Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation.

Autor: Zhang W; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Zhang P; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China., Xu LH; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China., Gao K; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Zhang JL; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Yao MN; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Li RL; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Guo C; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Wang JW; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: wangjingwen8021@163.com., Wu QX; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China. Electronic address: wuqx@lzu.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jan; Vol. 123, pp. 155237. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1016/j.phymed.2023.155237
Abstrakt: Background: The prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear.
Purpose: To investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex).
Study Design and Methods: The components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia-reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments.
Results: The HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway.
Conclusion: This work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest. Fig. 10 was generated using the online tool Figdraw2.0.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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