A novel triterpenoid saponin from Pimpinella candolleana alleviates postmenopausal osteoporosis via P38/JNK MAPK-mediated osteogenesis.

BACGROUND: Postmenopausal osteoporosis (PMOP) involves reduced bone mass and disrupted microarchitecture. Promoting osteoblast differentiation is a key therapeutic strategy. Pimpinella candolleana is a traditional Chinese herb used for bone-related disorders.

PURPOSE: To reveal novel osteogenic constituents and underlying mechanisms of P. candolleana in preventing PMOP.

METHODS

Triterpenoid saponins from P. candolleana (PCTS) were evaluated for anti-PMOP effects in ovariectomized (OVX) mice. Active constituents were isolated and evaluated for osteogenic activity in MC3T3-E1 cells. Bone effects were examined by micro-computed tomography and histology. Mechanisms were explored by transcriptomic and proteomic analyses, with target validation through Western blot, immunostaining, and cellular thermal shift assays.

RESULTS

PCTS ameliorated bone loss in OVX mice and obtained eight novel triterpenoid saponins. And CP-1 exhibited the strongest osteogenic activity, promoting osteoblast differentiation in MC3T3-E1 and improving trabecular bone structure in vivo with efficacy comparable to alendronate. Mechanistically, CP-1 activated the P38/JNK MAPK pathway and upregulated the OPG/RANKL axis, thereby regulating bone metabolism and promoting osteogenesis.

CONCLUSION

CP-1 is a promising natural candidate for PMOP therapy by enhancing osteogenesis via MAPK activation and bone metabolism regulation.