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蜜蜂花通过AMPK/SIRT1和STAT3/Nrf2信号通路减轻双氯芬酸诱导的肝肾毒性。

Melissa officinalis Attenuates Diclofenac-Induced Hepatorenal Toxicity via AMPK/SIRT1 and STAT3/Nrf2 Pathways.

作者信息

Salama Alyaa R, Ashoura Neveen R, Esmail Kariman A, Tohamy Hossam G, Shukry Mustafa, Alotaibi Badriyah S, Aboushouk Asmaa A

机构信息

Department of Clinical Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.

Department of Pharmacology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.

出版信息

J Appl Toxicol. 2025 Aug;45(8):1649-1663. doi: 10.1002/jat.4799. Epub 2025 Apr 28.

DOI:10.1002/jat.4799
PMID:40294906
Abstract

PURPOSE

This study aimed to assess whether Melissa officinalis (MO) or lemon balm could counteract the detrimental effects of diclofenac (DIC) on the liver and kidneys in male albino rats.

METHODS

Forty adult male Wistar rats were randomly assigned to four groups (n = 10 per group): control, DIC (10 mg/kg intraperitoneally), DIC + MO (10 mg/kg DIC IP + 200 mg/kg lemon balm orally), and MO only (200 mg/kg orally) for 28 days. Biochemical, molecular, and histopathological evaluations were conducted to assess organ function and tissue integrity.

RESULTS

DIC significantly impaired hepatic and renal function (p < 0.05), evidenced by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP). Oxidative stress increased, as shown by higher malondialdehyde levels and reduced antioxidants, including glutathione and catalase (CAT). Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were also elevated. Histopathological analysis indicated severe tissue damage and cell death in the liver and kidneys from DIC. However, adding MO alongside DIC mitigated these effects, improving both biochemical and histopathological parameters in the liver and kidneys. Gene expression analysis revealed upregulation of STAT3 and TNF-α and downregulation of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Coadministration of MO significantly reversed these alterations (p < 0.05), improved tissue architecture, and restored antioxidant and anti-inflammatory balance.

CONCLUSION

MO provided substantial protection against oxidative damage and functional disturbances induced by DIC in liver and kidney tissues.

摘要

目的

本研究旨在评估香蜂草(MO)或柠檬香脂是否能抵消双氯芬酸(DIC)对雄性白化大鼠肝脏和肾脏的有害影响。

方法

将40只成年雄性Wistar大鼠随机分为四组(每组n = 10):对照组、DIC组(腹腔注射10 mg/kg)、DIC + MO组(腹腔注射10 mg/kg DIC + 口服200 mg/kg柠檬香脂)和仅MO组(口服200 mg/kg),持续28天。进行生化、分子和组织病理学评估以评估器官功能和组织完整性。

结果

DIC显著损害肝脏和肾脏功能(p < 0.05),血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和甲胎蛋白(AFP)升高证明了这一点。氧化应激增加,丙二醛水平升高以及包括谷胱甘肽和过氧化氢酶(CAT)在内的抗氧化剂减少表明了这一点。肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)等炎性细胞因子也升高。组织病理学分析表明,DIC组大鼠的肝脏和肾脏出现严重组织损伤和细胞死亡。然而,在DIC的基础上加用MO可减轻这些影响,改善肝脏和肾脏的生化和组织病理学参数。基因表达分析显示信号转导和转录激活因子3(STAT3)和TNF-α上调,而腺苷酸活化蛋白激酶(AMPK)、沉默调节蛋白1(SIRT1)和核因子红细胞2相关因子2(Nrf2)下调。MO共同给药显著逆转了这些改变(p < 0.05),改善了组织结构,并恢复了抗氧化和抗炎平衡。

结论

MO对DIC诱导的肝脏和肾脏组织氧化损伤和功能紊乱提供了实质性保护。

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