Pharmaceutical Biology最新文献

{"title":"Correction.","authors":"","doi":"10.1080/13880209.2025.2444094","DOIUrl":"10.1080/13880209.2025.2444094","url":null,"abstract":"","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"14"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876902","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":"Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis.","authors":"Xueling Yang, Qinglin Luo, Zhifen Wu, Chunxuan Wang, Yuanjing Yang, Luquan Zheng, Ke Li, Lei Zhao, Yang Jurong","doi":"10.1080/13880209.2025.2498166","DOIUrl":"https://doi.org/10.1080/13880209.2025.2498166","url":null,"abstract":"<p><strong>Context: </strong>Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb <i>Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge)</i>, is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.</p><p><strong>Objective: </strong>This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.</p><p><strong>Materials and methods: </strong>Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.</p><p><strong>Results: </strong>Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. <i>In vitro</i> studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.</p><p><strong>Discussion and conclusions: </strong>Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"364-373"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987255","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":"Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process.","authors":"Zixuan Hu, Yuting Li, Nan Yao, Haining Gan, Qiaohuang Zeng, Xuejun Huang, Dane Huang, Dake Cai, Yuxing Chen","doi":"10.1080/13880209.2025.2509020","DOIUrl":"10.1080/13880209.2025.2509020","url":null,"abstract":"<p><strong>Context: </strong>Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.</p><p><strong>Objective: </strong>Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.</p><p><strong>Materials and methods: </strong>ApoE^-/- mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.</p><p><strong>Results: </strong>In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.</p><p><strong>Discussion and conclusions: </strong>The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"387-401"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128201","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":"Phenolic compounds from <i>Origanum majorana</i> with biofilm-inhibitory activity against methicillin-resistant <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> strains.","authors":"Annamária Kincses, Tasneem Sultan Abu Ghazal, Katalin Veres, Gabriella Spengler, Judit Hohmann","doi":"10.1080/13880209.2025.2511805","DOIUrl":"10.1080/13880209.2025.2511805","url":null,"abstract":"<p><strong>Context: </strong>Antibiotic resistance in bacteria is a growing global problem, with biofilm formation and efflux pumps playing crucial roles in this issue.</p><p><strong>Objective: </strong>This study explores the effects of phenolic compounds of <i>Origanum majorana</i> against <i>Escherichia coli</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strains by inhibiting biofilm formation and efflux pumps.</p><p><strong>Materials and methods: </strong>The methanolic extract of <i>O. majorana</i> was fractionated guided by an antibiofilm assay, and the active fractions were analyzed by multistep chromatographic separation to yield five pure compounds. Their structures were then determined using 1D and 2D nuclear magnetic resonance spectroscopy. The minimum inhibitory concentrations of the extracts, fractions, and isolated compounds were determined <i>via</i> the microdilution method in a 96-well plate. Antibiofilm activity was assessed using the crystal violet method, and the effect on efflux pumps was tested by a real-time ethidium bromide accumulation assay.</p><p><strong>Results: </strong>Arbutin (<b>1</b>), apigenin 7-<i>O</i>-glucoside (<b>2</b>), 6'-caffeoylarbutin (<b>3</b>), rosmarinic acid (<b>4</b>), and 2-deoxy-d-1,4-ribonolactone (<b>5</b>) were isolated from the aqueous methanolic extract. Compounds <b>1</b>, <b>2</b>, and <b>4</b> reduced <i>E. coli</i> biofilm formation by 24.82%-42.98% at 100 µM, whereas only arbutin (<b>1</b>) moderately suppressed biofilm formation of MRSA (23.15 ± 1.56% at 50 µM). Arbutin also demonstrated efflux pump inhibitory activity against MRSA (relative fluorescence index of 0.49 at 100 µM).</p><p><strong>Discussion and conclusions: </strong>The newly discovered natural antibiofilm agents show promise as candidates for treating biofilm-associated infections and combating antibiotic-resistant bacteria.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"402-410"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209116","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":"Modified Xiao-Qing-Long-decoction prevents inflammation and promotes Nur77 expression in mice with acute respiratory distress syndrome by inhibiting HDAC7 expression.","authors":"Qing Zhang, Yafen Liu, Lu Jiang, Dongdong Yang","doi":"10.1080/13880209.2025.2459247","DOIUrl":"10.1080/13880209.2025.2459247","url":null,"abstract":"<p><strong>Context: </strong>Modified Xiao-Qing-Long-decoction (MXQLD) is believed to have the potential to alleviate lung diseases.</p><p><strong>Objective: </strong>We explored the effects and mechanisms of MXQLD in acute respiratory distress syndrome (ARDS).</p><p><strong>Materials and methods: </strong>Thirty male C57BL/6 mice were randomized into sham (distilled water), model (distilled water), MXQLD (1 g/kg MXQLD), DEX (distilled water + 0.7 mg/kg dexamethasone), MXQLD + oe-HDAC7 (HDAC7 over-expression + 1 g/kg MXQLD) groups. Except for HDAC7 over-expression on day 0 and dexamethasone injection on day 12, all treatments were administered every two days from day 0 to day 10. On day 12, except for the sham group, all mice underwent cecal ligation and puncture surgery to establish ARDS models. After surgery, pulmonary functions, protein concentration of bronchoalveolar lavage fluid (BALF) and lung tissue morphology in mice were detected. Furthermore, pro-inflammatory cytokine concentrations (IL-6, IL-1β, and TNF-α) in BALF supernatant and serum were quantified. Additionally, HDAC7, Nur77, ZO-1, occludin, and claudin protein expressions were detected.</p><p><strong>Results: </strong>MXQLD treatment improved pulmonary functions and alleviated lung injury for ARDS mice. Furthermore, MXQLD treatment decreased protein concentration in BALF, and inhibited pro-inflammatory cytokine release in BALF supernatant and serum for ARDS mice. Additionally, MXQLD treatment down-regulated HDAC7 expression, but up-regulated Nur77, ZO-1, occludin, and claudin expressions for ARDS mice. Importantly, the preventive effects of MXQLD in ARDS mice were reversed by HDAC7 over-expression.</p><p><strong>Discussion and conclusion: </strong>MXQLD may prevent inflammation and promote Nur77 expression in ARDS by inhibiting HDAC7 expression, indicating that MXQLD may be a promising drug for preventing ARDS.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"110-117"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189931","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":"Non-linear oral bioavailability and clinical pharmacokinetics of high-dose <i>Andrographis paniculata</i> ethanolic extract: relevant dosage implications for COVID-19 treatment.","authors":"Phanit Songvut, Jaratluck Akanimanee, Tawit Suriyo, Nanthanit Pholphana, Nuchanart Rangkadilok, Duangchit Panomvana, Porranee Puranajoti, Jutamaad Satayavivad","doi":"10.1080/13880209.2024.2444446","DOIUrl":"10.1080/13880209.2024.2444446","url":null,"abstract":"<p><strong>Aim: </strong>Insufficient quality control and limited dissolution of <i>Andrographis paniculata</i> extract capsules restricts their bioavailability and hinder the clinical use for treating mild coronavirus disease 2019 (COVID-19) patients.</p><p><strong>Objective: </strong>This study aims to investigate pharmacokinetics and safety of high-dosage <i>A. paniculata</i> ethanolic extract (equivalent to 180 or 360 mg/day of andrographolide), relevant dosages used for mild COVID-19 treatment.</p><p><strong>Methods: </strong>An open-label, single-dose, and repeated-dose conducted in healthy volunteers. Subjects received capsules containing ethanolic extract equivalent to andrographolide dosage of either 60 or 120 mg per dose, taken every eight hours daily (totaling 180 or 360 mg/day). Safety was assessed through blood chemical analysis and adverse event monitoring after 7 days of ethanolic extract administration.</p><p><strong>Results: </strong>Pharmacokinetics of ethanolic extract indicated low plasma levels of the major diterpenoids. The maximum plasma concentration (Cmax) of andrographolide did not exhibit a dose-proportional increase, reaching 6.44 and 11.62 µg/L for single and repeated doses of 60 mg/day, respectively. Doubling the dose (120 mg/day) only resulted in slightly higher Cmax (6.97 and 15.03 µg/L for single and repeated doses, respectively). Safety evaluation revealed mild, transient adverse events, but all parameters remained within normal ranges.</p><p><strong>Conclusions: </strong>This study highlights limitations in the pharmacokinetics of the ethanolic extract of <i>A. paniculata</i>. It indicated non-linear proportionality in the oral bioavailability of andrographolide. These findings suggest that current extraction process of ethanolic extract may hinder its effectiveness. Further research is warranted to explore alternative extraction methods or formulation developments that can enhance the bioavailability of andrographolide and its potential therapeutic effects for COVID-19 treatment.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"42-52"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932585","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":"Research progress of Chinese medicinal monomers in the process of melanoma occurrence.","authors":"Yan Shang, Hailong Zhao","doi":"10.1080/13880209.2024.2445695","DOIUrl":"10.1080/13880209.2024.2445695","url":null,"abstract":"<p><strong>Context: </strong>Melanoma's aggressiveness and resistance to radiotherapy highlight an urgent need for innovative treatments. Traditional Chinese medicine (TCM) offers a unique approach through its 'four natures' theory-cold, cool, warm, and hot.</p><p><strong>Objective: </strong>This review aims to explore the potential of TCM's 'four natures' herbal monomers in melanoma treatment, providing an alternative to conventional therapies.</p><p><strong>Materials & methods: </strong>A systematic literature review was conducted by accessing various databases, including Baidu Scholar, PubMed, Science Citation Index Expanded (SCIE), and China National Knowledge Infrastructure (CNKI), to synthesize the most recent findings on traditional Chinese medicine monomers. Furthermore, this review elucidated the mechanisms underlying their role in melanoma retention.</p><p><strong>Results: </strong>TCM's multi-component, multi-target approach has shown promise in addressing melanoma's complexity, with specific monomers demonstrating the ability to modulate tumor behavior.</p><p><strong>Discussion and conclusions: </strong>The 'four natures' theory in TCM presents a novel perspective for melanoma treatment, warranting further investigation into its clinical applications and potential integration with modern oncology.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"53-67"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953117","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":"Medicinal plants of Sabah (North Borneo): lest we forget.","authors":"Carynn Tanbuda, Mazdida Sulaiman, Pauline Yong Pau Lin, Nor Azizun Rusdi, Jaya Sathiya Seelan, Ng Shean Yeaw, Fiffy Hasnidah Saikim, Mogana Rajagopal, Nicholas Pang Tze Ping, Melanie Martos Garcia, Jhonnel Villegas, Shari Jeffri, Veeranoot Nissapatorn, Mark S Butler, Christophe Wiart","doi":"10.1080/13880209.2025.2487557","DOIUrl":"https://doi.org/10.1080/13880209.2025.2487557","url":null,"abstract":"<p><strong>Context: </strong>The discovery of plants and bioactive compounds with the potential to become botanical or pharmaceutical drugs remains a cornerstone of drug innovation. Many of these valuable molecules originate from traditional botanical pharmacopeias, repositories of centuries-old knowledge that are often underappreciated in modern research.</p><p><strong>Objective: </strong>This review highlights the medicinal plants identified in Sabah from 1922 to 2024, analyzing their taxonomical distribution, uses, utilization among ethnic groups, and their potential for clinical uses.</p><p><strong>Methods: </strong>The data for this review were gathered from Google Scholar, PubMed, ScienceDirect, Web of Science, PubMed, the Internet Archive, and Google Books. A keyword combination of \"Medicinal\" and \"Plants\" and \"Sabah\" yielded 21,700 results. Each result was examined, and articles that did not contain information relevant to the topic or came from non-peer-reviewed journals were excluded. Each of the remaining 87 selected articles was critically reviewed to extract pertinent information.</p><p><strong>Results: </strong>A review of the available data indicates that 696 plant species are used in Sabah, including 412 angiosperms. These plants are primarily utilized to treat diseases or symptoms related to infections, digestive issues, injuries, and pains. Notably, 156 species employed by local Sabahan Dusunic, Murutic, and Kelabit ethnic groups remain unstudied in terms of their phytochemical and pharmacological properties, highlighting their potential for further investigation.</p><p><strong>Conclusion: </strong>Sabah's medicinal plants offer tremendous potential for discovering natural products of therapeutic value.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"288-332"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039237","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":"Tumor organoids in cancer medicine: from model systems to natural compound screening.","authors":"Rong Cong, Can Lu, Xinying Li, Zhijie Xu, Yaqin Wang, Shusen Sun","doi":"10.1080/13880209.2025.2458149","DOIUrl":"10.1080/13880209.2025.2458149","url":null,"abstract":"<p><strong>Context: </strong>The advent of tissue engineering and biomedical techniques has significantly advanced the development of three-dimensional (3D) cell culture systems, particularly tumor organoids. These self-assembled 3D cell clusters closely replicate the histopathological, genetic, and phenotypic characteristics of primary tissues, making them invaluable tools in cancer research and drug screening.</p><p><strong>Objective: </strong>This review addresses the challenges in developing <i>in vitro</i> models that accurately reflect tumor heterogeneity and explores the application of tumor organoids in cancer research, with a specific focus on the screening of natural products for antitumor therapies.</p><p><strong>Methods: </strong>This review synthesizes information from major databases, including Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, Google Scholar, Scopus, PubMed and Springer Link. Publications were selected without date restrictions, using terms such as 'organoid', 'natural product', 'pharmacological', 'extract', 'nanomaterial' and 'traditional uses'. Articles related to agriculture, ecology, synthetic work or published in languages other than English were excluded.</p><p><strong>Results and conclusions: </strong>The review identifies key challenges related to the efficiency and variability of organoid generation and discusses ongoing efforts to enhance their predictive capabilities in drug screening and personalized medicine. Recent studies utilizing patient-derived organoid models for natural compound screening are highlighted, demonstrating the potential of these models in developing new classes of anticancer agents. The integration of natural products with patient-derived organoid models presents a promising approach for discovering novel anticancer compounds and elucidating their mechanisms of action.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"89-109"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075290","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 triterpene-enriched natural extract from <i>Eucalyptus tereticornis</i> modulates the expression of genes involved in adipogenesis, lipolysis, and extracellular matrix remodeling in a primary human and mouse cell line adipocyte.","authors":"Sergio Acin, Alejandro Mejia-Garcia, Geysson Javier Fernandez, Norman Balcazar","doi":"10.1080/13880209.2025.2505443","DOIUrl":"10.1080/13880209.2025.2505443","url":null,"abstract":"<p><strong>Context: </strong>Obesity induces alterations in adipocyte size, tissue inflammation, vascularization, and extracellular matrix composition. Previous studies have shown that a leaf extract of <i>Eucalyptus tereticornis</i> Sm. (Myrtaceae), with ursolic acid, oleanolic acid, and ursolic acid lactone mixed with minor metabolites, provided a superior antiobesity effect than reconstituted triterpenoid mixtures in adipocyte cell lines and a pre-diabetic mouse model. Further identification of the molecular mechanisms of action of this mixture of triterpenes is required.</p><p><strong>Objective: </strong>This study analyzes the effect of the natural extract and its components on early RNA expression profiles in human primary cultured adipocytes and a mouse cell line.</p><p><strong>Materials and methods: </strong>RNA was sequenced using the DNBseq platform and the EnrichR software to perform gene enrichment analysis using the Gene Ontology database, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To conduct clustering analysis, the normalized counts of each gene and applied k-means clustering were standardized.</p><p><strong>Results: </strong>The combination of molecules in the natural extract has an additive or synergic effect that increases the number of genes regulated associated with the biological functionality of differentiating adipocytes, with UAL playing a central role. The natural extract modulates PPAR, Wnt, and Extracellular Matrix organization pathways significantly in both cellular models. Remarkably, the extract downregulates the expression of genes involved in lipid metabolism, adipogenesis, and adipocyte fat load, such as PRKAR2B, LPIN1, FABP4, Scd1, MC5R, CD36, PEG10, and HMGCS1.</p><p><strong>Discussion and conclusions: </strong>Our study shows that <i>Eucalyptus tereticornis</i> extract is a promising option for treating adipocyte tissue dysfunction derived from obesity.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"374-386"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094534","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}