4β-Hydroxywithanolide E

4β-Hydroxywithanolide E is a withanolide steroidal lactone that has been found in P. peruviana and has anti-inflammatory and anticancer activities.^1,2,3 It inhibits LPS-induced nitric oxide (NO) production in RAW 264.7 cells and TNF-α-induced NF-κB activity in HEK293 cells (IC₅₀s = 0.32 and 0.04 μM, respectively).¹ 4β-Hydroxywithanolide E (5 μM) inhibits LPS-induced increases in inducible nitric oxide synthase (iNOS) and COX-2 levels and Akt and STAT1 phosphorylation in RAW 264.7 cells.² It inhibits Wnt signaling in HCT116 and SW480 colorectal cancer cells (IC₅₀s = 1.85 and 2.67 μM, respectively).³ 4β-Hydroxywithanolide E inhibits the proliferation of HCT116, SW480, HT-29, and LoVo cells (IC₅₀s = 0.24-0.51 μM). It halts the cell cycle at the G₀/G₁ phase in HCT116 and HT-29 cells and induces apoptosis in HCT116 and SW480 cells in a concentration-dependent manner. 4β-Hydroxywithanolide E (10 mg/kg per day for 14 days) reduces tumor growth in an HCT116 mouse xenograft model.

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1. Sang-Ngern, M., Youn, U.J., Park, E.J., et al. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorg. Med. Chem. Lett. 26(12), 2755-2759 (2016).

2. Park, E.J., Sang-Ngern, M., Chang, L.C., et al. Physalactone and 4β-hydroxywithanolide E isolated from Physalis peruviana inhibit LPS-induced expression of COX-2 and iNOS accompanied by abatement of Akt and STAT1. J. Nat. Prod. 82(3), 492-499 (2019).

3. Ye, Z.N., Yuan, F., Liu, J.Q., et al. Physalis peruviana-derived 4β-hydroxywithanolide E, a novel antagonist of Wnt signaling, inhibits colorectal cancer in vitro and in vivo. Molecules 24(6), E1146 (2019).