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

Abstract

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.

Keywords: OPG/RANKL axis; Oleane-type triterpenoid saponins; Osteoblast differentiation; P38/JNK MAPK; Pimpinella candolleana; Postmenopausal osteoporosis.