PMID: 

Nutr Metab (Lond). 2018 ;15:86. Epub 2018 Dec 5. PMID: 30555521

Abstract Title: 

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in(Thunb.) Makino treated mice.

Abstract: 

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved.(Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism.Methods: High-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed.Results: Mice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum(). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylumes ( = 0.796)Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels.Conclusion: Our results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

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PMID: 

Planta Med. 2019 Mar ;85(5):394-405. Epub 2018 Dec 18. PMID: 30562828

Abstract Title: 

Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.

Abstract: 

Damulin B, a dammarane-type saponin from steamed, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects., human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.

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PMID: 

Int J Biol Macromol. 2019 Apr 1 ;126:209-214. Epub 2018 Dec 24. PMID: 30590141

Abstract Title: 

Anti-diabetic activity evaluation of a polysaccharide extracted from Gynostemma pentaphyllum.

Abstract: 

In current study, a polysaccharide (GPP) was successfully extracted from Gynostemma pentaphyllum herb. Monosaccharide composition of GPP was rhamnose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid and glucuronic acid in a molar ratio of 4.11: 7.34: 13.31: 20.99: 1.07: 0.91: 4.75: 0.36. Molecular weight and polydispersity (Mw/Mn) of GPP were 4.070 × 10 Da and 1.037, respectively. Primary structure features of GPP were determined to be a polysaccharide by FT-IR and NMR. Fasting blood sugar of diabetic mice decreased from 17.56 mmol/L to 7.42 mmol/L by orally administration of 0.5 mL GPP (1 mg/mL) for 30 days. GPP exhibited a dose-dependent inhibition effect on α-glucosidase activity. Moreover, GPP could inhibit the glucose absorption and affect the protein expression of GLUT2, but not the protein expression of SGLT1. These results indicated GPP could be used as an effective ingredient to prevent and cure diabetes.

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PMID: 

Phytomedicine. 2019 Jan ;52:198-205. Epub 2018 May 8. PMID: 30599899

Abstract Title: 

Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial.

Abstract: 

BACKGROUND: The ethanol extract of Gynostemma pentaphyllum Makino leaves (EGP) has been reported recently to have anxiolytic effects on chronically stressed mice models.PURPOSE: We aimed to investigate the efficacy and safety of EGP on anxiety level in healthy Korean subjects under chronic stressful conditions.STUDY DESIGN: Double-blind, placebo-controlled trial.METHODS: This study was conducted with 72 healthy adults who had perceived chronic stress and anxiety with a score on the State-Trait Anxiety Inventory (STAI) from 40 to 60. Participants were randomly assigned to receive either EGP (200 mg, twice a day, N = 36) or placebo (N = 36). All participants were exposed to repetitive loads of stress by performing the serial subtraction task for 5 min every second day during the 8-week intervention. Primary outcome of Trait-STAI and secondary outcomes of State-STAI, total score of STAI, Hamilton Anxiety Inventory (HAM-A), Beck Anxiety Inventory (BAI), blood norepinephrine and adrenocorticotropic hormone (ACTH), salivary cortisol and alpha-amylase, cardiovascular autonomic nervous system (ANS) functional test, and heart rate variability (HRV) test were measured before and after intervention.RESULTS: After the 8-week intervention, the EGP significantly lowered the score of the Trait Anxiety Scale of the STAI (T-STAI) by 16.8% compared to the placebo (p = 0.041). The total score on the STAI decreased by 17.8% in the EGP group and tended to improve compared with that of the placebo group (p = 0.067). There were no significant differences in the changes in score of S-STAI, HAM-A, BAI, and other parameters from baseline between the two groups. There was no causal relationship between the ingestion of EGP and adverse drug reactions.CONCLUSION: We found that supplementation with EGP reduced"anxiety proneness"in subjects under chronic psychological stress, as shown by a decrease in the score of T-STAI and the tendency for decrease in the total score of STAI. This result suggests that EGP supplementation can be used as a regimen to safely reduce stress and anxiety; however, more studies are needed to establish the long-term safety and effectiveness.

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PMID: 

Food Funct. 2019 Apr 1 ;10(4):2186-2197. Epub 2019 Apr 3. PMID: 30942219

Abstract Title: 

Immunomodulatory effects of an acidic polysaccharide fraction from herbal Gynostemma pentaphyllum tea in RAW264.7 cells.

Abstract: 

A new acidic polysaccharide (GPTP-3) with a molecular weight of 2.49× 10Da was extracted and purified from Gynostemma pentaphyllum tea. Monosaccharide analysis revealed that GPTP-3 mainly comprised mannose (20.4%), glucuronic acid (17.4%), glucose (33.4%), and galactose (21.4%) (parentheses indicate the molar percentages). Immunostimulating assays indicated that GPTP-3 could markedly promote the secretion of NO, TNF-α, IL-1β, and IL-6 in murine macrophage RAW264.7. TLR4 was found to be a recognized target of GPTP-3. Moreover, TLR4-related mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt, including ERK, JNK, p38, and Akt, were rapidly activated by GPTP-3 in RAW264.7 cells. Furthermore, GPTP-3 was found to induce the nuclear translocation of NF-κB subunit p65. All these findings suggest that MAPK, PI3K/Akt, and NF-κB pathways are involved in GPTP-3-induced macrophage activations, and GPTP-3 has the potential to be developed as a functional food with immunomodulatory functions.

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PMID: 

Neural Regen Res. 2020 Feb ;15(2):361-368. PMID: 31552910

Abstract Title: 

Ethanol extract fromameliorates dopaminergic neuronal cell death in transgenic mice expressing mutant A53T human alpha-synuclein.

Abstract: 

Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53Tα-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This studywas approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.

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PMID: 

Nutrients. 2019 Oct 15 ;11(10). Epub 2019 Oct 15. PMID: 31618980

Abstract Title: 

Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1.

Abstract: 

is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism ofextract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.

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PMID: 

Am J Chin Med. 2019 Oct 23:1-21. Epub 2019 Oct 23. PMID: 31645122

Abstract Title: 

Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage.

Abstract: 

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats – liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-B p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.

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PMID: 

Fitoterapia. 2019 Oct 17 ;139:104370. Epub 2019 Oct 17. PMID: 31629872

Abstract Title: 

Ginseng and heme oxygenase-1: The link between an old herb and a new protective system.

Abstract: 

Ginseng is an ancient herb, belonging to Asian traditional medicine, that has been considered as a restorative to enhance vitality for centuries. It has been demonstrated that the antioxidant action of ginseng may be mediated through activation of different cellular signaling pathways involving the heme oxygenase (HO) system. Several compounds derived from ginseng have been studied for their potential role in brain, heart and liver protection, and the Nrf2 pathway seems to be the most affected by these natural molecules to exert this effect. Ginseng is also popularly used in cancer patients therapy for the demonstrated capability to defend tissues from chemotherapy-induced damage. Reported results suggest that the effect of ginseng is primarily associated with ROS scavenging, mainly exerted through the activation of Nrf2 pathway, and the consequent induction of HO-1 levels. This review aims to discuss the connection between the antioxidant properties of ginseng and the activation of the HO system, as well as to outline novel therapeutic applications of this medicinal plant to human health.

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PMID: 

J Cardiovasc Pharmacol. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31658172

Abstract Title: 

Ginsenoside Rb1 alleviates ox-LDL-induced vascular endothelium senescence via the SIRT1/Beclin-1/autophagy axis.

Abstract: 

Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect HUVECs, but its effect on ox-LDL induced endothelium senescence and underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high fat diet and gRb1 was intraperitoneal injected. Senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis.