Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Multi-Target Renal Protection of Wine-Processed Polygonatum sibiricum Against Cisplatin-Induced Nephrotoxicity: Integrated Phytochemistry, Network Pharmacology and Experimental Validation","authors":"Yu Jiang,&nbsp;Wei Qiao,&nbsp;Kaili Guo,&nbsp;Hanbin Luo,&nbsp;Xin Liu,&nbsp;Jiping Liu,&nbsp;Hao Wei,&nbsp;Bin Wang,&nbsp;Xiao Chen,&nbsp;Hong Ren,&nbsp;Xingmei Zhu","doi":"10.1111/bcpt.70092","DOIUrl":"https://doi.org/10.1111/bcpt.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute kidney injury (AKI) is a serious complication of cisplatin chemotherapy, with limited treatment options. In this study, we investigated the protective effects of wine-processed <i>Polygonatum sibiricum</i> (WP. <i>P. sibiricum</i>) against cisplatin-induced acute kidney injury (DDP-AKI) using an integrated approach combining UPLC-Q-TOF-MS/MS analysis, network pharmacology, molecular docking and in vivo/vitro experimental validation. The WP. <i>P</i>. <i>sibiricum</i> extract demonstrated dose-dependent renal protection in mice with DDP-AKI, significantly attenuating weight loss (<i>p &lt;</i> 0.05), improving renal function (reduced serum BUN by 29.2%–38.9% and CRE by 8.0%–36.7%), reducing tubular necrosis and biomarkers (NGAL decreased 49.2%–86.6%, <i>p &lt;</i> 0.01), while showing no hepatotoxicity. In addition, WP. <i>P</i>. <i>sibiricum</i> elevated SOD activity by 15.5%–28.5% and reduced MDA levels by 13.5%–26.9% (<i>p &lt;</i> 0.01). UPLC-Q-TOF-MS/MS analysis elucidated eight bioactive components (e.g., flavonoids and glycosides). Network pharmacology revealed 132 targets shared by WP. <i>P</i>. <i>sibiricum</i> and DDP-AKI, such as mTOR, STAT3 and PPAR. Molecular docking confirmed strong binding (≤ −6.0 kcal·mol⁻¹) between core components and targets. Mechanistically, WP. <i>P</i>. <i>sibiricum</i> activated the mTOR pathway (<i>p &lt;</i> 0.01) and suppressed apoptosis (<i>p &lt;</i> 0.01), with effects comparable or superior to those of NAC. This study is the first to validate the nephroprotective effect of WP. <i>P</i>. <i>sibiricum</i>, linking its multi-target effects (mTOR/ROS/apoptosis) to enhanced phytochemical potency. These findings support WP. <i>P</i>. <i>sibiricum</i> as a clinically translatable adjuvant for DDP-AKI.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Carcinogenic Potential of PFOA: A Molecular Network Approach to Liver Toxicity","authors":"Libi Tan,&nbsp;Tianyu She,&nbsp;Siyan Huo,&nbsp;Rubing Lin,&nbsp;Nannan Cheng,&nbsp;Jing Li","doi":"10.1111/bcpt.70101","DOIUrl":"https://doi.org/10.1111/bcpt.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Perfluorooctanoic acid (PFOA), a prototypical per- and polyfluoroalkyl substance (PFAS), is widely used in industrial and consumer products but is classified as a Group 1 carcinogen by the IARC due to its environmental persistence and bioaccumulation. PFOA primarily targets the liver, inducing stress responses and mitochondrial-mediated apoptosis, while promoting hepatoma cell proliferation through the mTOR pathway. To investigate the molecular mechanisms of PFOA-induced liver cancer (LIHC), we will use a network toxicology approach that integrates multi-omics data to construct a compound–target–disease network, focusing on potential targets like ALDH1B1, which encodes the aldehyde dehydrogenase family in the major pathway of alcohol metabolism. It is hypothesized that hepatic metabolic homeostasis is disrupted and hepatocellular carcinogenesis is ultimately promoted by PFOA through direct binding to ALDH1B1 and interference with its function. To confirm this, we will employ molecular docking and dynamics simulations to validate the binding interactions and toxicity mechanisms at the molecular level. This research aims to provide a comprehensive understanding of PFOA's hepatotoxicity and carcinogenicity while identifying potential targets for risk assessment and intervention strategies related to environmental exposure.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Exposure to Medications and the Risk of Congenital and Early-Onset Hearing Loss in Children: A Systematic Review and a Meta-Analysis","authors":"Asli Sena Kücükyildiz,&nbsp;Mette Østergaard Thunbo,&nbsp;Christer Zøylner Swan,&nbsp;David P. Burgner,&nbsp;Jessica E. Miller,&nbsp;Therese Ovesen,&nbsp;Lars Henning Pedersen","doi":"10.1111/bcpt.70090","DOIUrl":"https://doi.org/10.1111/bcpt.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital hearing loss (CHL) affects approximately 1–2 in 1000 children and significantly impacts development. Exposure to medications during pregnancy may impact offspring hearing; however, the ototoxic effects of different drugs have not been systematically investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review and meta-analysis was conducted following PRISMA guidelines and analysed 21 experimental and observational studies examining 60 drugs across various categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Magnesium sulphate and systemic steroids, alone or in combination, showed potential protective effects towards CHL. Specific antibiotics (e.g., gentamicin and metronidazole) and non-steroidal anti-inflammatory drugs were associated with an increased risk of CHL. Modest evidence indicated that low-dose acetylsalicylic acid increased risk, whereas higher doses did not. Other drugs, such as anti-neoplastic agents and valproic acid, showed weaker associations with CHL. Most studies had methodological limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight the urgent need for robust research to minimise preventable hearing loss in children.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discontinuing Chronic Medications Suggested for Deprescribing in Routine Clinical Practice: Nationwide Evidence From Routinely Collected Data in Swedish Older Adults","authors":"Karl-Hermann Sielinou Kamgang,&nbsp;Carina Lundby,&nbsp;Máté Szilcz,&nbsp;Kristina Johnell,&nbsp;Jonas W. Wastesson","doi":"10.1111/bcpt.70093","DOIUrl":"https://doi.org/10.1111/bcpt.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>National estimates of drug discontinuation for deprescribing targets in older adults are limited, partly due to challenges distinguishing planned deprescribing from poor adherence. Focusing on individuals with multidose dispensing (MDD), characterized by high adherence by design, may yield realistic discontinuation rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To estimate the rates of discontinuation for chronically used drugs targeted for deprescribing among older adults, and to describe reinitiation among users of MDD and standard dispensing (non-MDD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this nationwide cohort study, Swedish adults aged ≥ 75 were identified from national registers. At baseline (1 January 2021), chronic users of seven drug classes were defined. We estimated the 12-month cumulative incidence of discontinuation (defined as no new dispensing during the treatment episode of the prior dispensing plus a 180-day grace period) and the proportion of patients restarting therapy within 180 days after discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 162 518 chronic users: benzodiazepines (<i>n</i> = 69 511), PPIs (<i>n</i> = 43 973), antidepressants (<i>n</i> = 41 577), statins (<i>n</i> = 36 085), cholinesterase inhibitors (<i>n</i> = 6408), bisphosphonates (<i>n</i> = 5801) and antipsychotics (<i>n</i> = 4380). Discontinuation rates were low (8.3–51.5 per 1000 person-years), and non-MDD users had higher discontinuation and reinitiation rates across all drugs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Discontinuation among Swedish older adults is infrequent. Irregular dispensing is likely misclassified as deprescribing, and MDD users may better reflect true discontinuation in routinely collected data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Deprescribing Intervention for Proton Pump Inhibitors in Primary Care: A Co-Design Approach With General Practitioners and Patients","authors":"Kristie Rebecca Weir,&nbsp;Clémentine Tombez,&nbsp;Yvonne Mattmann,&nbsp;Sofia C. Zambrano,&nbsp;Eliza Ferguson,&nbsp;Katharina Tabea Jungo,&nbsp;Martina Zangger,&nbsp;Shana Volken,&nbsp;Enriqueta Vallejo-Yagüe,&nbsp;Renata Vidonscky Lüthold,&nbsp;Angela Edith Schulthess-Lisibach,&nbsp;Christof Bieri,&nbsp;Michaela Barbier,&nbsp;Pascal Juillerat,&nbsp;Sven Streit,&nbsp;Jennifer Inauen","doi":"10.1111/bcpt.70091","DOIUrl":"https://doi.org/10.1111/bcpt.70091","url":null,"abstract":"<p>Proton Pump Inhibitors (PPIs) are widely prescribed medications globally. PPIs are often inappropriately used – for example, prescribed without a clear indication, at higher-than-necessary doses, or for longer durations than needed – resulting in increased risks of adverse health outcomes such as nutrient deficiencies, osteoporosis-related fractures, and kidney disease. The effectiveness of current deprescribing interventions is inconsistent; this may relate to the misalignment with behavioural mechanisms, supporting the need for a mechanism-driven approach that targets key behavioural determinants. We co-designed a PPI deprescribing intervention with patients and health professionals for the Swiss primary care setting. This involved identifying behavioural determinants of PPI deprescribing from the literature at both the general practitioner (GP) and patient levels, mapping them to behaviour change techniques, selecting intervention elements, and developing contextualised intervention tools to effectively influence these determinants. The intervention tools were iteratively developed and assessed through qualitative methods with 16 patients and 18 health professionals. Participants considered the tools to be acceptable and practical for use in the Swiss primary care context.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special Collection: Mechanisms of Vasodilatation Endothelium-Dependent Hyperpolarization (MOVD/EDH2024)","authors":"Christopher J. Garland","doi":"10.1111/bcpt.70095","DOIUrl":"https://doi.org/10.1111/bcpt.70095","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Rivaroxaban Plasma Concentration Using Chromogenic Anti-Xa Assays and UHPLC–MS/MS in Chinese Patients With Atrial Fibrillation","authors":"Xiao-qin Liu,&nbsp;Yi Gu,&nbsp;Yu-fei Zhang,&nbsp;Wei Shen,&nbsp;Zhi-chun Gu,&nbsp;Ming-kang Zhong,&nbsp;Hong-yan Ding,&nbsp;Chun-lai Ma","doi":"10.1111/bcpt.70088","DOIUrl":"https://doi.org/10.1111/bcpt.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>Accurate quantification of rivaroxaban concentration is essential in some specific clinical situations. A prospective study was conducted to compare the rivaroxaban concentration measured by Zhenyuan anti-Xa assay with that by reference methods (ultrahigh performance liquid chromatography with tandem mass spectrometry [UHPLC–MS/MS] and Biophen DiXal) in 243 plasma samples from 182 patients with non-valvular atrial fibrillation. Zhenyuan anti-Xa assays demonstrated less bias versus reference methods in samples with concentrations exceeding 50 μg/L compared to those in the &lt; 50 μg/L group. Strong correlations were observed between Zhenyuan anti-Xa assays and both reference methods (Pearson's correlation coefficient 0.976 and 0.988, respectively). However, Bland–Altman analysis revealed systematic underestimation by Zhenyuan anti-Xa assays, with mean biases of 41.87 μg/L (vs. UHPLC–MS/MS) and 26.76 μg/L (vs. Biophen DiXal), particularly pronounced at higher levels. Rivaroxaban concentration in patients from clinical settings was with greater variability compared to the expected ranges. Patients taking underdose of rivaroxaban are more likely to have a trough concentration falling below the targeted therapeutic range.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiao-Jie-An Capsule Alleviates Uterine Fibroids by Modulating Oestrogen–Progesterone Balance and Reducing Inflammatory Response","authors":"Yi Ying,&nbsp;Jihan Liu,&nbsp;Shanshan Ju,&nbsp;Meiyu Shen,&nbsp;Nannan Li,&nbsp;Yongpan An,&nbsp;Feng Lu,&nbsp;Yiwen Tang,&nbsp;Zhijing Wu,&nbsp;Baoxue Yang,&nbsp;Min Li","doi":"10.1111/bcpt.70072","DOIUrl":"https://doi.org/10.1111/bcpt.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Uterine fibroids (UF) are benign tumours composed of smooth muscle cells and fibrous connective tissue. UF are common among women aged 30–50 years and often present with symptoms such as anaemia, pelvic pain and bladder dysfunction. Xiao-Jie-An Capsule (XJA), a traditional Chinese medicine formula, has been clinically used to treat UF. However, the underlying mechanisms of its efficacy remain unclear. The aim of this study was to determine the therapeutic effect of XJA and related mechanisms in a UF rat model. The experimental results showed that XJA significantly alleviated abnormalities in uterine morphology, tissue structure and purulent discharge in the UF rats. XJA also reduced serum oestrogen and progesterone in UF rats. Moreover, XJA decreased blood pro-inflammatory factors in UF rats by modulating the TLR4/NF-κB pathway. Western blotting and immunohistochemistry analyses revealed that XJA decreased the expression of Bcl-2, PCNA and Ki67 while increasing the expression of Bax, indicating its role in inhibiting cell proliferation and promoting apoptosis. Additionally, XJA exhibited immunomodulation in UF rats. In summary, our study suggests that XJA alleviates UF by multiple targets and mechanisms, such as restoring the oestrogen–progesterone balance, reducing inflammation, inhibiting cell proliferation, inducing apoptosis and regulating immune function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LW-AFC Protects Against Neurological and Neuropsychiatric Effects of SARS-CoV-2 Spike Protein in Mice","authors":"Wenyi Xiao,&nbsp;Jiao Wang,&nbsp;Jianhui Wang,&nbsp;Lu Han,&nbsp;Donghui Wei,&nbsp;Wenxia Zhou,&nbsp;Ning Jiang","doi":"10.1111/bcpt.70085","DOIUrl":"https://doi.org/10.1111/bcpt.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>Numerous clinical studies show that besides respiratory symptoms, COVID-19 patients frequently undergo neurological and neuropsychiatric problems. However, effective treatments for these problems remain insufficient. LW-AFC, derived from traditional Chinese medicine Liuwei Dihuang decoction, is effective in improving cognitive and mental dysfunctions in many animal models. In this study, we aimed to investigate the impact of SARS-CoV-2 spike protein on the mouse nervous system, evaluate the beneficial effects of LW-AFC, and explore its underlying mechanisms. After a single intranasal administration of spike protein, mice showed a significant decline in motor performance from week 1, and this decline persisted until week 32. Three weeks after administration, anxiety-like behaviors and spatial memory deficits appeared but returned to normal by week 32. It is suggested that spike protein causes dynamic neurological and psychiatric impairments in mice, which is consistent with clinical findings. LW-AFC reversed these effects, enhancing motor performance, improving spatial memory, and alleviating anxiety. LW-AFC increased the number of NeuN-positive cells and decreased the number of Iba-1-positive cells. Additionally, LW-AFC reduced the levels of pro-inflammatory cytokines IL-6 and TNF-α, increased ATP levels, and enhanced the activity of mitochondrial respiratory chain complex I. These findings indicate that LW-AFC holds great potential as a therapeutic option for SARS-CoV-2-induced neuropsychiatric impairments.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triterpenoid From Persimmon Leaves (Diospyros kaki L.f.) Exerted Anti–Type 2 Diabetic Effects and No Toxicity in Experimental Animals","authors":"Hung Van Nguyen,&nbsp;Ha Thu Thi Nguyen,&nbsp;Nhan Trong Le,&nbsp;Trang Quynh Tran,&nbsp;Loan Thanh Thi Nguyen,&nbsp;Thanh Phuong Mai,&nbsp;Phong Xuan Pham,&nbsp;Anh Van Thi Pham,&nbsp;Hoai Thi Nguyen","doi":"10.1111/bcpt.70081","DOIUrl":"https://doi.org/10.1111/bcpt.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>The acute and subchronic toxicity, along with the anti–type 2 diabetic effects, of a triterpenoid extract from persimmon leaves (Tri DKL) was evaluated in animals. Acute oral toxicity was assessed in <i>Swiss</i> mice, whereas subchronic toxicity was investigated in <i>Wistar</i> rats given Tri DKL at 125 and 375 mg/kg body weight (BW) daily for 90 days. Type 2 diabetes was induced in <i>Swiss</i> mice via an 8-week high-fat diet, followed by a single intraperitoneal injection of streptozotocin (100 mg/kg BW). Diabetic mice were subsequently treated with Tri DKL at 250 and 750 mg/kg BW/day for 2 weeks. Results showed that Tri DKL, even at the highest dose of 2500 mg/kg, did not produce any signs of acute toxicity in mice. In rats, subchronic administration of 125 and 375 mg/kg BW/day caused no significant alterations in general behaviours, haematological parameters or hepatic/renal function markers. In diabetic mice, Tri DKL significantly reduced blood glucose levels at both doses. It also lowered total cholesterol and hepatic malondialdehyde levels. Notably, at 250 mg/kg BW/day, Tri DKL decreased triglyceride levels while improving liver and pancreatic tissue histology. Overall, Tri DKL exhibited no acute or subchronic toxicity in animals and demonstrated hypoglycemic and lipid-lowering effects in type 2 diabetic mice, suggesting potential therapeutic benefits.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}