Biologically active withanolides from Physalis peruviana

Abstract

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 IC₅₀ 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 IC₅₀ 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 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.

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.

Keywords: Novel and chlorinated withanolides; Physalis peruviana; anti-inflammatory; cape gooseberry; goldenberry; poha.

Figure 1.

ORTEP drawing of physalolactone (2); C₂₈H₃₉ClO₈⋅H₂O. Displacement ellipsoids are drawn at the 50% probability level at 120 K; the crystalline H₂O molecule is not shown. Absolute configuration is: C4(S), C5(R), C6(S), C8(R), C9(S), C10(R), C13(S), C14(R), C17(S), C20(S), C22(R).

Figure 2.

Chemical structures of compounds 1-8 and their acetylated derivatives 2a-6a.

Figure 3.

HMBC correlations for compounds 1 and 2.

Figure 4.

Key NOESY correlation for compounds 1 and 2.