withaferin-a and Body-Weight

Chronic stress has been associated with a number of illnesses, including obesity. Ashwagandha is a well-known adaptogen and known for reducing stress and anxiety in humans. The objective of this study was to evaluate the safety and efficacy of a standardized root extract of Ashwagandha through a double-blind, randomized, placebo-controlled trial. A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.

Topics: Adult; Body Weight; Chronic Disease; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Phytotherapy; Plant Extracts; Stress, Psychological; Weight Gain; Young Adult

The enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown.. To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway.. C57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used.. Treatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT.. WFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Body Weight; Diet, High-Fat; Energy Metabolism; Gene Expression; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Obesity; Thermogenesis; Uncoupling Protein 1; Withania; Withanolides

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Diet, High-Fat; Dietary Supplements; Energy Metabolism; Lipid Metabolism; Male; Mice, Inbred C57BL; Mitochondria; Muscle, Skeletal; Obesity; Oxygen Consumption; Phytotherapy; Plant Extracts; Withania; Withanolides

Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.

Topics: Animals; Blood Glucose; Body Weight; Cytokines; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Feeding Behavior; Inflammation; Inflammation Mediators; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress; RNA, Messenger; Withanolides

The increasing global prevalence of obesity and its associated disorders points to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules that have mRNA expression profiles similar to that of celastrol, a naturally occurring compound that we previously identified as a leptin sensitizer. Through this process, we identified another naturally occurring compound, withaferin A, that also acts as a leptin sensitizer. We found that withaferin-A treatment of mice with diet-induced obesity (DIO) resulted in a 20-25% reduction of body weight, while also decreasing obesity-associated abnormalities, including hepatic steatosis. Withaferin-A treatment marginally affected the body weight of ob/ob and db/db mice, both of which are deficient in leptin signaling. In addition, withaferin A, unlike celastrol, has beneficial effects on glucose metabolism that occur independently of its leptin-sensitizing effect. Our results show that the metabolic abnormalities of DIO can be mitigated by sensitizing animals to endogenous leptin, and they indicate that withaferin A is a potential leptin sensitizer with additional antidiabetic actions.

Topics: Animals; Blood Glucose; Blotting, Western; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Fatty Liver; Fluorescent Antibody Technique; Glucose Tolerance Test; Hypothalamus; Immunohistochemistry; Leptin; Liver; Mice; Mice, Obese; Obesity; Pentacyclic Triterpenes; Real-Time Polymerase Chain Reaction; Signal Transduction; STAT3 Transcription Factor; Triterpenes; Withanolides

Herbs, as food or medicine, can strengthen the body and increase its resistance to illnesses by acting on various components of the immune system. For example, Echinacea is noted for its ability to enhance immune function, primarily through activation of the innate immune responses. Here, we investigated the potential for two herbs commonly found in India, Ashwagandha (Withania somnifera) and Brahmi (Bacopa monnieri), to enhance immune function and compared their effects to that of Echinacea.. Sprague Dawley rats were fed a diet supplemented with 1% (w/w) Echinacea, Ashwagandha, or Brahmi for 4 weeks to examine their effects on immune function.. The Brahmi diet stimulated more secretion of IgA and IgG in the serum compared to Echinacea or Ashwagandha. Whether or not lectin was present in the diet, the production of IgA, IgG and IgM in spleen lymphocytes increased with herbal supplements. The concentrations of IFN-γ and IL-2 treated with LPS and ConA were significantly higher in the dietary herb than in the control. On the contrary, TNF-α production in rats receiving dietary herbal supplements was significantly lower compared to the control animals.. Herbal remedies based on Echinacea, Brahmi, or Ashwagandha can enhance immune function by increasing immunoglobulin production. Furthermore, these herbal medicines might regulate antibody production by augmenting both Th1 and Th2 cytokine production.

Topics: Administration, Oral; Animals; Bacopa; Body Weight; Cells, Cultured; Concanavalin A; Diet; Eating; Echinacea; Immunoglobulin A; Immunoglobulin G; Interferon-gamma; Interleukin-2; Lipopolysaccharides; Lymphocytes; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Spleen; Tumor Necrosis Factor-alpha; Withania

The aqueous suspensions of roots of an Indian drug Ashwagandha and the Korean drug Ginseng were tested comparatively for 2 pharmacological activities, namely the anti-stress activity by the 'mice swimming endurance test' and anabolic activity by noting gain in body weights and levator ani muscle in rats. A significant increase in mice swimming time was shown by Ginseng (P < 0.001) and Ashwagandha (P < 0.01) as compared to the control group. Significant increase in body weights in the Ashwagandha treated group (P < 0.05) was better than Ginseng (P < 0.5). Gain in wet weights of the levator ani muscle were also significant in Ginseng (P < 0.001) and Ashwagandha (P < 0.01) treated groups, however, the weight gain of dried levator ani muscles showed comparable results for both these drugs (P < 0.01).

Topics: Administration, Oral; Animals; Body Weight; Chromatography, Thin Layer; Male; Mice; Muscles; Panax; Physical Exertion; Plant Extracts; Plants, Medicinal; Rats; Stress, Physiological; Swimming; Withania