# The IL-17 pathway mediated by m6A-modified lncRNA H19: a new mechanism for Jianpi Qingre Tongluo Prescription in repressing inflammation and improving lipid metabolism in gout arthritis

## TL;DR

A traditional Chinese medicine prescription reduces gout arthritis inflammation and improves lipid metabolism by regulating a specific RNA modification and the IL-17 pathway.

## Contribution

The study reveals a novel mechanism by which a traditional Chinese medicine regulates inflammation and lipid metabolism in gout arthritis via m6A modification of lncRNA H19 and the IL-17 pathway.

## Key findings

- HQC alleviates joint injury and reduces inflammatory markers and lipid metabolites in gouty arthritis rats.
- The IL-17 pathway is a key mediator of HQC's anti-inflammatory and lipid-regulating effects.
- HQC inhibits inflammation and lipid imbalance by increasing m6A modification of lncRNA H19 via ALKBH5/FTO.

## Abstract

Jianpi Qingre Tongluo Prescription [also named Huangqin Qingrechubi Capsule (HQC)] is an empirical prescription for the treatment of gouty arthritis (GA) with excellent clinical efficacy. Mechanistically, HQC suppresses inflammation and lipid metabolism imbalance in GA by regulating long non-coding RNA H19 (lncRNA H19). Nevertheless, the detailed mechanism requires further investigation.

This study further explored the mechanism of HQC in suppressing inflammation and improving lipid metabolism via lncRNA H19 in GA.

A rat model of GA was established to analyze the effects of HQC on joint injury, inflammation, and lipid metabolism in GA. Subsequently, network pharmacology was employed to identify the key pathway involved in the effects of HQC on inflammation and lipid metabolism in GA. Based on clinical and animal experimental observations, a co-culture model of GA-peripheral blood mononuclear cells and GA-fibroblast-like synoviocytes was constructed to validate the mechanism of HQC in regulating GA-related inflammation and lipid metabolism from the perspective of N6-methyladenosine (m6A) modification of lncRNA H19.

HQC alleviated joint injury and improved the abnormal levels of inflammatory factors (hs-CRP, IL-4, IL-1β, and TNF-α) and lipid metabolites (TC, TG, lipoprotein, adiponectin, leptin, visfatin, and resistin) in GA rats. The IL-17 pathway was identified as an important node in HQC's effects on improving inflammation and lipid metabolism in GA. Alterations of lncRNA H19 and the IL-17 pathway were observed in GA patients and rats, which were closely correlated with inflammation and lipid metabolites. Cellular experiments revealed that high expression of lncRNA H19, attributed to ALKBH5/FTO-mediated demethylation, facilitated inflammation and lipid metabolism imbalance in GA via activating the IL-17 pathway. HQC could repress inflammation and improve lipid metabolism in GA through inhibiting the IL-17 pathway by increasing ALKBH5/FTO-mediated m6A modification of lncRNA H19; these effects might be achieved by Carthamidin.

HQC inhibited inflammation and improved lipid metabolism in GA via inactivation of the IL-17 pathway by regulating m6A modification of lncRNA H19. Our findings further support the great potential of HQC as a candidate drug for GA treatment.

The online version contains supplementary material available at 10.1186/s13020-026-01379-z.