Pharmaceutical BiologyPub Date : 2025-12-01Epub Date: 2025-05-07DOI: 10.1080/13880209.2025.2498166
Xueling Yang, Qinglin Luo, Zhifen Wu, Chunxuan Wang, Yuanjing Yang, Luquan Zheng, Ke Li, Lei Zhao, Yang Jurong
{"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}
Pharmaceutical BiologyPub Date : 2025-12-01Epub Date: 2025-02-04DOI: 10.1080/13880209.2025.2459247
Qing Zhang, Yafen Liu, Lu Jiang, Dongdong Yang
{"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}
Pharmaceutical BiologyPub Date : 2025-12-01Epub Date: 2025-01-10DOI: 10.1080/13880209.2024.2445695
Yan Shang, Hailong Zhao
{"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}
Pharmaceutical BiologyPub Date : 2025-12-01Epub Date: 2025-02-01DOI: 10.1080/13880209.2025.2458149
Rong Cong, Can Lu, Xinying Li, Zhijie Xu, Yaqin Wang, Shusen Sun
{"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}
Pharmaceutical BiologyPub Date : 2025-12-01Epub Date: 2025-05-02DOI: 10.1080/13880209.2025.2487557
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
{"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":"Overview of current research on traditional Chinese medicine in skin disease treatment: a bibliometric analysis from 2014 to 2024.","authors":"Lin Li, Lanfang Zhang, Yuan Li, Yuan Cai, Xue Wen, Chenjie Zheng, Chuyan Wu, Yunlei Bao, Feng Jiang, Nana Sun, Ni Zeng","doi":"10.1080/13880209.2024.2443415","DOIUrl":"10.1080/13880209.2024.2443415","url":null,"abstract":"<p><strong>Context: </strong>Recent research has revealed significant advancements in the field of traditional Chinese medicine (TCM) for skin diseases. However, there is a lack of visualization analysis within this research domain.</p><p><strong>Objective: </strong>To analyze the research directions and advancements in TCM research in skin diseases.</p><p><strong>Materials and methods: </strong>Publications related to TCM in skin diseases from 2014 to 2024 were searched on the Web of Science Core Collection (WoSCC), VOSviewer, CiteSpace, and the R package \"bibliometrix\" were employed to visualize and analyze the retrieved data.</p><p><strong>Results: </strong>The study included 527 articles published in 25 countries. The number of publications consistently increased from 2014 to 2024. The Guangzhou University of Chinese Medicine was the most noteworthy institution in this field. Among the journals in this domain, the <i>Journal of Ethnopharmacology</i> was the most popular, and most frequently co-cited journal. Chuanjian Lu published the most papers and Yin-Ku Lin was the most frequently co-cited author. Among keywords, \"psoriasis\" appeared the most frequently. Additionally, several emerging research hotspots were identified, indicating the transition from traditional Chinese therapies to investigations of the molecular interactions and network pharmacology of Chinese herbs in treatment of skin diseases over the past decade.</p><p><strong>Discussion and conclusion: </strong>This visualization analysis summarizes the research directions and advancements in TCM research on skin diseases. It presents a comprehensive examination of the latest research frontiers and trends and serves as a valuable reference for scholars engaged in the study of TCM research.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"27-41"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Apium graveolens</i> L. alleviates acute lung injury in human A-549 cells by reducing NF-κB and NLRP3 inflammasome signaling.","authors":"Lan-Chi Hsieh, Shu-Ling Hsieh, Tsu-Ni Ping, Yi-Chun Huang, Ssu-Jung Lin, Hsing-Yu Chi, Chih-Chung Wu","doi":"10.1080/13880209.2024.2433994","DOIUrl":"10.1080/13880209.2024.2433994","url":null,"abstract":"<p><strong>Background: </strong><i>Apium graveolens</i> L. (celery) is a dietary vegetable with anti-inflammatory properties. It has the potential to treat acute lung injury (ALI) caused by COVID-19 or other diseases.</p><p><strong>Objective: </strong>To investigate the effects of <i>Apium graveolens</i> water extract (AGWE) on ALI in human lung A-549 cells induced by lipopolysaccharide (LPS).</p><p><strong>Materials and methods: </strong>A-549 cells were treated with AGWE for 24 h and then stimulated with 10 μg/mL LPS for another 24 h. The effects of AGWE on cell viability, the inflammatory response, oxidative stress, and apoptosis and their regulatory factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling activation were analyzed.</p><p><strong>Results: </strong>Treatment with 5-50 μg/mL AGWE reversed the decrease in cell viability caused by LPS (<i>p</i> < 0.05). AGWE can reduce interleukin (IL)-1β, IL-6, IL-18, and TNF-α levels; their EC<sub>50</sub> values are 61.4, 65.7, 37.8, and 79.7 μg/mL, respectively. AGWE can reduce reactive oxygen species and thiobarbituric acid reactive substances in A-549 cells induced by LPS. AGWE also reduced the levels of apoptosis (EC50 of 74.8 μg/mL) and its regulators (Bid; Caspase-9, -8, and -3; Bax) and increased the levels of the mitochondrial membrane potential in A-549 cells induced by LPS. AGWE can also decrease the protein levels of NLRP3 and Caspase-1 and the activation of NF-κB signaling in A-549 cells induced by LPS.</p><p><strong>Conclusions: </strong>These results show that 10 and 50 μg/mL AGWE can reduce the acute inflammation induced by LPS by reducing NF-κB and NLRP3 inflammasome signaling and mitochondria-dependent apoptosis pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818844","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":"Total flavonoids of litchi seed inhibit breast cancer metastasis by regulating the PI3K/AKT/mTOR and MAPKs signaling pathways.","authors":"Xin Yang, Shoushi Liu, Ying Liu, Yuanshuo Wang, Dianxin Cui, Taijin Lan, Dan Zhu, Zhiheng Su, Erwei Hao, Lilan Qin, Hongwei Guo","doi":"10.1080/13880209.2025.2488135","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488135","url":null,"abstract":"<p><strong>Context: </strong>Total flavonoids from <i>Litchi chinensis</i> Sonn. (Sapindaceae) seeds (TFLS) effectively attenuate stem cell-like properties in breast cancer cells. However, their pharmacological effects and mechanisms in suppressing breast cancer metastasis remain unclear.</p><p><strong>Objective: </strong>This study aimed to elucidate the inhibitory effects and underlying mechanisms of TFLS on breast cancer metastasis.</p><p><strong>Materials and methods: </strong>The antiproliferative, migratory, and invasive activities of breast cancer cells following TFLS treatment were evaluated using CCK-8, wound-healing, and transwell assays. The epithelial-mesenchymal transition (EMT) biomarkers were evaluated <i>via</i> Western blot analysis. The anti-metastatic effects of TFLS were further validated <i>in vivo</i> using zebrafish and mouse models. Network pharmacology methodology was utilized to predict potential targets and signaling pathways, which were subsequently corroborated by Western blot. Potential active compounds were identified through molecular docking, and the chemical constituents of TFLS were analyzed and characterized using UPLC-QTOF/MS.</p><p><strong>Results: </strong>TFLS suppressed the proliferation of MDA-MB-231 and MDA-MB-468 cells, with IC<sub>50</sub> values of 44.47 μg/mL and 37.35 μg/mL at 72 h, respectively. It effectively suppressed breast cancer metastasis <i>in vitro</i>, demonstrated by a marked reduction in cellular motility and invasiveness, alongside the reversal of EMT. Consistent with pathway enrichment analysis, network pharmacology revealed that TFLS reduced the phosphorylation levels of PI3K, AKT, mTOR, JNK, ERK, and p38 in breast cancer cells. Molecular docking identified seven potential active ingredients, and UPLC-MS/MS confirmed the presence of key compounds, including procyanidin A2.</p><p><strong>Discussion and conclusion: </strong>TFLS effectively inhibits breast cancer cell proliferation, migration, and invasion <i>in vitro</i> by reversing the EMT phenotype, while suppressing metastasis <i>in vivo</i>. These effects are likely mediated <i>via</i> the attenuation of the PI3K/AKT/mTOR and MAPK signaling pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"229-249"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015311","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}