Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis

Zhang, Qian1,2,3; Luo, Piao1,2,3; Xia, Fei1; Tang, Huan1; Chen, Jiayun1; Zhang, Junzhe1; Liu, Dandan1; Zhu, Yongping1; Liu, Yanqing1; Gu, Liwei1; Zheng, Liuhai2; Li, Zhijie2; Yang, Fan2; Dai, Lingyun2; Liao, Fulong1; Xu, Chengchao1; Wang, Jigang1,2

2022-08-18

10.1016/j.chembiol.2022.06.011

CELL CHEMICAL BIOLOGY   Impact Factor & Quartile

2451-9456

2451-9448

Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have de-signed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.

SCI

English

Corresponding

National Key Research and Development Program of China[2020YFA0908000] ; Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; National Natural Science Foundation of China["81903588","81803456","81702580","82074098","81903866"] ; National Key R&D Program of China Key projects for international cooperation on science, technology and innovation, China[2020YFE0205100] ; Fundamental Research Funds for the Central Public Welfare Research Institutes["ZZ14-YQ-050","ZZ14-ND-010","ZZ15-ND-10","ZZ14-FL-002","ZZ14-YQ-059","ZZ15-YQ-063"]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000860117400002

CELL PRESS

Web of Science

1.China Acad Chinese Med Sci, Inst Chinese Mat Med, Artemisinin Res Ctr, Beijing 100700, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Dept Geriatr,Clin Med Coll 2,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
3.Southern Med Univ, Dept Tradit Chinese Med, Guangzhou 510515, Guangdong, Peoples R China

Zhang, Qian,Luo, Piao,Xia, Fei,et al. Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis[J]. CELL CHEMICAL BIOLOGY,2022,29(8).

Zhang, Qian.,Luo, Piao.,Xia, Fei.,Tang, Huan.,Chen, Jiayun.,...&Wang, Jigang.(2022).Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis.CELL CHEMICAL BIOLOGY,29(8).

Zhang, Qian,et al."Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis".CELL CHEMICAL BIOLOGY 29.8(2022).