PMID: 

Molecules. 2018 Dec 5 ;23(12). Epub 2018 Dec 5. PMID: 30563087

Abstract Title: 

The Potential of South African Herbal Tisanes, Rooibos and Honeybush in the Management of Type 2 Diabetes Mellitus.

Abstract: 

Diabetes mellitus is a metabolic disease that can lead to high morbidity, mortality and long-term complications. Available treatment strategies, which are mainly based on treating hyperglycemia, with insulin and other pharmacological agents are not completely efficient and can even lead to development of unwanted side effects. Scientific evidence suggests that bioactive compounds from teas and other plant-based foods, which are known source of natural antioxidants, could be an attractive strategy to preferentially treat and manage type 2 diabetes mellitus (T2DM) and thus, have significant therapeutic implications. In this review, we attempt an in-depth analysis and discussion of the current progress in our understanding of the antidiabetic potential of two commercialized South Africa herbal tisanes-Rooibos and Honeybush and their polyphenols.

read more

PMID: 

Antioxidants (Basel). 2019 Oct 21 ;8(10). Epub 2019 Oct 21. PMID: 31640245

Abstract Title: 

Impact of Cold versus Hot Brewing on the Phenolic Profile and Antioxidant Capacity of Rooibos () Herbal Tea.

Abstract: 

Consumption of rooibos () as herbal tea is growing in popularity worldwide and its health-promoting attributes are mainly ascribed to its phenolic composition, which may be affected by the brewing conditions used. An aspect so far overlooked is the impact of cold brewing vs regular brewing and microwave boiling on the poly(phenolic) profile and in vitro antioxidant capacity of infusions prepared from red ('fermented', oxidized) and green ('unfermented', unoxidized) rooibos, the purpose of the present study. By using an untargeted metabolomics-based approach (UHPLC-QTOF mass spectrometry), 187 phenolic compounds were putatively annotated in both rooibos types, with flavonoids, tyrosols, and phenolic acids the most represented type of phenolic classes. Multivariate statistics (OPLS-DA) highlighted the phenolic classes most affected by the brewing conditions. Similar antioxidant capacities (ORAC and ABTS assays) were observed between cold- and regular-brewed green rooibos and boiled-brewed red rooibos. However, boiling green and red rooibos delivered infusions with the highest antioxidant capacities and total polyphenol content. The polyphenol content strongly correlated with the in vitro antioxidant capacities, especially for flavonoids and phenolic acids. These results contribute to a better understanding of the impact of the preparation method on the potential health benefits of rooibos tea.

read more

PMID: 

Acta Histochem. 2019 Jul ;121(5):646-656. Epub 2019 May 29. PMID: 31153588

Abstract Title: 

A histomorphometric study on the hepatoprotective effects of a green rooibos extract in a diet-induced obese rat model.

Abstract: 

Obesity, type two diabetes mellitus and insulin resistance are associated with increased oxidative stress and inflammation. Unfermented green rooibos is an aspalathin rich variant of traditional fermented rooibos (Aspalathus linearis) and has a high polyphenol content. The present study aimed to determine the histologically observable effects of a commercially produced, aspalathin-rich green rooibos extract, Afriplex GRT™ (GRE) in a diet-induced obese rat model. Male Wistar rats (N = 28) were randomly assigned to four study groups (n = 7): control (C), green rooibos (GRT), high-fat diet (HFD) and experimental (HFD-GRT) group. Body mass was determined prior to euthanasia and liver mass was determined afterdeath. The left lateral lobe of the liver was processed to wax and stained using haematoxylin and eosin (H&E), Masson's trichrome stain, Gordons and Sweet's reticulin impregnation and periodic acid-Schiff stain. Frozen liver tissue sections were used for Oil red O staining. Morphometric quantification of steatosis, semiquantitative pathology grading and scoring were performed and verified by a veterinary histopathologist. A significant increase in body and liver mass was observed in the HFD groups while co-treatment with green rooibos significantly reduced both. The volume and area of steatosis were significantly increased in the HFD groups while the area of steatosis significantly reduced with green rooibos co-treatment. The percentage, location and type of steatosis as well as presence of inflammation and hepatocellular injury were reduced in the HFD group co-treated with GRE. These findings suggest that a GRE has potential as an anti-steatotic, anti-inflammatory and weight reducing agent in vivo.

read more

PMID: 

Phytomedicine. 2019 Aug 8 ;64:153068. Epub 2019 Aug 8. PMID: 31419729

Abstract Title: 

Rooibos suppresses proliferation of castration-resistant prostate cancer cells via inhibition of Akt signaling.

Abstract: 

BACKGROUND: Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PCa). However, the majority of PCa patients receiving the androgen deprivation therapy develop recurrent castration-resistant prostate cancer (CRPC) within two years. Chemotherapies show little effect on prolonging survival of CRPC patients and new treatments are needed. Previous studies reported that the extracts from rooibos (Aspalathus linearis) exhibit chemopreventive properties in some cancer models, including skin, liver and oesophagus cancers in animals. We therefore investigate if extracts from rooibos can suppress the proliferation of CRPC cells.PURPOSE: We investigated whether an aspalathin-rich green rooibos extract (GRT™; 12.78 g aspalathin/100 g extract) demonstrates anti-cancer activity against CRPC cells.METHODS: High performance liquid chromatography (HPLC) was used to profile the major flavonoids in GRT. Hoechst-dye proliferation assay, 3,4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) viability assay and flow cytometry assay were used to explore the effects of GRT on the proliferation and cell cycle progression of CRPC cells. Comet assay was used to survey whether GRT induces apoptosis in CRPC cells. LNCaP 104-R1 xenograft nude mice model was used to determine the inhibitory effect of GRT on CRPC tumors in vivo. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism.RESULTS: GRT contained aspalathin as the most abundant flavonoid. GRT suppressed the proliferation and survival of LNCaP 104-R1, LNCaP FGC and PC-3 PCa cells. Flow cytometry analysis showed that GRT decreased the population of PCa cells in S phase but increased the cell population in G2/M phase. Comet assay confirmed that GRT induced apoptosis in LNCaP 104-R1 cells. Gavage of 400 mg/kg GRT suppressed LNCaP 104-R1 xenografts in castrated nude mice. MWA and Western blot analysis indicated that GRT treatment suppressed Akt1, phospho-Akt Ser473, Cdc2, Bcl-2, TRAF4 and Aven, but increased activated Caspase 3, cytochrome c, and p27. Overexpression of Akt rescued the suppressive effects of GRT on CRPC cells. Co-treatment of GRT with Bcl-2 inhibitor ABT-737, PI3K inhibitor LY294002 and Akt inhibitor GSK 690693 exhibited additive inhibitory effect on proliferation of CRPC cells.CONCLUSIONS: GRT suppresses the proliferation of CRPC cells via inhibition of Akt signaling.

read more

PMID: 

Oncotarget. 2017 Oct 20 ;8(50):87401-87414. Epub 2017 Sep 18. PMID: 29152090

Abstract Title: 

saponins attenuate inflammationandby inhibition of NF-κB and STAT3 signaling.

Abstract: 

Recent advances in the development of anti-inflammatory agents have improved their therapeutic outcome in inflammatory bowel disease (IBD), however, the presence of side effects and limited effectiveness hinder their widespread use. Therefore, novel compounds with strong anti-inflammatory efficacy are still required. In this study, we investigated the anti-inflammatory effect and potential mechanisms of(Thunb.) Makino saponins (GpS), a major component of the herbal medicine widely used in Asian countries. Instudies, we demonstrated that GpS dose dependently suppressed activation of macrophages, one of the main effectors in IBD. GpS also suppressed cytokine production and the activation of NF-κB and STAT3 signaling in lipopolysaccharide-induced macrophages, without affecting their viability. Furtherstudies demonstrated that GpS could ameliorate the weight loss, increased disease activity index, colon shortening and histological damage associated with dextran sulfate sodium (DSS)-induced colitis in mice. In agreement with results from ourexperiments, GpS suppressed cytokine production and activation of NF-κB and STAT3 signaling in the colons of DSS-induced mice. In this study, we present for the first time, evidence of the therapeutic effect of GpS in IBD, highlighting its potential as an effective therapeutic against the disease.

read more

PMID: 

Evid Based Complement Alternat Med. 2018 ;2018:8384631. Epub 2018 Mar 21. PMID: 29743925

Abstract Title: 

Attenuates the Progression of Nonalcoholic Fatty Liver Disease in Mice: A Biomedical Investigation Integrated with In Silico Assay.

Abstract: 

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. Oxidative stress plays a critical role in the progression of NAFLD. Modern pharmacological study and clinical trials have demonstrated the remarkable antioxidant activity of(GP) in chronic liver disease. One aim of this study was to explore the potential protective effects and mechanisms of action of GP extract on NAFLD. Theresults showed that GP extract could alleviate fatty degeneration and haptic fibrosis in NAFLD mice. For exploring the hepatoprotective mechanisms of GP, we used network pharmacology to predict the potential active components of GP and their intracellular targets in NAFLD. Based on the network pharmacology results, we further utilized biomedical assays to validate this in silico prediction. The results showed that Gypenoside XL could upregulate the protein level of PPARin NAFLD; the transcription level of several PPARdownstream target genes such as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1) also increased after Gypenoside XL treatment. The overexpression of ACO and CPT-1 may involve the hepatoprotective effects of GP and Gypenoside XL on NAFLD by regulating mitochondrial fatty acid-oxidation.

read more

PMID: 

J Cell Mol Med. 2018 09 ;22(9):4437-4448. Epub 2018 Jul 11. PMID: 29993180

Abstract Title: 

Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation.

Abstract: 

NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti-hyperglycaemia and anti-inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL-1β and IL-18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome cdramatically down-regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C-reactive proteins (CRPs), IL-1β and IL-18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS-mediated NLRP3 inflammasome activation.

read more

PMID: 

Evid Based Complement Alternat Med. 2018 ;2018:8098059. Epub 2018 Jul 12. PMID: 30105069

Abstract Title: 

Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat Diet.

Abstract: 

Gypenosides extracted from(Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL-C levels. The gene expression level ofwas downregulated while the levels of,,,,, andwere upregulated by gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine-conjugated bile acids while decreasing glycine-conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.

read more

PMID: 

Biomed Pharmacother. 2018 Oct ;106:1153-1160. Epub 2018 Jul 18. PMID: 30119182

Abstract Title: 

Gypenosides reverses depressive behavior via inhibiting hippocampal neuroinflammation.

Abstract: 

Gypenosides, a saponins extract isolated from the Gynostemma pentaphyllum plant, produces neuroprotective effects in the brain. Our previous studies have shown that hippocampal glucocorticoid receptor (GR)-brain-derived neurotrophic factor (BDNF)-TrkB signaling was involved in the antidepressant-like effects of gypenosides. It remains unknown whether gypenosides could alleviate neuroinflammation in depressive-like animals. The aim of the present study was to address this issue in chronic unpredictable mild stress (CUMS). Gypenosides was administrated for four weeks, followed by sucrose preference test and tail suspension test, which were performed to evaluate the effects of gypenosides. The results showed that gypenosides reversed both the decreased sucrose preference and increased immobility time in CUMS mice. In addition, gypenosides also attenuated the increase of pro-inflammatory cytokine levels in the hippocampus of CUMS animals. Furthermore, the activation of NF-κB, as well as its upstream mediators IKKα and IKKβ were inhibited by gypenosides. Last but not the least, CUMS promoted the activation of microglia, while gypenosides suppressed it according to the reduced number of iba1 positive cells. In conclusion, this study demonstrates that gypenosides exhibits the antidepressant-like effects in mice, which may be mediated by the inhibition of microglia and NF-κB signaling in the hippocampus.

read more

PMID: 

Am J Chin Med. 2018 ;46(6):1315-1332. Epub 2018 Sep 5. PMID: 30180767

Abstract Title: 

Gypenoside UL4-Rich Gynostemma pentaphyllum Extract Exerts a Hepatoprotective Effect on Diet-Induced Nonalcoholic Fatty Liver Disease.

Abstract: 

Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.

read more