Dataset Information

Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

ABSTRACT: Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.

SUBMITTER: Wang C

PROVIDER: S-EPMC9602736 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

Wang Cuizhu C Tan Luying L Liu Juntong J Fu Dongxing D Wang Caixia C Li Pingya P Li Zhuo Z Liu Jinping J

International journal of molecular sciences 20221011 20

Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the ...[more]

PMID: 36292949

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Project description:Background and aimGoupi Plaster (GP) is topical traditional Chinese medicine preparation. It has been used to treat Knee Osteoarthritis (KOA) in clinical practice of traditional Chinese medicine (TCM). However, the mechanisms of GP relieve KOA are poorly understood.Experimental procedureRabbit models of KOA were established and treated with GP. Knee cartilage pathology was analyzed using hematoxylin and eosin staining, while plasma levels of inflammatory factors (interleukin (IL)-4, IL-6, and IL-17) and skin neurotransmitters (calcitonin gene-related peptide (CGRP), substance P (SP), and5-hydroxytryptamine (5-HT)) were measured by enzyme linked immunosorbent assay. Metabolomics based on GC-TOF-MS analysis screened for skin biomarkers as well as relevant pathways. Network pharmacology screened for relevant skin targets as well as relevant pathways, and finally, MetScape software was utilized to integrate the results of metabolomics and network pharmacology to screen for key skin targets, key metabolites, and key pathways for GP treatment of KOA.Results and conclusionGP administration substantially repaired cartilage surface breaks in KOA and led to relatively intact cartilage structure and normal cell morphology. GP decreased plasma levels of IL-6 and IL-17 and skin levels of CGRP, SP and 5-HT while increased plasma IL-4. GP administration normalized the levels of 15 metabolites which were changed in KOA. Network pharmacology analysis identified 181 targets. Finally, 3 key targets, 5 key metabolites and 3 related pathways were identified, which suggested that GP improved skin barrier function and skin permeability by regulating skin lipid metabolism. GP treatment also regulated skin amino acid levels and subsequently affected neurotransmitters and signaling molecules. In addition, the purinergic signaling pathway was also involved in the treatment of GP against KOA.In conclusion, GP treatment is associated with changes in skin lipid metabolism, neurotransmitters, and the purinergic signaling pathway.

Dataset Information

Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

Publications

Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

Similar Datasets

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