Pharmaceutical Biology最新文献

{"title":"Effects of total coumarins from <i>Pileostegia tomentella</i> on exosomal miRNA expression and angiogenesis in colorectal cancer cells.","authors":"Ying Liu, Dao-Hai Cheng, Zheng-Ying Su, Ji-Hua Lv, Li Wang, Yu-Yin Deng, Li Li","doi":"10.1080/13880209.2024.2309871","DOIUrl":"10.1080/13880209.2024.2309871","url":null,"abstract":"<p><strong>Context: </strong><i>Pileostegia tomentella</i> Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.</p><p><strong>Objective: </strong>To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.</p><p><strong>Materials and methods: </strong>HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.</p><p><strong>Results: </strong>HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.</p><p><strong>Discussion and conclusion: </strong>TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of <i>Pileostegia tomentella</i> in CRC.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"153-161"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723544","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":"Design, synthesis and biological evaluation of novel podophyllotoxin derivatives as tubulin-targeting anticancer agents.","authors":"Yujin Guo, Beibei Chen, Jinxiu Guo, Pei Jiang, Jianhua Wang, Wenxue Sun","doi":"10.1080/13880209.2024.2318350","DOIUrl":"10.1080/13880209.2024.2318350","url":null,"abstract":"<p><strong>Context: </strong>Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.</p><p><strong>Objective: </strong>This study synthesizes PPT derivatives to assess their anticancer activities.</p><p><strong>Materials and methods: </strong>Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound <b>E5</b> on A549 cell growth were evaluated through molecular docking, <i>in vitro</i> assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and <i>in vivo</i> tests in female BALB/c nude mice treated with <b>E5</b> (2 and 4 mg/kg). <b>E5</b> (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.</p><p><strong>Results: </strong>Among the 16 PPT derivatives tested for cytotoxicity, <b>E5</b> exhibited potent effects against A549 cells (IC₅₀: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. <b>E5</b>-induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of <b>E5</b> to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.</p><p><strong>Discussion and conclusions: </strong>This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with <b>E5</b> call for extended research and clinical validation, leading to novel and more effective cancer therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"233-249"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932375","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":"Proanthocyanidin offers protection against diabetic nephropathy: elucidation of its mechanism of action using animal models.","authors":"Dengpiao Xie, Huan Wang, Qing Ji, Jianting Wang","doi":"10.1080/13880209.2024.2409772","DOIUrl":"10.1080/13880209.2024.2409772","url":null,"abstract":"<p><strong>Context: </strong>Diabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.</p><p><strong>Objective: </strong>This study evaluates the efficacy and potential mechanisms of PA in animal models of DN.</p><p><strong>Methods: </strong>Preclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.</p><p><strong>Results: </strong>A total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.</p><p><strong>Conclusion: </strong>These findings suggest that PA alleviates DN by mediating multiple targets and pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"702-712"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381408","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":"Guidelines for the clinical application of the <i>Xihuang</i> pill for the prevention and treatment of breast hyperplasia diseases.","authors":"Hongmei Tang, Qin Lu, Shiyin Feng, Zhiwei Xiao, Wanyin Wu, Gaofeng Chen, Li Deng, Tianqi Yu, Junyan Wu, Hua Lin, Bo Ji, Jietao Lin, Chengguang Zhang, Liming Li, Tao Liu, Yong Ouyang, Kaijun Lei, Jun Chen, Weiwen Peng, Zhenwen Qiu, Qingqun Cai, Qi Liang, Cuiling Liu, Yuzhen Li, Lixia Zhu, Zexin Zhang, Xueting Liu, Lizhu Lin, Zhihua Zheng","doi":"10.1080/13880209.2024.2350233","DOIUrl":"10.1080/13880209.2024.2350233","url":null,"abstract":"<p><strong>Context: </strong>The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.</p><p><strong>Objective: </strong>The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.</p><p><strong>Methods: </strong>We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.</p><p><strong>Results: </strong>Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.</p><p><strong>Conclusions: </strong>Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"472-479"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071663","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":"Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.","authors":"Kaijing Yang, Xiaoli Shan, Yang Songru, Mengwei Fu, Pei Zhao, Wei Guo, Ming Xu, Huihua Chen, Rong Lu, Chen Zhang","doi":"10.1080/13880209.2024.2354335","DOIUrl":"10.1080/13880209.2024.2354335","url":null,"abstract":"<p><strong>Context: </strong>The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.</p><p><strong>Objective: </strong>This study explores the mechanisms of GGD against cardiac hypertrophy.</p><p><strong>Materials and methods: </strong>Network pharmacology analysis was carried out to identify the potential targets of GGD. <i>In vivo</i> experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). <i>In vitro</i> experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10^-5 g/mL) and GGD (10^-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested <i>via</i> real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.</p><p><strong>Results: </strong>Network pharmacology identified ADORs among those of the core targets of GGD. <i>In vitro</i> experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC₅₀ of 5.484 × 10^-6 g/mL). <i>In vivo</i> data shown that GGD attenuated PE-induced ventricular wall thickening. <i>In vitro</i> and <i>in vivo</i> data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.</p><p><strong>Discussion and conclusions: </strong>Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"456-471"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074532","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":"Comprehensive profiling of the chemical constituents in Dayuanyin decoction using UPLC-QTOF-MS combined with molecular networking.","authors":"Jing Peng, Chengyu Ge, Kaiqi Shang, Shao Liu, Yueping Jiang","doi":"10.1080/13880209.2024.2354341","DOIUrl":"10.1080/13880209.2024.2354341","url":null,"abstract":"<p><strong>Context: </strong>Dayuanyin decoction is a traditional Chinese medicine formulation that is commonly used in modern clinical practice to treat viral infections such as viral pneumonia, viral fever, influenza, and hepatitis. Although the usage rate of Dayuanyin decoction is gradually increasing in clinical practice, its pharmacological constituents are still unclear.</p><p><strong>Objective: </strong>This study comprehensively characterized the chemical constituents in Dayuanyin decoction using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular networking.</p><p><strong>Materials and methods: </strong>The overall strategy involved retrieving structural information, such as fragment ions and precursor ion masses, from self-built databases to identify the target constituents of the Dayuanyin decoction extract. The identification of non-targeted constituents was achieved by analyzing different categories, fragment pathways, mass spectrometry data, and the relationships between clusters of structures in molecular networking. Unannotated constituents were inferred from secondary mass spectrometry similarity and molecular weight differences and annotated constituents in the same constituent cluster. A few predicted constituents were selected and validated by comparing them to reference standards under identical mass spectrometry conditions.</p><p><strong>Results: </strong>This study preliminarily identified 216 constituents, including flavonoids, amino acids, alkaloids, triterpenes, steroidal saponins, phenylpropanoids, and other constituents.</p><p><strong>Conclusions: </strong>This integrated strategy using UPLC-QTOF-MS and molecular networking lays the foundation for clinical research on pharmacologically active substances in Dayuanyin decoction and could be popularized for the comprehensive profiling of chemical constituents of other traditional Chinese medicines.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"480-498"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162222","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":"Clinical observations and mechanistic insights of traditional Chinese medicine in the management of diabetic retinopathy.","authors":"Jie Chen, Yadong Ni, Wenhui Yao, Xuansheng Ding","doi":"10.1080/13880209.2024.2369292","DOIUrl":"10.1080/13880209.2024.2369292","url":null,"abstract":"<p><strong>Context: </strong>Diabetic retinopathy (DR) is one of the leading causes of vision impairment and blindness among diabetic patients globally. Despite advancements in conventional treatments, the quest for more holistic approaches and fewer side effects persists. Traditional Chinese medicine (TCM) has been used for centuries in managing various diseases, including diabetes and its complications.</p><p><strong>Objective: </strong>This review evaluated the efficacy and underlying mechanisms of TCM in the management of DR, providing information on its potential integration with conventional treatment methods.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) with the search terms 'traditional Chinese medicine', 'diabetic retinopathy', 'clinical efficacies' and their combinations. Studies published before 2023 without language restriction were included, focusing on clinical trials and observational studies that assessed the effectiveness of TCM in DR treatment.</p><p><strong>Results: </strong>The review synthesized evidence of empirical traditional Chinese formulas, traditional Chinese patent medicines, and isolated phytochemicals on DR treatment. The key mechanisms identified included the reduction of oxidative stress, inflammation, and neovascularization, as well as the improvement in neurovascular functionality and integrity of the retinal blood barrier.</p><p><strong>Conclusions: </strong>TCM shows promising potential to manage DR. More large-scale, randomized controlled trials are recommended to validate these findings and facilitate the integration of TCM into mainstream DR treatment protocols.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"529-543"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451139","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":"Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: a network meta-analysis.","authors":"Kefeng Liu, Qiong Li, Xiaojing Lu, Xintong Fan, Yongjie Yang, Wei Xie, Jian Kang, Shusen Sun, Jie Zhao","doi":"10.1080/13880209.2024.2351940","DOIUrl":"10.1080/13880209.2024.2351940","url":null,"abstract":"<p><strong>Context: </strong>Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs.</p><p><strong>Objective: </strong>This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC.</p><p><strong>Methods: </strong>The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data.</p><p><strong>Results: </strong>Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia.</p><p><strong>Conclusions: </strong>Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"404-422"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911910","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":"Yi-Shen-Hua-Shi regulates intestinal microbiota dysbiosis and protects against proteinuria in patients with chronic kidney disease: a randomized controlled study.","authors":"Xingtong Dong, Jialing Zhang, Wen Li, Yinping Li, Linpei Jia, Zhaohui Liu, Wenjing Fu, Aihua Zhang","doi":"10.1080/13880209.2024.2345080","DOIUrl":"10.1080/13880209.2024.2345080","url":null,"abstract":"<p><strong>Context: </strong>Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.</p><p><strong>Objective: </strong>This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.</p><p><strong>Materials and methods: </strong>120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (<i>n</i> = 56) or RAAS inhibitor (<i>n</i> = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.</p><p><strong>Results: </strong>Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as <i>Faecalibacterium</i>, <i>Lachnospiraceae</i>, <i>Lachnoclostridium,</i> and <i>Sutterella</i> increased significantly, while pathogenic bacteria such as the <i>Eggerthella</i> and <i>Clostridium innocuum group</i> decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as <i>Lachnospiraceae</i> and the <i>Lachnoclostridium</i> genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.</p><p><strong>Discussion and conclusion: </strong>The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.</p><p><strong>Trial registration: </strong>ChiCTR2300076136, retrospectively registered.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"356-366"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892323","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":"Berberine decreases S100B generation to regulate gut vascular barrier permeability in mice with burn injury.","authors":"Aiwen Feng, Shaosheng Su, Cheng Li, Yutian Kang, Jiasheng Qiu, Jun Zhou","doi":"10.1080/13880209.2023.2291679","DOIUrl":"10.1080/13880209.2023.2291679","url":null,"abstract":"<p><p><b>Context:</b> Berberine (BBR) can regulate enteric glial cells (EGCs) and the gut vascular barrier (GVB).<b>Objective:</b> To explore whether BBR regulates GVB permeability <i>via</i> the S100B pathway.<b>Materials and methods:</b> GVB hyperpermeability in C57BL/6J mice was induced by burns or S100B enema. BBR (25 or 50 mg/kg/d, 3 d) was gavaged preburn. S100B monoclonal antibody (S100BmAb) was i.v. injected postburn. Mouse intestinal microvascular endothelial cells (MIMECs) were treated with S100B, S100B plus BBR, or Z-IETD-FMK. GVB permeability was assayed by FITC-dextran, S100B by ELISA, caspase-8, β-catenin, occludin and PV-1 by immunoblot.<b>Results:</b> Burns elevated S100B in serum and in colonic mucosa to a peak (147.00 ± 4.95 ng/mL and 160.30 ± 8.50 ng/mg, respectively) at 36 h postburn, but BBR decreased burns-induced S100B in serum (126.20 ± 6.30 or 90.60 ± 3.78 ng/mL) and in mucosa (125.80 ± 12.40 or 91.20 ± 8.54 ng/mg). Burns raised GVB permeability (serum FITC-dextran 111.40 ± 8.56 pg/mL) at 48 h postburn, but BBR reduced GVB permeability (serum FITC-dextran 89.20 ± 6.98 or 68.60 ± 5.50 ng/mL). S100B enema (1 μM) aggravated burns-raised GVB permeability (142.80 ± 8.07 pg/mL) and PV-1, but the effect of S100B was antagonized by BBR. Z-IETD-FMK (5 μM) increased S100B-induced permeability to FITC-dextran (205.80 ± 9.70 to 263.80 ± 11.04 AUs) while reducing β-catenin in MIMECs. BBR (5 μM) reduced S100B-induced permeability (104.20 ± 9.65 AUs) and increased caspase-8, β-catenin and occludin.<b>Discussion and conclusion:</b> BBR decreases burns-induced GVB hyperpermeability <i>via</i> modulating S100B/caspase-8/β-catenin pathway and may involve EGCs.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"53-61"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806725","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}