Zhao Ruowei, Zhang Qing, Liu Wenjing, Lin Yifan, He Yuhui, Chang Dennis, Li Shaohua, Xu Wen, Lin Yanxiang, Zheng Yanfang, Zhou Xian, Huang Mingqing
College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China.
NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2145, Australia.
J Ethnopharmacol. 2023 Jul 15;311:116285. doi: 10.1016/j.jep.2023.116285. Epub 2023 Mar 16.
Pien Tze Huang is a classic traditional Chinese medicinal product, used for inflammatory diseases as stated in Chinese Pharmacopoeia. In particular, it is effective in treating liver diseases and pro-inflammatory conditions. Acetaminophen (APAP) is a widely used analgesic drug, but its over-dose is associated with acute liver failure where the clinical approved antidote treatment is limited. Inflammation has been considered as one of the therapeutic targets against APAP-induced liver injury.
We aimed to explore the therapeutic potential of Pien Tze Huang tablet (PTH) on protecting liver against APAP-induced liver injury through its strong anti-inflammatory pharmacological action.
Wild-type C57BL/6 mice were given PTH (75, 150 and 300 mg/kg) by oral gavage 3 days before the APAP injection (400 mg/kg). The protective effect of PTH was assessed by aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and pathological staining. The mechanisms underlying PTH's hepatoprotective effects were investigated in nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) knock-out (NLRP3), over expression NLRP3 (oe-NLRP3) mice, and wild-type mice with the injection of autophagy inhibitor (3-methyladenine, 3-MA).
APAP-exposed mice resulted in evident liver injury which was evidenced by hepatic necrosis and elevated levels of AST and ALT in the wild-type C57BL/6 mice. PTH dose-dependently reduced ALT, AST and upregulated autophagy activity. In addition, PTH significantly reduced elevated levels of proinflammatory cytokines and NLRP3 inflammasome. The liver protective effect of PTH (300 mg/kg) was still obvious in the oe-NLRP3 mice, however, it became insignificant in the NLRP3 mice. When PTH (300 mg/kg) was co-treated with 3-MA to the wild-type C57BL/6 mice, the NLRP3 inhibition were reversed when autophagy was blocked.
PTH exerted a beneficial effect in protecting liver against APAP-induced liver injury. The underlying molecular mechanism was associated with the NLRP3 inflammasome inhibition which was likely driven by the upregulated autophagy activity. Our study underpins the traditional use of PTH in protecting liver through its anti-inflammatory action.
片仔癀是一种经典的传统中药产品，如《中国药典》所述，可用于治疗炎症性疾病。特别是，它对治疗肝脏疾病和炎症状态有效。对乙酰氨基酚（APAP）是一种广泛使用的镇痛药，但其过量使用与急性肝衰竭相关，而临床批准的解毒治疗有限。炎症被认为是对抗APAP诱导的肝损伤的治疗靶点之一。
我们旨在探讨片仔癀片（PTH）通过其强大的抗炎药理作用对保护肝脏免受APAP诱导的肝损伤的治疗潜力。
在注射APAP（400mg/kg）前3天，通过口服灌胃给予野生型C57BL/6小鼠PTH（75、150和300mg/kg）。通过天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平以及病理染色评估PTH的保护作用。在核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）基因敲除（NLRP3）、过表达NLRP3（oe-NLRP3）小鼠以及注射自噬抑制剂（3-甲基腺嘌呤，3-MA）的野生型小鼠中研究PTH肝保护作用的潜在机制。
在野生型C57BL/6小鼠中，APAP暴露导致明显的肝损伤，表现为肝坏死以及AST和ALT水平升高。PTH剂量依赖性地降低ALT、AST并上调自噬活性。此外，PTH显著降低促炎细胞因子和NLRP3炎性小体的升高水平。PTH（300mg/kg）对oe-NLRP3小鼠的肝脏保护作用仍然明显，然而，在NLRP3小鼠中这种作用变得不显著。当将PTH（300mg/kg）与3-MA共同处理野生型C57BL/6小鼠时，自噬被阻断时NLRP3的抑制作用被逆转。
PTH对保护肝脏免受APAP诱导的肝损伤发挥了有益作用。潜在的分子机制与NLRP3炎性小体抑制有关，这可能是由上调的自噬活性驱动的。我们的研究支持了PTH通过其抗炎作用保护肝脏的传统用途。
