International immunopharmacology最新文献

{"title":"Kinesin superfamily proteins in cancer: unveiling their role in chemotherapy","authors":"Hamza Abu Owida ,&nbsp;Suleiman Ibrahim Mohammad ,&nbsp;Asokan Vasudevan ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;S. RenukaJyothi ,&nbsp;Rajashree Panigrahi ,&nbsp;Munthar Kadhim Abosaoda ,&nbsp;Gunjan Garg ,&nbsp;Amrita Pargaien","doi":"10.1016/j.intimp.2025.115621","DOIUrl":"10.1016/j.intimp.2025.115621","url":null,"abstract":"<div><div>Kinesin superfamily proteins (KIFs) are driver proteins used by microtubules for intracellular transport, cellular homeostasis, and mitosis. Reportedly, the aberration in the expression of these proteins has been found to mediate sensitivity to chemotherapy. KIF5A, KIF11, and KIF20A are consistently involved in resistance to paclitaxel and docetaxel in breast, lung, and prostate cancers, while KIF14 overexpression is a prognostic marker for poor outcomes in paclitaxel-treated triple-negative breast and cervical cancer. KIF14 and KIF23 in HCC enhance sorafenib and cisplatin resistance, while suppression of KIF5B or KIF20A increases sensitivity to oxaliplatin in colorectal cancer. Clinic-applied fusions of KIF5B with ALK or EGFR have made it possible to use targeted therapy in non-small cell lung cancer. From a mechanistic point of view, PI3K/Akt, JAK/STAT, and NF-κB activation, metabolic reprogramming, and inhibition of cellular programmed death are involved in KIF-mediated resistance. KIF3A or KIF11 silencing increases chemosensitivity, suggesting a dual role here. Present approaches-small-molecule inhibitors, microRNA modulation, and KIF20A peptide vaccines-are hopeful but are beset by issues of toxicity and specificity. Overall, KIFs are context-dependent regulators of chemoresistance and are multifunctional but promising precision oncology targets.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115621"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic elimination of bacillus Calmette-Guérin biofilm and tissue restoration facilitated by ultrasound-mediated nanoparticles and antioxidants","authors":"Yuqing Zhang ,&nbsp;Chaorong Huang ,&nbsp;Yan Qiu ,&nbsp;Ruicheng Li ,&nbsp;Jialing Liu ,&nbsp;Yonghong Du ,&nbsp;Dairong Li","doi":"10.1016/j.intimp.2025.115582","DOIUrl":"10.1016/j.intimp.2025.115582","url":null,"abstract":"<div><div>Biofilm formation in <em>Mycobacterium tuberculosis</em> (MTB) enhances antibiotic resistance by impeding drug penetration and evading host immunity. This poses a significant challenge to conventional drug therapies, highlighting the urgent need for novel treatment strategies to overcome MTB's biofilm-mediated resistance. This study introduces the development of low-intensity ultrasound-mediated levofloxacin (LEV) and catalase (CAT) -loaded PEG-PLGA nanoparticles (LEV@CAT-NPs) for antimicrobial sonodynamic therapy (aSDT), offering an innovative strategy to combat BCG biofilm infection, by utilizing BCG as a model for MTB. <em>N</em>-acetylcysteine (NAC) was supplemented during the latter stages of the treatment process of anti-infection therapy to facilitate the transformation of macrophages to the M2 phenotype and to promote tissue repair. Ultrasound-mediated LEV@CAT-NPs, along with the subsequent addition of NAC not only enhanced repair at the infection site but also led to a progressive resolution of the inflammatory response in tissues. The treatment regimen induced a shift in macrophage polarization towards the M2 phenotype and modulated cytokine expression, decreasing pro-inflammatory while increasing anti-inflammatory cytokines, which contributed to the restoration of redox balance in the infected tissues. This study proposes a novel therapeutic strategy that not only targets drug-resistant MTB but also promotes tissue repair, highlighting its dual role in infection management.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115582"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emodin facilitates the transformation of A1/A2 reactive astrocytes through the 11β-HSD1/AKT signaling pathway in the context of cerebral ischemia","authors":"Wenfang Lai ,&nbsp;Huiling Wu ,&nbsp;Yuting Jiang ,&nbsp;Xuerui Zheng ,&nbsp;Jingquan Chen ,&nbsp;Zehao Huang ,&nbsp;Haimian Hong ,&nbsp;Yingzheng Wang ,&nbsp;Wen Xu ,&nbsp;Guizhu Hong ,&nbsp;Ya Lin","doi":"10.1016/j.intimp.2025.115628","DOIUrl":"10.1016/j.intimp.2025.115628","url":null,"abstract":"<div><div>Emodin is the main active ingredient of <em>Rhei Radix et Rhizoma</em>, a herb widely used for ischemic stroke treatment. This study demonstrates for the first time that emodin exerts neuroprotective effects against ischemic stroke by regulating astrocyte phenotypic transformation via the 11β-HSD1/AKT signaling pathway. In rat MCAO and astrocyte/neuron OGD/R models, emodin improved neurological function, reduced infarction volume, and shifted astrocytes from detrimental A1 to beneficial A2 phenotypes. Mechanistically, emodin activated AKT phosphorylation while suppressing the NF-κB pathway (reducing p-IκBα/IκBα and p-p65/p65 ratios). These effects—along with functional improvements—were reversed by AKT inhibitor LY294002. Furthermore, 11β-HSD1 siRNA mimicked emodin's actions in vitro, and supernatants from both emodin- and siRNA-treated astrocytes enhanced neuronal MAP2 expression. These findings identify astrocyte phenotypic modulation via 11β-HSD1/AKT as a key therapeutic mechanism of emodin.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115628"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yueju pill and its active component- Myricetin attenuate the reinstatement of methamphetamine-seeking behavior in mice","authors":"Yanfeng Du ,&nbsp;Shuyuan Fan ,&nbsp;Xialin Yang ,&nbsp;Wei Ma ,&nbsp;Shiqi Li ,&nbsp;Yixin Xu ,&nbsp;Cui Li ,&nbsp;Shuman Chen ,&nbsp;Yueyuan Wang ,&nbsp;Meifang Wang ,&nbsp;Tengfei Ma ,&nbsp;Junlong Zhang","doi":"10.1016/j.intimp.2025.115601","DOIUrl":"10.1016/j.intimp.2025.115601","url":null,"abstract":"<div><div>Yueju pill (YJ), a traditional Chinese medicine, is widely used for the treatment of depression and pain due to its ability to prevent neuroinflammatory responses, regulate synaptic plasticity, and enhance cognitive function. Methamphetamine (METH) addiction is a chronic brain disease associated with inflammation and aberrant synaptic plasticity. However, whether and how YJ with its active components attenuates the METH-induced behavior remain unclear. In this study, we demonstrated that YJ attenuated the reinstatement of METH-seeking behavior while decreasing the activity of hippocampal CA1 neurons. Furthermore, YJ prevented METH-induced aberrant potentiation of glutamatergic transmission and restored physiological synaptic plasticity, likely mediated by upregulated expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95). Importantly, hippocampal CA1-specific knockdown of BDNF abolished the protective effects of YJ on METH-seeking behavior and synaptic dysfunction, confirming BDNF's pivotal role in YJ's mechanism of action. Mechanistically, YJ exerts its therapeutic effects by suppressing NLRP3 inflammasome activation. Notably, pharmacological activation of NLRP3 counteracted YJ-induced BDNF upregulation, suggesting that YJ restores synaptic plasticity, at least in part, through NLRP3 inhibition and subsequent microglial inactivation. Among its bioactive constituents, myricetin was identified as a key component responsible for reducing METH-seeking behavior and inflammatory responses. Collectively, our findings reveal that YJ attenuates aberrant synaptic plasticity by downregulating the NLRP3 inflammasome and enhancing BDNF expression in the hippocampus. These insights highlight the potential of targeting neuroimmune pathways and synaptic plasticity to develop novel therapeutic strategies for METH addiction.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115601"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived histamine exacerbates psoriasis by promoting γδT17 cell differentiation via the Hrh1/Wnt Axis","authors":"Waiming Cheng ,&nbsp;Meihong He ,&nbsp;Elfira Jurat ,&nbsp;Luoyi Jin ,&nbsp;Shunchang Luo ,&nbsp;Zerong Guan ,&nbsp;Yingying Zeng ,&nbsp;Xianghong Wang ,&nbsp;Jianlei Hao ,&nbsp;Xin Tang ,&nbsp;Haiyan Zhu ,&nbsp;Zhinan Yin ,&nbsp;Hengwen Yang","doi":"10.1016/j.intimp.2025.115571","DOIUrl":"10.1016/j.intimp.2025.115571","url":null,"abstract":"<div><div>Psoriasis is associated with gut microbiota dysbiosis and aberrantly elevated histamine levels, yet the pathological role of microbiota-derived histamine remains unclear. In this study, colonization of mice with histamine-producing engineered <em>E. coli</em> (BL21_pET-17b_hdc) revealed that microbiota-derived histamine (non-dietary origin) significantly exacerbated skin inflammation in a psoriasis model and induced γδT17 cell expansion across multiple immune organs. These effects were abolished in γδT cell-deficient mice. RNA sequencing demonstrated that histamine exposure upregulated the histamine receptor gene Hrh1 and activated the Wnt signaling pathway via pathway enrichment analysis. Further in vitro experiments confirmed that histamine promoted γδT17 cell differentiation in an Hrh1 receptor-dependent manner, with this process being associated with Wnt pathway activity. Our findings elucidate that gut microbiota-derived histamine exacerbates psoriatic inflammation by coordinately regulating the Hrh1 receptor and Wnt signaling pathway to drive γδT17 cell differentiation, providing a theoretical foundation for therapeutic strategies targeting microbial metabolites.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115571"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HNRNPA1 promotes TRIM37 mRNA stability and mediates TRAF6 ubiquitination to alleviate osteoarthritis","authors":"Hailin Deng ,&nbsp;Wanlan Liu ,&nbsp;Liang Xiang,&nbsp;Junxing Wu","doi":"10.1016/j.intimp.2025.115568","DOIUrl":"10.1016/j.intimp.2025.115568","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA), characterized by progressive cartilage degeneration, involves inflammation and dysregulated cell death. The functional role of the RNA-binding protein HNRNPA1 via TRIM37-mediated TRAF6 ubiquitination in OA pathogenesis remains unclear.</div></div><div><h3>Methods</h3><div>Using a destabilization of the medial meniscus (DMM)-induced OA mouse model, we assessed cartilage histopathology, inflammation, and expression of HNRNPA1, TRIM37, and TRAF6. Interleukin-1β (IL-1β)-treated chondrocytes were analyzed for viability, apoptosis, pyroptosis, and extracellular matrix (ECM) synthesis. Mechanistic studies included RNA-fluorescence in situ hybridization (RNA-FISH), RNA immunoprecipitation (RIP), mRNA stability assays, and co-immunoprecipitation (Co-IP) following TRIM37 knockdown to examine TRAF6 ubiquitination.</div></div><div><h3>Results</h3><div>OA progression correlated with decreased HNRNPA1 and TRIM37 but increased TRAF6 expression. HNRNPA1 overexpression mitigated cartilage degradation, inflammation, and autophagy impairment. Mechanistically, HNRNPA1 stabilized TRIM37 mRNA, thereby enhancing TRIM37-mediated TRAF6 ubiquitination. This cascade suppressed pyroptosis while activating autophagy, conferring chondroprotection.</div></div><div><h3>Conclusion</h3><div>The HNRNPA1/TRIM37/TRAF6 axis regulates the balance between autophagy and pyroptosis, offering a novel therapeutic target to alleviate OA.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115568"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-formyl methionine mediates NETosis of neutrophil to promote sepsis-induced cardiomyopathy via the FPR1 pathway","authors":"Sen Chen ,&nbsp;Hui Lin ,&nbsp;Haodi Gu ,&nbsp;Xinrou Yu ,&nbsp;Junjie Xiang ,&nbsp;Lili Xu ,&nbsp;Gang Ye ,&nbsp;Yue Shan ,&nbsp;Yun Wang","doi":"10.1016/j.intimp.2025.115602","DOIUrl":"10.1016/j.intimp.2025.115602","url":null,"abstract":"<div><h3>Introduction</h3><div>Sepsis-induced cardiomyopathy (SIC) is a rapidly advancing condition associated with a poor prognosis due to the lack of effective treatments. Neutrophil extracellular traps (NETs), however, act as a double-edged sword in the innate immune response during sepsis. N-formyl methionine (fMet) has been documented to induce NETs in inflammatory conditions, yet its clinical significance and biological function in SIC remain unclear. In this study, we investigated whether fMet induces excessive NETs, thereby promoting SIC.</div></div><div><h3>Methods and results</h3><div>Clinically, serum fMet levels were quantified using ELISA, revealing a significant elevation in patients with SIC compared to non-sepsis patients and healthy controls. The fMet levels were positively correlated with the NETs-related markers myeloperoxidase (MPO) and double-stranded DNA (dsDNA) in patients with SIC. Treatment with lipopolysaccharide and fMet increased NET formation in human neutrophils and upregulated the expression of formyl peptide receptor 1 (FPR1) and hypoxia-inducible factor 1-alpha (HIF-1α). Furthermore, bone marrow-derived neutrophils (BMDNs) were isolated from global FPR1 knockout mice, and FPR1 deficiency in BMDNs was found to suppress NETosis. The cecal ligation and puncture (CLP) model was employed to induce SIC in mice and we found knockout of FPR1 improved outcomes in CLP mice, as evidenced by survival benefit, increased cardiac function, attenuated cytokine storm, reduced neutrophil infiltration, improved mitochondrial function and suppressed NETosis, compared with those of wild-type (WT) mice. In addition, treatment with FPR1 inhibitor HCH6–1 improved cardiac outcome and inhibits NETosis in CLP mice.</div></div><div><h3>Conclusion</h3><div>These data reveal the role of fMet-mediated FPR1/HIF-1α activation in promoting SIC through the NETosis, indicating novel therapeutic strategy for SIC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115602"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-HDHA, a DHA metabolite screened by targeted lipidomic, alleviates DSS-induced colitis by inhibiting apoptosis and reducing inflammation","authors":"Ruijia Li ,&nbsp;Mengqi Zheng ,&nbsp;Yunjiao Zhai ,&nbsp;Lixiang Li ,&nbsp;Weijia Li ,&nbsp;Shiyang Li ,&nbsp;Xiuli Zuo ,&nbsp;Yanqing Li","doi":"10.1016/j.intimp.2025.115614","DOIUrl":"10.1016/j.intimp.2025.115614","url":null,"abstract":"<div><div>Ulcerative colitis (UC) remains a global health challenge, with current therapeutic strategies limited by efficacy and adverse effects. In this study, we observed that the lipid peroxide scavenger Liproxstatin-1 unexpectedly promoted TNF-α–induced apoptosis in HT-29 cells and murine colonic organoids, in contrast to the protective effects previously reported for typical peroxide scavengers in UC. To identify alternative protective metabolites, we performed targeted lipidomics, which revealed 4-hydroxy-docosahexaenoic acid (4-HDHA), a metabolite of DHA, as a candidate with pronounced anti-apoptotic activity in vitro and ex vivo. Intraperitoneal administration of 4-HDHA effectively ameliorated DSS-induced colitis in mice. RNA sequencing indicated significant enrichment of the PPAR signaling pathway following 4-HDHA treatment. Dual-luciferase reporter assays confirmed that 4-HDHA enhances PPARγ transcriptional activity, while pharmacological inhibition with GW9662 abrogated its therapeutic effects. Furthermore, 4-HDHA suppressed NF-κB signaling and apoptosis via PPARγ activation. Collectively, these findings demonstrate that 4-HDHA, identified through targeted lipidomics, attenuates DSS-induced colitis by reducing apoptosis and inflammation through PPARγ activation, highlighting its potential as a promising therapeutic agent for UC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115614"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gpr109a alleviates mammary fibrosis via PPARγ-mediated reduction of ROS and mitochondrial damage","authors":"Junlong Bi ,&nbsp;Dewei He ,&nbsp;Feng Li ,&nbsp;Ping Xu ,&nbsp;Yaping Huang ,&nbsp;Wenjin Guo ,&nbsp;Shoupeng Fu ,&nbsp;Xingchi Kan ,&nbsp;Yongneng Li","doi":"10.1016/j.intimp.2025.115603","DOIUrl":"10.1016/j.intimp.2025.115603","url":null,"abstract":"<div><div>Mammary fibrosis is a serious pathological process, which seriously threatens life and health. <em>Gpr109a</em> is a membrane receptor that has been reported to be protective in liver/lung fibrosis, but the mechanism of mammary tissue specificity still needs to be verified. Therefore, the purpose of this experiment was to explore the effect of <em>Gpr109a</em> on mammary fibrosis and its potential regulatory mechanism. The results show that <em>Gpr109a</em> deletion exacerbates the TGF-β induced mouse mammary fibrosis phenotype and mitochondrial damage (including mitochondrial nuclear shrinkage, cristae reduction, membrane potential decrease, and ATP reduction, <em>etc.</em>). However, backfilling of <em>Gpr109a</em> could effectively reverse the above experimental results. RNA-seq results of mice mammary gland tissue showed that <em>Gpr109a</em> knock-out significantly affect PPARγ signaling, which may be an important signal for alleviating fibrosis. Mechanistic results showed that silencing of PPARγ significantly blocked the alleviation effect of Gpr109a on mitochondrial damage and elevated fibrotic phenotype indicators in mMECs. However, activating PPARγ effectively reversed the above experimental phenomena. Further studies found that PPARγ alleviated mammary tissue fibrosis and mitochondrial damage by reducing ROS accumulation. In conclusion, <em>Gpr109a</em>/PPARγ signaling reduces the tendency of mammary fibrosis by reducing the accumulation of ROS and mitochondrial damage, suggesting that Gpr109a has the potential to become an anti-mammary fibrosis target.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115603"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sofalcone inhibits osteoclastogenesis through Keap1/Nrf2 signaling activation and mitigates ovariectomy-induced bone loss","authors":"Haibo Liang ,&nbsp;Qihang Wu ,&nbsp;Tianyong Hua ,&nbsp;Yiqi Chen ,&nbsp;Jiangtao Luo ,&nbsp;Jiansen Miao ,&nbsp;Hong Su ,&nbsp;Shu Yang ,&nbsp;Jiake Xu ,&nbsp;Xiangyang Wang ,&nbsp;Haiming Jin","doi":"10.1016/j.intimp.2025.115589","DOIUrl":"10.1016/j.intimp.2025.115589","url":null,"abstract":"<div><div>Osteoporosis, a metabolic bone disorder, predominantly affects postmenopausal women and frequently results in pathological fractures. Current treatments for this condition often entail significant side effects, limiting their clinical utility. Sofalcone (SFC), a phenolic derivative isolated from the Chinese herb <em>Sophora tonkinensis</em>, has demonstrated antioxidative, anti-inflammatory, and anti-ulcer capabilities, has been less studied for its effects on osteoclasts and osteoporosis. Our in vitro studies reveal that SFC inhibits osteoclastogenesis and reduces osteoclastic bone resorption. It achieves this by enhancing the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which boosts the expression of antioxidant genes, decreases the production of reactive oxygen species (ROS), and suppresses activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Further investigations using ovariectomized (OVX) mice have shown that SFC mitigates bone density loss and improves bone microarchitecture, suggesting its utility as both a preventive and therapeutic measure against osteoporosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115589"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}