Abstract
Background Cancer-related fatigue (CRF) is an increasingly appreciated complication in cancer patients, which severely impairs their quality of life for a long time. Astragali Radix (AR) is a safe and effective treatment to improve CRF, but the related mechanistic studies are still limited. Objective To systematically analyze the mechanism of AR against CRF by network pharmacology. Methods TCMSP was searched to obtain the active compounds and targets of AR. The active compound-target (AC-T) network was established and exhibited by related visualization software. The GeneCards database was searched to acquire CRF targets, and the intersection targets with AR targets were used to make the Venny diagram. The protein-protein interaction (PPI) network of intersection targets was established, and further, the therapeutic core targets were selected by topological parameters. The selected core targets were uploaded to Metascape for GO and KEGG analysis. Finally, AutoDock Vina and PyMOL were employed for molecular docking validation. Results 16 active compounds of AR were obtained, such as quercetin, kaempferol, 7-O-methylisomucronulatol, formononetin, and isorhamnetin. 57 core targets were screened, such as AKT1, TP53, VEGFA, IL-6, and CASP3. KEGG analysis manifested that the core targets acted on various pathways, including 137 pathways such as TNF, IL-17, and the AGE-RAGE signaling pathway. Molecular docking demonstrated that active compounds docked well with the core targets. Conclusion The mechanism of AR in treating CRF involves multiple targets and multiple pathways. The present study laid a theoretical foundation for the subsequent research and clinical application of AR and its extracts against CRF.
Highlights
Cancer-related fatigue (CRF) is a long-lasting physical, emotional, and/or cognitive tiredness or exhaustion associated with cancer or cancer treatment [1]. ere is a huge distinction between CRF and other types of fatigue, which do not match the amount of recent activity, seriously interfere with body function, and even lead to the interruption of antitumor therapy
More than one-fourth of patients still experience fatigue for more than 5 years after successful treatment, which seriously reduces the quality of life [3]. e development of CRF is mainly associated with inflammation, immune dysregulation, hypothalamic-pituitary-adrenal axis disturbances, and reduced energy metabolism [4]
“Huangqi” (AR) was used as a search term in TCMSP [13] to acquire related compounds. e aforementioned compounds that conformed to the criterion were selected and regarded as active compounds of Astragali Radix (AR): oral bioavailability (OB) ≥ 30% and drug likeness (DL) ≥ 0.18 [14]. e corresponding targets were extracted as AR targets
Summary
Cancer-related fatigue (CRF) is a long-lasting physical, emotional, and/or cognitive tiredness or exhaustion associated with cancer or cancer treatment [1]. ere is a huge distinction between CRF and other types of fatigue, which do not match the amount of recent activity, seriously interfere with body function, and even lead to the interruption of antitumor therapy. E study result indicates that 30%–60% of cancer patients develop moderate to severe fatigue in therapy that leads to the discontinuation of oncological treatment. AR was first contained in the ancient Chinese herbal book Shennong Ben Cao Jing in the Han Dynasty and is listed as a good product for tonifying qi and tonifying deficiency It was Evidence-Based Complementary and Alternative Medicine demonstrated that AR has immunomodulatory, antioxidant, and anti-inflammatory effects by modern pharmacological studies [6]. Astragali Radix (AR) is a safe and effective treatment to improve CRF, but the related mechanistic studies are still limited. E active compound-target (AC-T) network was established and exhibited by related visualization software. Molecular docking demonstrated that active compounds docked well with the core targets. Conclusion. e mechanism of AR in treating CRF involves multiple targets and multiple pathways. e present study laid a theoretical foundation for the subsequent research and clinical application of AR and its extracts against CRF
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