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大籽栝楼在改善高脂饮食诱导的慢性肾病中的治疗作用:NF-κB和TGF-β/smad在肾纤维化中的双重作用

The therapeutic role of Coccinia grandis in flavor-enhancing high-lipid diet-induced chronic kidney disease: a dual role of NF-kB and TGF-β/smad in renal fibrosis.

作者信息

Banerjee Arnab, Roy Jayati, Sarkar Diptendu, Shil Aparna, Das Debasmita, Seal Tapan, Mukherjee Sandip, Maji Bithin Kumar

机构信息

Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly, West Bengal, 712201, India.

Department of Microbiology, Ramakrishna Mission Vidyamandira, Belur Math, Howrah, West Bengal, 711202, India.

出版信息

Mol Biol Rep. 2025 Aug 7;52(1):798. doi: 10.1007/s11033-025-10798-4.

DOI:10.1007/s11033-025-10798-4
PMID:40775474
Abstract

BACKGROUND

Coccinia grandis (CG), a plant used as traditional medicine, possesses antioxidant, anti-inflammatory, and anti-fibrotic activities. Chronic kidney disease (CKD) and renal fibrosis are public health issues, further promoted by monosodium glutamate in high-lipid diets (MH) via oxidative stress and inflammation. CG could potentially alleviate MH-induced CKD by modulating cell signaling. The purpose of this study is to hypothesize that CG, with known anti-inflammatory and antioxidant properties, might counteract MH-induced kidney dysfunction through its putative modulation of the signaling pathway.

METHODS AND RESULTS

Male Wistar rats were administered ethanol extracts of CG leaves (etCGL) with or without MH for 28 days, and their effects on renal homeostasis, inflammation, and fibrosis were assessed. Finally, the major components of the MH and CG were docked to identify a better docking affinity and a stable interaction of the ligand with its receptor, highlighting the therapeutic target specificity. etCGL effectively improved kidney function, prevented oxidative stress, and decreased pro-inflammatory cytokines (TGF-β, collagen) in rats fed with MH. Histology demonstrated restored renal structure and minimal fibrosis in the MH + etCGL-fed group. The renoprotective activities of etCGL with its phytocompounds such as catechin, p-coumaric acid, and naringenin as a composite extract were mediated by inhibiting NF-kB and TGF-β/Smad pathways.

CONCLUSIONS

Therefore, it can be concluded that CG, with its active compounds, can be a useful dietary approach in MH-associated CKD. Clinical trials across populations would establish the efficacy of etCGL, and understanding its molecular mechanism will be crucial for elucidating the mechanisms of its protective action.

摘要

背景

大花栝楼(CG)是一种用作传统药物的植物,具有抗氧化、抗炎和抗纤维化活性。慢性肾脏病(CKD)和肾纤维化是公共卫生问题,高脂饮食中的味精(MH)通过氧化应激和炎症进一步加剧这些问题。CG可能通过调节细胞信号传导来减轻MH诱导的CKD。本研究的目的是假设具有已知抗炎和抗氧化特性的CG可能通过其对信号通路的假定调节来对抗MH诱导的肾功能障碍。

方法与结果

雄性Wistar大鼠接受含或不含MH的CG叶乙醇提取物(etCGL)处理28天,并评估其对肾脏稳态、炎症和纤维化的影响。最后,将MH和CG的主要成分进行对接,以确定更好的对接亲和力以及配体与其受体的稳定相互作用,突出治疗靶点特异性。etCGL有效改善了喂食MH大鼠的肾功能,预防了氧化应激,并降低了促炎细胞因子(TGF-β、胶原蛋白)。组织学显示,在喂食MH + etCGL的组中,肾脏结构得以恢复,纤维化程度最小。etCGL及其植物化合物(如儿茶素、对香豆酸和柚皮苷)作为复合提取物的肾脏保护活性是通过抑制NF-κB和TGF-β/Smad信号通路介导的。

结论

因此,可以得出结论,CG及其活性化合物可成为与MH相关的CKD的一种有用的饮食方法。针对不同人群的临床试验将确定etCGL的疗效,而了解其分子机制对于阐明其保护作用机制至关重要。

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