Compatibility of cold herb CP and hot herb AZ in Huanglian Ganjiang decoction alleviates colitis mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming.
10.1016/S1875-5364(25)60869-7
- Author:
Yanyang LI
1
;
Chang LIU
2
;
Yi WANG
1
;
Peiqi CHEN
1
;
Shihua XU
1
;
Yequn WU
1
;
Lingzhi REN
1
;
Yang YU
3
;
Lei YANG
4
Author Information
1. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
2. Guangdong Provincial Engineering Research Center for Quality and Safety of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Chemical Measurement and Emergency Test Technology, Institute of Analysis, Guangdong Academy of Sciences (China National Analytical Center, Guangzhou), Guangzhou 510070, China.
3. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: yuyang@gzucm.edu.cn.
4. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: yanglei@gzucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Cold herb;
Colitis;
Compatibility;
Glucose metabolism reprogramming.;
Hot herb;
Huanglian Ganjiang decoction;
M1/M2 macrophage polarization;
PDK4
- MeSH:
Animals;
Drugs, Chinese Herbal/chemistry*;
Mice;
Macrophages/immunology*;
Glucose/metabolism*;
Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics*;
Male;
Mice, Inbred C57BL;
Humans;
Colitis/drug therapy*;
Disease Models, Animal;
Colitis, Ulcerative/drug therapy*;
Metabolic Reprogramming
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(10):1183-1194
- CountryChina
- Language:English
-
Abstract:
Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
