Pharmaceutical Biology最新文献

{"title":"Cyanoglycosides isolated from <i>Moringa oleifera</i> seeds inhibited PFKFB3/TGF-β1/smads pathway to alleviate diabetic nephropathy through driving metabolic reprogramming.","authors":"Chengyu Ge, Zhihua Shi, Jia He, Xu Feng, Kaiqi Shang, Xiaolin Liao, Yufeng Liu, Yueping Jiang, Shao Liu","doi":"10.1080/13880209.2025.2607563","DOIUrl":"10.1080/13880209.2025.2607563","url":null,"abstract":"<p><strong>Context: </strong>Diabetic nephropathy (DN) is a major complication of diabetes. <i>Moringa oleifera</i> seeds are recognized as a source of bioactive compounds with potential health benefits, prompting investigation into their specific components and effects on DN.</p><p><strong>Objective: </strong>This study aimed to isolate bioactive compounds from <i>M. oleifera</i> seeds and evaluate their renoprotective effects and underlying mechanisms of action against high-glucose-induced diabetic nephropathy.</p><p><strong>Materials and methods: </strong>Four cyanoglycosides and one cyanoaglycone were isolated from <i>M. oleifera</i> seeds using chromatographic techniques. The renoprotective effects of these compounds were then evaluated using an <i>in vitro</i> model of high-glucose-induced diabetic nephropathy in HBZY-1 mesangial cells. Mechanistic studies further investigated the compounds' effects on oxidative stress, inflammation, mitochondrial function, expression of the glycolysis-related protein PFKFB3, and the TGF-β1/Smad signaling pathway.</p><p><strong>Results: </strong>Two previously undescribed cyanoglycosides were isolated alongside three known compounds. All five compounds demonstrated significant renoprotective effects in the high-glucose-induced HBZY-1 cell model. Mechanistically, these effects were achieved by suppressing oxidative stress and inflammation, protecting mitochondrial function, modulating the expression of the glycolysis-related protein PFKFB3, and inhibiting the TGF-β1/Smad signaling pathway, collectively contributing to beneficial metabolic reprogramming.</p><p><strong>Conclusions: </strong>This study isolated two novel cyanoglycosides from <i>M. oleifera</i> seeds. These compounds, alongside known ones, protect against high-glucose-induced renal injury. Their renoprotection involves metabolic reprogramming <i>via</i> suppressing oxidative stress/inflammation, preserving mitochondrial function, modulating PFKFB3, and inhibiting TGF-β1/Smad signaling. These findings offer insights for utilizing <i>M. oleifera</i> seeds and suggest these cyanoglycosides as potential diabetic nephropathy therapeutics.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"130-142"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857430","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":"(±)-Rutacycoumarins A and B: two pairs of unprecedented coumarin enantiomers from the aerial part of <i>Ruta graveolens</i> L. and chemically synthesized.","authors":"Xu Feng, Jing Fang, Yanyang Liu, Chengyu Ge, Xiaolin Liao, Tao Jiang, Xiongjun Hou, Hao Huang, Shao Liu, Aimin Wang, Yueping Jiang","doi":"10.1080/13880209.2025.2600291","DOIUrl":"10.1080/13880209.2025.2600291","url":null,"abstract":"<p><strong>Context: </strong>Benzofuran derivatives are important structural motifs found in natural products, often exhibiting significant biological activities. <i>Ruta graveolens</i> L. is a plant source known for containing diverse bioactive compounds.</p><p><strong>Objective: </strong>This study aimed to isolate and characterize compounds from the aerial parts of <i>R. graveolens</i>, confirm their structures through synthesis, develop a novel synthetic methodology, and evaluate their potential anti-inflammatory effects and monoamine oxidase inhibitory activity.</p><p><strong>Materials and methods: </strong>The structures of benzofuran enantiomers were elucidated using integrated NMR, HRMS, and ECD analyses. (±)-Rutacycoumarins A and B were synthesized <i>via</i> a novel direct C3 alkylation of coumarin bearing phenolic hydroxyl groups. Biological evaluation assessed the anti-inflammatory effects of (±)-Rutacycoumarins A and B in LPS-stimulated HepG2 cells by measuring liver biomarkers and pro-inflammatory cytokines, and their inhibitory activity against monoamine oxidase B (MAO-B).</p><p><strong>Results: </strong>Two novel Z/E pairs of benzofuran enantiomers, (±)-Rutacycoumarins A and B, featuring fused cyclopropane motifs, were isolated and structurally confirmed. Their synthesis employed a novel catalytic EDA complex (DIPEA/potassium ethyl xanthate donor, NHPI ester acceptor). (±)-Rutacycoumarins A and B reduced liver biomarkers and pro-inflammatory cytokines in LPS-treated HepG2 cells, and all four enantiomers inhibited MAO-B.</p><p><strong>Conclusions: </strong>This study isolated two novel benzofuran enantiomer pairs with fused cyclopropane motifs from <i>R. graveolens</i> Their structures were confirmed <i>via</i> a new catalytic EDA complex synthesis. Racemic mixtures reduced LPS-induced liver/cellular damage and cytokines in HepG2 cells, while all enantiomers inhibited MAO-B.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1-16"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743839","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":"A scoping review of turmeric adulteration based on data from six continents.","authors":"Stefan Gafner, Nilüfer Orhan, Çiğdem Kahraman, Mark Blumenthal","doi":"10.1080/13880209.2025.2606229","DOIUrl":"10.1080/13880209.2025.2606229","url":null,"abstract":"<p><strong>Context: </strong>Turmeric (<i>Curcuma longa</i>) is widely used as a spice and in dietary/food supplements and herbal medicines. Reports assessing the authenticity of commercial products have shown that the ingredient is subject to adulteration with, among others, artificial dyes, undeclared diluents, and synthetic curcumin.</p><p><strong>Objective: </strong>This scoping review summarizes published data on adulteration of turmeric products sold as spice and dietary or food supplements to estimate the prevalence of non-authentic turmeric on the market.</p><p><strong>Methods: </strong>This scoping review was based on a literature analysis from Google Scholar, PubMed, ScienceDirect, Scopus, and Web of Science databases, covering publications from 2000 to 2025. Article selection was performed according to PRISMA-ScR guidelines. After the initial search, specific countries were added to refine the search. Of the 375 publications retrieved, 347 were eliminated as duplicates or because they lacked information on turmeric adulteration, adulteration of commercial products, or did not provide the number of adulterated samples. An additional 19 papers were found searching the citations, or by using Google Search with the keywords \"Curcuma longa\", \"turmeric\", \"government report\", and \"adulteration\". One more report from the CVUA Stuttgart was found using the keywords \"Kurkuma\", \"Verfälschung\", and \"Report\". In total, 48 papers were included in the review.</p><p><strong>Results: </strong>A total of 48 publications representing 2235 commercial turmeric samples were included in the study. The overall adulteration rate was 20.0%, with spice samples having a slightly lower percentage of adulterated samples (20.4%) than dietary and food supplements (22.0%).</p><p><strong>Conclusion: </strong>Adulteration of turmeric remains a concern on markets worldwide.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"87-107"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843902","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":"lncRNA MALAT1-mediated regulation of cholesterol-oxidative stress-iron metabolic dysregulation by paeoniflorin in osteoarthritic chondrocytes.","authors":"Changlong Fu, Shujie Lan, Yanming Lin, Danling Chen, Zhenzhen Yang, Changxian Chen, Yue Chen, Yijing Yuan, Weihong Zhong, Qing Lin, Zhiqiang Huang","doi":"10.1080/13880209.2026.2620862","DOIUrl":"10.1080/13880209.2026.2620862","url":null,"abstract":"<p><strong>Context: </strong>Osteoarthritis is a chronic degenerative disease characterized by metabolic dysregulation, inflammation, and oxidative stress. MALAT1 plays a key role in OA pathogenesis. Pae exhibits anti-inflammatory activity, but its regulatory role in cholesterol-oxidative stress-iron metabolism in chondrocytes remains unclear.</p><p><strong>Objective: </strong>To investigate whether Pae can alleviate cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes <i>via</i> modulation of MALAT1.</p><p><strong>Materials & methods: </strong>OA was induced in mice using a modified Hulth method, followed by intra-articular injection of MALAT1 overexpression plasmid. Cartilage morphology and the expression of MALAT1 and related genes/proteins were assessed by histology, RT-PCR, and Western blot. <i>In vitro</i>, IL-1β-treated chondrocytes were used to model OA, and MALAT1 knockdown was achieved <i>via</i> lentiviral transfection. FISH, RT-PCR, Western blot, and flow cytometry were used to evaluate the effects of Pae on molecular markers and apoptosis.</p><p><strong>Results: </strong>In vivo In vivo, Pae improved cartilage morphology and restored the expression of key genes and proteins, whereas MALAT1 overexpression attenuated these effects. In IL-1β-treated OA chondrocytes, Pae reversed abnormal mRNA expression of MALAT1 and related genes. FISH analysis showed that Pae reduced MALAT1 fluorescence in chondrocytes. Western blot revealed that Pae significantly restored protein expression in sh-MALAT1 chondrocytes. Furthermore, flow cytometry analysis revealed that Pae intervention significantly reduced the apoptosis rate of IL-1β-induced chondrocytes from 34.57% to 27.74%. sh-MALAT1 resulted in a more pronounced reduction in chondrocyte apoptosis, with the apoptotic rate further decreasing to 13.21%.</p><p><strong>Discussion and conclusion: </strong>Paeoniflorin ameliorates cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes <i>via</i> modulation of MALAT1, providing mechanistic insight into its potential therapeutic effects.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"278-294"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181570","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":"Phytochemical study of <i>Homalanthus giganteus</i>: isolation, antiproliferative activity, and computational mechanistic insights of tigliane diterpenes against colorectal cancer.","authors":"Dyke Gita Wirasisya, Annamária Kincses, Arif Setiawansyah, Anita Barta, Fang-Rong Chang, Judit Hohmann","doi":"10.1080/13880209.2026.2629733","DOIUrl":"10.1080/13880209.2026.2629733","url":null,"abstract":"<p><strong>Context: </strong>Colorectal cancer is the third most common and second deadliest cancer worldwide. Late diagnosis, poor outcomes in metastatic cases, and multidrug resistance emphasize the need for new therapies.</p><p><strong>Objective: </strong>This study aimed to isolate bioactive compounds from <i>Homalanthus giganteus</i> Zoll. ex Miq. (Euphorbiaceae), evaluate their antiproliferative effects on colorectal cancer cells, and identify mechanisms through network pharmacology and molecular docking.</p><p><strong>Materials and methods: </strong>Compounds were isolated by chromatographic separations, and the structures were elucidated by NMR and HRESIMS. The antiproliferative activity was measured by MTT assay. DFT calculations were performed in ORCA 6.1.0. Network pharmacology was used to identify targets and pathways, molecular docking with AutoDock Vina was used to determine binding affinities, and pkCSM was applied to predict pharmacokinetics and toxicity.</p><p><strong>Results: </strong>7β-Hydroxysitosterol (<b>1</b>), 7α-hydroxysitosterol (<b>2</b>), 12-<i>O</i>-palmitoyl-phorbol-13-acetate (<b>3</b>), 12-<i>O</i>-palmitoyl-7-oxo-5-ene-phorbol-13-acetate (<b>4</b>), cerevisterol (<b>5</b>), and β-sitosterol-3-<i>O</i>-glucoside (<b>6</b>) were isolated from <i>H. giganteus</i>. Compound <b>4</b> exhibited the highest activity against Colo 205 (IC₅₀ 3.58 ± 0.37 μM) and Colo 320 cells (IC₅₀ 6.06 ± 1.70 μM) and higher DFT stability. Network pharmacology and docking study revealed kinase-specific targeting (STAT3, JUN, PRKCA, GSK3β), with <b>4</b> preferentially binds PRKCA/GSK3β, whereas <b>3</b> favors STAT3/JUN. The pkCSM prediction server predicted good oral bioavailability, CYP3A4 metabolism, limited CNS penetration, and acceptable toxicity for both diterpenes.</p><p><strong>Discussion and conclusions: </strong>Six compounds were isolated from <i>H. giganteus,</i> with <b>4</b> exhibiting antiproliferative activity through PRKCA and GSK3β modulation. These findings provide the first phytochemical and mechanistic evidence that support <i>H. giganteus</i> as a promising source of active anti-colon cancer leads.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"312-333"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220490","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":"Wubie Fanchun Formula-inducible metabolites in primary ovarian insufficiency model mice that facilitate ovarian renovation.","authors":"Yun Chen, Shanshan Chen, Bingbing Song, Xinfang Xia, Kaiqing Zhang, Li Chen, Lei Chi, Qiong Wang","doi":"10.1080/13880209.2026.2668132","DOIUrl":"10.1080/13880209.2026.2668132","url":null,"abstract":"<p><strong>Context: </strong>Premature ovarian insufficiency (POI), defined as ovarian activity cessation before age 40, significantly impacts both fertility and long-term health, with currently inadequate treatment options available. Wubie Fanchun Formula (WBFC) has been clinically used for over 20 years, showing benefits in TCM symptoms and hormone levels in POI patients with liver-kidney deficiency. However, its active components and mechanistic basis are still largely unknown.</p><p><strong>Objective: </strong>To characterize the active ingredients and delineate the pharmacological basis of WBFC's action in managing POI.</p><p><strong>Materials and methods: </strong>LC-TOF-MS was used to identify WBFC's chemical constituents. Network pharmacology analysis pinpointed candidate mechanisms, which were tested in a 4-VCD-induced POI mouse model. Metabolic dysfunction was characterized <i>via</i> pyruvate tolerance tests, liver glycogen staining, and untargeted metabolomics. Key metabolites regulated by WBFC in model mice, phosphatidylinositol 38:5 (PI) and glutamine (GLN), were supplemented to validate their roles in POI pathology.</p><p><strong>Results: </strong>25 bioactive constituents in WBFC were found by LC-TOF-MS analysis. WBFC ameliorated ovarian dysfunction and activated the PI3K/AKT/FOXO3a pathway in parallel with simultaneously improving systemic metabolic parameters. Metabolomics identified PI and GLN among the top 30 most significantly altered metabolites, both showing marked depletion in POI mice and substantial restoration following WBFC treatment. Functional validation through exogenous supplementation demonstrated that combined PI and GLN administration effectively rescued ovarian dysfunction and specifically reactivated the ovarian PI3K-AKT pathway in 4-VCD induced POI mice.</p><p><strong>Discussion and conclusion: </strong>Amino acids, saponins, anthraquinones, and carbohydrates are the main chemical components of WBFC. WBFC ameliorated POI and activated PI3K/AKT/FOXO3a signaling through metabolic regulation, with PI and GLN identified as critical therapeutic mediators.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"725-748"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932374","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":"Therapeutic potential of <i>Asiaticoside</i> in wound healing after endoscopic submucosal dissection (ESD).","authors":"Qinghua Li, Wangqi Chen, Yuxia Xie, Hong Zhu","doi":"10.1080/13880209.2026.2638602","DOIUrl":"10.1080/13880209.2026.2638602","url":null,"abstract":"<p><strong>Context: </strong>Endoscopic submucosal dissection (ESD) is the standard treatment for early gastrointestinal cancers but is often complicated by delayed healing and stenosis. Current therapies like proton pump inhibitors primarily suppress acid without actively promoting mucosal regeneration. <i>Asiaticoside</i> (AS), a triterpenoid from <i>Centella asiatica</i>, shows promise in tissue repair.</p><p><strong>Objective: </strong>This review evaluates the therapeutic potential of AS for ESD-induced wound healing, focusing on its pharmacological mechanisms and emerging delivery strategies.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). Relevant <i>in vitro</i>, preclinical, and clinical studies regarding AS, wound healing, fibrosis, and drug delivery systems were selected and synthesized to analyze efficacy and safety.</p><p><strong>Results: </strong>AS accelerates healing through multifaceted mechanisms: it exerts anti-inflammatory effects <i>via</i> NF-κB and MAPK pathways, reduces oxidative stress through Nrf2/HO-1 signaling, and inhibits fibrosis by modulating TGF-β/Smad axes. Additionally, AS promotes angiogenesis and collagen synthesis. While clinical data supports its use in skin wounds, its gastrointestinal application is hindered by poor bioavailability. Novel delivery systems, including hydrogels and microneedles, are identified as solutions for localized, sustained release.</p><p><strong>Conclusion: </strong>AS offers a promising therapeutic evolution, moving from reliance on passive acid suppression toward a synergistic model that integrates acid control with active mucosal regeneration for ESD management. Future research should focus on optimizing endoscope-compatible delivery platforms to facilitate clinical translation and reduce postoperative complications.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"487-513"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499637","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":"Honokiol, a structurally defined natural product, promotes SIRT3-linked bone formation in osteoporotic bone remodeling and fracture repair.","authors":"Shanshan Xie, Changbiao Guan, Jia Zhou","doi":"10.1080/13880209.2026.2729885","DOIUrl":"10.1080/13880209.2026.2729885","url":null,"abstract":"<p><strong>Context: </strong>Honokiol is a structurally defined biphenolic natural product with reported mitochondrial and cytoprotective activities. Whether honokiol modifies pathological skeletal remodeling through sirtuin 3 (SIRT3)-linked mechanisms remains unclear.</p><p><strong>Objective: </strong>This study investigated whether honokiol regulates bone cell lineage responses and improves osteoporotic bone remodeling and fracture repair through SIRT3-associated bone formation.</p><p><strong>Materials and methods: </strong>Mouse bone marrow-derived mesenchymal stem cells and RAW264.7 cells were used to assess osteogenesis, adipogenesis, and osteoclastogenesis after recombinant SIRT3, honokiol, or SIRT3 siRNA transfection. <i>In vivo</i> effects were examined in ovariectomized mice and stabilized femoral fracture models. Local AAV-shSIRT3 delivery was used to evaluate target dependence. Outcomes included micro-computed tomography, histology, osteocalcin immunohistochemistry, calcein double labeling, and three-point bending analysis.</p><p><strong>Results: </strong>Recombinant SIRT3 enhanced osteogenic mineralization and suppressed adipogenic differentiation and osteoclastogenesis. Honokiol increased SIRT3 expression and produced a similar lineage-shifting profile. SIRT3 knockdown markedly attenuated honokiol-induced osteogenesis, whereas its anti-adipogenic and anti-osteoclastogenic effects were only partly reduced. In ovariectomized mice, honokiol improved trabecular microarchitecture, mineral apposition, osteoblast activity, and femoral strength while reducing marrow adiposity and osteoclast burden. In fractured femora, honokiol increased mineralized callus formation, osteoblast activity, and biomechanical recovery. Local AAV-shSIRT3 intervention weakened these benefits, particularly for bone-forming and structural endpoints.</p><p><strong>Discussion and conclusion: </strong>Honokiol demonstrates a preclinical skeletal pharmacological profile characterized by predominantly SIRT3-linked bone formation. Its broader effects on adipogenic and osteoclast-associated responses appear only partly SIRT3-dependent.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1045-1061"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137827","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":"Mechanisms of action and therapeutic potential of PCSK9-regulating drugs.","authors":"Chenrui Qi, Daming Fan, Lei Wang, Lubo Guo, Huihui Jiang, Lu Wang","doi":"10.1080/13880209.2025.2514021","DOIUrl":"10.1080/13880209.2025.2514021","url":null,"abstract":"<p><strong>Context: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) metabolism and is a key target for cardiovascular therapies. It also plays roles in inflammation, cancer, and metabolic disorders, prompting interest in repurposing PCSK9-targeting drugs for non-lipid conditions.</p><p><strong>Objective: </strong>This review comprehensively summarizes PCSK9-regulating medications, delves into their mechanisms of action, and explores their increasingly expanding therapeutic potential across multiple organ systems, such as the liver, immune system, small intestine, heart, brain, and pancreas.</p><p><strong>Methods: </strong>A comprehensive literature search was carried out in databases such as PubMed, with keywords like 'PCSK9 inhibitors', 'lipid metabolism', 'liver', 'immune system', 'neoplasms' and 'PCSK9-related diseases'. The search was meticulously designed to cover relevant research extensively. Only those studies that delved into the molecular mechanisms underlying PCSK9 regulation and the practical clinical applications of PCSK9-targeting therapies were selected for inclusion.</p><p><strong>Results: </strong>PCSK9-regulating drugs, encompassing monoclonal antibodies, small peptides, antisense oligonucleotides, small interfering RNAs, and vaccines, modulate PCSK9 expression or activity at different levels. These drugs are effective in lowering LDL-C levels and demonstrate potential benefits in the treatment of inflammation, non-alcoholic fatty liver disease, renal lipotoxicity, and various metabolic disorders. They mainly exert their effects by controlling PCSK9 gene transcription, influencing mRNA translation, and blocking the interaction between PCSK9 and LDL-R.</p><p><strong>Conclusions: </strong>PCSK9-regulating drugs hold great promise for treating a diverse array of diseases. Future research should focus on optimizing their application in personalized therapies that target multiple pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"428-446"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476283","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":"An exploratory evaluation of the interaction risk between herbal products and pharmaceutical medicines used concurrently for disease management in Blantyre, Malawi.","authors":"Kumbukani K Nyirenda, John Mponda, Ibrahim Chikowe, Esther Kawonga, Nellie Twatasha Gomani Phiri, Mervis Msukwa, Chimota Phiri, Amy L Roe, Mary F Paine, Bill Gurley, Hellen Oketch-Rabah, Stefan Gafner, Julie Krzykwa, Constance A Mitchell, Michelle R Embry, Syril Pettit, Dallas J Smith","doi":"10.1080/13880209.2025.2586351","DOIUrl":"10.1080/13880209.2025.2586351","url":null,"abstract":"<p><strong>Context: </strong>The use of herbal products in Malawi remains widespread and culturally significant, often occurring alongside pharmaceutical medicine treatments. As the burden of non-communicable diseases such as diabetes and hypertension continues to rise, the potential for herbal-drug interactions (HDIs) represents an underexamined public health concern.</p><p><strong>Objective: </strong>Evaluate the concurrent use of herbal products and pharmaceutical medicines among patients with diabetes or hypertension in a large health care facility in Malawi and identify potential adverse HDIs.</p><p><strong>Materials & methods: </strong>An exploratory mixed-methods, cross-sectional study was conducted with 301 patients attending a diabetes or hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants self-reported herbal and pharmaceutical use, and a targeted literature review was undertaken to assess potential pharmacokinetic and pharmacodynamic interactions between commonly reported herbal products and prescribed medications.</p><p><strong>Results: </strong>Participants reported concurrent use of a wide variety of herbal products (e.g., garlic, ginger, okra, lemon, mango, moringa) with prescription medicines (e.g., metformin, insulin, glibenclamide, hydrochlorothiazide, enalapril, amlodipine). While clinical outcomes were not independently verified, literature review findings, in some cases, indicated meaningful potential for HDIs.</p><p><strong>Discussion and conclusion: </strong>This study provides foundational data on herbal-pharmaceutical co-use in Malawi and highlights the need for expanded research, improved documentation of herbal use in healthcare settings, and improved education for patients and providers. Integrating awareness of herbal product use into clinical care is essential, and the methodology and findings may inform future hypothesis-driven studies across Africa and other regions where traditional and modern medicine use overlaps.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"877-895"},"PeriodicalIF":6.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12632214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557416","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}