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

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.

TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine

“…Subsequently, both pieces of information were input into the molecular docking module of TCMNPAS to analyze the binding affinity of quercetin towards Akt1. The results demonstrated a strong binding affinity of − 8.9 kJ/mol, indicating a favorable interaction between quercetin and Akt1 [61].…”

Yifei Sanjie formula alleviates lung cancer progression via regulating PRMT6‐YBX1‐CDC25A axis

“…In a case control study of 376 NSCLC patients, it was found that YFSJF plus chemotherapy improves the median overall survival compared with chemotherapy alone 12 . Additional clinical research shown that YFSJF with chemotherapy could improve quality of life and lessen fatigue 13,14 . Nevertheless, the pharmacological mechanisms of YFSJF in lung cancer remain poorly understood.…”

“…12 Additional clinical research shown that YFSJF with chemotherapy could improve quality of life and lessen fatigue. 13,14 Nevertheless, the pharmacological mechanisms of YFSJF in lung cancer remain poorly understood.…”