evident by the use of rapamycin.

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