# Qing-Kai-Ling oral liquid alleviates non-alcoholic fatty liver disease via remodeling gut microbiota and activating AMPK/ACC1 axis

## TL;DR

Qing-Kai-Ling oral liquid reduces non-alcoholic fatty liver disease by improving gut bacteria and activating a key liver metabolism pathway.

## Contribution

QKL's novel therapeutic mechanism for NAFLD via gut microbiota remodeling and AMPK/ACC1 activation is established.

## Key findings

- QKL reduced liver fat, improved glucose tolerance, and lowered body weight in NAFLD mice.
- QKL enriched beneficial gut bacteria and increased short-chain fatty acid production.
- QKL activated AMPK/ACC1 signaling to suppress fat production and enhance lipid oxidation.

## Abstract

Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, has demonstrated hepatoprotective, lung-protective, and gut microbiota-modulating properties. However, its efficacy in preventing high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and its relationship with gut microbiota and hepatic inflammation remain unclear.

The study aims to investigate whether QKL can prevent HFD-induced NAFLD, focusing on the mechanistic role of gut microbiota, microbial metabolites, and hepatic inflammation.

QKL was subjected to extraction and chemical profiling to identify its active compounds. In vivo studies were conducted in HFD-fed mice to assess the effects of QKL on hepatic lipid accumulation, inflammation, gut microbiota composition, SCFAs production, intestinal permeability, body weight, and fat mass.

Chemical analysis revealed that the major components of QKL are gallic acid, corilagin, and chebulagic acid. QKL administration (12.33 and 24.66 mL/kg) for 8 weeks significantly reduced hepatic steatosis, serum lipid profiles (TG, LDL-C), and body weight in high-fat diet-induced NAFLD mice, while improving glucose tolerance and intestinal barrier integrity. Gut microbiota analysis revealed QKL enriched beneficial taxa (e.g., Akkermansia, Bacteroides) and suppressed pathobionts (e.g., Lachnospiraceae NK4A136_group), effects replicated through faecal microbiota transplantation from QKL-treated donors. QKL upregulated intestinal gene GPR41/43 and hepatic protein GPR135 expression, enhanced SCFAs production (acetic, propionic, and butyric acids), and activated AMPK/ACC1 signaling to suppress lipogenesis and promote lipid oxidation. Untargeted metabolomics demonstrated QKL restored hepatic fatty acid metabolism by reducing palmitic acid and arachidonic acid accumulation.

These findings established QKL as a microbiota-modulating therapeutic agent for NAFLD through SCFA-AMPK/ACC1 axis activation, providing a foundation for developing QKL-based treatments.

The online version contains supplementary material available at 10.1186/s13020-025-01237-4.