Deciphering the Molecular Mechanism of Yifei-Sanjie Pill in Cancer-Related Fatigue

Yingchao Wu; Shuyao Zhou; Dajin Pi; Yangyang Dong; Wuhong Wang; Huan Ye; Zhongjia Yi; Yiliu Chen; Lizhu Lin; Mingzi Ouyang

doi:10.1155/2023/5486017

Deciphering the Molecular Mechanism of Yifei-Sanjie Pill in Cancer-Related Fatigue

J Oncol. 2023 Feb 13:2023:5486017. doi: 10.1155/2023/5486017. eCollection 2023.

Authors

Yingchao Wu¹, Shuyao Zhou², Dajin Pi¹, Yangyang Dong³, Wuhong Wang¹, Huan Ye¹, Zhongjia Yi¹, Yiliu Chen¹, Lizhu Lin⁴, Mingzi Ouyang¹

Affiliations

¹ School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, China.
² College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, Guangdong 510642, China.
³ Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
⁴ Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China.

Abstract

Background: The incidence of cancer-related fatigue (CRF) is increasing, but its lack of clear pathogenesis makes its prevention and treatment difficult. Therefore, it is of great significance to clarify the pathogenesis of CRF and find effective methods to treat it.

Methods: The CRF model was established by intraperitoneal injection of LLC cells in ICR mice to explore the pathogenesis of CRF and verify the therapeutic effect of the Yifei-Sanjie pill (YFSJ). The active components of YFSJ were found by LC/MS, the in vitro inflammatory infiltration model of skeletal muscle was constructed by TNF-α and C2C12 myoblasts, and the results of in vivo experiments were verified by this model.

Results: Behavioral analysis results showed that YFSJ alleviated CRF; histological examination results showed that YFSJ could reverse the tumor microenvironment leading to skeletal muscle injury; ELISA and RNA-seq results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the tumor inflammatory microenvironment; IHC and WB results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the Stat3-related signaling pathway and autophagy.

Conclusions: YFSJ can reduce the level of inflammation in the tumor microenvironment in vivo, inhibit the abnormal activation of the Stat3/HIF-1α/BNIP3 signaling pathway induced by tumor-related inflammation, thereby inhibiting the overactivation of mitophagy in skeletal muscle, and finally alleviate CRF. Quercetin, one of the components of YFSJ, plays an important role in inhibiting the phosphorylation activation of Stat3.