Kulkarni Chirag, Kumar Saroj, Khatoon Shamima, Sadhukhan Sreyanko, Washimkar Kaveri R, Kumar Akhilesh, Sharma Shivani, Rajput Swati, Porwal Konica, Mugale Madhav Nilakanth, Rath Srikanta Kumar, Godbole Madan Madhav, Sanyal Sabyasachi, Kumar Navin, Mithal Ambrish, Chattopadhyay Naibedya
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI), Lucknow, India.
Food and Micronutrient Analysis Laboratory, KLE Academy of Higher Education and Research, Belagavi, India.
Endocrine. 2025 May 14. doi: 10.1007/s12020-025-04251-6.
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.
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.
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.
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.
异荭草素是脂联素受体（AdipoRs）的激动剂。脂联素除了对代谢健康有积极影响外，还对骨骼和肌肉功能具有有益作用。然而，脂联素的临床前和临床应用面临可扩展性挑战，这促使人们在甲基强的松龙（MP）诱导的骨质疏松模型中研究异荭草素。
建立MP诱导的大鼠骨质疏松模型，以评估异荭草素对骨骼健康的影响，包括骨量和微结构（显微CT）、骨转换标志物（P1NP和CTX-1）、强度（三点弯曲和纳米压痕）和质量（傅里叶变换红外光谱）。我们还通过测量关键的肌肉分解代谢（萎缩相关基因）蛋白来研究异荭草素对肌肉的保护作用。
异荭草素有效预防了MP诱导的关键负重、易骨折部位（如股骨近端和腰椎）的骨质减少。骨转换标志物显示出其成骨和抗吸收特性，这对于对抗糖皮质激素诱导的骨质流失至关重要。异荭草素治疗保留了骨的矿物质和物质组成，表明它有助于维持组织完整性和机械强度。迄今为止观察到的异荭草素的作用可能导致骨质量的保留，这通过保留机械行为和骨强度得到证明，而机械行为和骨强度对于预防骨折至关重要。MP治疗导致肌肉萎缩，腓肠肌直径和横截面积减小证明了这一点。异荭草素对抗了这些影响并抑制了萎缩相关基因（atrogin-1和MuRF-1）的诱导。
异荭草素不仅减轻骨质减少，还维持整体骨质量和组成，表现出双重成骨和抗吸收作用。其减少肌肉萎缩的能力突出了其作为糖皮质激素诱导的骨质疏松和肌肉减少症综合治疗方法的潜力。
