Protective effects of Atractylodes macrocephala polysaccharides on acetaminophen-induced liver injury

Jiali Wu; Biao Jia; Shuai Gong; Yangpeng Li; Jiaqi Wang; Yuqiao Huang; Jiao Guo

doi:10.3389/fphar.2025.1583334

Protective effects of Atractylodes macrocephala polysaccharides on acetaminophen-induced liver injury

Front Pharmacol. 2025 Jun 19:16:1583334. doi: 10.3389/fphar.2025.1583334. eCollection 2025.

Authors

Jiali Wu¹, Biao Jia¹, Shuai Gong¹, Yangpeng Li¹, Jiaqi Wang¹, Yuqiao Huang¹, Jiao Guo¹

Affiliation

¹ Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou Higher Education Mega Center, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.

Abstract

Background: Drug-induced liver injury (DILI) is a major clinical concern due to its unpredictable nature and lack of effective therapeutic options.

Methods: This study investigated the hepatoprotective effects of Atractylodes macrocephala polysaccharides (AMPs) in a mouse model of acetaminophen (APAP)-induced liver injury. Mice were pretreated with AMPs for 7 days prior to APAP challenge, and liver injury was evaluated through histopathology, serum biochemistry, molecular assays, and gut microbiota analysis.

Results: AMPs treatment significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to the APAP group (p < 0.05). Hepatic oxidative stress was alleviated, as indicated by increased levels of glutathione (GSH, p < 0.05) and superoxide dismutase (SOD, p < 0.05), and reduced malondialdehyde (MDA, p < 0.05). AMPs also suppressed inflammatory cytokines, including Il-1β, Tnf-α, Il-6, and Nlrp3 (p < 0.05), and modulated apoptosis-related proteins by downregulating Bax and upregulating Bcl-2 and Bcl-xl expression (p < 0.05). Furthermore, AMPs improved gut microbiota diversity and enriched beneficial genera such as Roseburia, as revealed by 16S rDNA sequencing. Fecal microbiota transplantation from AMPs-treated mice replicated these hepatoprotective effects, highlighting the involvement of the gut-liver axis.

Conclusion: These findings support the therapeutic potential of AMPs as a multifaceted agent for DILI, exerting protective effects through modulation of oxidative stress, inflammation, apoptosis, and intestinal dysbiosis.

Keywords: NLRP3 inflammasome; hepatoprotection; herbal polysaccharides; intestinal microbiota; oxidative stress.