Wu Qijin, Zhou Jing, Du Donghua, Guo Bing, Wang Haifeng, Lv Wenting
Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China.
Int J Biol Macromol. 2025 Mar;292:139166. doi: 10.1016/j.ijbiomac.2024.139166. Epub 2024 Dec 30.
Osteoporosis (OP) is a significant global public health concern that requires the development of safe and effective drugs for prevention and treatment. Sugemule-7 (SGML-7) decoction, a traditional Mongolian herbal prescription, has long been used for treating OP, but its components and mechanisms of action remain unclear. The study identified the main compounds of SGML-7 using UHPLC-Q Exactive MS and explored the multi-target mechanisms of SGML-7 in OP through network pharmacology and molecular docking. A retinoic acid (RA)-induced mouse OP model was utilized to confirm the therapeutic effects and potential mechanism of SGML-7. Additionally, mouse pre-osteoblastic (MC3T3-E1) cells treated with SGML-7 medicated serum were employed to delve deeper into the molecular mechanisms. The UHPLC-Q Exactive MS analysis, network pharmacology, and molecular docking suggested that the synergistic effect of multiple active compounds could be the main contributor to SGML-7 for its anti-OP activities. Moreover, MAPK1, JUN, ESR1, TP53, AKT1, NCOA1, FOS, and NR3C1 were identified as potential key targets, and the MAPK signaling pathway was among the signaling pathways possibly involved in the anti-OP activities of SGML-7. Consistent with these findings, experimental studies confirmed that SGML-7 prevented bone loss, enhanced bone quality in OP mice, and promoted osteoblastic activity and bone formation in MC3T3-E1 cells by modulating MAPK-associated targets. Taken together, SGML-7 shows promise as an effective and appealing anti-OP drug candidate.
骨质疏松症（OP）是一个重大的全球公共卫生问题，需要研发安全有效的预防和治疗药物。苏格木勒-7（SGML-7）汤是一种传统的蒙药方剂，长期以来一直用于治疗OP，但其成分和作用机制尚不清楚。本研究采用超高效液相色谱-四极杆飞行时间质谱（UHPLC-Q Exactive MS）鉴定了SGML-7的主要化合物，并通过网络药理学和分子对接探讨了SGML-7在OP中的多靶点作用机制。利用维甲酸（RA）诱导的小鼠OP模型来证实SGML-7的治疗效果和潜在机制。此外，还使用经SGML-7含药血清处理的小鼠前成骨细胞（MC3T3-E1）来深入研究分子机制。UHPLC-Q Exactive MS分析、网络药理学和分子对接表明，多种活性化合物的协同作用可能是SGML-7抗OP活性的主要贡献因素。此外，丝裂原活化蛋白激酶1（MAPK1）、原癌基因蛋白c-Jun（JUN）、雌激素受体1（ESR1）、肿瘤蛋白p53（TP53）、蛋白激酶B（AKT1）、核受体辅激活因子1（NCOA1）、原癌基因蛋白c-Fos（FOS）和糖皮质激素受体（NR3C1）被确定为潜在的关键靶点，且MAPK信号通路是可能参与SGML-7抗OP活性的信号通路之一。与这些发现一致，实验研究证实，SGML-7通过调节MAPK相关靶点，预防了OP小鼠的骨质流失，提高了骨质量，并促进了MC3T3-E1细胞中的成骨细胞活性和骨形成。综上所述，SGML-7有望成为一种有效且有吸引力的抗OP候选药物。
