|SANG-NGERN, MAYURAMAS - University Of Hawaii|
|YOUN, YI - University Of Hawaii|
|PARK, EUN-JUNG - University Of Hawaii|
|KONDRATYU, TAMARA - University Of Hawaii|
|SIMMONS, CHARLES - University Of Hawaii|
|LORCH, SAM - Lani Ko Honua Berry Farm|
|PEZZUTO, JOHN - University Of Hawaii|
|CHANG, LENG CHEE - University Of Hawaii|
Submitted to: Bioorganic and Medicinal Chemistry Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/25/2016
Publication Date: 6/15/2016
Citation: Sang-Ngern, M., Youn, Y., Park, E., Kondratyu, T.P., Simmons, C.J., Lorch, S.E., Wall, M.M., Pezzuto, J.M., Chang, L. 2016. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorganic and Medicinal Chemistry Letters. 26(12):2755-2759.
Interpretive Summary: Physalis peruviana (Cape gooseberry, goldenberry, or Hawaiian poha) is used in traditional folk medicine for the treatment of cancer and other diseases. Withanolides occur as secondary metabolites in Physalis, and have reputed anti-inflammatory, antitumor, cytotoxic, hepatotoxic, and antimicrobial activities. Three new withanolides, together with seven known compounds, were isolated and identified from P. peruviana plants grown in Hawaii. Their chemical structures and biological activities were elucidated. The isolated compounds were evaluated in anti-inflammatory bioassays, and four of the compounds exhibited high or moderate levels of activity. This natural products research furthers our understanding of the medicinal properties of poha and expands our cache of biologically active constituents from tropical plants.
Technical Abstract: Three new withanolides, physaperuvin G (1), physaperuvin I (2), physaperuvin J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by spectroscopic methods, including, 1D and 2D NMR, and mass spectrometry. The absolute configuration of compound 1 was confirmed using X-ray diffraction method. Compounds 1-10 were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, and the tumor necrosis factor alpha (TNF-a)-activated nuclear factor-kappa B (NF-kB) pathway with transfected human embryonic kidney cells 293. Compounds 4, 5, 6, and 7 inhibited TNF-a-induced NF-kB activity with the half maximal inhibitory concentration (IC50) values of 0.04, 5.6, 2.1, and 1.1 uM, respectively; compounds 4, 5, and 10 exhibited NO inhibitory activity with IC50 values of 0.32, 2.4, and 7.8 uM respectively.