Taraxasterol ameliorates bone loss of ovariectomized mice via suppressing the NLRP3 inflammasome and modulating the gut microbiota.

Yen-Ni Liu, Shan Liang, Yanjun Lei, Yun-fen Zhou, Yuanchao Zhang, Shih-Wein Li, Peng Sun, Qi Dong

Biochem Biophys Res Commun

Mar 26, 2026

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Abstract

Postmenopausal osteoporosis (PMOP) is a common disease linked to aging, and estrogen deficiency is considered to be the primary cause of PMOP. Inflammation and the gut microbiota (GM) have emerged as promising therapeutic targets for treating PMOP. Taraxasterol (Tara), a pentacyclic triterpenoid primarily derived from Taraxacum officinale, demonstrates broad biological functions and pharmacological properties. However, whether Tara in question exerts an anti-osteoporosis (OP) effect remains unclear. To investigate the potential anti-OP effects of Tara, an experimental OP model was developed using female C57BL/6 mice via bilateral ovariectomy (OVX). The mice of Tara groups received treatments via oral gavage once daily for 8 consecutive weeks. Bone microstructure parameters, the NLRP3 inflammasome, intestinal barrier and GM were assessed. Network pharmacology was employed to predict and validate its anti-OP-related molecular targets and pathways. The results revealed that Tara treatment significantly reduced bone loss and improved bone metabolism. ELISA revealed that Tara reduced proinflammatory cytokine levels, suppressed the NLRP3 inflammasome (caspase-1, IL-1βand IL-18) and affected adipokine content. The expression levels of Occludin and ZO-1 exhibited a significant increase in the Tara groups. Moreover, 16S rRNA sequencing demonstrated that the relative abundances of Ileibacterium, Erysipelotrichaceae and Oscillospiraceae decreased significantly, whereases the relative abundance of Parabacteroides increased after Tara administration. Network pharmacology identified 75 core anti-OP targets. The binding energy of target proteins and Tara ranged from approximately -5.0 to -9.0 kcal/mol, with EGFR showing the lowest binding energy. Overall, Tara ameliorated OVX-induced OP by suppressing the NLRP3 inflammasome and modulating the GM.