Biomedicines
Total Phenylethanoid Glycosides from Cistanche tubulosa Alleviate 5-Fluorouracil-Induced Fatigue-Like Behavior and Skeletal Muscle Injury in Mice
By Chen J, Yang J, Cao Y and 6 others.
Abstract
Objectives
This study investigated the effects of total phenylethanoid glycosides from Cistanche tubulosa (CPhGs) on 5-fluorouracil (5-FU)-induced fatigue-like behavior and tissue injury in mice and examined associated molecular changes.
Methods
Public transcriptomic datasets (GSE80473, GSE121972, and GSE77745) were analyzed to provide exploratory pathway-level context for hypothesis-driven markers associated with chemotherapy- or cachexia-related skeletal muscle injury. Forty tumor-free BALB/c mice were randomly assigned to a normal control group or treated with 5-FU (20 mg/kg, intraperitoneally) for five consecutive days. The 5-FU-treated mice were subsequently divided into model, low-dose-CPhG (250 mg/kg), and high-dose-CPhG (500 mg/kg) groups and treated orally for 14 days. Exercise endurance, forelimb grip strength, serum markers of tissue injury and inflammation, and histopathological changes in skeletal muscle, epididymal adipose tissue, and liver were evaluated. Proteins involved in Akt/FoxO3a signaling, muscle protein degradation, and mitochondrial metabolism were measured in skeletal muscle. Molecular docking was used to assess the predicted interactions of echinacoside and acteoside with selected proteins.