Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity

  • Bioorg Med Chem Lett. 2016 Jun 15;26(12):2755-2759. doi: 10.1016/j.bmcl.2016.04.077.
Mayuramas Sang-Ngern  1 Ui Joung Youn  1 Eun-Jung Park  1 Tamara P Kondratyuk  1 Charles J Simmons  2 Marisa M Wall  3 Michael Ruf  4 Sam E Lorch  5 Ethyn Leong  6 John M Pezzuto  1 Leng Chee Chang  7
Affiliations
  • 1. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
  • 2. Chemistry Department, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
  • 3. United States Department of Agriculture, Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center, Hilo, HI 96720, United States.
  • 4. Bruker AXS Inc., East Cheryl Parkway, Madison, WI 53711, United States.
  • 5. Lani ko Honua Berry Farm, Pepeekeo, HI 96783, United States.
  • 6. Department of Food Science, Cornell University College of Agriculture and Life Science, Founders Hall, Ithaca, NY 14853, United States.
  • 7. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States. Electronic address: [email protected].
Abstract

Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and 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 NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM.

Keywords
Anti-inflammatory activity; Physalis peruviana; Withanolides; X-ray crystallography.