{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:08:20Z","timestamp":1790172500317,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>Uncaria rhynchophylla<\/jats:italic>\n                    , is known for its significant anti\u2010inflammatory 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\u2010chain fatty acids (SCFAs) and the intestinal barrier. The research methods include network pharmacology, molecular docking, and in\u00a0vivo 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\u2010Akt signaling pathway. In\u00a0vivo assessment showed that IRN treatment reduced serum levels of the inflammatory cytokines, such as TNF\u2010\u03b1, IL\u20101\u03b2 and IL\u20106, while increasing serum levels of the anti\u2010inflammatory cytokine IL\u201010 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\u2013MS analysis found that IRN modulated the gut microbiota composition, reducing the abundance of\n                    <jats:italic>Campylobacterota<\/jats:italic>\n                    and\n                    <jats:italic>Helicobacter<\/jats:italic>\n                    , 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\u20101, Claudin\u20101, and Occludin. These results suggest that IRN, through its anti\u2010inflammatory 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.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70803","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T12:16:33Z","timestamp":1756124193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Isorhynchophylline Mitigates Bone Loss in OVX Mice by Modulating Inflammatory Responses, Oxidative Stress, Gut Microbiota Composition and SCFAs Production"],"prefix":"10.1002","volume":"13","author":[{"given":"Yitao","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Guangdong Pharmaceutical University  Guangzhou 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