Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression.
Abstract
Ethnopharmacological relevance The compatibility of Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is one of the most accepted herb pairs in traditional Chinese medicine (TCM) prescriptions for treating depression. However, the combination mechanisms of this herb pair for anti-depression remain unclear.Materials and methods In this study, the combined effect of Chaihu-Baishao was evaluated by the chronic unpredictable mild stress (CUMS) rat model. Secondly, network pharmacology was constructed to dissect the united mechanisms. Based on the results of network pharmacology analysis, plasma metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was performed to discover the collaborative effect on metabolite regulation. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA.Results The antidepressant effect of Chaihu-Baishao herb pair was significantly better than Chaihu or Baishao in sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). In network pharmacology, herb pair played synergetic effect through regulating shared pathways, such as MAPK signaling pathway and arachidonic acid metabolism, etc. Besides, by metabolomics, the herb pair improved more metabolites (14) than a single herb (10 & 9) and has a stronger regulation effect on metabolites. Correspondingly, herb pair adjusted more metabolism pathways (5) than individual herb (4 & 4). Furthermore, the arachidonic acid metabolism was selected as crucial metabolism pathways by a joint analysis of 199 targets and 14 metabolites. The results showed that herb pair regulated arachidonic acid metabolism by synergetic reducing the level of arachidonic acid, and inhibiting the enzyme activity of prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxide synthase 2 (PTGS2).Conclusions This work provided an integrated strategy for revealing the combination mechanisms of Chaihu-Baishao herb pair for treating depression, and also a rational way for clarifying the composition rules of TCM.
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- Authors
- Li, X., Qin, X.-M., Tian, J.-S., Gao, X.-X., Du, G.-H., & Zhou, Y.-Z.
- Affiliations
- Shanxi University (CN)
- ORCID
- Li, Xiao
- Venue
- Journal of Ethnopharmacology
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 264
- Pages
- 113281
- ISSN
- 0378-8741 (ISSN-L)
- OpenAlex
- W3049502358
- Cited by
- 92
- References
- 49
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 16 · 2023: 14 · 2022: 22 · 2021: 10
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Ethnopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Nature Science Foundation of China (81673572)
- the major science and technology project for “Significant New Drugs Creation” (2017ZX09301047)
- the Innovation project of higher education institutions in Shanxi Province (2016120)
- Shanxi Scholarship Council of China (2020019)
- scholar science and technology activities (201991)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Medicinal Plants and Bioactive Compounds
- Keywords
- Bupleurum chinense, Paeonia lactiflora, depression, antidepressant mechanism, arachidonic acid metabolism, MAPK signaling, PTGS1, cyclooxygenase-2, chronic unpredictable mild stress, plasma metabolites, traditional Chinese medicine prescriptions, network pharmacology, metabolomics
- MeSH terms
- Animals, Antidepressive Agents, Depression, Drug Therapy, Combination, Drugs, Chinese Herbal, Male, Rats, Sprague-Dawley, Paeonia, Bupleurum, Rats, Metabolomics
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