UPLC–MS/MS and Network Pharmacology-Based Analysis of Bioactive Anti-Depression Compounds in Betel Nut

Abstract

Background: 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. "Compounddisease 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.

Integrated Transcriptomic and Metabolomic Analyses Reveal the Molecular and Metabolic Basis of Flavonoids in Areca catechu L.

“…Many of these metabolites have yet to be reported in A. catechu previously, although multiple catechins, epicatechins, quercetin, and anthocyanins have been detected in previous studies. 7,41 Flavonoids have anti-free radicals and antioxidant effects. For example, by penetrating the blood− brain barrier and reducing the damage to neurons, kaempferol can protect the brain from oxidative damage.…”

“…5 These activities include antidepressant, antifatigue, antihypertensive, anti-inflammatory, analgesic, and antiallergic effects. 6,7 Various metabolites have been identified from A. catechu extracts, such as alkaloids, steroids, flavonoids, triterpenoids, and fatty acids. 8 Most metabolomic studies focus on 16 pyridine alkaloids in areca nuts, such as arecoline, arecaidine, guavacoline, guavacine, etc.…”

“…catechu have a long medical history due to their pharmacological activities . These activities include antidepressant, antifatigue, antihypertensive, anti-inflammatory, analgesic, and antiallergic effects. , Various metabolites have been identified from A. catechu extracts, such as alkaloids, steroids, flavonoids, triterpenoids, and fatty acids .…”

“…catechu extracts, such as alkaloids, steroids, flavonoids, triterpenoids, and fatty acids . Most metabolomic studies focus on 16 pyridine alkaloids in areca nuts, such as arecoline, arecaidine, guavacoline, guavacine, etc. ,, Although most studies have focused on pyridine alkaloids, other metabolites with medicinal activity, such as flavonoids, have been found previously. Flavonoids can decrease the risk of chronic diseases, especially cancer, regulate apoptosis, angiogenesis, inflammation, and metastasis, and enhance the human body’s antioxidant capacity against free radicals. − The abundance of flavonoids in the peel of A.…”

Brief psychotic disorder caused by areca nut use: a case report

“…Users report experiencing pleasurable and stimulating effects, including a sense of well-being, euphoria, heightened alertness, a warm bodily sensation, and increased work capacity 15 . Scienti c studies have also suggested that arecoline, a major alkaloid present in areca nut, exhibits anxiolytic-like activity 16 and contains bioactive compounds with potential anti-depression properties 17 . Furthermore, research has indicated its potential in ameliorating symptoms of schizophrenia 18 .…”