Lei Yitao, Zhao Xiao, Liang Shihui, Liu Yanming, Zhou Yilin, Zhang Yingtong, Li Shimei, Dong Qunwei, Sun Ping
Department of Endocrinology The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou China.
Guangzhou University of Chinese Medicine Guangzhou China.
Food Sci Nutr. 2025 Aug 25;13(9):e70803. doi: 10.1002/fsn3.70803. eCollection 2025 Sep.
Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and deteriorated bone architecture. Isorhynchophylline (IRN), an active alkaloid derived from the plant , is known for its significant anti-inflammatory and antioxidant properties. However, its potential role in mitigating bone loss has not been investigated. This study examines the protective effects of IRN against bone loss in ovariectomized (OVX) mice, with a focus on its regulation of inflammatory responses, oxidative stress, gut microbiota composition, the production of short-chain fatty acids (SCFAs) and the intestinal barrier. The research methods include network pharmacology, molecular docking, and in vivo experiment. Network pharmacology analysis identified 50 intersecting targets between IRN and OP, with molecular docking demonstrating strong binding affinities of IRN to EGFR and GSK3B. GO and KEGG enrichment analyses revealed that IRN is involved in many key pathways related to cell survival, inflammation, and oxidative stress, such as the PI3K-Akt signaling pathway. In vivo assessment showed that IRN treatment reduced serum levels of the inflammatory cytokines, such as TNF-α, IL-1β and IL-6, while increasing serum levels of the anti-inflammatory cytokine IL-10 in OVX mice. IRN effectively managed the oxidative stress in the OVX model, characterized by lowered serum levels of NO, iNOS, and ROS. Combination of 16S rRNA sequencing and GC-MS analysis found that IRN modulated the gut microbiota composition, reducing the abundance of and , and increasing the level of butanoic acid. Additionally, immunohistochemical analysis indicates that IRN repaired the compromised intestinal barrier in OVX mice by upregulating the expression of tight junction proteins, including ZO-1, Claudin-1, and Occludin. These results suggest that IRN, through its anti-inflammatory and antioxidant properties, modulation of gut microbiota composition, enhancement of SCFAs production, and protection of the intestinal barrier, provides a new therapeutic approach for natural products to alleviate bone loss.
骨质疏松症（OP）是一种全身性骨骼疾病，其特征是骨量减少和骨结构恶化。异钩藤碱（IRN）是一种从植物中提取的活性生物碱，以其显著的抗炎和抗氧化特性而闻名。然而，其在减轻骨质流失方面的潜在作用尚未得到研究。本研究考察了IRN对去卵巢（OVX）小鼠骨质流失的保护作用，重点关注其对炎症反应、氧化应激、肠道微生物群组成、短链脂肪酸（SCFAs）产生和肠道屏障的调节。研究方法包括网络药理学、分子对接和体内实验。网络药理学分析确定了IRN和OP之间的50个交叉靶点，分子对接表明IRN与表皮生长因子受体（EGFR）和糖原合成酶激酶3β（GSK3B）具有很强的结合亲和力。基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，IRN参与了许多与细胞存活、炎症和氧化应激相关的关键途径，如磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路。体内评估显示，IRN治疗降低了OVX小鼠血清中炎症细胞因子如肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的水平，同时提高了抗炎细胞因子白细胞介素-10（IL-10）的血清水平。IRN有效控制了OVX模型中的氧化应激，其特征是血清中一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）和活性氧（ROS）水平降低。16S核糖体RNA（rRNA）测序和气相色谱-质谱联用（GC-MS）分析发现，IRN调节了肠道微生物群组成，降低了[具体微生物名称1]和[具体微生物名称2]的丰度，并提高了丁酸水平。此外，免疫组织化学分析表明，IRN通过上调紧密连接蛋白（包括闭合蛋白1（ZO-1）、紧密连接蛋白1（Claudin-1）和闭合蛋白（Occludin））的表达修复了OVX小鼠受损的肠道屏障。这些结果表明，IRN通过其抗炎和抗氧化特性、调节肠道微生物群组成、增强SCFAs产生以及保护肠道屏障，为天然产物减轻骨质流失提供了一种新的治疗方法。
