Biomolecules & Therapeutics最新文献

{"title":"A Novel DRD2 Antagonist, SD2-2305, Exerts Anticancer Effects in Colorectal Cancer Cells through G1 Arrest and Caspase-Dependent Apoptosis.","authors":"Na Hyun Kim, Geun Young Cho, In-Tae Kim, You-Jin Choi, Keunwan Park, Kyungsu Kang, Joon-Seok Choi, Sujin Lee","doi":"10.4062/biomolther.2026.111","DOIUrl":"10.4062/biomolther.2026.111","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains difficult to treat due to challenges in early detection and the development of therapeutic resistance. Dopamine receptor D2 (DRD2) plays a critical role in regulating cell proliferation and apoptosis in various solid tumors. Given the relatively high levels of dopamine in the gastrointestinal tract, colorectal tumors may be particularly susceptible to DRD2-mediated signaling. In this study, we evaluated the anticancer activity of a newly synthesized DRD2 antagonist, SD2-2305, and investigated its underlying mechanisms in human CRC cell lines HCT116 and HT-29. SD2-2305 reduced cell viability in a time- and dose-dependent manner. Induction of apoptosis was confirmed by Annexin V/PI staining and immunoblot analysis, with activation of caspase-3, caspase-7, and caspase-9, although no significant changes were observed in the expression of Bcl-2 family proteins. Furthermore, SD2-2305 induced G1 phase cell cycle arrest, accompanied by downregulation of Cyclin A, Cyclin B, CDK1, and CDK2, and upregulation of p21. While key survival pathways (JAK2/STAT3, PI3K/Akt, and MAPK) remained relatively unaffected, SD2-2305 modulated growth factor receptors post-transcriptionally, decreasing HER2/ErbB2 and increasing TGF-beta receptor 1 expression. Collectively, these findings demonstrate that the DRD2 antagonist SD2-2305 exerts potent anticancer effects through the induction of cell cycle arrest and apoptosis, and suggest that the anticancer activity of SD2-2305 is associated with coordinated modulation of growth factor receptor signaling and cell-cycle regulators in CRC cells.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"901-909"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multitargeted Neuroprotective Strategies of Ethyl Pyruvate: From Molecular Mechanisms to Clinical Perspectives in CNS Disorders.","authors":"Seung-Woo Kim, Hong Seok Kim","doi":"10.4062/biomolther.2025.259","DOIUrl":"10.4062/biomolther.2025.259","url":null,"abstract":"<p><p>Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, is a potent neuroprotective compound with diverse properties, including anti-inflammatory, antioxidant, anti-apoptotic, and metabolic regulatory activities. Given the intricate nature of neurological disorders, the multi-target mechanism of action of EP offers significant therapeutic advantages. Preclinical studies across various models of central nervous system (CNS) injury have consistently shown that EP mitigates neuronal loss, preserves blood-brain barrier integrity, and promotes functional recovery. The therapeutic efficacy of EP is attributed to its multifaceted mechanisms of action. It modulates key signaling pathways, such as nuclear factor kappa B (NF-κB) and high mobility group box 1 (HMGB1), activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and provides metabolic support. Specifically, EP suppresses neuroinflammation by preventing HMGB1 release through calcium chelation and by modulating NF-κB signaling via covalent modification of the p65 subunit and stabilization of IκB-α. Furthermore, it enhances endogenous antioxidant defenses by scavenging reactive oxygen species (ROS) and inducing Nrf2 translocation. EP also acts as a bioavailable pyruvate donor, restoring intracellular adenosine triphosphate and nicotinamide adenine dinucleotide levels under ischemic or oxidative stress conditions. Comparative studies with other pyruvate derivatives have highlighted the superior efficacy and safety of EP. Additionally, structural isosteres such as N,N-diisopropyl-2-oxopropanamide (DIPOPA) and N,N-diethyl-2-oxopropanamide (DEOPA) demonstrate even greater neuroprotective potency, primarily through enhanced NF-κB inhibition by suppressing IκB-α degradation. EP is a promising therapeutic candidate for addressing oxidative stress, inflammation, and metabolic dysregulation associated with CNS diseases. However, further research is necessary to optimize the appropriate dosage, evaluate its long-term efficacy, and facilitate its clinical translation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"738-754"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR-Based Metabolic Profiling of Biobank Derived Blood Samples for the Identification of Liver Disease Biomarkers.","authors":"Munki Choo, Chaeyoung Lee, Sunghyouk Park, Hyuk Nam Kwon","doi":"10.4062/biomolther.2026.084","DOIUrl":"10.4062/biomolther.2026.084","url":null,"abstract":"<p><p>Liver disease remains a leading cause of global cancer mortality and predominantly originates from chronic liver cirrhosis. Current surveillance strategies often suffer from suboptimal sensitivity which necessitates the discovery of robust biomarkers for early detection. In this study we utilized blood resources from the National Biobank of Korea to evaluate the diagnostic potential of Nuclear Magnetic Resonance spectroscopy-based metabolomics in patients with cirrhosis and liver cancer. We aimed to identify specific biomarkers and investigate their correlation with clinical blood parameters by comparing the metabolic profiles of disease and healthy control groups. Multivariate statistical analysis demonstrated significant metabolic distinctions between liver disease patients and healthy controls. While the models successfully differentiated disease states the global metabolic landscape exhibited an overlap between cirrhosis and cancer groups suggesting a shared pathological background driven by systemic metabolic shifts. Quantitative assessment identified specific metabolic alterations characterizing the disease progression. We observed a marked accumulation of lactate and phenylalanine reflecting the Warburg effect and impaired hepatic hydroxylation capacity. Conversely branched chain amino acids specifically valine and isoleucine were significantly depleted in the disease groups indicating systemic metabolic stress. Receiver operating characteristic analysis revealed that a combinatorial biomarker panel yielded superior diagnostic accuracy compared to single markers. Furthermore, the validity of our metabolic profiling was corroborated by a strong correlation between the values predicted from metabolic profiles and clinically measured physiological parameters. Overall, our findings confirm the feasibility of utilizing retrospective biobank resources for high resolution metabolic phenotyping.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"922-932"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Shogaol Complements Levodopa Therapy by Modulating Brain-Gut Metabolomes in a Parkinson's Disease Model.","authors":"Jin Hee Kim, Seungmin Lee, Yujin Choi, Choong Hwan Lee, Myung Sook Oh","doi":"10.4062/biomolther.2026.053","DOIUrl":"10.4062/biomolther.2026.053","url":null,"abstract":"<p><p>Levodopa remains the primary therapy for Parkinson's disease (PD); however, its benefits are largely confined to motor symptom relief, without altering disease progression. Growing evidence implicates the gut-brain axis in PD, linking gastrointestinal dysfunction and microbial shifts to neuronal cell death. Gut-brain metabolomics is critical for clarifying these interactions and guiding adjunct strategies to enhance intestinal motility and neuroprotection beyond levodopa. Therefore, this study aimed to characterize gut and brain metabolomic alterations induced by levodopa and to evaluate whether co-administration with 6-shogaol, previously identified as a gut-brain axis modulator, modifies these changes in relation to motor and gastrointestinal functions. Male C57BL/6 mice were assigned to normal, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid, levodopa, or 6-shogaol+levodopa groups. PD was induced by repeated MPTP/probenecid injections, and 6-shogaol was administered orally with levodopa. Motor performance, gut motility, dopamine levels in the brain, and metabolomic profiles were subsequently assessed. Levodopa improved motor deficits in the MPTP/probenecid model, while 6-shogaol co-administration preserved these benefits and additionally restored gastrointestinal motility, a non-motor feature unresponsive to levodopa alone. The combination further increased striatal dopamine and levodopa levels, suggesting enhanced dopaminergic availability. Metabolomic profiling revealed distinct brain-gut signatures, including alterations in energy, lipid, and amino acid pathways, with specific metabolites linked to motor function, dopamine regulation, and gut activity. These findings suggest that 6-shogaol complements levodopa by modulating brain-gut metabolomic networks to improve motor and non-motor features of PD.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"855-865"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin Protects the Dopaminergic Neurons from MPTP-Mediated Injury by Inducing BDNF via PPARα Activation.","authors":"Ganesh Bohara, Nikesh Rimal, Shristi Khanal, Pil-Hoon Park, Dong-Young Choi","doi":"10.4062/biomolther.2026.026","DOIUrl":"10.4062/biomolther.2026.026","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disease characterized by preferential loss of the dopaminergic neurons in the nigrostriatal pathway. The specific molecular mechanisms for the neuronal loss remain unclear, and no cure currently exists. BDNF is a neurotrophic factor that restores the dopaminergic neurons in variant PD models. Emerging evidence suggests that simvastatin could upregulate BDNF in the brain. This study aimed to assess the neuroprotective effect of simvastatin and delineate its action mechanism. We found that simvastatin rescued the SH-SY5Y cells from MPP⁺ toxicity at 10 nM by upregulating BDNF and activating its downstream signaling pathways, and the protective action was significantly counteracted by BDNF siRNA or TrkB antagonist (K252a). Importantly, simvastatin upregulated BDNF via peroxisome proliferator-activated receptor alpha (PPARα) activation, as silencing the PPARα gene decreased the simvastatin-mediated BDNF upregulation and the cell viability upon exposure to MPP⁺. Next, we evaluated its neuroprotective effects in the PD animal model mediated by MPTP. Pretreatment with simvastatin for 2 weeks attenuated the MPTP-caused loss of the nigrostriatal dopaminergic neurons as determined by immunohistochemical staining for tyrosine hydroxylase. In parallel with the results, simvastatin ameliorated the decrease in the striatal dopamine level and behavioral impairment elicited by the neurotoxicant. Consistent with the <i>in vitro</i> study, simvastatin upregulated BDNF expression and restored the BDNF level in the MPTP-treated striatonigral regions. These findings suggest that simvastatin's neuroprotection may be linked to the upregulation of BDNF via activation of PPARα, and it could be a possible therapeutic intervention for the treatment of PD.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"841-854"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-Based Strategies for Addressing Cancer- and Treatment-Related Cognitive Impairment: A Review.","authors":"Suqin Wu, Yan Li, Xue Yan Wang, Huifeng Ye","doi":"10.4062/biomolther.2026.005","DOIUrl":"10.4062/biomolther.2026.005","url":null,"abstract":"<p><p>Cancer-related cognitive impairment (CRCI) has become a notable long-term consequence for cancer survivors, especially among those receiving chemotherapy, radiotherapy, or targeted treatments. Despite the advances in the treatment of cancer, CRCI still disrupts the quality of life of patients, daily activities, and work performance, as well as emotional well-being. This review provides a summary of the existing information on the neurobiological basis of CRCI, including neuroinflammation, disturbed neuroplasticity, oxidative stress, and tumour-related factors. It analyses diagnostic methods, from cognitive screening to high-level neuroimaging, and reviews evidence-based interventions that play a significant role in providing highly disciplined, personalized care. The ongoing constraints on advancing machine learning-based CRCI interventions include persistent obstacles, a lack of long-term trials, and difficulties accessing data and achieving interpretability, among others. Other important risk factors are also identified in this review, as are the performance of different predictive models with respect to accuracy, generalization ability, and clinical utility. Moreover, it addresses the challenges of validating these models and biomarkers across different populations, as well as the need for further studies to enhance their validity and enable personalized interventions.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"764-779"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV4 Activation Promotes Hair Growth via TSLP Signaling in the Skin.","authors":"Wook-Joo Lee, Won-Sik Shim","doi":"10.4062/biomolther.2026.080","DOIUrl":"10.4062/biomolther.2026.080","url":null,"abstract":"<p><p>Hair follicle cycling is regulated by complex signaling networks that coordinate stem cell activation and quiescence. Although transient receptor potential vanilloid 4 (TRPV4) is expressed in the skin and implicated in cutaneous physiology, its role in hair growth remains unclear. Here, we investigated the contribution of TRPV4 activation to hair growth and its relationship with thymic stromal lymphopoietin (TSLP). Pharmacological activation of TRPV4 using GSK1016790A significantly promoted hair regrowth and elongation in mice, whereas TRPV4 inhibition attenuated these effects. Consistently, <i>Trpv4⁻^/⁻</i> mice exhibited spontaneous hair loss, supporting a role for TRPV4 in maintaining hair homeostasis. TRPV4 activation increased TSLP production in the skin, and exogenous TSLP recapitulated the pro-growth effects of TRPV4 activation. These effects were suppressed by pharmacological blockade of the TSLP receptor, indicating TSLP-dependent signaling. Notably, TSLP restored hair growth in <i>Trpv4⁻^/⁻</i> mice, whereas TRPV4 activation did not, supporting the notion that TSLP acts downstream of TRPV4. In contrast, activation of TRPV3, another TRP channel abundantly expressed in the skin, did not significantly affect hair growth, highlighting the specific role of TRPV4 in this process. Overall, these findings identify a TRPV4-TSLP signaling axis that promotes hair growth and regulates hair follicle function, suggesting a potential therapeutic target for hair loss disorders.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"942-952"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin Signaling at the Crossroads of Obesity, Immunity, and Cancer: Mechanistic Insights and Therapeutic Implications.","authors":"Gitima Deka, Pil-Hoon Park","doi":"10.4062/biomolther.2026.100","DOIUrl":"10.4062/biomolther.2026.100","url":null,"abstract":"<p><p>Leptin, an adipokine predominantly secreted by adipose tissue, has exhibited a wide range of biological functions, including regulation of energy balance, appetite, and metabolism. Accumulating evidence has demonstrated that leptin also plays a role in obesity-associated tumor progression. Elevated circulating leptin levels in obese individuals, together with the close association between obesity and increased cancer risk, have led to growing interest in leptin as a potential mediator linking adiposity to tumor growth and immune dysregulation. Recent studies have shown that leptin can directly interact with immune cells within the tumor microenvironment and promote dysfunction or exhaustion in various immune cell populations, thereby impairing anti-tumor immunity. These findings suggest that tumor-promoting effects of leptin may be mediated, at least in part, through modulation of anti-tumor immune responses. Notably, metabolic reprogramming of both immune cells and cancer cells appears to be a critical mechanism underlying leptin-mediated tumor progression and immune dysfunction. Since obesity is characterized by altered adipokine production, chronic low-grade inflammation, and immune dysregulation, leptin may serve as a critical mediator linking excess adiposity to impaired immune surveillance and cancer progression. However, the biological effects of leptin are highly context-dependent. Although leptin predominantly supports tumor progression and immune suppression in many obesity-associated cancers, it may also exert immune-stimulatory or anti-tumor effects under specific conditions. This review summarizes current mechanistic insights into the role of leptin in tumor progression and immune regulation. We also highlight therapeutic strategies that integrate leptin-targeted approaches with immunotherapy.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"780-799"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.","authors":"Jisun Kim, Young-Jin Yu, Hyun-Kyoung Kim, Ahsan Ullah, Mehedi Hasan Bappi, Hyun Joo Shim, JaeHoon Cheong, Nicole Bon Compomayor, Hee Jin Kim, Han-Jung Chae","doi":"10.4062/biomolther.2025.160","DOIUrl":"10.4062/biomolther.2025.160","url":null,"abstract":"<p><p>Sleep disruption is associated with increased risks of metabolic, cardiovascular, and neuropsychiatric disorders. Cannabidiol (CBD) and L-theanine have attracted attention as potential sleep-supporting agents due to their neuroactive properties. This study investigated the individual and combined effects of CBD and L-theanine in a caffeine-induced sleep disturbance mouse model using behavioral assessments and neurochemical analyses. Mice were orally administered CBD and L-theanine at ratios of 1:1, 2:1, or 1:2 prior to pentobarbital-induced sleep testing. Co-administration significantly reduced sleep onset latency and increase total sleep duration compared with single treatments under sleep-disturbed conditions. Combination index analysis indicated a synergistic interaction at lower doses, whereas such interaction was not observed at higher doses under normal conditions. To further characterize associated neurochemical changes, serum serotonin and melatonin levels, as well as cortical gamma-aminobutyric acid (GABA), were measured using enzyme-linked immunosorbent assay. CBD increased serotonin levels in a dose-dependent manner, while L-theanine elevated serotonin at lower doses. Combination treatment was associated with increased serotonin and melatonin levels which rose by more than 40% relative to the caffeine-treated group. Cortical GABA levels were also elevated following combination treatment. Collectively, these findings indicate that co-administration of CBD and L-theanine improves sleep-related outcomes and is associated with neurochemical changes, although the precise mechanisms remain to be determined. This study suggests the potential of CBD and L-theanine co-administration as an alternative approach for managing stimulant-induced sleep disturbances.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"830-840"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoschaftoside Inhibits Osteoclastogenesis by Suppressing the NF-κB and MAPK Pathways.","authors":"Jangmi Yun, Ki Yong Lee, Byoungduck Park","doi":"10.4062/biomolther.2025.271","DOIUrl":"10.4062/biomolther.2025.271","url":null,"abstract":"<p><p>Bone remodeling is regulated by the equilibrium between bone formation and resorption. However, excessive bone resorption by osteoclasts disrupts bone homeostasis and contributes to several bone-related disorders. Hematopoietic lineage cells differentiate into multinucleated osteoclasts through osteoclastogenesis, a process driven by M-CSF and RANKL. Multiple signaling pathways are involved in osteoclast maturation. RANKL-induced activation of NF-κB has been recognized as a crucial mechanism in osteoclast differentiation. Additionally, MAPK signaling activated by RANKL plays a significant role in this process. The stimulation of NF-κB and MAPK by RANKL enhances the transcription of numerous genes associated with osteoclastogenesis. Isoschaftoside (ISH), a C-glycosyl flavonoid, can be isolated from <i>Viola yedoensis</i>. The herb <i>Viola yedoensis</i> has traditionally been used to manage inflammation-related diseases, and its crude extracts have demonstrated pharmacological effects. Nonetheless, the influence of ISH on osteoclastogenesis has not been documented previously. In this study, we explored the effect of ISH on osteoclastogenesis. Our findings indicate that ISH attenuates RANKL-induced activation of NF-κB and MAPK; moreover, ISH inhibits osteoclastogenesis and bone resorption stimulated by RANKL and M-CSF.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"933-941"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}