Study on the mechanism of Huatan qushi huoxue formula in improving metabolic dysfunction-associated steatohepatitis by inhibiting macrophage pyroptosis
- VernacularTitle:化痰祛湿活血方抑制巨噬细胞焦亡改善代谢相关脂肪性肝炎的作用机制研究
- Author:
Yajie GUAN
1
;
Qizhen ZHANG
1
;
Junjiao XU
1
;
Yijia SONG
1
;
Dongfang SHANG
2
;
Wenxia ZHAO
2
;
Minghao LIU
3
Author Information
1. Liver Disease （Spleen & Stomach） Diagnosis and Treatment Center，the First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450006，China;The First Clinical Medical College，Henan University of Chinese Medicine，Zhengzhou 450046，China
2. Liver Disease （Spleen & Stomach） Diagnosis and Treatment Center，the First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450006，China;Henan Academy of Chinese Medical Science，Zhengzhou 450046，China;Henan Provincial Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine，Zhengzhou 450046，China;Henan Collaborative Innovation Center for the Whole Industry Chain R&D of Yu Medicines，Zhengzhou 450046，China
3. Liver Disease （Spleen & Stomach） Diagnosis and Treatment Center，the First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450006，China;Henan Academy of Chinese Medical Science，Zhengzhou 450046，China;Henan Provincial Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine，Zhengzhou 450046，China
- Publication Type:Journal Article
- Keywords:
Huatan qushi huoxue formula;
metabolic dysfunction-associated steatohepatitis;
macrophage;
pyroptosis;
NOD-
- From:
China Pharmacy
2026;37(7):864-869
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.
