PMID: 

J Physiol Anthropol. 2014 Jul 17 ;33:20. Epub 2014 Jul 17. PMID: 25034805

Abstract Title: 

Intake of green tea inhibited increase of salivary chromogranin A after mental task stress loads.

Abstract: 

BACKGROUND: Green tea has become renowned for its health benefits. In this study, we investigated the anti-stress effect of two kinds of green tea against a mental stress task load.METHODS: Warm water, ordinary green tea (Sagara), and shaded white tea, which contains more amino acid components than Sagara, were used as test samples in a randomized cross-over design study. Eighteen students (nine male and nine female) participated in three experimental trials on different days at intervals of seven days. Saliva was collected before beverage intake and after performing the mental stress load tasks. Concentration of chromogranin A (CgA) in the saliva was used as an index of autonomic nervous system activity.RESULTS: CgA level increased after the mental tasks, but intake of green tea inhibited this increase; the anti-stress effect was even greater after consumption of shaded white tea. Intake of shaded white tea also lowered Total Mood Disturbance (TMD) score on the Profile of Mood States (POMS); subjects in this condition tended to perform more calculations in the arithmetic task than those in the warm water treatment condition.CONCLUSIONS: Salivary CgA concentration levels increased after mental stress load tasks, but ingestion of green tea inhibited this increase. This anti-stress effect was larger after the consumption of shaded white tea than after Sagara. Shaded white tea intake also lowered TMD score (POMS) and tended to improve performance on an arithmetic task compared to warm water, suggesting that shaded white tea might also improve mood during and after mental stress load.

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PMID: 

Biomed Pharmacother. 2019 Jan ;109:1547-1555. Epub 2018 Nov 14. PMID: 30551407

Abstract Title: 

Mate tea reduces high fat diet-induced liver and metabolic disorders in mice.

Abstract: 

High-fat diet (HFD)-induced obesity is a worldwide health problem and can cause lipid accumulation in the liver. We evaluated the hepatoprotective effect of mate tea treatment in mice submitted to an HFD. C57BL/6 mice were fed an HFD for 13 weeks with and without mate tea. A separate group of mice was treated with fenofibrate as a positive control (a regular drug for lipid disorders). Histological analyses, glucose tolerance tests (GTT), and quantification of mediators related to lipid peroxidation, oxidative stress and blood biomarkers for lipid profile were performed. The weight of animals and major organs related to hepatic steatosis was determined, and proinflammatory cytokines and the participation of the Nrf2 pathway and adiponectin were evaluated. Mate tea prevented the accumulation of lipid droplets in hepatocytes as well as weight gain in animals submitted to the HFD. Mate tea treatment also prevented increases in the liver weight, heart weight and amount of visceral and subcutaneous white adipose tissue. Mate tea was able to prevent the deregulation of glucose uptake, as evaluated by GTT, and improved the indicators of oxidative stress, such as nitrite levels, catalase activity, and oxidative damage, as evaluated by protein carbonylation and the MDA levels. Mate tea had an anti-inflammatory effect, preventing the increase of IL-1β and KC and upregulating the expression of Nrf2. Mate tea prevented insulin increase and HDL cholesterol decrease but did not affect total cholesterol or triglycerides levels. Treatment also prevented adiponectin increase. Mate tea may be a good resource to reduce hepatic steatosis in the future since it has anti-diabetic, anti-inflammatory and antioxidant effects, which prevent the accumulation of fat in the liver.

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The CDC has been lying about ordinary flu for decades. So why wouldn’t they continue their fine tradition of lying about COV?

PMID: 

World J Gastroenterol. 2018 Feb 14 ;24(6):693-705. PMID: 29456408

Abstract Title: 

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome.

Abstract: 

AIM: To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D).METHODS: We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3× 10mol/L to 1× 10mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1× 10mol/L to 1× 10mol/L); (2) neurotransmitter antagonists including N-nitro-L-arginine methyl ester hydrochloride (10μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5'-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATPlevel of Kreb's solution was also determined.RESULTS: PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC) was 41.9μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 ± 3.34) was significantly decreased in the peak tension (

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PMID: 

Dig Dis Sci. 2019 Sep 26. Epub 2019 Sep 26. PMID: 31559550

Abstract Title: 

In Vitro Anti-hepatoma Activities of Notoginsenoside R1 Through Downregulation of Tumor Promoter miR-21.

Abstract: 

BACKGROUND: Notoginsenoside R1 (NG-R1) is the predominant active ingredient and a novel triterpene saponin compound extracted from the roots of Panax notoginseng. To date, to the best of our knowledge, there are no previous studies concerning the effect of NG-R1 on hepatocellular carcinoma (HCC).AIMS: To investigate the effects of NG-R1 on HCC cell growth, apoptosis, and invasion and to explore the underlying mechanisms.METHODS: Cell viability and lactate dehydrogenase (LDH) release were evaluated by cell counting kit-8 and LDH assay, respectively. Apoptosis was assessed using flow cytometry analysis and caspase-3/7 activity assay. Cell invasion was detected by Transwell invasion assay and western blot analysis of matrix metallopeptidase (MMP)-2 and MMP-9. The effects of NG-R1 on miR-21 expression and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway were examined by qRT-PCR and western blot, respectively.RESULTS: NG-R1 inhibited the viability, increased LDH release and caspase-3/7 activity, induced apoptosis, and suppressed invasion in HCC cells. NG-R1 reduced miR-21 expression in HCC cells. miR-21 overexpression significantly attenuated the effects of NG-R1 on the viability, LDH release, apoptosis, caspase-3/7 activity, and invasion of HCC cells. We further demonstrated that NG-R1 inhibited the activation of the PI3K/Akt pathway in HCC cells, which was abolished by miR-21 overexpression.CONCLUSIONS: NG-R1 exerted anti-hepatoma activity through inactivation of the PI3K/Akt pathway by downregulating miR-21, contributing to further understanding of the anti-tumor activities of NG-R1 in HCC.

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PMID: 

Obesity (Silver Spring). 2020 Apr ;28(4):783-792. Epub 2020 Mar 6. PMID: 32144882

Abstract Title: 

Ginsenoside Rd Ameliorates High Fat Diet-Induced Obesity by Enhancing Adaptive Thermogenesis in a cAMP-Dependent Manner.

Abstract: 

OBJECTIVE: With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied.METHODS: High-fat diet-induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied.RESULTS: Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes.CONCLUSIONS: Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway.

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PMID: 

Phytomedicine. 2020 Feb 26 ;69:153197. Epub 2020 Feb 26. PMID: 32146298

Abstract Title: 

Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways.

Abstract: 

BACKGOUND: Ginsenoside Rb1, the main active constituent of Panax ginseng, displays significant anti-inflammatory activity, although the mechanism has not been clearly unraveled. In this study, Rb1's mechanism of anti-inflammatory effects were investigated.METHODS: The flow cytometry and enzyme-linked immunosorbent assay (ELISA) were empolyed to detect pro-inflammatory cytokines release. The related protein and gene expression was investigated by western blotting and qRT-PCR. The dimerization of TLR4 was measured by co-immunoprecipitation and molecular docking assays. Cellular thermal shift assay was used for the determination of the binding of Rb1 and TLR4. For animal moldels, LPS- or cantharidin-induced acute kidney injury, LPS-induced septic death, and dimethyl benzene-induced ear edema were employed to investigate Rb1's anti-inflammatory activity in vivo.RESULTS: Rb1 significantly decreased inflammatory cytokines release in LPS-stimulated RAW264.7 cells and BMDMs, as well as COX-2 and iNOS amounts. Rb1 reduced LPS-associated calcium influx, ROS production, and NO generation. The NF-κB and MAPK axes participated in Rb1's anti-inflammatory effects. Molecular docking simulation indicated Rb1 bound to TLR4 to prevent TLR4 dimerization, as confirmed by co-immunoprecipitation and cellular thermal shift assay. Furthermore, MyD88 recruitment and TAK1 expression were altered by reduced TLR4 dimerization, indicating the TLR4-MyD88-NF-κB/MAPK pathways contributed to Rb1's anti-inflammatory process. In animal models, Rb1 markedly alleviated LPS- or cantharidin-induced acute kidney injury, rescued LPS-induced septic mice from death, and inhibited dimethyl benzene-induced mouse earedema.CONCLUSION: Overall, these findings demonstrate Rb1 exhibits marked anti-inflammatory effects, suggesting Rb1 represents an optimal molecule for treating inflammatory diseases.

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PMID: 

J Ginseng Res. 2020 Mar ;44(2):247-257. Epub 2018 Nov 8. PMID: 32148406

Abstract Title: 

Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter:andstudy.

Abstract: 

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporterand.Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5.Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose.Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

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PMID: 

J Ginseng Res. 2020 Mar ;44(2):258-266. Epub 2018 Dec 16. PMID: 32148407

Abstract Title: 

The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells.

Abstract: 

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study.Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein.Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity, with a half-maximal effective concentration of≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells.Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

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PMID: 

Cancers (Basel). 2020 Mar 5 ;12(3). Epub 2020 Mar 5. PMID: 32151067

Abstract Title: 

Ginsenoside Rp1, A Ginsenoside Derivative, Augments Anti-Cancer Effects of Actinomycin D via Downregulation of an AKT-SIRT1 Pathway.

Abstract: 

Novel strategies for overcoming multidrug resistance are urgently needed to improve chemotherapy success and reduce side effects. Ginsenosides, the main active components of, display anti-cancer properties and reverse drug resistance; however, the biological pathways mediating this phenomenon remain incompletely understood. This study aimed to evaluate the anti-cancer effects of ginsenoside Rp1, actinomycin D (ActD), and their co-administration in drug-resistant cells and murine xenograft model of colon cancer, and explore the underlying mechanisms. ActD increased expression and activity of SIRT1 in drug-resistant LS513 colon cancer, OVCAR8-DXR ovarian cancer, and A549-DXR lung cancer cells, but not in ActD-sensitive SW620 colon cancer cells. Inhibition of SIRT1, either pharmacologically, with EX527 or through siRNA, stimulated p53 acetylation and apoptosis in LS513 cells when treated with ActD. ActD also increased AKT activation in drug-resistant cells. Inhibition of AKT abrogated ActD-induced upregulation of SIRT1, suggesting that the AKT-SIRT1 pathway is important in ActD resistance. Rp1 inhibited both ActD-induced AKT activation and SIRT1 upregulation and re-sensitized the cells to ActD. Synergistic antitumor effects of Rp1 with ActD were also observed in vivo. Our results suggest that combining Rp1 with chemotherapeutic agents could circumvent drug resistance and improve treatment efficacy.

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