BIOACTIVITY AND SAFETY OF HYDRO-ETHANOLIC LYOPHILISED WITHANIA SOMNIFERA FOR THE POTENTIAL MANAGEMENT OF THE BIOLOGICAL END POINTS OF STRESS

Introduction & Objective: Chronic stress activates the HPA axis and the sympathetic nervous system, leading to inflammation and oxidative toxic stress (OTS). Conventional therapies face bottlenecks like high costs, limited accessibility, and side effects. This study evaluates the chemical safety and metabolomics of Zimbabwean Withania somnifera. Methodology: Dried Withania somnifera roots were extracted via 70%hydroethanolic maceration and lyophilized. Phenolic and flavonoid contents were mapped. Acute oral toxicity was evaluated in female Sprague-Dawley rats up to 5000″ mg/kg” (OECD 425). In-vitro anti-inflammatory and antioxidant activities were quantified via egg albumin denaturation and DPPH assays. Results: A 12% yield of lyophilised extract was obtained from 258g of raw root powder. The metabolomics verified high-density withanolides, alkaloids, tannins, saponins, and polyphenols. Acute testing established an exceptionally wide safety threshold (LD₅₀>5000 mg/kg), with normal weight gain and zero anomalies. The extract demonstrated significant anti-inflammatory inhibition (80% inhibition at 1000 μg/mL compared to 83% diclofenac). A robust anti-oxidant profile showed mean IC₅₀=124.33 μg/mL compared to 20.5μg/mL pure ascorbic acid. The total phenolic content was calculated at 69mg gallic acid equivalents/g extract and the flavonoid content at 32.47mg quercetin equivalents per gram. Conclusion: Naturalized Zimbabwean Withania somnifera is a safe, metabolite-dense source phytochemicals which can be used for the alleviation of the biologic end points of stress.