Study of the correlation between the anti-ischemic stroke mechanism of 4-hydroxybenzaldehyde and its response to reactive oxygen species in brain metabolism.

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacology and Experimental Therapeutics Pub Date : 2025-01-31 DOI:10.1016/j.jpet.2025.103395
Jin Feng, Qian Yang, Ming Chen, Long Ning, Yan Wang, Dan Luo, Dongxiong Hu, Qing Lin, Fangyan He
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Abstract

The active ingredient of Gastrodia elata, 4-hydroxybenzaldehyde (4-HBd), can rapidly enter the brain and undergo massive oxidation to produce the metabolite 4-hydroxybenzoic acid, which has no significant activity after equal dose gavage. It is crucial to clarify the metabolic pathway of 4-HBd and its correlation with the anti-ischemic stroke mechanism. The objective of this study was to explore the possible mechanism of 4-HBd in clearing reactive oxygen species (ROS) and protecting blood-brain barrier from oxidative stress damage during brain metabolism from the perspective of ROS response. A rat model of cerebral ischemia-reperfusion injury and a cellular oxidative stress response model were replicated to simulate the accumulation process of ROS in the brain. The changes in ROS and peroxidation products before and after 4-HBd intervention were detected, and the changes in oxidative metabolism were also measured to confirm the correlation between antioxidant stress damage and ROS capture/clearance in oxidative metabolism. 4-HBd has significant antioxidant stress resistance both in vitro and in vivo, and can reduce the levels of malondialdehyde and 4-hydroxy-2-nonenal in ischemic brain tissue. It can capture O2⋅- and ⋅OH in vitro and use the captured ROS to oxidize and metabolize 4-hydroxybenzoic acid. The oxidative metabolism process of 4-HBd in the brain is one of its mechanisms for exerting antioxidant stress damage and protecting blood-brain barrier. SIGNIFICANCE STATEMENT: The active ingredient 4-hydroxybenzaldehyde of Gastrodia elata can be converted into metabolite 4-hydroxybenzoic acid in the brain mainly through oxidative metabolic pathway. The mechanism of its action against oxidative stress damage of blood-brain barrier is related to the oxidative metabolic process in the brain that traps/clears reactive oxygen species and forms stable intermediates to terminate the free radical chain reaction. This is one of the main mechanisms of 4-hydroxybenzaldehyde's anti-ischemic stroke effect in the brain.

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CiteScore
6.90
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审稿时长
1 months
期刊介绍: A leading research journal in the field of pharmacology published since 1909, JPET provides broad coverage of all aspects of the interactions of chemicals with biological systems, including autonomic, behavioral, cardiovascular, cellular, clinical, developmental, gastrointestinal, immuno-, neuro-, pulmonary, and renal pharmacology, as well as analgesics, drug abuse, metabolism and disposition, chemotherapy, and toxicology.
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