Abstract
Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.
Highlights
Cancer-related fatigue (CRF) occurs in nearly 60−90% of advanced cancer patients [1]
The in vivo experiments found that Shengqi Fuzheng Injection (SFI) had little influence on the reduced tumor volume throughout the experimental period (Figure 1(e)) and that there was no reduction in tumor weight after the SFI treatment (Figure 1(d))
By using the fluorescent probe JC-1 (Figure 2(b)) the effect of SFI on ΔΨCm could be measured, and the results showed that the ratio of JC-1 red to green fluorescence in the C2C12 myotubes significantly decreased after exposure to CT-26 or H2O2 conditions, indicating that the malignant microenvironment resulted in the dissipation of ΔΨCm
Summary
Cancer-related fatigue (CRF) occurs in nearly 60−90% of advanced cancer patients [1]. CRF is characterized as a painful, persistent, subjective physical, emotional, and cognitive fatigue or exhaustion that is out of proportion to recent activities and interferes with normal functions [2]. CRF may be caused by mitochondrial dysfunction or peripheral immune dysfunction related to cancer or its treatment [3]. The cause of CRF is obvious, there is currently no effective management or prevention strategy available [2]. Novel and safe management strategies for CRF are urgently required. The synergistic effects of natural phytochemicals have been identified as being of increasing importance for the improvement of CRF symptoms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
