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

Abstract

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.

Sex-Specific Anxiety and Prefrontal Cortex Glutamatergic Dysregulation Are Long-Term Consequences of Pre-and Postnatal Exposure to Hypercaloric Diet in a Rat Model

“…Our results also discard a potential diet-associated neuroinflammation factor in these observed long-term alterations, despite previous reports suggesting that a hypercaloric diet might result in neuroinflammation, thus contributing to behavioral disorders [ 40 , 45 ]. Our results do not support this hypothesis, since we did not find alterations in the mRNA expression of several genes that would indicate the activation of inflammatory pathways, such as the toll-like receptor related to pathogen recognition and the activation of innate immunity Tlr4 , the cyclooxygenase key in prostaglandin biosynthesis Ptgs2 , the microglia/macrophage-specific calcium-binding protein Iba1 , the major intermediate filament proteins of mature astrocytes Gfap , and the cannabinoid receptor Cnr2 , induced by the perinatal and/or postnatal P diet in the adult offspring PFC.…”

Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation

“…Various experimental and clinical studies have reported memory enhancing and learning improvement potential of alcoholic and water based formulation of Ashwagandha [52]. Recently our lab reported that aqueous extract of Ashwagandha has immunomodulatory and anxiolytic effects and improved memory retention and learning ability by alleviating cellular stress via regulating synaptic plasticity and cell survival signaling cascades in acute sleep deprived and HFD fed obese rats [32, 33, 35, 53].…”

Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus

“…Moreover, similar antioxidant and anti-inflammatory effects have been reported for luteolin in diabetic mice [120]. Other studies in prediabetic models have shown a protective role for Withania somnifera , which may reduce gliosis and microgliosis as well as expression of inflammation markers such as PPARγ, iNOS, MCP-1, TNF-α, IL-1β, and IL-6 [121]. In line with these observations, oral administration of an hexanic extract of Eryngium carlinae inflorescences to diabetic rats not only reduced glucose levels but also limited overall oxidation, by reducing lipid peroxidation, protein carbonylation and reactive oxigen species production, while increasing catalase activity in the brain [122].…”