Wang Xiaojuan, Zhang Guohui, Bian Zhiwei, Chow Vimanda, Grimaldi Marina, Carivenc Coralie, Sirounian Savannah, Li Hao, Sladekova Lucia, Motta Stefano, Luperi Yulia, Gong Yufeng, Costello Cait, Li Linhao, Jachimowicz Matthew, Guo Miao, Hu Shian, Wilson Derek, Balaguer Patrick, Bourguet William, Mani Sridhar, Bonati Laura, Peng Hui, March John, Wang Hongbing, Wang Shengpeng, Krause Henry M, Liu Jiabao
School of Pharmacy, Lanzhou University, Lanzhou, Gansu, People's Republic of China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.
Nat Commun. 2025 Feb 3;16(1):1280. doi: 10.1038/s41467-025-56624-0.
The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.
记录天然产物中类药物分子价值的文献浩如烟海。尽管已发现许多膳食和草药疗法对治疗肠道炎症有效，但其活性成分的鉴定却滞后了。在本研究中，我们发现生姜的一种主要成分，呋喃二烯酮（FDN），是一种具有激动性转录结果的选择性孕烷X受体（PXR）配体。我们表明，FDN结合在PXR配体结合域（LBD）的一个亚口袋内，随后LBD结构发生改变。使用雄性小鼠，我们表明口服给予的FDN具有强效的、依赖PXR的抗炎作用，且具有结肠特异性。在协同作用激动剂存在下亲和力增加和靶基因激活表明增强FDN活性、疗效和安全性还有更多机会。总体而言，这些结果支持FDN作为治疗和预防结肠疾病治疗剂的转化潜力。
