PHYTOMEDICINE
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2025
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IF 8.3
Chenying Zeng,Linjian Chen,Jiajie Lin,Zipeng Xiao,Qingqiang Tu,Wenhui Yu,Weihao Zhang,Qibo Li,Yanfeng Wu,Zhongyu Xie,Ziji Zhang
Background The shift in BMSC differentiation potential toward adipogenesis at the expense of osteogenesis is a critical mechanism underlying reduced bone formation in osteoporosis. Necroptosis has been implicated as a key driver of bone-fat imbalance in osteoporosis, though its mechanisms remain unclear. Taraxasterol (TAX), a bioactive triterpenoid derived from Taraxacum officinale , exhibits antitumor, antioxidant, and immunomodulatory properties. However, its potential role in osteoporosis has not yet been explored. Objective This study aimed to investigate whether TAX alleviates osteoporosis by regulating necroptosis and osteogenic–adipogenic differentiation in BMSCs, and to elucidate the underlying molecular mechanisms. Methods An ovariectomized (OVX) mouse model of osteoporosis was established for in vivo evaluation. Treatment groups received daily oral administration of TAX (5 or 20 mg/kg), with estradiol (E₂, 10 μg/kg) serving as a positive control. Bone microarchitecture and therapeutic response were assessed via micro-CT and immunohistochemistry, while femoral necroptosis and differentiation markers were evaluated by immunostaining. For in vitro studies, BMSCs isolated from osteoporosis patients were treated with the necroptosis inducer TSZ (TNF-α, SM-164, Z-VAD-FMK), with or without TAX. Flow cytometry was used to analyze the phenotype of MSCs. To identify molecular targets and mechanisms, an integrated approach combining network pharmacology, RNA sequencing, SPR assays, and molecular docking was employed. Subsequent analyses included western blotting, PI staining, and RNA interference to assess TAX-regulated necroptosis and PI3K/AKT/PPARγ pathway activity. ARS and ORO staining were employed to analyze osteogenic and adipogenic differentiation, respectively, and mitochondrial function was evaluated with TMRE and MitoSOX Red probes. Results TAX (20 mg/kg) significantly ameliorated bone loss in OVX mice, suppressed femoral necroptotic signaling, and reversed osteogenic–adipogenic imbalance in OVX-derived BMSCs. In vitro , TAX pretreatment attenuated TSZ-induced differentiation imbalance and necroptosis in patient-derived BMSCs and mitigated mitochondrial damage. Integrated network pharmacology and RNA sequencing revealed that TAX targets the PI3K/AKT/PPARγ axis. Immunohistochemical analysis demonstrated upregulation of the PI3K/AKT/PPARγ axis in the femurs of OVX mice following TAX administration. Molecular docking and SPR assays confirmed effective binding between TAX and PI3K. The protective effects of TAX were abolished by the PI3K inhibitor LY294002. Furthermore, TAX enhanced the rebalancing of osteogenic–adipogenic differentiation in PPARγ-silenced BMSCs. Conclusion Our study reveals for the first time that TAX restores osteogenic-adipogenic equilibrium in OP-BMSCs and promotes bone regeneration through PI3K/AKT/PPARγ activation and mitochondrial protection-mediated suppression of necroptosis. These results position TAX as a promising therapeutic candidate for osteoporosis.
研究领域:
药理学
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分子生物学
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内分泌学
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干细胞研究
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骨代谢
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Xiaodan Zhu,Hongmin Li,Yang Wang,Yuan Zhang,Fanglei Ye
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.
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2026
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IF 2.5
Yanming Liu,Shihui Liang,Yitao Lei,Yilin Zhou,Yingtong Zhang,Shimei Li,Ping Sun,Qunwei Dong
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.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Shuting Xu,Guangyi Liao,Tingting Li,Wenmin Li,Wanli Huang,Lihaopeng Cao,Shanshan Chen,Xiao Yang,Tianle Qin,Yuqing Zhou,Rong Yu,Chuanquan Lin
Ethnopharmacological relevance Dandelion (also known as Taraxaci Herba), a plant used in traditional Chinese medicine for both medicinal and dietary purposes, serves as a key ingredient in various liver-protecting herbal formulations. Its primary bioactive compound, taraxasterol (TAR), exhibits antioxidant and anti-inflammatory properties and can inhibit lipid synthesis. Nevertheless, the specific mechanism underlying its role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Materials and methods The study integrated ethnopharmacological knowledge with modern techniques. Following in vitro assessment of lipid clearance in mouse hepatocytes, network pharmacology analysis was performed to identify potential targets. The therapeutic effects of TAR were subsequently validated in a high-fat diet-induced MASLD mouse model, with a focus on the FXR signaling pathway. Results TAR effectively reduced hepatic lipid accumulation and inflammation, confirming its ethnopharmacological relevance. Network analysis revealed that TAR's multi-target effects converge on the FXR signaling pathway. In vivo experiments demonstrated that TAR significantly alleviated HFD-induced metabolic dysregulation and liver injury through FXR activation, with efficacy abolished upon FXR knockdown. Conclusion TAR ameliorates HFD-induced MASLD by modulating and enhancing the expression of hepatic FXR, thereby normalizing glucolipid metabolism and restraining oxidative and inflammatory damage. These findings position TAR as a promising plant-derived candidate for MASLD therapy and provide mechanistic insight into its hepatoprotective action.
研究领域:
民族药理学
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肝病学
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代谢性疾病
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天然产物研究
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分子生物学
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DOI
PubMed
高影响因子
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