Identification of Anti-Cancer Components of Astragalus Mongholicus Bunge–Curcuma Aromatica Salisb. Via Integrated Metabolomics and Network Pharmacology Analysis

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies that can diminish patients’ quality of life. Astragalus mongholicus Bunge–Curcuma aromatica Salisb. (AC) is an ancient Chinese medication combination used for the treatment of many malignancies. However, its core components and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. In this study, we aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods.

Methods: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in CRC murine feces and serum. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC–target–component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction.

Results: AC treatment reduced liver metastasis and tumor volume. Compared with the CRC group, 14 lipid metabolites were upregulated and 15 amino acid metabolites and 9 lipid metabolites were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors.

Conclusion: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.

Note:

Funding Information: This research was supported by the grants from the National Natural Science Foundation of China (Grant No. 82274116, Grant No. 81873021, Grant No. 81904059), the TCM Science and Technology Development Special Project of Jiangsu Province (No. 2020ZX01), the Natural Science Research in Jiangsu Province (No. BK20190803), the Youth Project of Nanjing University of Chinese Medicine (No. NZY81904059), the Innovation Program for Graduate Students of Jiangsu Province (No. KYCX22_1885), and the National College Students' innovation and entrepreneurship training program(No.201910315002Z).

Declaration of Interests: None declared.

Ethics Approval Statement: All experimental procedures were performed in accordance with the National Institutes of Health Guidelines for Laboratory Animals and approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine (202010A026).

Keywords: Colorectal cancer, Astragalus mongholicus Bunge-Curcuma aromatica Salisb., Metabolomics, Network pharmacology, molecular docking, tumor immunity