Biologically active withanolides from Physalis peruviana.

CONTEXT: Physalis peruviana L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer. OBJECTIVE: To study the chemical composition and potential medicinal properties of Poha. MATERIALS AND METHODS: The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; 1) from the edible fruit, and seven withanolides (2-8), including a rare chlorinated withanolide (physalolactone; 2) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (2a-6a), and the compounds were evaluated with in vitro assays indicative of anti-inflammatory activity. RESULTS: The structure of 1 was elucidated through NMR spectroscopic analyses. The absolute configuration of compound 2 was determined using single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC(50) values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds 1-3 reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC(50) values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound 4, wherein the IC(50) values in the NF-κB and NO assays were reduced from 11.0 to 0.33 μM, and 1.8 to 0.24 μM, respectively. CONCLUSIONS: These findings enhance our understanding of Poha's constituents and potential medicinal properties. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.