School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
Outpatient Department of PLA Unit 92919, Ningbo, Zhejiang, 315000, China.
Cell Biochem Biophys. 2024 Dec;82(4):3425-3435. doi: 10.1007/s12013-024-01429-z. Epub 2024 Jul 21.
Xanthohumol (XAN) is an isoprenyl flavonoid from Humulus lupulus L. known for beer brewing, and an osteoprotective agent due to its active improvement in bone loss of osteoporosis. This study was first time to investigate its effects on anti-gouty bone injury in rats of gouty arthritis (GA) induced by monosodium urate (MSU). Results showed that XAN could significantly exert anti-inflammatory activity by alleviating swelling degree of joints, reducing serum level of inflammatory factors, improving inflammatory injury and degrading the Markin's score in lesion joint. Meanwhile, XAN could also fight against gouty bone damage by improving pathological changes of bone tissue and parameters of bone micro-structure. Moreover, XAN could even promote bone formation by effectively enhancing expression of Runx2 and OPG, while inhibit bone resorption with depressing matrix metalloproteinase-9 (MMP-9), MMP-13 and CTSK expression, reducing RANKL secretion, and abating the ratio of RANKL/OPG. Therefore, it was the first time to reveal the mechanism of XAN against gouty bone injury via inhibiting RANKL/OPG/RANK signaling pathway. Above all, this study provided potential strategy for the treatment of GA, and further contributed to research and resource development for hops.
黄腐酚(XAN)是啤酒酿造中所用的蛇麻草属植物的异戊烯类黄酮,因其对骨质疏松症导致的骨丢失具有积极的改善作用,故被认为是一种具有护骨作用的物质。本研究首次探讨了黄腐酚对尿酸单钠盐(MSU)诱导的痛风性关节炎(GA)大鼠抗痛风性骨损伤的作用。结果表明,黄腐酚可通过减轻关节肿胀程度、降低血清炎症因子水平、改善炎症损伤和降低病变关节的 Markin 评分,显著发挥抗炎作用。同时,黄腐酚还可以通过改善骨组织的病理变化和骨微结构参数来对抗痛风性骨损伤。此外,黄腐酚还可以通过有效增强 Runx2 和 OPG 的表达来促进骨形成,同时通过抑制基质金属蛋白酶-9(MMP-9)、MMP-13 和 CTSK 的表达,减少 RANKL 的分泌,降低 RANKL/OPG 的比值,抑制骨吸收。因此,本研究首次揭示了黄腐酚通过抑制 RANKL/OPG/RANK 信号通路来防治痛风性骨损伤的作用机制。综上所述,本研究为 GA 的治疗提供了潜在策略,并进一步促进了对啤酒花的研究和资源开发。