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Research Paper|Volume 16, Issue 10|pp 9023—9046

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage

Yanling Li1, Qingying Yu2, Huiyuan Peng3, Xie Mingjun4, WenHua Xu5, Tingting Zheng1, Tingting Zhao6, Mengyao Xia1, Jibiao Wu7, Pantelis Stavrinou8, Roland Goldbrunner8, Yicheng Xie9, Guimin Zhang10, Yu Feng1, Yongxia Guan10, Feng Zheng11, Peng Sun7
  • 1School of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji’nan, China
  • 2Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 3Department of Pharmacy, Zhongshan Hospital of Traditional Chinese Medicine, Zhong Shan, China
  • 4College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, China
  • 5Prevention and Treatment Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
  • 6Shandong University of Traditional Chinese Medicine, Ji’nan, China
  • 7Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, China
  • 8Department of Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
  • 9The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
  • 10State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
  • 11Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
* Equal contribution
# Lead contact, further information and requests for resources and reagents should be directed to and will be fulfilled by Peng Sun, [email protected]
Received: October 16, 2023Accepted: April 10, 2024Published: May 28, 2024
https://doi.org/10.18632/aging.205854

Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1β (IL-1β). Molecular docking analyses revealed an average affinity of −8.633 kcal/mol, indicating a binding strength of less than −5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.