Biologically active withanolides from <i>Physalis peruviana</i>.

Abstract

<h4>Context</h4><i>Physalis peruviana</i> L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer.<h4>Objective</h4>To study the chemical composition and potential medicinal properties of Poha.<h4>Materials and methods</h4>The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; <b>1</b>) from the edible fruit, and seven withanolides (<b>2</b>-<b>8</b>), including a rare chlorinated withanolide (physalolactone; <b>2</b>) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (<b>2a</b>-<b>6a</b>), and the compounds were evaluated with <i>in vitro</i> assays indicative of anti-inflammatory activity.<h4>Results</h4>The structure of <b>1</b> was elucidated through NMR spectroscopic analyses. The absolute configuration of compound <b>2</b> was determined using single-crystal X-ray diffraction. Compounds <b>1</b>, <b>2</b>, and <b>3</b> exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC₅₀ values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds <b>1</b>-<b>3</b> reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC₅₀ values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound <b>4</b>, wherein the IC₅₀ 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.<h4>Conclusions</h4>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.