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通过上调胰岛素信号蛋白表达和下调MAPK/JNK通路改善链脲佐菌素诱导的糖尿病大鼠的糖代谢控制

Improves Glycometabolic Control in Streptozotocin-Induced Diabetic Rats by Up-Regulating the Expression of Insulin Signaling Proteins and Down-Regulating the MAPK/JNK Pathway.

作者信息

Ehsan Maryam, Ahmed Sibtain, Majeed Wafa, Iftikhar Asra, Iftikhar Maryam, Abbas Mateen, Mehmood Tahir

机构信息

Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan.

Department of Biochemistry, Bahauddin Zakariya University (BZU), Multan 60800, Pakistan.

出版信息

Pharmaceuticals (Basel). 2025 Mar 2;18(3):361. doi: 10.3390/ph18030361.

DOI:10.3390/ph18030361
PMID:40143138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11944882/
Abstract

is a bioactive flavonoid that possesses strong antioxidant and anti-inflammatory activities. The current investigation aimed to examine the anti-diabetic potential of in streptozotocin-induced diabetic rats. Dose-dependent (10 and 20 mg/kg) anti-hyperglycemic, anti-hyperlipidemic, anti-inflammatory, and antioxidant effects of were evaluated by measuring fasting blood glucose, serum glucose, serum insulin, HOMA-IR, lipidemic status, inflammatory cytokines, and hepatic antioxidant markers. To identify the underlying mechanism behind the anti-diabetic activity of , qRT-PCR was carried out using rat pancreatic and hepatic tissues. The results have shown that produced antioxidant effects, as exhibited by DPPH and ABTS assays, respectively. showed potent alpha-amylase and alpha-glucosidase inhibitory activities. enhanced the serum insulin level, significantly decreased the serum glucose, HOMA-IR, and cytokine levels, and improved the lipid profile. also showed a substantial decline in insulin resistance in the treated rats. significantly raised catalase and superoxide dismutase levels in hepatic tissues while potentially decreasing the malondialdehyde levels. Moreover, significantly down-regulated the MAPK-8, TRAF-6, and TRAF-4 expressions and up-regulated the PDX-1, SIRT-1, INS-1, and GLUT-4 expressions in treated groups. Our results indicate that exhibits a hypoglycemic effect, which appears to be associated with its regulatory impact on metabolic inflammation and oxidative stress markers. This was accompanied by a lower HOMA-IR index, highlighting its potential role in promoting glucose homeostasis and mitigating insulin resistance. According to preliminary results, could further be tested to introduce it as another viable treatment option for diabetes.

摘要

是一种具有强抗氧化和抗炎活性的生物活性类黄酮。当前的研究旨在考察其在链脲佐菌素诱导的糖尿病大鼠中的抗糖尿病潜力。通过测量空腹血糖、血清葡萄糖、血清胰岛素、HOMA-IR、血脂状况、炎性细胞因子和肝脏抗氧化标志物,评估了其剂量依赖性(10和20毫克/千克)的降血糖、降血脂、抗炎和抗氧化作用。为了确定其抗糖尿病活性背后的潜在机制,使用大鼠胰腺和肝脏组织进行了qRT-PCR。结果表明,分别通过DPPH和ABTS试验显示其具有抗氧化作用。表现出强大的α-淀粉酶和α-葡萄糖苷酶抑制活性。提高了血清胰岛素水平,显著降低了血清葡萄糖、HOMA-IR和细胞因子水平,并改善了血脂谱。在治疗的大鼠中,胰岛素抵抗也显著下降。显著提高了肝脏组织中的过氧化氢酶和超氧化物歧化酶水平,同时可能降低了丙二醛水平。此外,在治疗组中显著下调了MAPK-8、TRAF-6和TRAF-4的表达,并上调了PDX-1、SIRT-1、INS-1和GLUT-4的表达。我们的结果表明,具有降血糖作用,这似乎与其对代谢炎症和氧化应激标志物的调节作用有关。这伴随着较低的HOMA-IR指数,突出了其在促进葡萄糖稳态和减轻胰岛素抵抗方面的潜在作用。根据初步结果,可进一步进行测试,将其作为糖尿病的另一种可行治疗选择引入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/074f9d2fdda4/pharmaceuticals-18-00361-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/5906e376c92d/pharmaceuticals-18-00361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/53b49e8a5932/pharmaceuticals-18-00361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/69dbdc4ffe16/pharmaceuticals-18-00361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/483949e5f9c6/pharmaceuticals-18-00361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/fe670fdbeddf/pharmaceuticals-18-00361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/514d69737d4b/pharmaceuticals-18-00361-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/074f9d2fdda4/pharmaceuticals-18-00361-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/5906e376c92d/pharmaceuticals-18-00361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/53b49e8a5932/pharmaceuticals-18-00361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/69dbdc4ffe16/pharmaceuticals-18-00361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/483949e5f9c6/pharmaceuticals-18-00361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/fe670fdbeddf/pharmaceuticals-18-00361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/514d69737d4b/pharmaceuticals-18-00361-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0346/11944882/074f9d2fdda4/pharmaceuticals-18-00361-g007.jpg

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