Hypoglycemic activity of withanolides and elicitated Withania somnifera

Gorelick, Jonathan; Rosenberg, Rivka; Smotrich, Avinoam; Hanŭs, L; Bernstein, Nirit

doi:10.1016/j.phytochem.2015.02.029

Cited by 80 publications

(24 citation statements)

References 35 publications

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“…The best candidates among the components present in PP to improve glucose uptake are withanolides [17,31]. Gorelick et al reported an increase in insulin-dependent glucose uptake in skeletal muscle cell line C2C12 after the treatment with a W. somnifera extract rich in withanolides [32].…”

Section: Discussionmentioning

confidence: 99%

Physalis peruviana L. Pulp Prevents Liver Inflammation and Insulin Resistance in Skeletal Muscles of Diet-Induced Obese Mice

et al. 2020

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A chronic high-fat diet (HFD) produces obesity, leading to pathological consequences in the liver and skeletal muscle. The fat in the liver leads to accumulation of a large number of intrahepatic lipid droplets (LD), which are susceptible to oxidation. Obesity also affects skeletal muscle, increasing LD and producing insulin signaling impairment. Physalis peruviana L. (PP) (Solanaceae) is rich in peruvioses and has high antioxidant activity. We assessed the ability of PP to enhance insulin-dependent glucose uptake in skeletal muscle and the capacity to prevent both inflammation and lipoperoxidation in the liver of diet-induced obese mice. Male C57BL/6J mice were divided into groups and fed for eight weeks: control diet (C; 10% fat, 20% protein, 70% carbohydrates); C + PP (300 mg/kg/day); HFD (60% fat, 20% protein, 20% carbohydrates); and HFD + PP. Results suggest that PP reduces the intracellular lipoperoxidation level and the size of LD in both isolated hepatocytes and skeletal muscle fibers. PP also promotes insulin-dependent skeletal muscle glucose uptake. In conclusion, daily consumption of 300 mg/kg of fresh pulp of PP could be a novel strategy to prevent the hepatic lipoperoxidation and insulin resistance induced by obesity.

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Section: Discussionmentioning

confidence: 99%

Physalis peruviana L. Pulp Prevents Liver Inflammation and Insulin Resistance in Skeletal Muscles of Diet-Induced Obese Mice

et al. 2020

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“…Recently, the withanolides from W . somnifera have been shown to impart hypoglycemic activity in in vitro model system [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation

Kaur

2017

J Neuroinflammation

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BackgroundThe epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation. Withania somnifera has been used in numerous Ayurvedic formulations owing to its wide array of health-promoting properties. The current study was designed to test the hypothesis whether dry leaf powder of W. somnifera has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity.MethodsYoung adult female rats were divided into four groups: low fat diet group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet containing 30% fat by weight and supplemented with ASH. All the animals were kept on respective feeding regimen for 12 weeks; following which, the animals were tested for their anxiety-like behavior using elevated plus maze test. The animals were sacrificed and used to study various inflammatory markers such as GFAP, Iba1, PPARγ, iNOS, MCP-1, TNFα, IL-1β, IL-6, and various markers of NF-κB pathway by Western blotting and quantitative real-time PCR. Serum levels of leptin, insulin and pro-inflammatory cytokines were also assayed.ResultsASH treated rats showed less anxiety levels as compared to HFD animals. At molecular level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and suppressed the expression of inflammatory markers such as PPARγ, iNOS, MCP-1, TNFα, IL-1β, and IL-6. Further, ASH ameliorated leptin and insulin resistance and prevented HFD-induced apoptosis.ConclusionsDry leaf powder of W. somnifera may prove to be a potential therapeutic agent to attenuate neuroinflammation associated with obesity and may prevent its co-morbidities.

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“…Promising chemotherapeutic agents will emerge if extensive research is carried out on such underexploited molecules. On this ground, search for the identification of potent plant-derived cytotoxic molecules was initiated, which disclosed withasteroids group of molecules possessing wide spectrum of biological effects including antimicrobial, antiinflammatory, hepatoprotective, immunomodulatory, and antidiabetic along with antitumor activities [1][2][3]. Co mpo unds representin g three m ajor groups of withasteroids, viz., withanolides with 17-α side chain, withanolides with 17-β side chain, and withaphysalins were selected for the study.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of withasteroids: withametelin induces cell cycle arrest at G2/M phase and mitochondria-mediated apoptosis in non-small cell lung cancer A549 cells

et al. 2016

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Considerable interest has been gained by withasteroids because of their structural uniqueness and wide spectrum of biological activities. However, limited systematic studies for proving their cytotoxic potential have so far been reported. Hence, an attempt was made to test the cytotoxicity of six withasteroids viz., withametelin (WM), withaphysalin D, withaphysalin E, 12-deoxywithastramonolide, Withaperuvin B, and physalolactone against A549, HT-29, and MDA-MB-231 cancer cell lines. Significant cytotoxic effect of WM against A549 cells (IC value of 6.0 μM), MDA-MB-231 cells (IC value of 7.6 μM), and HT-29 cells (IC value of 8.2 μM) was observed. Withaperuvin B and physalolactone were found to be effective against MDA-MB-231 cells. The significantly active WM arrested the A549 cells at G2/M phase and downregulated the expression of G2/M regulatory proteins such as cdc2, cyclin B1, and cdc25C. Apoptosis induced by WM in A549 cells was associated with the generation of ROS and depletion of MMP. Furthermore, WM treatment resulted in Bax upregulation, Bcl-2 downregulation, translocation of cytochrome c to mitochondria, activation of caspase-9 and -3, and PARP cleavage corroborating the apoptosis induction through intrinsic apoptotic pathway. Thus, WM possessing broader cytotoxic effect is a promising lead molecule which has the potential to be developed as a new therapeutic agent for NSCLC.

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Hypoglycemic activity of withanolides and elicitated Withania somnifera

Cited by 80 publications

References 35 publications

Physalis peruviana L. Pulp Prevents Liver Inflammation and Insulin Resistance in Skeletal Muscles of Diet-Induced Obese Mice

Physalis peruviana L. Pulp Prevents Liver Inflammation and Insulin Resistance in Skeletal Muscles of Diet-Induced Obese Mice

Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation

Cytotoxicity of withasteroids: withametelin induces cell cycle arrest at G2/M phase and mitochondria-mediated apoptosis in non-small cell lung cancer A549 cells

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