Biologically active withanolides from Physalis peruviana

Authors: SANG-NGERN, MAYURAMAS - University Of Hawaii; FUKUCHI, ASHLEY - University Of Hawaii; KONDRATYUK, TAMARA - University Of Hawaii; PARK, EUN-JUNG - University Of Hawaii; SIMMONS, CHARLES - University Of Hawaii; Wall, Marisa; LORCH, SAM - Lani Ko Honua Berry Farm; PEZZUTO, JOHN - University Of Hawaii; CHANG, LENG CHEE - University Of Hawaii

Submitted to: Pharmaceutical Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2025
Publication Date: 4/26/2025
Citation: Sang-Ngern, M., Fukuchi, A., Kondratyuk, T.P., Park, E-J., Simmons, C.J., Wall, M.M., Lorch, S.E., Pezzuto, J.M., Chang, L.C. 2025. Biologically active withanolides from Physalis peruviana. Pharmaceutical Biology. 63(1):334-343. https://doi.org/10.1080/13880209.2025.2488136.
DOI: https://doi.org/10.1080/13880209.2025.2488136

Interpretive Summary: Physalis peruviana, commonly known as poha, Cape gooseberry, or goldenberry, is a perennial herbaceous plant of the Solanaceae family with edible fruit rich in vitamin C and antioxidants. P. peruviana has been used as a traditional medicine, particularly in the treatment of cancer. The plant parts are known to be a source of withanolides, which are a type of phytosterols with anti-cancer, anti-microbial, and anti-inflammatory activities. In this study, a novel withanolide was isolated from fruit and seven withanolides were isolated from aerial parts. Their structures were elucidated using spectroscopic and X-ray diffraction methods. Several isolated compounds showed anti-tumor and anti-inflammatory effects in bioassays. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.

Technical Abstract: Physalis peruviana L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer. Our objectives were to study the chemical composition and potential medicinal properties of Poha. 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. 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 factor-'-induced nuclear factor-kappa B (NF-'B) 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 0.32-13.3 µM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound 4, wherein the IC50 values in the NF-'B and NO assays were reduced from 11.0 to 0.33 µM, and 1.8 to 0.24 µM, respectively. 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.