Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia

Wei Li; Zijia Zhang; Entezar Berik; Yawen Liu; Wenqiang Pei; Sihan Chen; Wenyong Wu; Zhaojun Wang; Xinqin Kong; Huali Long; Min Lei; Jennifer Yiyang Wang; Zhaoxia Li; Liangfeng Liu; Jinjun Hou; Wanying Wu; De-An Guo

doi:10.1016/j.phymed.2023.155269

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia

Phytomedicine. 2024 Mar:125:155269. doi: 10.1016/j.phymed.2023.155269. Epub 2023 Dec 9.

Authors

Wei Li¹, Zijia Zhang¹, Entezar Berik², Yawen Liu¹, Wenqiang Pei³, Sihan Chen¹, Wenyong Wu⁴, Zhaojun Wang¹, Xinqin Kong¹, Huali Long¹, Min Lei¹, Jennifer Yiyang Wang³, Zhaoxia Li⁵, Liangfeng Liu⁶, Jinjun Hou⁷, Wanying Wu⁸, De-An Guo¹

Affiliations

¹ National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
³ National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, China.
⁵ Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
⁶ Limin Pharmaceutical Factory, Livzon Group Limited, Shaoguan 512028, China; Guangdong Corporate Key Laboratory of High-End Liquid Medicine R&D, Industrilization, Shaoguan 512028, China.
⁷ National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jinjun_hou@simm.ac.cn.
⁸ National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, China. Electronic address: wanyingwu@simm.ac.cn.

PMID: 38237510
DOI: 10.1016/j.phymed.2023.155269

Abstract

Background: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored.

Purpose and methods: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels.

Results: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay.

Conclusion: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Keywords: Bioenergetic profiles; Chemotherapy-induce cachexia; Glycolysis; Shenqi Fuzheng injection; TCA cycle; lipid metabolism.

MeSH terms

Animals
Antineoplastic Agents*
Cachexia* / chemically induced
Cachexia* / drug therapy
Cachexia* / metabolism
Drugs, Chinese Herbal*
Energy Metabolism
Mice
Muscle, Skeletal / metabolism
Pyruvates / metabolism

Substances

shenqi fuzheng
Antineoplastic Agents
Pyruvates
Drugs, Chinese Herbal