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

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-26 DOI:10.1016/j.phymed.2025.157004

Jiajia Wu , Zhen Cao , Chuyin Ou , Lina Wang , Yan Ji , Mingyu Ma , Syed Shams ul Hassan , Xue Xiao , Shikai Yan , Huizi Jin

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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.

Abstract Image

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一种新型三萜皂苷通过P38/JNK mapk介导的成骨作用减轻绝经后骨质疏松症

绝经后骨质疏松症（PMOP）涉及骨量减少和微结构破坏。促进成骨细胞分化是关键的治疗策略。凤仙花是一种用于治疗骨相关疾病的传统中药。目的揭示蜡烛假单胞菌预防ppu的新成骨成分及其机制。方法采用去卵巢小鼠实验方法，观察烛檀三萜皂苷（PCTS）对去卵巢小鼠的抗ppu作用。分离有效成分并评估MC3T3-E1细胞的成骨活性。通过显微计算机断层扫描和组织学检查骨效应。通过转录组学和蛋白质组学分析探索机制，并通过Western blot、免疫染色和细胞热移试验验证靶点。结果spcts可改善OVX小鼠骨丢失，获得8种新型三萜皂苷。其中CP-1的成骨活性最强，在体内可促进MC3T3-E1成骨细胞分化，改善骨小梁结构，其疗效与阿仑磷酸钠相当。在机制上，CP-1激活P38/JNK MAPK通路，上调OPG/RANKL轴，从而调节骨代谢，促进成骨。结论cp -1通过活化MAPK和调节骨代谢促进骨生成，是一种很有前景的天然候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.