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二甲双胍与叶提取物联合应用对2型糖尿病大鼠模型肾脏氧化应激、炎症和纤维化的协同改善作用

Synergistic amelioration of renal oxidative stress, inflammation, and fibrosis by combination of metformin and leave extracts in a type 2 diabetic rat model.

作者信息

Laorodphun Pongrapee, Thongyim Saruda, Suriyaprom Sureeporn, Maphet Pornchita, Tragoolpua Yingmanee, Kaewkod Thida, Panya Aussara, Arjinajarn Phatchawan

机构信息

Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.

Office of Research Administration, Chiang Mai University, Chiang Mai, Thailand.

出版信息

Front Pharmacol. 2025 Apr 29;16:1558341. doi: 10.3389/fphar.2025.1558341. eCollection 2025.

DOI:10.3389/fphar.2025.1558341
PMID:40365311
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069279/
Abstract

BACKGROUND

Combination treatment enhances the therapeutic potential for diabetes, particularly for patients with severe complications. Combining standard therapeutic drugs with alternative bioactive compounds provides a promising option for long-term treatment, given the high safety profile of bioactive substances. Objective in this study, we aimed to evaluate the synergistic effects of metformin and (Burm. f.) Lindau (CN) on glucose metabolism and renal dysfunction parameters in a type 2 diabetic rat model.

METHODS

Male Wistar rats were fed a high-fat diet for 4 weeks and then received a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were randomly divided into four groups: untreated diabetic rats (DM), diabetic rats treated with CN at doses of 100 or 200 mg/kg/day (DM100 or DM200), diabetic rats treated with a combination of CN and metformin (DMCOM), and diabetic rats treated with metformin at 100 mg/kg/day (DMMET). The treatments were administered by gavage for 4 weeks.

RESULTS

Compared to single treatments, DMCOM showed a remarkable effect in reducing several parameters, including serum creatinine and blood urea nitrogen, while enhancing creatinine clearance in diabetic rats. Additionally, DMCOM significantly decreased malondialdehyde levels. Notably, diabetic rats treated with DMCOM exhibited a significant reduction in parameters associated with renal dysfunction, as evidenced by decreased inflammation markers, along with downregulated fibrotic markers.

CONCLUSION

Our findings provide a scientific basis for the clinical application of CN and suggest a new strategy for preventing nephrotoxicity and other kidney diseases in diabetic patients.

摘要

背景

联合治疗可增强糖尿病的治疗潜力,尤其是对于有严重并发症的患者。鉴于生物活性物质具有较高的安全性,将标准治疗药物与其他生物活性化合物联合使用为长期治疗提供了一个有前景的选择。在本研究中,我们旨在评估二甲双胍和萝芙木(Burm. f.)Lindau(CN)对2型糖尿病大鼠模型中葡萄糖代谢和肾功能障碍参数的协同作用。

方法

雄性Wistar大鼠先喂食高脂饮食4周,然后接受低剂量链脲佐菌素诱导2型糖尿病。将糖尿病大鼠随机分为四组:未治疗的糖尿病大鼠(DM)、接受100或200mg/kg/天CN治疗的糖尿病大鼠(DM100或DM200)、接受CN与二甲双胍联合治疗的糖尿病大鼠(DMCOM)以及接受100mg/kg/天二甲双胍治疗的糖尿病大鼠(DMMET)。通过灌胃给药4周。

结果

与单一治疗相比,DMCOM在降低包括血清肌酐和血尿素氮在内的多个参数方面显示出显著效果,同时提高了糖尿病大鼠的肌酐清除率。此外,DMCOM显著降低了丙二醛水平。值得注意的是,接受DMCOM治疗的糖尿病大鼠与肾功能障碍相关的参数显著降低,炎症标志物减少以及纤维化标志物下调证明了这一点。

结论

我们的研究结果为CN的临床应用提供了科学依据,并为预防糖尿病患者的肾毒性和其他肾脏疾病提出了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/1d7ddcf0fc13/fphar-16-1558341-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/6bcf5a0b1181/fphar-16-1558341-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/b716071c941c/fphar-16-1558341-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/ac886b93b8b9/fphar-16-1558341-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/53efaa2c87d5/fphar-16-1558341-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/5d41710670ba/fphar-16-1558341-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/35876c99d804/fphar-16-1558341-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/dae492011705/fphar-16-1558341-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/1d7ddcf0fc13/fphar-16-1558341-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/6bcf5a0b1181/fphar-16-1558341-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/b716071c941c/fphar-16-1558341-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/ac886b93b8b9/fphar-16-1558341-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/53efaa2c87d5/fphar-16-1558341-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/5d41710670ba/fphar-16-1558341-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/35876c99d804/fphar-16-1558341-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/dae492011705/fphar-16-1558341-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/923a/12069279/1d7ddcf0fc13/fphar-16-1558341-g008.jpg

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