{"title":"Isovitexin, a natural adiponectin agonist, prevents glucocorticoid-induced osteosarcopenia.","authors":"Chirag Kulkarni, Saroj Kumar, Shamima Khatoon, Sreyanko Sadhukhan, Kaveri R Washimkar, Akhilesh Kumar, Shivani Sharma, Swati Rajput, Konica Porwal, Madhav Nilakanth Mugale, Srikanta Kumar Rath, Madan Madhav Godbole, Sabyasachi Sanyal, Navin Kumar, Ambrish Mithal, Naibedya Chattopadhyay","doi":"10.1007/s12020-025-04251-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Isovitexin is an agonist of adiponectin receptors (AdipoRs). Adiponectin has been shown to have beneficial effects on bone and muscle function, in addition to its positive impact on metabolic health. However, the preclinical and clinical application of adiponectin faces scalability challenges, prompting the investigation of isovitexin in a methylprednisolone (MP)-induced osteoporosis model.</p><p><strong>Methods: </strong>A rat model of MP-induced osteoporosis was developed to evaluate isovitexin's effects on bone health, including bone mass & microarchitecture (MicroCT), turnover markers (P1NP and CTX-1), strength (three-point bending, and nanoindentation), and quality (FTIR). We also investigated the muscle protective effects of isovitexin by measuring key muscle catabolic (atrogenes) proteins.</p><p><strong>Results: </strong>Isovitexin effectively prevented MP-induced osteopenia in critical weight-bearing, fracture-prone sites, such as the proximal femur and lumbar vertebrae. Bone turnover markers revealed its osteogenic and anti-resorptive properties, crucial for countering glucocorticoid-induced bone loss. Isovitexin treatment preserved the mineral and material composition of bone, indicating that it helps maintain the tissue integrity and mechanical strength. Hitherto observed effects of isovitexin likely resulted in the preservation of bone quality, demonstrated by preserving mechanical behavior and bone strength, which are essential for preventing fractures. MP treatment led to muscle atrophy, evidenced by reduced gastrocnemius diameter and cross-sectional area. Isovitexin countered these effects and inhibited atrogenes (atrogin-1 and MuRF-1) induction.</p><p><strong>Conclusion: </strong>Isovitexin not only mitigates osteopenia but also maintains overall bone quality and composition, exhibiting dual osteogenic and anti-resorptive effects. Its capacity to reduce muscle atrophy underscores its potential as a comprehensive treatment for glucocorticoid-induced osteoporosis and sarcopenia.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-025-04251-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Isovitexin is an agonist of adiponectin receptors (AdipoRs). Adiponectin has been shown to have beneficial effects on bone and muscle function, in addition to its positive impact on metabolic health. However, the preclinical and clinical application of adiponectin faces scalability challenges, prompting the investigation of isovitexin in a methylprednisolone (MP)-induced osteoporosis model.
Methods: A rat model of MP-induced osteoporosis was developed to evaluate isovitexin's effects on bone health, including bone mass & microarchitecture (MicroCT), turnover markers (P1NP and CTX-1), strength (three-point bending, and nanoindentation), and quality (FTIR). We also investigated the muscle protective effects of isovitexin by measuring key muscle catabolic (atrogenes) proteins.
Results: Isovitexin effectively prevented MP-induced osteopenia in critical weight-bearing, fracture-prone sites, such as the proximal femur and lumbar vertebrae. Bone turnover markers revealed its osteogenic and anti-resorptive properties, crucial for countering glucocorticoid-induced bone loss. Isovitexin treatment preserved the mineral and material composition of bone, indicating that it helps maintain the tissue integrity and mechanical strength. Hitherto observed effects of isovitexin likely resulted in the preservation of bone quality, demonstrated by preserving mechanical behavior and bone strength, which are essential for preventing fractures. MP treatment led to muscle atrophy, evidenced by reduced gastrocnemius diameter and cross-sectional area. Isovitexin countered these effects and inhibited atrogenes (atrogin-1 and MuRF-1) induction.
Conclusion: Isovitexin not only mitigates osteopenia but also maintains overall bone quality and composition, exhibiting dual osteogenic and anti-resorptive effects. Its capacity to reduce muscle atrophy underscores its potential as a comprehensive treatment for glucocorticoid-induced osteoporosis and sarcopenia.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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