Yang Li, Yin Peng, Guangning Nie, Fangping Cheng, Yuling Zhou, Jian Liu, Hongyan Yang
{"title":"Huyang Yangkun Formula Enhances Ovarian Function and Delays Reproductive Aging by Influencing Hypothalamic GnRH/LH Pulse Release Through GAT-1/GABA/GABAAR2.","authors":"Yang Li, Yin Peng, Guangning Nie, Fangping Cheng, Yuling Zhou, Jian Liu, Hongyan Yang","doi":"10.2147/DDDT.S504610","DOIUrl":"https://doi.org/10.2147/DDDT.S504610","url":null,"abstract":"<p><strong>Background: </strong>Huyang Yangkun Formula (HYF), based on Yin and Yang principles, is effective in treating Premature Ovarian Insufficiency (POI) and enhancing reproduction, but its mechanism needs to be clarified.</p><p><strong>Aim: </strong>This study investigates HYF's impact on enhancing ovarian follicles development via GABA/GnRH neuron regulation.</p><p><strong>Materials and methods: </strong>The chemical components of water extract of HYF were analyzed by combining the ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrum analysis (UHPLC-QE-MS). Female SD rats received HYF for 90 days to assess changes in the ovarian function. In addition, female SD rats underwent ovariectomy to evaluated the impact of HYF or GABA treatments on LH release induced by E2 to address age-related neuroendocrine damage. Reproductive neuroendocrine markers were analyzed through immunohistochemistry and immunofluorescence.</p><p><strong>Results: </strong>HYF treatment improved the disrupted estrous cycle in aged female rats, breaking the continuous keratinized epithelial cell state and alternating between estrous periods. Aging reduces ovarian volume and follicle numbers, but after 3 months of HYF treatment, ovarian follicle development increased, and mature follicle and luteum numbers changed significantly. HYF improved sex hormone levels, advancing and enhancing the LH peak in older rats, thus boosting total 24-hour LH release. GABA injection into the lateral ventricle increased GnRH release in aging rats, highlighting GABA's excitatory role. HYF also increased GnRH secretion by reducing GAT-1, leading to more GABA release, which activates GABAAR2 receptors in GnRH neurons, enhancing their function in the hypothalamic arcuate nucleus of elderly rats.</p><p><strong>Conclusion: </strong>HYF shows promise as a treatment for improving ovarian and reproductive neuroendocrine function in early reproductive aging, providing insights into its effects on hypothalamic GnRH/LH pulse release via the GAT-1/GABA/GABAAR2/GnRH pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2677-2691"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981370","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}
Weisen Fan, Fengting Zhai, Zheng Yuan, Guotao Hu, Li Wang
{"title":"The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis.","authors":"Weisen Fan, Fengting Zhai, Zheng Yuan, Guotao Hu, Li Wang","doi":"10.2147/DDDT.S500129","DOIUrl":"https://doi.org/10.2147/DDDT.S500129","url":null,"abstract":"<p><strong>Introduction: </strong>In traditional Chinese medicine texts, Xuanyu Tongjing Decoction (XYTJD) is a prescribed remedy for premenstrual belly pain and dysmenorrhea. It is currently routinely used to treat ovarian endometriosis (OEM) with good outcomes.</p><p><strong>Aim: </strong>In order to investigate the underlying processes of Xuanyu Tongjing Decoction in treating OEM inflammation and reducing ovarian damage.</p><p><strong>Methods: </strong>We created a rat model of OEM and carried out transcriptome sequencing. Batch molecular docking technique in conjunction with Ultra-high-performance liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry was used to screen the main active components in Xuanyu Tongjing Decoction.</p><p><strong>Results: </strong>The ectopic cyst was firmly attached to the ovary in our successfully created rat model of ovarian endometriosis. According to GSEA enrichment study, XYTJD may up-regulate pathways linked to oocyte formation in ovarian tissues and down-regulate immunological and inflammatory pathways in ectopic tissues. Rat ectopic tissues and human ectopic tissues showed a similar pattern in the expression of the NOD/NFκB pathway during the proliferative phase. In ectopic tissues of rats, XYTJD may down-regulate the NOD/NFκB pathway and suppress the expression of TNF-α and IL-1β, which are downstream inflammatory factors in this pathway. In addition, XYTJD may restore the down-regulation of cAMP/PI3K/AKT and lower the expression of apoptotic factor CASP9, endoplasmic reticulum stress protein SEC61B and antioxidant protein GSTM5 in the ovary with ectopic tissue attachment. Following identification, the three samples' intersection included 10 active compounds in total. There was a 21-component overlap in active ingredients between rat and human serum. After a preliminary virtual screening, β-Hederin, Proanthocyanidin A2, and Cimiside E were suggested to be the essential components that interfere with NOD/NFκB.</p><p><strong>Conclusion: </strong>In rats with proliferative OEM, XYTJD may down-regulate the NOD/NFκB pathway in ectopic tissues, consequently alleviating ovarian tissue damage by reducing inflammation brought on by ectopic tissues.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2717-2735"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986579","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}
Zhicong Song, Shuai Bu, Suzhen Sang, Jie Li, Xihai Zhang, Xu Song, Yuqin Ran
{"title":"The Active Components of Traditional Chinese Medicines Regulate the Multi-Target Signaling Pathways of Metabolic Dysfunction-Associated Fatty Liver Disease.","authors":"Zhicong Song, Shuai Bu, Suzhen Sang, Jie Li, Xihai Zhang, Xu Song, Yuqin Ran","doi":"10.2147/DDDT.S514498","DOIUrl":"https://doi.org/10.2147/DDDT.S514498","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD), which is characterized by hepatocyte lipid accumulation driven by systemic metabolic dysregulation, represents a critical therapeutic challenge in the context of the global metabolic syndrome epidemic. The clinically recommended drugs for MAFLD mainly include antioxidants, hepatoprotective anti-inflammatory drugs, and weight-loss drugs. However, the mechanisms underlying the progression of MAFLD is characterized by nonlinearity, highlighting the urgent need for safer multi-target alternative therapies. Although existing single-target pharmacological interventions often show limited efficacy and adverse effects, the multi-component and multi-target nature of the active ingredients in traditional Chinese medicine (TCM) formulations represent new opportunities for systemic metabolic regulation. In this study, by searching PubMed and Web of Science, we identified 108 experimental studies. By evaluating multiple mechanisms, such as improving lipid metabolism and insulin resistance, alleviating oxidative stress damage, inhibiting liver inflammation, suppressing liver fibrosis, reducing endoplasmic reticulum stress, regulating hepatocyte autophagy, inhibiting hepatocyte apoptosis, improving mitochondrial dysfunction, and regulating the intestinal flora, we constructed a cross-scale regulatory network for the treatment of MAFLD by the active components of TCM. Subsequently, the dynamic target groups were screened, and a new paradigm of \"mechanism-oriented and spatiotemporal-optimized\" design for TCM compound prescriptions was proposed, providing a theoretical framework for the development of precise therapies that can improve liver lipid metabolism, block inflammation and fibrosis, and restore intestinal homeostasis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2693-2715"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984456","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":"Knowledge Mapping and Global Research Trends of Ginseng Polysaccharides: a Bibliometric Analysis with Visualizations from 1985 to 2023.","authors":"Pingli Mo, Bowen Gao, Rui Wang, Shiying Huang, Qiugu Chen, Muxia Li, Jiazhen Wu, Shangbin Zhang, Jianping Chen","doi":"10.2147/DDDT.S508387","DOIUrl":"https://doi.org/10.2147/DDDT.S508387","url":null,"abstract":"<p><strong>Background: </strong><i>Panax ginseng</i> C. A. Meyer (Ginseng) has a lengthy historical background of utilization and is frequently utilized for the treatment and prevention of various diseases. In recent times, researchers have shown an increasing inclination towards investigating the extraction, purification, structural analysis, and pharmacological properties of polysaccharides present in ginseng. However, there was still a lack of comprehensive and integrated analysis of ginseng polysaccharides.</p><p><strong>Methods: </strong>This study employed the Web of Science Core Collection (WoSCC) as the data source and utilized software tools including Bibliometrix R Package, VOSviewer, and CiteSpace for the purpose of conducting data visualization and analysis of ginseng polysaccharides publications.</p><p><strong>Results: </strong>China emerged as the foremost and most impactful nation in the realm of ginseng polysaccharide research, fostering robust collaborative ties with Republic of Korea and the USA. Yifa Zhou was the most influential author and the International Journal of Biological Macromolecules exerted as the significant influence in this field. The reference DUBOIS M, 1956, ANAL CHEM, V28, P350 received the highest citations. Through a comprehensive examination results of keywords clustering, keywords with the strong burst, and trend topic, the research hot directions of ginseng polysaccharides were focused on structural analysis and pharmacological activities. Specifically, gut microbiota and oxidative stress were active research hotspots of investigating the pharmacological activities of ginseng polysaccharides at present, it also was corroborated in disciplinary category analysis.</p><p><strong>Conclusion: </strong>This study revealed the multidimensional field of research on ginseng polysaccharides. Current hot research directions encompassed structural analysis and pharmacological activities in this field, with research hotspots focused on exploring the pharmacological activities of ginseng polysaccharides in gut microbiota and oxidative stress.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2749-2766"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968849","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":"Effects of Multiple Intravenous Doses of Perioperative Vitamin C on Pain Management Following Total Hip Arthroplasty.","authors":"Guangtao Han, Yuna Ye, Pengde Kang","doi":"10.2147/DDDT.S506262","DOIUrl":"https://doi.org/10.2147/DDDT.S506262","url":null,"abstract":"<p><strong>Purpose: </strong>Although the benefits of numerous intravenous vitamin C doses during the perioperative phase on postoperative pain following total hip arthroplasty for whether patients could have pain relief for a longer period of time have not yet been tested, a single dose of vitamin C can assist control pain after the procedure on the first post-operative day.</p><p><strong>Methods: </strong>One hundred patients undergoing total hip arthroplasty (THA) at our institution were enrolled in this prospective, double-blind, placebo-controlled, randomized experiment. These patients were randomized to either the control group or the vitamin C group. While the control group received an equivalent daily dose of a placebo, the vitamin C group received an intravenous injection of 3g of vitamin C every day during the perioperative period. Ten milliliters of morphine were injected subcutaneously as a rescue analgesic for patients who complained of discomfort following surgery. The amount of morphine used for rescue analgesia and the levels of inflammatory markers were the main outcomes that we evaluated. Additionally, we evaluated postoperative pain and hip joint recovery using the Visual Analog Scale (VAS) as secondary outcomes.</p><p><strong>Results: </strong>In the vitamin C group, the subcutaneous morphine injection dosage was considerably lower (0-24h 6.1mg ± 2.7mg vs 4.0mg ± 2.9mg, p = 0.000, total use 8.3mg ± 3.1mg vs 6.6mg ± 3.9mg, p = 0.018). During the perioperative term, the vitamin C group experienced better hip motion and lower VAS pain levels at rest and during exercise.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2667-2675"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984452","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":"Establishing the Median and 95% Effective Doses of Oliceridine for Immediate Post-Surgical Analgesia Following Laparoscopic Cholecystectomy: A Double-Blind, Sequential Dose-Finding Study.","authors":"Xianghua Cao, Huiling Xiao, Haoran Yan, Yujiao Wei, Qiting Wen, Zhijian Zhang, Guizhen Xu, Binbin Xu, Jian Chen, Xueping Li","doi":"10.2147/DDDT.S505079","DOIUrl":"https://doi.org/10.2147/DDDT.S505079","url":null,"abstract":"<p><strong>Background: </strong>This investigation aimed to establish the optimal dosing parameters of oliceridine for postoperative pain control in laparoscopic cholecystectomy (LC) procedures. Using Dixon and Massey's up-and-down sequential allocation method, the median effective dose (ED50) and the dose required for 95% effective dose (ED95) were determined, alongside an evaluation of the agent's safety profile.</p><p><strong>Methods: </strong>In this prospective trial, 82 participants scheduled for LC were enrolled and randomly assigned to receive either oliceridine or saline (control). Prior to surgical incision, the intervention group received varying doses of intravenous oliceridine, while control subjects received equivalent volumes of saline solution. Post-surgical pain management involved standardized multimodal analgesic protocols for both cohorts. Baseline demographic data was documented for all participants. Pain evaluations using the 11-point verbal numeric rating scale (NRS) at 15 min, 30 min, and 2h post-extubation. Using Dixon's up-and-down methodology, the ED50 and ED95 were determined. Hemodynamic variables were tracked and pain levels quantified throughout the procedure. The study protocol included monitoring post-anesthetic recovery characteristics and documenting adverse effects.</p><p><strong>Results: </strong>Probability unit regression analysis indicated that the ED50 of oliceridine for the prevention of early postoperative pain was calculated to be 18.45 µg/kg (95% CI: 16.85-19.82 µg/kg), while the ED95 was determined to be 22.39 µg/kg (95% CI: 20.75-26.98 µg/kg). Statistical analysis showed comparable rates of adverse events between study groups (p > 0.05). Additional analyses demonstrated similar outcomes between oliceridine and control cohorts regarding hemodynamic stability, and adverse effect profiles. Pain management satisfaction assessment at 24 hours post-LC revealed high approval rates in the oliceridine group, with 90% of patients (36/40, p=0.31) and 97.5% of surgeons (39/40, p=0.03) expressing satisfaction, regardless of administered dose.</p><p><strong>Conclusion: </strong>Our findings establish that for early postoperative pain management, oliceridine demonstrates optimal therapeutic efficacy at an ED50 of 18.45 ug/kg, with the ED95 determined to be 22.39 ug/kg.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2737-2747"},"PeriodicalIF":4.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973208","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":"Unveiling the Novel Anti - Tumor Potential of Digitonin, a Steroidal Saponin, in Gastric Cancer: A Network Pharmacology and Experimental Validation Study.","authors":"Dongdong Lu, Leijie Huang, Chunyan Weng","doi":"10.2147/DDDT.S504671","DOIUrl":"https://doi.org/10.2147/DDDT.S504671","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a leading cause of cancer-related mortality, with limited effective treatment options for advanced stages. As a steroidal saponin with documented anti-neoplastic properties in multiple cancers, digitonin's mode of action in GC pathogenesis has yet to be fully elucidated. This research focused on exploring the potential of Digitonin in GC treatment using a combination of network pharmacology and experimental validation.</p><p><strong>Methods: </strong>The inhibitory effects of Digitonin on the proliferation, invasion, and migration of gastric cancer cells were evaluated using CCK-8, colony formation, wound healing, and transwell assays. Key targets of Digitonin were identified through network pharmacology. Molecular docking and various experiments, including Western blot, immunofluorescence, and a subcutaneous xenograft model, were used for validation.</p><p><strong>Results: </strong>Digitonin exhibited stronger cytotoxicity against GC cells and significantly inhibited GC cell proliferation, migration, and invasion. Network pharmacology analysis revealed that the core targets of Digitonin are involved in key cancer-related signaling pathways, including HIF-1α, Ras, and PI3K-Akt pathways, with HSP90AA1 and NFKB1 identified as central targets. Further molecular docking, Western blotting, and immunofluorescence experiments confirmed that Digitonin significantly suppressed the expression of HSP90AA1 and inhibited the nuclear translocation of NFKB1, inducing cell apoptosis. Additionally, a subcutaneous xenograft model of GC further validated that Digitonin effectively inhibited tumor growth.</p><p><strong>Conclusion: </strong>Digitonin serves as a promising multi-target therapeutic agent for GC. This study underscores the potential of combining network pharmacology with traditional Chinese medicine to identify novel therapeutic targets and develop effective anti-cancer strategies. In addition, these findings suggest that digitonin could be a promising candidate for future clinical trials in GC treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2653-2666"},"PeriodicalIF":4.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986432","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":"GA-LDV: A Promising Derivative of 18β-Glycyrrhetinic Acid with Enhanced in vitro and in vivo Anti-Cancer Properties.","authors":"Jiaying Zheng, Qiqi Feng, Qi Gao, Yaonan Wang, Shurui Zhao, Xiaoyi Zhang, Ming Zhao","doi":"10.2147/DDDT.S492303","DOIUrl":"10.2147/DDDT.S492303","url":null,"abstract":"<p><strong>Purpose: </strong>The clinical translation of 18β-Glycyrrhetinic acid (GA) is impeded by its relatively low antitumor potency and poor aqueous solubility, we developed a novel derivative of GA by incorporating the Leu-Asp-Val (LDV) tripeptide to enhance its anti-tumor and anti-metastatic activities both in vitro and in vivo, thereby increasing its potential as a therapeutic agent for cancer treatment.</p><p><strong>Methods: </strong>The water solubility of GA-LDV was evaluated. The inhibitory effects of GA-LDV on cell viability were assessed in four different human cancer cell lines. In vitro assays were conducted to measure the compound's impact on tumor cell adhesion, migration, and invasion. In vivo studies were performed using S180 and LLC xenograft models to evaluate the tumor inhibition and anti-metastatic properties.</p><p><strong>Results: </strong>GA-LDV water solubility was increased 4.1 folds compared with GA. In vitro assays suggested that GA-LDV, at a concentration of 25 μM, significantly impeded the adhesion, migration, and invasion of LLC tumor cell lines, with inhibition rates of 52.7%, 55.5% (vs GA 16.9%, P < 0.05) and 35.9% (vs GA 27.5%, P < 0.05). Moreover, GA-LDV demonstrated stronger tumor inhibition ability than GA (P < 0.05), and anti-metastasis activities in a dose-dependent manner, at the concentration of 5 μmol/kg/d, 1 μmol/kg/d, 0.2 μmol/kg/d with lung metastatic nodules 7.5 (P < 0.01 compared with the control group), 9.8 (P < 0.05 compared with the control group) and 14.5. And GA-LDV had almost no systemic toxicity in S180 or LLC xenograft models.</p><p><strong>Conclusion: </strong>The newly synthesized GA-LDV derivative demonstrates superior water solubility and significantly enhanced anti-tumor and anti-metastatic activities. The in vitro and in vivo studies indicate that GA-LDV is a promising candidate for further development as a cancer therapeutic agent, with the benefit of potentially reduced systemic toxicity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2641-2652"},"PeriodicalIF":4.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810725","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":"Mechanism of the Traditional Chinese Medicine Simiao Biejia Decoction Improves the Diabetes Mellitus-Induced Erectile Dysfunction in Rats.","authors":"Yuanyuan Liu, Dalin Sun, Dong Xing, Yiqi Rui, Yihan Jin, Peng Wang, Bin Cai, Chuyu Li, Chao Gao, Yugui Cui, Baofang Jin","doi":"10.2147/DDDT.S495366","DOIUrl":"10.2147/DDDT.S495366","url":null,"abstract":"<p><strong>Objective: </strong>Simiao Biejia (SMBJ) granules, a traditional Chinese herbal remedy, have been used to treat erectile dysfunction caused by diabetes mellitus (DMED). However, the molecular mechanisms underlying SMBJ's therapeutic effects remain unclear. This study aimed to investigate the effects and mechanisms of SMBJ in a rat model of DMED using network pharmacology, proteomics, and molecular docking.</p><p><strong>Methods: </strong>A rat model of DMED was established, and SMBJ granules were administered (0, 7.1, 14.2, and 28.4 mg/kg/d, respectively) for 4 weeks. Erectile function was evaluated by measuring intracavernous pressure and mean arterial pressure. The active compounds in SMBJ were analyzed by gas chromatography and identified using network pharmacology and bioinformatics. Potential targets in the penile tissue was identified via proteomics and validated by Western blotting. Molecular docking was used to assess the binding affinity between bioactive compounds and primary targets.</p><p><strong>Results: </strong>SMBJ significantly improves erectile function and ameliorates DMED in rats by reducing corpus cavernosum fibrosis, decreasing eNOS and nNOS levels, alleviating oxidative stress in penile tissue, and mitigating damage to smooth muscle cells (SMCs) and vascular endothelial cells (VECs). Network pharmacology and proteomics identified 24 potential SMBJ targets in DMED. The 4 drug molecules identified were involved in the therapeutic effects of SMBJ, among which luteolin was predicted to be the core drug component. Luteolin bound directly with AKT1, a key differentially expressed protein in the penile tissue of DMED rats. Further analysis showed that luteolin in SMBJ activates the PI3K/Akt pathway and regulation of nNOS and NF-kB expression in the penile tissue of DMED rats to improve erectile function.</p><p><strong>Conclusion: </strong>SMBJ improved oxidative stress damage, vascular endothelial repair, and angiogenesis in the penile tissue of DMED rats. Luteolin is one of the core drug components of SMBJ in DMED treatment that regulates PI3K/AKT-related pathways.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2609-2628"},"PeriodicalIF":4.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802599","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}
Wenjie Zhang, Yinming Zhang, Jiawei Tang, Xuejiao Wang, Chao Meng, Ji Wu, Jun Li
{"title":"The Changing Landscape of Heart Failure Drug Clinical Trials in China, 2013-2023.","authors":"Wenjie Zhang, Yinming Zhang, Jiawei Tang, Xuejiao Wang, Chao Meng, Ji Wu, Jun Li","doi":"10.2147/DDDT.S511608","DOIUrl":"10.2147/DDDT.S511608","url":null,"abstract":"<p><strong>Objective: </strong>This review aimed to delineate the changing landscape of heart failure (HF) drug clinical trials conducted in China during 2013<b>-</b>2023.</p><p><strong>Methods: </strong>Detailed information on HF drug trials registered on the National Medical Products Administration Clinical Trial Information Disclosure Platform from January 1, 2013, to December 31, 2023, was collected. The characteristics, drug mechanisms, data safety, participant protection, geographical locations, and scales of HF drug clinical trials were analyzed.</p><p><strong>Results: </strong>China initiated 354 hF drug clinical trials during 2013<b>-</b>2023, encompassing eight acute heart failure (AHF) trials and 346 trials for chronic heart failure (CHF). The overall number of HF trials continued to increase, whereas the number of AHF trials remained consistently low. Significant differences were observed between AHF and CHF trials regarding trial phases, drug types, trial designs, blinding methods, and geographical coverage. 85.8% CHF trials were bioequivalence studies, whereas AHF trials were exclusively Phase I<b>-</b>III studies. Most trial drugs were chemical drugs, with renin-angiotensin-aldosterone system inhibitors accounting for the highest proportion. Sixteen new drug studies involved 13 different new drugs. The proportion of studies establishing independent data monitoring committees annually remained generally low, whereas the proportion of studies purchasing clinical trial insurance for participants annually exhibited an overall upward trend. The 354 trials were led by principal investigators from 27 provinces, autonomous regions, or municipalities in China. 47.2% leading units for these studies were distributed in the eastern coastal regions of China. There were 30 drug clinical trials with more than ten participating centers and 16 drug clinical trials with a target number of participants of over 1000 individuals.</p><p><strong>Conclusion: </strong>Over the past decade, China has experienced rapid development in HF drug trials, particularly in drug consistency evaluations. All stakeholders involved in drug trials should carefully consider the inadequate innovations in first-in-class drugs.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2597-2608"},"PeriodicalIF":4.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802724","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}