Journal of ethnopharmacology · 2024
Classical prescription Daqinjiao decoction inhibit cerebral ischemia/reperfusion induced necroptosis and ferroptosis through multiple mechanisms.
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Liu Yuwen, Liu Jiping, Hu Naping, Li Zhengrong, Liu Anqi, Luo Ruyue, Du Siyu, Guo Dongyan, Li Jiankang, Duan Jialin
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: The Daqinjiao decoction (DQJT), a classical prescription, has been utilized for millennia in stroke management, yet its underlying mechanisms remained obscure.
AIM OF THE STUDY: The aim of this study was to elucidate the mechanisms through which DQJT mitigates cerebral ischemia/reperfusion injury (CI/RI).
MATERIALS AND METHODS: The quantification of DQJT's primary components were performed by HPLC. Pharmacological assessments were then conducted to ascertain DQJT's efficacy in a Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) model. Following this, untargeted metabolomics, lipidomics and network pharmacology analyses were undertaken to unveil potential mechanisms, which were subsequently validated. UPLC-Q-TOF/MS was utilized to detect DQJT-derived chemicals in brain tissue, and molecular docking techniques were employed to investigate the bioactive compounds.
RESULTS: DQJT treatment reduced brain damage induced by MCAO/R, as evidenced by decreased infarct sizes, enhanced behavioral function scores, and diminished neuronal damages. Untargeted metabolomics and lipidomics revealed that DQJT improved metabolism of unsaturated fatty acids. According to network pharmacology, lipid metabolism, cAMP signaling pathway and toll-like receptor signaling pathway pathways were notably affected, with HSP90AA1, TLR4, and PKA identified as potential targets of DQJT. Immunofluorescence and Western blot analyses further demonstrated that DQJT counteracted necroptosis and ferroptosis by inhibiting the HSP90AA1 and TLR4 pathways and enhancing the PKA pathway. Molecular docking results supported that the possible pharmacodynamic substances of DQJT in protecting against CI/RI.
CONCLUSION: This research established that DQJT attenuates brain injury induced by MCAO/R through the modulation of necroptosis and ferroptosis via pathways including HSP90AA1, TLR4, and PKA. It shed light on the potential mechanisms and effective constituents of DQJT in stroke treatment, paving the way for further exploration of this ancient formula.
AIM OF THE STUDY: The aim of this study was to elucidate the mechanisms through which DQJT mitigates cerebral ischemia/reperfusion injury (CI/RI).
MATERIALS AND METHODS: The quantification of DQJT's primary components were performed by HPLC. Pharmacological assessments were then conducted to ascertain DQJT's efficacy in a Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) model. Following this, untargeted metabolomics, lipidomics and network pharmacology analyses were undertaken to unveil potential mechanisms, which were subsequently validated. UPLC-Q-TOF/MS was utilized to detect DQJT-derived chemicals in brain tissue, and molecular docking techniques were employed to investigate the bioactive compounds.
RESULTS: DQJT treatment reduced brain damage induced by MCAO/R, as evidenced by decreased infarct sizes, enhanced behavioral function scores, and diminished neuronal damages. Untargeted metabolomics and lipidomics revealed that DQJT improved metabolism of unsaturated fatty acids. According to network pharmacology, lipid metabolism, cAMP signaling pathway and toll-like receptor signaling pathway pathways were notably affected, with HSP90AA1, TLR4, and PKA identified as potential targets of DQJT. Immunofluorescence and Western blot analyses further demonstrated that DQJT counteracted necroptosis and ferroptosis by inhibiting the HSP90AA1 and TLR4 pathways and enhancing the PKA pathway. Molecular docking results supported that the possible pharmacodynamic substances of DQJT in protecting against CI/RI.
CONCLUSION: This research established that DQJT attenuates brain injury induced by MCAO/R through the modulation of necroptosis and ferroptosis via pathways including HSP90AA1, TLR4, and PKA. It shed light on the potential mechanisms and effective constituents of DQJT in stroke treatment, paving the way for further exploration of this ancient formula.