Academic Journal
Integrated network pharmacology and metabolomics reveal vascular protective effects of Ilex pubescens on thromboangiitis obliterans.
| Title: | Integrated network pharmacology and metabolomics reveal vascular protective effects of Ilex pubescens on thromboangiitis obliterans. |
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| Authors: | Chen J; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China., Wang Y; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China., Chen C; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China., Song X; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China., Shen X; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China., Cao D; Wannan Medical College, Wuhu 241002, China., Zhao Z; State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: zzx37@gzucm.edu.cn. |
| Source: | Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jul 25; Vol. 130, pp. 155720. Date of Electronic Publication: 2024 May 11. |
| Abstract: | Background: Ilex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear. Aim of the Study: This study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. Methods: In this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO. Results: The study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway. Conclusion: In this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier GmbH. All rights reserved.) |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE |
| Imprint Name(s): | Publication: Stuttgart : Urban & Fischer Verlag Original Publication: Stuttgart ; New York : G. Fischer, c1994- |
| MeSH Terms: | Thromboangiitis Obliterans*/drug therapy , Metabolomics* , Network Pharmacology* , Ilex*/chemistry , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Rats, Sprague-Dawley*, Animals ; Male ; Rats ; Disease Models, Animal ; Femoral Artery/drug effects ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/blood supply ; Muscle, Skeletal/metabolism ; Tandem Mass Spectrometry |
| Contributed Indexing: | Keywords: Ilex pubescens; SPHK1/S1PR1 signaling pathway; Sphingolipid metabolism; Thromboangiitis obliterans |
| Substance Nomenclature: | 0 (Plant Extracts) |
| Entry Date(s): | Date Created: 20240519 Date Completed: 20240614 Latest Revision: 20240614 |
| Update Code: | 20240615 |
| DOI: | 10.1016/j.phymed.2024.155720 |
| PMID: | 38763010 |
| ISSN: | 1618-095X |
| DOI: | 10.1016/j.phymed.2024.155720 |
| Database: | MEDLINE |