Ahmed Taher Hamza, Zalzala Munaf Hashim
Directorate of Health Diyala, Ministry of Health, Baghdad, Iraq.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
J Complement Integr Med. 2025 Feb 11;22(2):296-303. doi: 10.1515/jcim-2024-0425. eCollection 2025 Jun 1.
The liver is vital for metabolism, detoxification, storage, and secretion. Cholestasis, in which bile flow is hindered, can cause serious harm to the liver. This study examines the potential of ellagic acid to prevent cholestasis in male rats that has been caused by alpha-naphthyl isothiocyanate (ANIT).
Male rats were divided into four groups for an 8-day study. The control group received 5 % dimethyl sulfoxide (DMSO) orally for eight days and maize oil (1 mL/kg, orally) 48 h before sacrifice. The ANIT Group received 5 % DMSO orally for 8 days, the ANIT (100 mg/kg, orally) administered on the 6th day, 48 h before sacrifice. The low-Dose Ellagic Acid + ANIT Group was given ellagic acid (5 mg/kg, orally) for eight days, with ANIT (100 mg/kg, orally) on the 6th day, 48 h prior to sacrifice. The high-Dose Ellagic Acid + ANIT Group received ellagic acid (10 mg/kg, orally) for eight days, the ANIT (100 mg/kg, orally) on the 6th day, 48 h before sacrifice. Different biochemical and histopathological analyses were conducted to assess the protective effects of ellagic acid on ANIT-induced liver injury.
ANIT significantly elevated serum of liver enzymes. It caused severe bile duct inflammation and reduced bile salt export pump (BSEP) and Na+-taurocholate cotransporting polypeptide (NTCP) expression, indicating liver injury. Ellagic acid treatment mitigated these changes, improving biochemical parameters and reducing liver damage. ANIT-induced cholestasis results in bile acid accumulation due to decreased BSEP and NTCP expression linked to impaired farnesoid X receptor (FXR) signaling. Ellagic acid restored BSEP and NTCP levels via FXR activation, reducing bile acids and inflammatory markers IL-1β and TNF-α. Ellagic acid also enhanced SIRT1 activity, further improving FXR function and bile acid homeostasis.
Ellagic acid exhibits protective effects against cholestasis by enhancing the FXR signaling and and expression with mitigating liver damage and inflammation.
肝脏对于新陈代谢、解毒、储存和分泌至关重要。胆汁淤积，即胆汁流动受阻，会对肝脏造成严重损害。本研究考察了鞣花酸预防由异硫氰酸α-萘酯（ANIT）所致雄性大鼠胆汁淤积的潜力。
将雄性大鼠分为四组进行为期8天的研究。对照组连续8天口服5%二甲亚砜（DMSO），并在处死前48小时口服玉米油（1 mL/kg）。ANIT组连续8天口服5%DMSO，在处死前48小时的第6天给予ANIT（100 mg/kg，口服）。低剂量鞣花酸+ANIT组连续8天给予鞣花酸（5 mg/kg，口服），在处死前48小时的第6天给予ANIT（100 mg/kg，口服）。高剂量鞣花酸+ANIT组连续8天给予鞣花酸（10 mg/kg，口服），在处死前48小时的第6天给予ANIT（100 mg/kg，口服）。进行不同的生化和组织病理学分析以评估鞣花酸对ANIT诱导的肝损伤的保护作用。
ANIT显著升高肝酶血清水平。它导致严重的胆管炎症，并降低胆汁盐输出泵（BSEP）和牛磺胆酸钠共转运多肽（NTCP）的表达，表明肝损伤。鞣花酸治疗减轻了这些变化，改善了生化参数并减少了肝损伤。ANIT诱导的胆汁淤积由于与法尼醇X受体（FXR）信号传导受损相关的BSEP和NTCP表达降低而导致胆汁酸积聚。鞣花酸通过激活FXR恢复BSEP和NTCP水平，降低胆汁酸以及炎症标志物白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）。鞣花酸还增强了沉默调节蛋白1（SIRT1）的活性，进一步改善了FXR功能和胆汁酸稳态。
鞣花酸通过增强FXR信号传导以及减轻肝损伤和炎症来发挥对胆汁淤积的保护作用。
