Integrated Network Pharmacology and GC-MS–Based Metabolomics to Investigate the Effect of Xiang-Su Volatile Oil Against Menopausal Depression

Abstract

Menopausal depression perplexes a great number of women in later life. Xiangfu-Zisu (Xiang-Su), a traditional Chinese herbal pair composed of rhizomes of Cyperus rotundus L. (Xiangfu) and leaves of Perilla frutescens (L.) Britt. (Zisu), is frequently reported with antidepressant-like effects. The volatile oil from Xiangfu and Zisu has shown good antidepressant action, but its mechanism is still unclear. This study aimed to investigate the pharmacological mechanism of Xiang-Su (XS) volatile oil against menopausal depression through gas chromatography–mass spectrometry (GC-MS)-based network pharmacology and metabolomics. First, ADME screening was performed on actual detected components of XS volatile oil to obtain active constituents, and then duplicates of active constituent–related targets and menopausal depression–related targets were collected. These duplicates were considered as targets for XS volatile oil against menopausal depression, followed by GO and KEGG enrichment analyses. It showed that a total of 64 compounds were identified in XS volatile oil, and 38 active compounds were screened out. 42 overlapping genes between 144 compound-related genes and 780 menopausal depression–related genes were obtained. Results showed that targets of SLC6A4 and SLC6A3, regulation of serotonergic and dopaminergic synapses, were involved in the antidepressant mechanism of XS volatile oil. Next, antidepressant-like effect of XS volatile oil was validated in menopausal rats by ovariectomy (OVX) combined with chronic unpredictable mild stress (CUMS). Behavioral tests, biochemical analysis, and GC-MS–based non-targeted plasma metabolomics were employed to validate the antidepressant effect of XS volatile oil. Experimental evidence demonstrated that XS volatile oil reversed behavioral parameters in the sucrose preference test (SPT), open-field test (OFT), forced swim test (FST), and serum estradiol levels in OVX rats. Furthermore, results of metabolomics indicated that XS volatile oil mainly acts on regulating metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and tryptophan metabolism, which were corresponding with the above-predicted results. These data suggest that network pharmacology combined with metabolomics provides deep insight into the antidepressant effect of XS volatile oil, which includes regulating key targets like SLC6A4 and SLC6A3, and pathways of serotonergic and dopaminergic synapses.

Exploring the mechanism of Si-Ni-San against depression by UPLC-Q-TOF-MS/MS integrated with network pharmacology: experimental research

“…Inspired by this, our previous study performed network pharmacology of Xiang-Su volatile oil against menopausal depression based on the actual determined components by a method of gas chromatography-mass spectrometry. Subsequently, the antidepressant effect of Xiang-Su volatile oil was verified by metabolomics 18 . Thus, in this study, the actual determined compounds of Si-Ni-San water extract were employed by a method of UPLC-Q-TOF-MS/MS to perform the network pharmacology, which was aimed to increase the reliability and accuracy of the predicted results for the antidepressant mechanism of Si-Ni-San.…”

“…In that way, it may be lack of reliability and accuracy for the actual antidepressant mechanism of Si-Ni-San. Only a few studies use actual determined components to clarify the possible mechanism of TCM by the method of network pharmacology 17 , 18 . Besides, In the modern pharmacological studies of TCM, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) method is often used to detect the actual components of TCM formulas, such as Si-Ni-San 19 .…”

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer’s Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

“…YZP, a TCM medicine, is extensively used to treat AD patients, but no quality control mechanism exists to ensure its effectiveness. HPLC has recently been extensively used to build a quality control technique for herbal medicine [19,20]. However, it cannot discriminate between quality indicators, which indicate its effectiveness, and chemical markers.…”

Applications of Perilla frutescens Extracts in Clinical Practice

“…As a result of the many TCM practitioners’ recommendations for the leaves, stems, and seeds of this plant for a variety of medicinal objectives, the chemical contents and pharmacological properties of these sections of the plant have been both experimentally and scientifically verified. Furthermore, Perilla frutescens plays an essential role in various TCM-based prescriptions to augment the therapeutic effects of specific herbs in medical applications [ 5 , 6 ].…”