Curcumin Analog J7 Attenuates Liver Fibrosis and Metabolic Dysregulation in a Rat Model of Type 2 Diabetes via Modulation of TGF-β/Smad and NF-κB/BCL-2/BAX Pathways.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S511372

Jun Ma, Wei Chen, Deep K Vaishnani, Congying Wang, Shuman Xue, Qiuqin Yang, Yuheng Tong, Ningjia Lei, Zhichao Zhao, Furong Ying

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引用次数: 0

Abstract

Objective: To evaluate the therapeutic potential of the curcumin analog J7 in protecting the liver and regulating glucose and lipid metabolism in rats with type 2 diabetes.

Methods: Bioinformatics methods were used to identify signaling pathways linked to diabetic liver disease. Diabetic rats were treated with curcumin, low-dose J7, or high-dose J7, and liver function and fibrosis were assessed through biochemical analyses, histopathology, immunohistochemistry, and ELISA.

Results: J7 administration significantly improved lisver function, reduced fibrosis, and regulated metabolic profiles in diabetic rats. J7 downregulated TGF-β1, NF-κB p65, and BAX, while upregulating BCL-2, showing superior effects to traditional curcumin in reducing TGF-β1 and inhibiting α-SMA expression.

Conclusion: J7 demonstrates potential as a therapeutic agent for managing liver complications in type 2 diabetes, effectively attenuating liver fibrosis and regulating metabolism through the modulation of key signaling pathways and proteins.

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姜黄素类似物J7通过调节TGF-β/Smad和NF-κB/BCL-2/BAX通路减轻2型糖尿病大鼠模型的肝纤维化和代谢失调

目的：探讨姜黄素类似物J7对2型糖尿病大鼠肝脏的保护作用及调节糖脂代谢的作用。方法：采用生物信息学方法确定与糖尿病性肝病相关的信号通路。用姜黄素、低剂量J7、高剂量J7治疗糖尿病大鼠，通过生化分析、组织病理学、免疫组化、ELISA等方法评估肝功能和纤维化。结果：J7显著改善糖尿病大鼠肝功能，减少纤维化，调节代谢谱。J7下调TGF-β1、NF-κB p65、BAX，上调BCL-2，在降低TGF-β1、抑制α-SMA表达方面优于传统姜黄素。结论：J7有潜力作为治疗2型糖尿病肝脏并发症的药物，通过调节关键信号通路和蛋白质有效减轻肝纤维化和调节代谢。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.