Taraxasterol

Cisplatin (DDP) is a potent chemotherapeutic agent with ototoxicity. It elicits oxidative stress (OS) and cell apoptosis in cochlear hair cells (HCs), leading to irreversible hearing loss. Taraxasterol (TAR) is a pentacyclic triterpene compound with anti-oxidative and anti-apoptotic properties. Here we identified that TAR inhibited DDP-induced cell apoptosis and OS in a mouse cochlear hair cell line (HEI-OC1). Besides, the beneficial effect of TAR on cochlear HC loss was validated in DDP-induced mice. Proteomics analysis identified the upregulation of G protein subunit alpha q (GNAQ) in TAR-treated HEI-OC1 cells, and it is predicted to bind with TAR via molecular docking. GNAQ inhibited cell apoptosis and OS injury in DDP-induced HEI-OC1 cells, accounting for TAR-mediated protection against DDP-induced cochlear HC injury. Collectively, this study validates the protective effect of TAR on DDP-induced cochlear HC loss, and highlights the potential role of TAR in preventing against DDP-induced hearing loss.

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-1β and 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.