Drug Design, Development and Therapy最新文献

{"title":"Therapeutic Potential of Flavonoids and Flavonoid-Rich Compounds in Irritable Bowel Syndrome.","authors":"Yuan Xia, Chang Liang, Hesheng Luo, Yan Zhang","doi":"10.2147/DDDT.S515004","DOIUrl":"10.2147/DDDT.S515004","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is a group of functional gastrointestinal disorders, characterized by impaired brain-gut axis (BGA) interactions, leading to symptoms such as abdominal pain, bloating, and discomfort, which significantly affect patients' quality of life. Although individuals with IBS are commonly treated with medications and lifestyle modifications, the side effects of various treatments and their inconsistent efficacy often leads to a recurrence that poses a significant burden for patients. Flavonoids, flavonoid-rich compounds extensively found in plants and known for their low toxicity, have been identified as potentially beneficial for various digestive disorders in recent years; however, clinical trials have not been widely conducted. It was suggested that flavonoids and flavonoid-rich compounds may positively influence IBS symptoms through regulation of low-grade inflammation, oxidative stress in the gut, visceral hypersensitivity (VH), intestinal motility dysfunction, dysbiosis of gut microbiome, and BGA. This article reviews the potential role of flavonoids and their compounds in the therapy of IBS, along with the associated mechanisms. Additionally, we highlight key issues that warrant further investigation and discuss the prospects and challenges of using flavonoids for managing IBS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4895-4910"},"PeriodicalIF":4.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study.","authors":"Shuang Liu, Qingsong Liu, Ronger Gu, Mian Wu, Shuo Meng, Le Yan, Qi Chen, Cuiling Zhu, Si Chen, Bei Xu, Fengjing Liu, Haibing Chen","doi":"10.2147/DDDT.S522154","DOIUrl":"10.2147/DDDT.S522154","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia (HUA) has been linked to an elevated risk of impaired glucose metabolism. This study aimed to investigated the impact of the urate-lowering drug febuxostat on blood glucose levels, insulin sensitivity, and β-cell function in subjects with HUA who present with normoglycemia, prediabetes, or newly diagnosed type 2 diabetes (T2DM).</p><p><strong>Methods: </strong>We assessed the glucose metabolism of participants with HUA using a 3-h oral glucose tolerance test (OGTT). Participants were categorized into two groups: those with HUA and normal glucose metabolism (NGM, n=28), and those with HUA and abnormal glucose metabolism (AbGM, n=32), including prediabetes (n=20) and newly diagnosed T2DM (n=12). Both groups received a daily dose of 40 mg febuxostat for 24 consecutive weeks and underwent 3-h OGTT at 12 and 24 weeks. Glucose, insulin, and C-peptide were measured to calculate insulin sensitivity (Stumvoll index, Gutt index) and β-cell function (Insulin Secretion-Sensitivity Index-2 and Disposition Index) indices. Differences in glucose levels and indices were analyzed by repeated measures ANOVA including interaction terms between groups and the time of visit.</p><p><strong>Results: </strong>After 24 weeks of febuxostat treatment, subjects with HUA and AbGM showed significant reductions in postprandial 1-h (11.88±1.39mmol/L at baseline, 10.97±2.74mmol/L at 12 weeks, and 11.12±1.92mmol/L at 24 weeks, Ptime=0.031) and 2-h glucose (10.25±1.71mmol/L at baseline, 9.39±2.77mmol/L at 12 weeks, and 9.16±2.67mmol/L at 24 weeks, Ptime=0.014). Febuxostat significantly improved insulin sensitivity of subjects in the AbGM group, but did not affect β-cell function. Moreover, the improvement in insulin sensitivity in these subjects was not directly correlated with the improvement in uric acid. No significant changes were observed in subjects with NGM.</p><p><strong>Conclusion: </strong>In subjects with HUA and prediabetes or newly diagnosed T2DM, febuxostat significantly enhanced postprandial glucose and insulin sensitivity, though it did not notably improve β-cell function. Further research is required to explore how febuxostat enhances insulin sensitivity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4875-4884"},"PeriodicalIF":4.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Menopausal Hormone Therapy to Chinese Patients with Menopausal Syndrome: A Real-World Retrospective Study from Chinese Hospitals.","authors":"Zhenling Zhu, Aiping Shi, Lanhua Liu, Guixiu Jin, Xianli Wang","doi":"10.2147/DDDT.S517420","DOIUrl":"10.2147/DDDT.S517420","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate and analyse the changing trends in the use of menopausal hormone therapy (MHT) for patients with menopausal syndrome (MPS) in hospitals in nine Chinese cities from 2019 to 2023 and to provide an evidence base for the rational clinical use of MHT.</p><p><strong>Methods: </strong>Data on the use of MHT by patients with menopausal syndrome were collected and a trend analysis was conducted, including trends in the number of prescriptions, patient age, total prescription amount, average prescription amount, defined daily doses (DDDs), defined daily cost (DDC), and drug rank ratio (B/A).</p><p><strong>Results: </strong>From 2019 to 2023, the prescriptions of MPS patient were concentrated in East China and North China, with an average age of 48.22±5.94 years. In a span of five years, the number of prescriptions increased by 86.08%, the total prescription amount increased by 126.58%, and the average prescription amount increased by 21.76%. The B/A ratios for estradiol/estradiol dydrogesterone and tibolone were both determined to be 1, thus indicating that the sales amounts and DDDs of these two drugs were in good agreement and that the drug costs are reasonable.</p><p><strong>Conclusion: </strong>From 2019 to 2023, the number of MPS patients and the total number of treatment drug prescriptions in nine cities throughout the country demonstrated an increasing trend. The estradiol/estradiol dydrogesterone and tibolone were the main sex hormone drugs that were used to treat MPS. The state's abolition of the drug price addition policy and the organization of centralized drug procurement in some areas had alleviated the financial burdens on patients to a certain extent.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4861-4873"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese Medicine and Ferroptosis in Intracerebral Hemorrhage: A Potential Therapeutic Approach.","authors":"Hanying Xu, Jing Lu, Xiaolei Tang, Pengfei Li, Lei Wu, Jian Wang, Ying Zhang, Dongmei Zhang","doi":"10.2147/DDDT.S513343","DOIUrl":"10.2147/DDDT.S513343","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a severe cerebrovascular disorder associated with high morbidity and mortality. Ferroptosis, a regulated form of cell death characterized by iron accumulation and lipid peroxidation, plays a critical role in secondary injury following ICH. Traditional Chinese Medicine (TCM) has demonstrated distinct therapeutic benefits in cerebrovascular disease, and emerging evidence suggests its potential to modulate ferroptosis. This review explores the therapeutic effects of TCM and TCM-based interventions for ICH, with a focus on their regulation of ferroptosis-related mechanisms. In ICH, ferroptosis is driven by disrupted iron metabolism, lipid peroxidation, oxidative stress, and neuroinflammation-key contributors to secondary brain injury. TCM interventions, including herbal medicines, active compounds, and acupuncture, may counteract these processes by restoring iron homeostasis and reducing oxidative stress, thereby improving neurological outcomes. Given the critical role of ferroptosis in ICH pathophysiology, TCM represents a promising avenue for targeting ferroptosis-related pathways and advancing therapeutic strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4789-4808"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Mechanism of 2'-Hydroxychalcone Improving Copper Sulfate-Induced Inflammation in Zebrafish Through Network Pharmacology.","authors":"YuZhou Shen, Yan Dong Yao, Haili Li, Qian Zhang, Cheng Lin Wang, Li Hu, Ying Chun Hu, Mu Hu Chen","doi":"10.2147/DDDT.S510195","DOIUrl":"10.2147/DDDT.S510195","url":null,"abstract":"<p><strong>Introduction: </strong>2'-Hydroxychalcone is universally acknowledged as a Chinese medicine monomer featured by aromatic properties, exhibiting anti-inflammatory and antioxidant effects. As a consequence, the study emphasis was placed on the anti-inflammatory, anti-oxidative and exercise capacity reinforcement effects of 2'-Hydroxychalcone on <i>Danio rerio</i> young fish under the action of CuSO4. Simultaneously, research endeavors were made to delve into how functional changes of target affect the inflammation and exercise capacity of <i>Danio rerio</i> young fish.</p><p><strong>Methods: </strong>Upon mating breeding, mature transgenic zebrafish and type AB zebrafish expressing red fluorescent macrophages T g (mpeg1:m Cherry) were cultured for 72 h and exposed to 12.5, 6.25, 3.14 and 0uM 2'-Hydroxychalcone, respectively, for three hours of pretreatment, which were subsequently incubated in CuSO4 at 20uM concentration for 12 h. A diverse array of test indexes was hereby utilized, encompassing the migration of red fluorescent-labeled macrophages, levels of inflammatory cytokines, zebrafish behavioral motility, and gene expression patterns correlated with oxidative stress and mitochondrial biogenesis, to assess the drugs' efficacy in alleviating inflammation.</p><p><strong>Results: </strong>2'-Hydroxychalcone anti-inflammatory target protein was found by adopting the bioinformatics method. Its effect on zebrafish behavior ability and the change trend of oxidative stress index were explored by changing the functional state of the target, such as changing the functional activity of the target by micro-injection technology. As indicated by the results, 2'-Hydroxychalcone could hinder the migration of macrophages and the mitochondrial function of CuSO4. Apart from that, 2'-Hydroxychalcone could lessen the level of inflammatory factors and oxidative stress. In addition, 2'-Hydroxychalcone conspicuously hindered the expression of interleukin-1β and interleukin-TNF-α, and lowered the expression of COX2. An augment in the levels of the target protein TRPV1 was observed during inflammation.</p><p><strong>Discussion: </strong>The experimental findings validated the anti-inflammatory and anti-oxidant activities of 2'-Hydroxychalcone and preliminarily confirmed the effect of the target on the behavior and oxidative stress level of zebrafish.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4809-4834"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jingfang Granules for Diabetic Wound Healing: Insights from Network Pharmacology and Experimental Validation.","authors":"Rongrong Wang, Qian Wang, Mingfei Liu, He Xiao, Guimin Zhang, Jingchun Yao, Ming Liu","doi":"10.2147/DDDT.S516298","DOIUrl":"10.2147/DDDT.S516298","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wounds are one of the most common complications of diabetes mellitus. Jingfang Granules (JFG), a combination of 11 herbs, has been clinically used for treating colds and the flu and for preventing various skin diseases.</p><p><strong>Purpose: </strong>The present study was designed to evaluate the therapeutic effect of JFG on diabetic wounds and to elucidate the associated mechanisms.</p><p><strong>Methods: </strong>JFG serum was prepared using Sprague-Dawley rats and the phytochemicals of JFG in the serum were identified using UHPLC-ESI-QE-Orbitrap-MS. A cell viability assay and cellular angiogenesis methods were performed to evaluate wound healing in vitro. Diabetic wounds were developed using streptozotocin-induced diabetic rats to investigate the efficacy of JFG on diabetic wounds in vivo. Network pharmacology analysis, molecular docking, and Western blot were performed to elucidate the potential mechanisms of JFG in diabetic wound healing.</p><p><strong>Results: </strong>JFG serum attenuated H₂O₂-induced and high glucose-induced oxidative damage, significantly reduced lipopolysaccharide-induced upregulation of inflammatory cytokines, and promoted angiogenesis in vitro. In diabetic rats, JFG effectively promoted wound healing, reduced blood glucose and lipid levels, and alleviated oxidative stress and inflammation. A total of 56 phytochemicals were identified in the JFG serum. Six core targets (AKT1, EGFR, MAPK3, MAPK1, IL6, and TNF) and the PI3K-AKT and MAPK signaling pathways were identified by network pharmacology analysis, which were further validated by subsequent experimental methods.</p><p><strong>Conclusion: </strong>JFG could accelerate diabetic wound healing by alleviating oxidative damage, suppressing inflammation, promoting angiogenesis, and regulating metabolic abnormalities, with involvement of the PI3K-AKT and MAPK signaling pathways.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4835-4860"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Pharmacodynamics with Enterohepatic Recirculation of Co-Medication of Rosuvastatin and Ezetimibe.","authors":"Hyungmi An, Dongseong Shin","doi":"10.2147/DDDT.S522863","DOIUrl":"10.2147/DDDT.S522863","url":null,"abstract":"<p><strong>Objective: </strong>Combination therapy with rosuvastatin and ezetimibe is generally administered to patients with high cardiovascular risk. The objective of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the interaction between rosuvastatin and ezetimibe that incorporates enterohepatic recirculation (EHC).</p><p><strong>Methods: </strong>Concentration-time data were obtained from a two-part, open-label, multiple-dose crossover, drug interaction study. In total, 50 healthy male subjects received both monotherapy and co-therapy (Part A: rosuvastatin and co-therapy; Part B: ezetimibe and co-therapy). Rosuvastatin (20 mg) or ezetimibe (10 mg) were administered once daily for 7 days as monotherapy or co-therapy. Plasma concentrations were measured for PK analysis until 72 h post-dose at steady state. The changes in low-density lipoprotein cholesterol (LDL-C) levels from baseline to steady state at 24 h after the last administration were measured. A population PK/PD model incorporating EHC was developed using Monolix 2024R1. Covariate effects were explored, and the final model was evaluated through goodness-of-fit diagnostics and visual predictive checks. Model-based simulations were conducted to compare the LDL-C lowering effects of monotherapy and co-therapy.</p><p><strong>Results: </strong>A population PK/PD model was established using a two-compartment model for rosuvastatin and a four-compartment model for ezetimibe incorporating EHC via intermittent gallbladder emptying. No significant PK interaction was observed. An indirect response PD model reflected the independent LDL-C lowering effects of both drugs. Simulations showed LDL-C reductions of -51.0% (rosuvastatin), -25.3% (ezetimibe), and -60.7% (co-therapy), supporting the additive efficacy of co-therapy. EHC increased the exposure of total ezetimibe with limited LDL-C lowering effects.</p><p><strong>Conclusion: </strong>The overall PK interaction between rosuvastatin and total ezetimibe was not significant. The developed PK/PD model incorporating EHC successfully described the independent LDL-C lowering effects. These findings support the additive benefit of co-therapy of rosuvastatin and ezetimibe and may guide future research toward personalized lipid-lowering strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4777-4787"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Liposomal Bupivacaine and Ropivacaine in Serratus Anterior Plane Block for Thoracoscopic Lobectomy: A Randomized Controlled Trial.","authors":"Yang Zhang, Wei Li, Aiping Wei, Shibiao Chen, Xiuhong Wang","doi":"10.2147/DDDT.S513287","DOIUrl":"10.2147/DDDT.S513287","url":null,"abstract":"<p><strong>Background: </strong>The optimal analgesic regimen after video-assisted thoracoscopic surgery (VATS) is unclear. We aimed to examine whether ultrasound-guided serratus anterior plane block (SAPB) with liposomal bupivacaine could provide continuous and effective analgesic effects for lung cancer patients undergoing VATS.</p><p><strong>Methods: </strong>A total of 64 patients were randomly allocated to receive either the liposomal bupivacaine (LB group) or the ropivacaine (RO group). The primary outcome was pain score at rest and on movement in the first three days after surgery. The secondary outcomes included intraoperative remifentanil consumption, perioperative consumption of sufentanil and flurbiprofen axetil, time to extubation, time to first bowel movement, time to first flatus, incidence of postoperative nausea and vomiting (PONV), length of intensive care unit (ICU) stay, length of hospital stay, hospitalization costs, and early recovery quality as assessed by QoR-15 score.</p><p><strong>Results: </strong>The LB group had significantly lower pain scores at rest and on movement at 12h, 24h, 36h, 48h, and 72h after surgery, and lower pain scores on movement at 8h after surgery, when compared with the RO group. Perioperative sufentanil consumption and postoperative flurbiprofen axetil consumption were significantly reduced in the LB group than in the RO group. In addition, compared with the RO group, the LB group had earlier first flatus, mobilization, and urinary catheter removal, shorter ICU stay, lower incidence of PONV, and lower hospitalization costs. The QoR-15 scores in the first three days after surgery were significantly higher in the LB group than in the RO group. There were no statistically significant differences between the two groups regarding time to extubation, intraoperative remifentanil consumption, and length of hospital stay.</p><p><strong>Conclusion: </strong>Ultrasound-guided SAPB with liposomal bupivacaine was effective in relieving postoperative pain for three days after surgery in patients undergoing VATS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4717-4726"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lobetyolin Suppressed Osteoclastogenesis and Alleviated Bone Loss in Ovariectomy-Induced Osteoporosis via Hindering p50/p65 Nuclear Translocation and Downstream NFATc1/c-Fos Expression.","authors":"Chunmei Xiu, Hua Luo, Weixing Huang, Shaohua Fan, Chiting Yuan, Jiangjie Chen, Chenghao Xu, Can Yao, Dun Hong, Liwei Zhang","doi":"10.2147/DDDT.S515930","DOIUrl":"10.2147/DDDT.S515930","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the therapeutic potential of lobetyolin (LBT), a bioactive compound derived from <i>Codonopsis pilosula</i>, against bone loss in postmenopausal osteoporosis (PMOP).</p><p><strong>Methods: </strong>To investigate the therapeutic potential of LBT in osteoporosis, a multifaceted approach involving network pharmacology and molecular docking was employed to identify relevant targets and elucidate mechanisms of action. In vitro experiments evaluated LBT's impact on osteoclastogenesis, bone resorption, and osteoblast differentiation using bone marrow macrophages (BMMs) and bone marrow mesenchymal stromal cells (BMSCs). The inhibition of RANKL-activated NF-κB signaling and downstream NFATc1/c-Fos pathways was analyzed via Western blot and immunofluorescence. Additionally, an in vivo ovariectomy (OVX)-induced osteoporosis mouse model was utilized to examine the effects of LBT on bone architecture, assessed through micro-CT imaging and histological analyses.</p><p><strong>Results: </strong>LBT effectively suppressed RANKL-driven osteoclast differentiation in vitro without cytotoxic effects, reducing osteoclast numbers, size, and resorptive function. It also downregulated osteoclast-specific genes expressions, inhibited ROS production, and disrupted the NF-κB signaling cascade by blocking p50/p65 nuclear translocation. Moreover, LBT mitigated LPS-induced osteogenic impairment, enhancing osteoblast differentiation and mineralization. In the OVX mouse model, LBT treatment improved bone microstructure. Histological analyses further corroborated LBT's role in reducing osteoclast activity and promoting bone formation.</p><p><strong>Conclusion: </strong>LBT exerts a dual effect on bone remodeling, simultaneously inhibiting osteoclast-mediated bone resorption and promoting osteoblast-driven bone formation. By targeting key pathways such as NF-κB/NFATc1/c-Fos and reducing inflammatory responses, LBT emerges as a potential therapeutic agent for managing PMOP and other conditions associated with excessive bone loss, offering a safer alternative to current treatments.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4689-4715"},"PeriodicalIF":4.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Sheng-Jiang Powder</i> Alleviates Th17/Treg Immune Imbalance of Experimental Autoimmune Encephalomyelitis by Regulating the Fatty Acids Metabolism.","authors":"Lulu Wu, Haoyou Xu, Hui Xia, Lilin Peng, Lulu Qin, Qian Gong, Min Zhao, Zhibing Wu, Yuanqi Zhao, Zequan Zheng","doi":"10.2147/DDDT.S510620","DOIUrl":"10.2147/DDDT.S510620","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is one of the leading causes of disability among young people, and the immune imbalance between T helper cell 17 (Th17) and regulatory T cells (Tregs) plays a crucial role in its pathogenesis. Currently, MS treatment relies significantly on immunosuppressive drugs or glucocorticoids, which often have side effects and limitations in efficacy. Sheng-Jiang powder (SJP), a traditional Chinese medicine formula, has demonstrated anti-inflammatory effects and may offer a novel therapeutic option for MS.</p><p><strong>Aim: </strong>This study aimed to investigate the therapeutic efficacy and underlying mechanism of SJP in myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) mice.</p><p><strong>Methods: </strong>The efficacy of SJP was assessed using the MOG35-55-induced EAE model. Disease severity was monitored based on the clinical symptoms, body weight, and pathological damage. Furthermore, Th17/Treg balance in the peripheral and central immune systems was assessed. Metabolomic analysis was performed to detect differential metabolites in serum, and the effects of fatty acids on the lipoxygenase (LOX) metabolic pathway were investigated.</p><p><strong>Results: </strong>SJP alleviated MOG35-55-induced EAE symptoms and histological damage, restored the peripheral Th17/Treg immune balance, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. SJP intervention also influenced omega-3 polyunsaturated fatty acid (PUFA) metabolism and absorption in EAE mice, promoting an anti-inflammatory process associated with 12/15-lipoxygenase(12/15-LOX) upregulation and 5-lipoxygenase(5-LOX) downregulation.</p><p><strong>Conclusion: </strong>This study suggests that SJP is a viable treatment option for MS, and traditional Chinese medicine therapies for autoimmune diseases will continue to be developed.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4755-4776"},"PeriodicalIF":4.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}