Drug Design, Development and Therapy (Nov 2021)
UPLC–MS/MS and Network Pharmacology-Based Analysis of Bioactive Anti-Depression Compounds in Betel Nut
Abstract
Yunjia Yang,1,* Hairong Huang,1,* Zeying Cui,2 Jun Chu,3 Guankui Du2,4,5 1School of Public Health, Hainan Medical University, Haikou, People’s Republic of China; 2Key Laboratory of Molecular Biology, Hainan Medical University, Haikou, People’s Republic of China; 3Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 4Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, People’s Republic of China; 5Biotechnology and Biochemisty Laboratory, Hainan Medical University, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guankui DuDepartment of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, 571101, People’s Republic of ChinaTel +86-898-66893779Fax +86-898-66893600Email [email protected] ChuKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, Anhui, People’s Republic of ChinaEmail [email protected]: Betel nuts have long been used in traditional Chinese medicine. In our study, the bioactive components of betel nut were systematically investigated, and the main components and their target genes in the treatment of depression were predicted.Methods: The metabolites of the kernels and peels were analyzed with a UPLC–MS/MS system. Mass spectrometry outcomes were annotated by MULTIAQUANT. “Compound‐disease targets” were utilized to construct a pharmacology network.Results: A total of 873 metabolites were identified, with a high abundance of flavonoids, alkaloids, and phenols. Moreover, the abundance of flavonoids, alkaloids, and phenols in the kernel was significantly higher than that in the peel. A high abundance of catechin, arginine, and phenylalanine was detected in the kernel, while a high abundance of arginine, arecoline, and aminobutyric acid was detected in the peel. Catechins and cyanoside were the most abundant flavonoids in the kernel and peel, respectively. Arecoline was the most abundant alkaloid. A total of 111 metabolites showed a significant difference between the kernels and peels. The relative abundance of 40 differential metabolites was higher than 100,000, including 14 primary metabolites, 12 flavonoids, 4 phenols, and 4 alkaloids. Among the 40 high abundance metabolites, 20 were higher in the kernel and 20 in the peel. In addition, the enrichment of metabolic pathways found that the kernel and peel of the fruit adopted different metabolic pathways for the synthesis of flavonoids and alkaloids. Network pharmacology prediction showed that 93 metabolites could target 141 depression-related genes. The main components of betel nut intervention in depression were predicted to include L-phenylalanine, protocatechuic acid, okanin, nicotinic acid, L-tyrosine, benzocaine, syringic acid, benzocaine, phloretic acid, cynaroside, and 3,4-dihydroxybenzaldehyde.Conclusion: Betel nuts are rich in natural metabolites, and some of these metabolites can participate in the intervention of depression. In addition, the metabolites showed distinct characteristics between the kernel and peel. Therefore, it is necessary to comprehensively and rationally use betel nuts.Keywords: betel nut, metabolites, flavonoid, alkaloids, phenols
