Mongolian medicine Sugemule-7 decoction prevents osteoporosis via Erk1/2 and p38 MAPK signaling pathways according to network pharmacology analysis

Abstract

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.

Keywords: MAPK signaling pathway; Osteoporosis; SGML-7.