Abstract
To date, there is still no specific treatment for neonatal hypoxic-ischemic encephalopathy and new therapies are urgently needed. The excessive neuroinflammatory response activated by hypoxia-ischemia plays an important role in the occurrence and exacerbation of hypoxic-ischemic brain injury in neonates. Metabolites extracted from plants exhibit positive anti-inflammatory effects, among which curcumin has been demonstrated to have powerful anti-inflammatory, antioxidant, and antitumor effects. In the present study, we explored the potential mechanisms by which curcumin protects against hypoxic-ischemic brain injury. On postnatal day 7, mice were randomly divided into three groups: the sham group, the HI+PBS group, and the HI+curcumin group. Curcumin (200 mg/kg) was administered to mice in the HI+curcumin group by intraperitoneal injection. The hypoxic-ischemic brain injury model was established by the Rice-Vannucci method, and the neuroprotective effects as well as the underlying mechanisms of curcumin on neonatal hypoxic-ischemic brain injured mice were analyzed using a neurobehavioral test (i.e., Morris water maze), 2,3,4-triphenyltetrazolium chloride staining, quantitative real-time polymerase chain reaction, and western blot methods. Curcumin inhibited hypoxia-ischemia insult-induced neurobehavioral deficits, cerebral infarction, and abnormal inflammatory responses in neonatal mice and further downregulated the acetylation level of the high-mobility group protein B1. In conclusion, curcumin attenuated hypoxic-ischemic brain injury in neonatal mice by inhibiting the neuroinflammatory response mediated by acetylation modification of HMGB1, thus providing a new theoretical basis for curcumin as a treatment for neonatal hypoxic-ischemic encephalopathy.
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Acknowledgements
We thank Jinhua Liu for her help during the preparation of this manuscript.
Funding
This study was supported by the National Natural Science Foundation of China (Grant No. 82060290), the Natural Science Foundation of Jiangxi Province (Grant No. 20212BAB216040), the Science and Technology Planed Projects of Jiangxi Provincial Health Commission (Grant No. 202110021), and the Science and Technology Project of Jiangxi Provincial Administration of traditional Chinese Medicine (Grant No. 2020A0297).
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KL conceived and designed the study. XY and QX conducted the experiments. XY and KL drafted initial manuscript. KL and XY edited and revised the whole manuscript. All authors reviewed and contributed to the final version of the manuscript.
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All experiments were approved by the Animal Ethical and Welfare Committee of Southeast University (Animal Ethics No.20190215016) and Nanchang University (Animal Ethics No.W20210121).
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Yu, X., Xia, Q. & Le, K. Curcumin Attenuates Hypoxic-Ischemic Brain Injury in Neonatal Mice Through Inhibition of HMGB1 Acetylation-Mediated Inflammation. Rev. Bras. Farmacogn. 32, 767–773 (2022). https://doi.org/10.1007/s43450-022-00305-2
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DOI: https://doi.org/10.1007/s43450-022-00305-2