Lonan Piyanuch, Ariyabukalakorn Varitha, Yoysungnoen Bhornprom, Singsai Kanathip, Praphasawat Ratsada, Sangkham Sarawut, Jantarach Nattanida, Riyamongkhol Prathakphong, Somparn Nuntiya, Munkong Narongsuk
Traditional Chinese Medicine Program, School of Public Health, University of Phayao, Phayao, Thailand.
Applied Thai Traditional Medicine Program, School of Public Health, University of Phayao, Phayao, Thailand.
J Exp Pharmacol. 2025 Aug 5;17:527-543. doi: 10.2147/JEP.S517411. eCollection 2025.
N-acetyl-p-aminophenol (APAP) overdose remains a leading cause of acute liver failure worldwide. The aril extracts derived from Gac () (MC) fruit contain diverse phytonutrients that exhibit a range of pharma-nutritional properties, including antioxidant and anti-hepatic damage properties. Despite the therapeutic potential, the molecular mechanisms underlying its hepatoprotective action, particularly in preventing drug-induced toxicity, remain unelucidated.
This study investigated the hepatoprotective potential of MC in a mouse model of APAP-induced acute liver injury and characterized its bioactive compounds.
MC was prepared using aqueous extraction. Mice were pre-treated with either 500 or 1,000 mg/kg of MC for seven consecutive days prior to intraperitoneal administration of APAP 300 mg/kg to induce hepatotoxicity. Serum and liver samples were then collected to analyze biochemical changes, histopathological changes, oxidative stress markers, and/or mRNA expression. Standard chemical tests were used to identify bioactive compounds.
APAP administration caused a marked rise in liver enzymes, extensive histological necrosis, suppression of hepatocyte proliferation, infiltration of neutrophils and macrophages, and significant oxidative damage ( < 0.05). Studies revealed the constitution of MC as phenolic compounds, flavonoids, proanthocyanidins, and ascorbic acid, significantly attenuated the hepatotoxicity ( < 0.05). Mechanistically, MC ameliorated hepatic mRNA expression of CYP2E1, JNK, Ddit3, Bax, Casp3, NF-κB, and MCP-1, while increasing Bcl-2, IL-10, VEGF, Nrf2, SOD2, and GCLC mRNA ( < 0.05). Furthermore, MC prevented hyperglycemia by influencing the expression of AdipoR1, GLUT-2, and PEPCK ( < 0.05).
MC exhibits hepatoprotective effects against APAP-induced liver injury through multifaceted modulation of toxic metabolism (CYP2E1), cell death and ER stress (JNK, Ddit3, Bax, Casp3, and Bcl-2), antioxidant response (Nrf2 pathway), inflammation (NF-κB pathway and IL-10), tissue repair (VEGF), and glucose metabolism (AdipoR1, GLUT-2, and PEPCK).
对乙酰氨基酚（APAP）过量仍是全球急性肝衰竭的主要原因。从罗汉果（Gac）果实中提取的罗汉果提取物（MC）含有多种植物营养素，具有一系列药理营养特性，包括抗氧化和抗肝损伤特性。尽管具有治疗潜力，但其肝保护作用的分子机制，尤其是在预防药物诱导的毒性方面，仍未阐明。
本研究在APAP诱导的急性肝损伤小鼠模型中研究了MC的肝保护潜力，并对其生物活性化合物进行了表征。
采用水提法制备MC。在腹腔注射300mg/kg APAP诱导肝毒性之前，小鼠连续7天接受500或1000mg/kg的MC预处理。然后收集血清和肝脏样本，分析生化变化、组织病理学变化、氧化应激标志物和/或mRNA表达。使用标准化学测试来鉴定生物活性化合物。
APAP给药导致肝酶显著升高、广泛的组织学坏死、肝细胞增殖抑制、中性粒细胞和巨噬细胞浸润以及显著的氧化损伤（P<0.05）。研究表明，MC的成分包括酚类化合物、黄酮类化合物、原花青素和抗坏血酸，可显著减轻肝毒性（P<0.05）。从机制上讲，MC改善了CYP2E1、JNK、Ddit3、Bax、Casp3、NF-κB和MCP-1的肝脏mRNA表达，同时增加了Bcl-2、IL-10、VEGF、Nrf2、SOD2和GCLC mRNA（P<0.05）。此外，MC通过影响AdipoR1、GLUT-2和PEPCK的表达预防了高血糖（P<0.05）。
MC通过对毒性代谢（CYP2E1）、细胞死亡和内质网应激（JNK、Ddit3、Bax、Casp3和Bcl-2）、抗氧化反应（Nrf2途径）、炎症（NF-κB途径和IL-10）、组织修复（VEGF）和葡萄糖代谢（AdipoR1、GLUT-2和PEPCK）的多方面调节，对APAP诱导的肝损伤具有肝保护作用。
