Biochemical pharmacology最新文献

{"title":"Cajanolactone A alleviates high-fat diet-induced MAFLD by modulating liver de novo lipogenesis, inflammatory signaling, and bile acid composition in the gut-liver axis","authors":"Zaibin Xu ,&nbsp;Kongyan Wang ,&nbsp;Xiaoqin Wu ,&nbsp;Tingting Chen ,&nbsp;Like Xu ,&nbsp;Yi Qiu ,&nbsp;Huiyu Hu ,&nbsp;Yan Chen ,&nbsp;Jiazhong Cai ,&nbsp;Yingjie Hu ,&nbsp;Jiawen Huang ,&nbsp;Zhuohui Luo","doi":"10.1016/j.bcp.2026.117717","DOIUrl":"10.1016/j.bcp.2026.117717","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease worldwide, affecting more than a quarter of the adult population. Cajanolactone A (CLA), a stilbenoid derived from <em>Cajanus cajan</em>, has been shown to significantly reduce hepatic lipid accumulation. However, its molecular mechanisms in MAFLD remain unclear. In this high-fat diet (HFD)-induced mice model of MAFLD, CLA significantly improved dyslipidemia, suppressed liver <em>de novo</em> lipogenesis by downregulating the expression of core genes and proteins involved in glycolysis and the tricarboxylic acid (TCA) cycle, and regulated SREBP-1c/ChREBP signaling to improve lipid metabolism and maintain lipid homeostasis. Furthermore, CLA markedly ameliorated the TLR4/NF-κB p65 signaling-mediated inflammatory microenvironment induced by HFD-stimulated intestinal endotoxins, increased the expression of intestinal tight junction (TJ) biomarkers Claudin-1 and ZO-1, protected intestinal barrier permeability, and enhanced intestinal immune function homeostasis, inhibited NF-κB p65/NLRP3-mediated inflammatory cascades in the liver by suppressing gut-liver axis signaling, activated liver FXR to regulate bile acid (BA) composition, thereby alleviating MAFLD. Overall, these findings suggest that CLA reduces HFD-induced MAFLD by regulating <em>de novo</em> lipogenesis, lipolysis, inflammatory signaling, and BA composition in the gut-liver axis, laying a scientific foundation for clinical prevention and treatment of MAFLD.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117717"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002978","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 isoxanthohumol metabolite, 8-prenylnaringenin, mitigates endothelial dysfunction in Angiotensin II-induced hypertension through G protein-coupled estrogen receptor-mediated eNOS activation","authors":"Seung Yeon Lee ,&nbsp;Anh Thi Ngoc Bui ,&nbsp;Tuyet Ngan Thai ,&nbsp;Gi Ho Lee ,&nbsp;Minseo Kim ,&nbsp;Su Yeon Kim ,&nbsp;Jeonghwan Maeng ,&nbsp;Jae-Kyung Jung ,&nbsp;Moo-Yeol Lee ,&nbsp;Sang Ki Lee ,&nbsp;Hwi-yeol Yun ,&nbsp;Nam Doo Kim ,&nbsp;Eun Hee Han ,&nbsp;Hye Gwang Jeong","doi":"10.1016/j.bcp.2026.117728","DOIUrl":"10.1016/j.bcp.2026.117728","url":null,"abstract":"<div><div><em>Humulus lupulus</em> L. (hops), which is traditionally used in brewing, is a rich botanical source of prenylated flavonoids with potential cardiovascular protective properties. Of these, 8-prenylnaringenin (8-PN), a potent phytoestrogen formed from isoxanthohumol by the gut microbiota, has been implicated in vascular health. Nitric oxide (NO), which is produced by endothelial nitric oxide synthase (eNOS), exerts profound effects on vascular tone and endothelial integrity. This study examined the protective effects of 8-PN on endothelial signaling and vascular function using <em>in vitro</em> endothelial cell assays, <em>ex vivo</em> isolated artery preparations, and an <em>in vivo</em> mouse model of Angiotensin II (Ang II)-induced endothelial dysfunction. In endothelial cells, 8-PN increased phosphorylation of eNOS on Ser1177 and NO production through G-protein coupled estrogen receptor (GPER)-mediated Ca²⁺-dependent signaling pathways involving phosphorylation of Ca²⁺/calmodulin-dependent protein kinase β (CaMKKβ) and AMPK-activated protein kinase (AMPK). Furthermore, 8-PN activated eNOS via GPER-mediated epidermal growth factor receptor (EGFR) activation, with c-Src facilitating phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-related kinase (ERK) phosphorylation. Molecular docking results indicated that 8-PN could bind to GPER and facilitate the activation of downstream signaling cascades. Both of 8-PN-mediated eNOS phosphorylation are mediated through the Gβγ subunit. <em>In vivo</em>, 8-PN attenuated angiotensin II-induced endothelial dysfunction in mice and induced vasorelaxation <em>in vivo.</em> 8-PN stimulated eNOS phosphorylation and NO production via dual GPER-dependent pathways, supporting its potential as a therapeutic candidate for endothelial dysfunction-related vascular diseases.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117728"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024476","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":"MitoQ upregulates CYP19A1 to protect dermal papilla cells from DHT-induced mitochondrial dysfunction and apoptosis in androgenetic alopecia","authors":"Yujie Li ,&nbsp;Tingru Dong ,&nbsp;Jiamin Wu ,&nbsp;Fenglan Yang ,&nbsp;Shiyu Jin ,&nbsp;Renxue Xiong ,&nbsp;Meiya Li ,&nbsp;Xiuzu Song ,&nbsp;Cuiping Guan","doi":"10.1016/j.bcp.2026.117729","DOIUrl":"10.1016/j.bcp.2026.117729","url":null,"abstract":"<div><div>Androgenetic alopecia (AGA) is a progressive hair loss disorder characterized by follicular miniaturization primarily driven by dihydrotestosterone (DHT). Mitochondrial dysfunction in dermal papilla cells (DPCs) has emerged as a key pathological feature, yet the upstream regulatory mechanisms remain unclear. Our previous work revealed that the mitochondria-targeted antioxidant MitoQ upregulates CYP19A1 (aromatase) and alleviates AGA-like pathology. Here, we investigated whether CYP19A1 modulates mitochondrial function and mediates the protective effects of MitoQ. Using a DHT-induced AGA mouse model and DPCs with <em>CYP19A1</em> knockdown or overexpression, we examined hormone profiles, mitochondrial activity, and hair growth–related factors. DHT markedly reduced <em>CYP19A1</em> expression and increased inhibitory factors such as DKK1, TGF-β, and IL-6, whereas <em>CYP19A1</em> overexpression or MitoQ pretreatment reversed these effects. Both CYP19A1 and MitoQ decreased mitochondrial reactive oxygen species (mtROS), improved respiratory capacity, and preserved mitochondrial morphology. Importantly, our findings reveal a previously unrecognized aromatase–mitochondria cross-talk in hair-follicle cells, whereby CYP19A1-derived estrogens sustain mitochondrial homeostasis under androgenic stress. MitoQ amplifies this cross-talk through CYP19A1 activation, restoring redox balance and mitochondrial integrity. Collectively, these results identify CYP19A1 as a pivotal regulator of mitochondrial resilience and suggest that the CYP19A1–mitochondrial axis represents a promising pharmacological target for treating AGA.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117729"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024709","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":"Targeting the FBXW7-AKAP13-YAP axis suppresses gliomagenesis by dual inhibition of tumor invasion and macrophage recruitment","authors":"Changfu Zhang,&nbsp;Haichun Li,&nbsp;Yushuai Gao,&nbsp;Kaiyuan Deng,&nbsp;Rongjun Qian","doi":"10.1016/j.bcp.2026.117677","DOIUrl":"10.1016/j.bcp.2026.117677","url":null,"abstract":"<div><div>Glioma, a highly lethal and common malignant tumor of the central nervous system, is characterized by its aggressive invasive behavior. Tumor-associated macrophage (TAM) represent the most abundant infiltrating immune cell population in the glioma microenvironment and play a critical role in gliomagenesis and progression. Although A-kinase anchoring protein 13 (AKAP13) has been implicated in other cancers, its specific role in glioma progression and TAM infiltration remains unclear. In this study, we identify AKAP13 is significantly upregulated in glioma tissues and associated with poor patient survival. Functionally, AKAP13 silencing inhibited glioma cell invasion and TAM recruitment in both in vitro and in vivo models. Mechanistically, AKAP13 drives tumor progression by enhancing YAP expression and nuclear translocation, which subsequently upregulates the TAM-recruiting chemokines CSF1 and CCL2. We further identified F-box and WD repeat domain-containing 7 (FBXW7) as an upstream regulator that promotes ubiquitin-mediated degradation of AKAP13. Together, our findings reveal a novel FBXW7/AKAP13/YAP/chemokine signaling axis that promotes glioma pathogenesis through both tumor-autonomous invasion and TAM recruitment, highlighting a promising therapeutic target for this lethal malignancy.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117677"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931430","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":"Phosphate binders suppress glutaminase activity for treatment of cirrhosis and hepatic encephalopathy murine models","authors":"Ze-ning Chen ,&nbsp;Zhi-xing Liu ,&nbsp;Chen-kai Huang ,&nbsp;Lu Yu ,&nbsp;Yu-long Ji ,&nbsp;Yang-feng Lv ,&nbsp;Qing-rong Liang ,&nbsp;Qun Tang","doi":"10.1016/j.bcp.2026.117752","DOIUrl":"10.1016/j.bcp.2026.117752","url":null,"abstract":"<div><div>Hyperactivated glutaminase1 (GLS1) promotes the progression of cirrhosis via the reprogramming of hepatic stellate cells (HSCs). Hepatic encephalopathy (HE), the main complication of cirrhosis characterized by abnormal ammonia metabolism, is also associated with increased glutaminase activation in intestinal epithelial cells (IECs). The enzymatic activity of glutaminase depends on inorganic phosphate (Pi). In this study, a retrospective study of serum Pi levels was performed in 185 cirrhosis–HE patients. The pharmacology and pharmacodynamics of Pi binders (sevelamer and lanthanum carbonate) were evaluated in CCl₄-induced cirrhosis and both type A and C HE murine models. The biological events downstream of Pi binders were evaluated via glutamate rescue in activated HSCs and GLS1-overexpressing IECs. We found that <strong>s</strong>erum Pi is an independent risk factor for cirrhosis progression to HE. Both binders stimulated HSC senescence and rebalanced interorgan ammonia, alleviating cirrhosis and HE and reversing liver dysfunction. They had better therapeutic effects than L-ornithine L-aspartate (OA). Pi deprivation weakened glutaminase enzymatic activity, lowering collagen and Alpha-smooth muscle actin (α-SMA) production in HSCs and ammonia production in both wild-type and GLS1-overexpressing IECs. Since Pi deprivation alleviates glutaminolysis and ammonia production by decreasing glutaminase activity, Pi binders might hold great promising to treat cirrhosis and HE.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117752"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050331","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":"DNMT1 and DNMT3A drive hepatocellular carcinoma progression via epigenetic regulation and are inhibited by 5-azacytidine","authors":"Jinhua Jiang ,&nbsp;Dan Cui ,&nbsp;Jiachang Chi ,&nbsp;Caixia Xu ,&nbsp;Tinghua Yan ,&nbsp;Fang Guo","doi":"10.1016/j.bcp.2026.117670","DOIUrl":"10.1016/j.bcp.2026.117670","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a major global health challenge with limited therapeutic options. This study investigates the roles of DNA (deoxyribonucleic acid) methyltransferase 1 (DNMT1) and DNA methyltransferase 3 alpha (DNMT3A) in the advancement of HCC and evaluates their therapeutic potential. Bioinformatics interrogation using Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Kaplan–Meier Plotter, and cBioPortal revealed pronounced upregulation of DNMT1 and DNMT3A in HCC tissues and cell lines, which was tightly associated with unfavorable clinical outcomes. <em>In vitro</em> assays demonstrated that DNMT1 and DNMT3A regulate cell cycle progression and proliferation, with silencing inducing G0/G1 arrest and reducing cell viability, while overexpression reversed these effects. <em>In vivo</em>, 5-azacytidine (5-AZA), a DNMT inhibitor, significantly suppressed tumor growth in a mouse orthotopic liver tumor model, as evidenced by reduced tumor volume and proliferation markers (Ki67) and increased apoptosis (caspase-3). These findings indicate that DNMT1 and DNMT3A drive hepatocellular carcinoma through epigenetic regulation and are viable prognostic biomarkers. Targeting these enzymes with 5-azacytidine offers a promising therapeutic strategy for hepatocellular carcinoma management.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117670"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917036","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":"Optical control of H1 receptor signaling with a BODIPY-photocaged antihistamine","authors":"Ivana Josimovic ,&nbsp;Yang Zheng ,&nbsp;Zhiyong Wang,&nbsp;Tiffany van der Meer,&nbsp;Maikel Wijtmans,&nbsp;Henry F. Vischer,&nbsp;Rob Leurs","doi":"10.1016/j.bcp.2026.117705","DOIUrl":"10.1016/j.bcp.2026.117705","url":null,"abstract":"<div><div>Photopharmacology strives for light-dependent regulation of the activity of drug molecules, as a mean for precise control of drug targets on demand and the promise of reduced systemic side effects. Photocaging makes use of photoremovable protecting groups (PPGs), which can be introduced at key positions to inactivate drug ligands. Photocaged ligands can release active drug molecules following light-mediated uncaging with spatiotemporal precision. Here, a boron-dipyrromethene (BODIPY)-based PPG is used to inactivate desloratadine, which is a clinically used histamine H₁ receptor (H₁R) antagonist for the treatment of allergic disorders. The photocaged desloratadine analogue <strong>1</strong> (VUF25549) displays more than 290-fold lower H₁R affinity compared to desloratadine. Irradiation of <strong>1</strong> with 560 nm light results in photo-uncaging and the release of the parent drug desloratadine, resulting in optical modulation of histamine-induced H₁R signaling. The presented BODIPY-based photocaging of desloratadine offers a powerful new tool for the precise optical control of H₁R function.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117705"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987869","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":"Entinostat suppresses hepatocellular carcinoma metastasis by upregulating AZGP1 through histone acetylation","authors":"Weiguo Cai ,&nbsp;Xinru Pei ,&nbsp;Xiaodie Ye ,&nbsp;Yan Zhai ,&nbsp;Na Wu ,&nbsp;Ziyi Wang ,&nbsp;Wei Lu","doi":"10.1016/j.bcp.2026.117718","DOIUrl":"10.1016/j.bcp.2026.117718","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) has a high mortality rate, primarily driven by metastasis. The role of the histone deacetylase inhibitor (HDACi) entinostat in this process remains controversial, limiting its clinical application. This study aims to define entinostat’s function and mechanism in HCC metastasis. We employed <em>in vitro</em> models, transcriptomic sequencing, chromatin immunoprecipitation-qPCR, and an orthotopic mouse model to assess the effects of entinostat on epithelial-mesenchymal transition (EMT), invasion, and tumor growth. Our findings demonstrate that entinostat potently prevented and reversed transforming growth factor-β (TGF-β)-induced EMT, suppressing HCC cell invasion and metastasis <em>in vivo</em> without significant toxicity. Transcriptomics identified <em>alpha-2-glycoprotein 1, zinc-binding</em> (<em>AZGP1</em>) as a key target. In addition, entinostat promotes histone H4 acetylation at the <em>AZGP1</em> promoter, activating its transcription. <em>AZGP1</em> overexpression mimicked entinostat’s effects, while its knockdown largely abolished them. Clinically, high <em>AZGP1</em> expression was associated with an improved prognosis. In conclusion, our work elucidates a coherent epigenetic pathway wherein entinostat activates <em>AZGP1</em> to inhibit HCC metastasis. These findings nominate <em>AZGP1</em> as both a critical mediator and a potential biomarker for entinostat-based therapy in advanced HCC.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117718"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002926","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":"Liquiritigenin suppresses osteoclastogenesis via multi-target mechanisms involving NF-κB/PI3K-AKT signaling pathways and metabolic reprogramming","authors":"Wenhua Zhao ,&nbsp;Wei Deng ,&nbsp;Yi Wang ,&nbsp;Ruochen Zhu ,&nbsp;Jianguo Liu ,&nbsp;Huiming Chen ,&nbsp;Wen Tang ,&nbsp;Yang Luo ,&nbsp;Aihua Du ,&nbsp;Hongmei Zhu ,&nbsp;Mingxing Sun ,&nbsp;Gengyang Shen ,&nbsp;Hui Ren ,&nbsp;Jiyao Luan ,&nbsp;Xiaobing Jiang ,&nbsp;Shenghui Yi","doi":"10.1016/j.bcp.2026.117678","DOIUrl":"10.1016/j.bcp.2026.117678","url":null,"abstract":"<div><div>Osteoporosis (OP) is a prevalent systemic metabolic disease characterized by reduced bone density and compromised skeletal integrity, leading to increased fragility and fractures. This study investigated the therapeutic potential of Liquiritin (LIQ) in inhibiting osteoclastogenesis through integrated computational and experimental approaches. Molecular docking and dynamics simulations were employed to explore the interactions between LIQ and key osteoclastogenic proteins RANK and RANKL. In vitro experiments assessed LIQ’s inhibitory effects on mature osteoclast (OC) formation using RNA sequencing, cellular immunofluorescence, surface plasmon resonance (SPR), cellular thermal shift assays (CETSA), and Western blot analysis. In vivo studies validated the effects of LIQ on OC formation and bone loss. The results demonstrated that LIQ (≤20 μM) exhibited no cytotoxicity to bone marrow-derived macrophages (BMMs) while potently suppressing mature OC formation. LIQ downregulated OC-specific proteins and inhibited phosphorylation in the MAPK, NF-κB, and PI3K pathways. RNA sequencing revealed that LIQ modulates mitochondrial oxidative phosphorylation and induces OC precursor apoptosis, which was confirmed by immunofluorescence and OCR/ECAR assays indicating metabolic reprogramming. Molecular docking and dynamics simulations demonstrated stable LIQ binding to RANK/RANKL, disrupting their interaction and downstream TRAF2/RIPK signaling, as verified by SPR, CETSA, and Western blot analyses. In vivo experiments confirmed that LIQ able significantly attenuated bone loss in an OVX mouse model. These findings indicate that LIQ inhibits OC formation by binding to RANK/RANKL, suppressing MAPK/NF-κB/PI3K pathway activation, and inducing metabolic reprogramming and apoptosis in OC precursors, supporting its potential as a therapeutic candidate for OP.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117678"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916980","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":"Ginsenoside compound K exerts osteoprotective effects by suppressing osteoclastogenesis and promoting preosteoclast PDGF-BB-induced angiogenesis via targeting CSF1R","authors":"Shuai Chen ,&nbsp;Bizhi Tan ,&nbsp;Shangbin Cui ,&nbsp;Mingbin Zhan ,&nbsp;Yibo Wang ,&nbsp;Fangli Huang ,&nbsp;Tingxuan Wang ,&nbsp;Zemin Ling ,&nbsp;Yuan Zhang ,&nbsp;Junnan Hu ,&nbsp;Wei Guo ,&nbsp;Hao Hu ,&nbsp;Xuenong Zou","doi":"10.1016/j.bcp.2025.117661","DOIUrl":"10.1016/j.bcp.2025.117661","url":null,"abstract":"<div><div>We previously found that oral administration of Panax notoginseng saponins (PNS) alleviated bone loss in ovariectomy(OVX)-induced osteoporotic mice. However, the specific active component responsible for this effect and its underlying mechanism remained unclear. Ginsenoside compound K (CK), one of the main active components of PNS, may serve as a promising therapeutic agent for osteoporosis. This study demonstrated that CK inhibited osteoclastogenesis and promoted type H vessel formation to alleviate bone loss in OVX mice. In vitro, CK concentration-dependently inhibited RANKL-induced osteoclastogenesis. In addition, high concentration CK inhibited the migration and tubule formation of HUVECs. However, treating HUVECs with CK + RANKL-stimulated RAW264.7 conditional medium showed enhancement of migration and tubule formation ability, which was blocked by adding PDGF-BB neutralising-antibody. Proteomics and network pharmacological analysis revealed CK may directly target CSF1R and inhibit osteoclast differentiation via PI3K/AKT/NFκB pathway, which subsequently conformed by drug affinity responsive target stability, cellular thermal shift, surface plasmon resonance and western blot assays. Furthermore, adding macrophage colony-stimulating factor (M−CSF) mitigated the inhibitory effect of CK on osteoclast differentiation and PI3K/AKT/NFκB pathway activation. Taken together, we demonstrated that CK exerts osteoprotective effects by targeting CSF1R to inhibit PI3K/AKT/NFκB pathway, thereby suppressing osteoclastogenesis and promoting preosteoclast PDGF-BB-induced angiogenesis.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117661"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817664","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}