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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1640272

Total flavonoids of Dracocephalum moldavica L. alleviate cognitive impairment via TNF-α/NF-κB p65 signaling pathway in vascular dementia rats

Provisionally accepted
Shangjia  MaShangjia Ma1Jianxin  JiaJianxin Jia2Li'e  WuLi'e Wu1Kai  TianKai Tian3Lu  WangLu Wang1Hua  LiHua Li1Jiayu  LvJiayu Lv1Dewang  GaoDewang Gao1Zhanjun  YangZhanjun Yang4*Xia  GuoXia Guo1*
  • 1First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
  • 2Baotou Medical College, Baotou, China
  • 3The Third Hospital of BaoGang Group, Baotou, China
  • 4Chifeng University, Chifeng, China

The final, formatted version of the article will be published soon.

Objective: This study aims to elucidate the neuroprotective effects and underlying mechanisms of total flavonoids of Dracocephalum moldavica L. (TFDM) in VaD by using network pharmacology and in vivo validation.The network pharmacology was used to explore the mechanism of TFDM to improve VaD.A rat model of VaD was established using permanent bilateral common carotid artery occlusion (2VO). The Morris water maze test assessed spatial learning and memory capacities. Nissl staining was used to examine the neuronal damage. Western blot and Immunofluorescence analysis was employed to evaluate protein levels of factors associated with neuroinflammation, blood-brain barrier integrity, and angiogenesis.The network pharmacology suggests TFDM may combat VaD through TNF-α/NF-κB p65 signaling pathways.TFDM treatment may attenuate memory deficits associated with 2VO and reduce neuronal damage. TFDM improved blood-brain barrier integrity and promoted angiogenesis by downregulating MMP-9 and upregulating ZO-1 and VEGFA. Moreover, TFDM exhibited antiinflammatory properties by inhibiting TNF-α and NF-κB p65 production, thereby mitigating the neuroinflammatory response in VaD rats.Conclusion:TFDM demonstrated significant improvement in cognitive function in VaD rats. This improvement was attributed to the multifaceted effects, including the improvement of blood-brain barrier integrity, promotion of angiogenesis, and reduction of neuroinflammation. These findings suggest that TFDM may represent a promising therapeutic approach for VaD management.

Keywords: Total flavonoids of Dracocephalum Moldavica L., Vascular Dementia, Network Pharmacology, Neuroinflammation, TNF-α/NF-κB p65 signaling pathway, Blood-Brain Barrier

Received: 05 Jun 2025; Accepted: 25 Jul 2025.

Copyright: © 2025 Ma, Jia, Wu, Tian, Wang, Li, Lv, Gao, Yang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Zhanjun Yang, Chifeng University, Chifeng, China
Xia Guo, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China

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