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.

Graphical Abstract

中文翻译：

---

姜黄素通过抑制 HMGB1 乙酰化介导的炎症减轻新生小鼠缺氧缺血性脑损伤

迄今为止，新生儿缺氧缺血性脑病尚无特效治疗方法，迫切需要新的治疗方法。缺氧缺血激活的过度神经炎症反应在新生儿缺氧缺血性脑损伤的发生和加重中起重要作用。从植物中提取的代谢物具有积极的抗炎作用，其中姜黄素已被证明具有强大的抗炎、抗氧化和抗肿瘤作用。在本研究中，我们探讨了姜黄素预防缺氧缺血性脑损伤的潜在机制。出生后第7天，将小鼠随机分为三组：假手术组、HI+PBS组和HI+姜黄素组。HI+姜黄素组小鼠腹腔注射姜黄素（200mg/kg）。即，莫里斯水迷宫）、2,3,4-三苯基四唑氯化物染色、定量实时聚合酶链反应和蛋白质印迹方法。姜黄素抑制新生小鼠缺氧缺血损伤引起的神经行为缺陷、脑梗塞和异常炎症反应，并进一步下调高迁移率组蛋白 B1 的乙酰化水平。总之，姜黄素通过抑制HMGB1乙酰化修饰介导的神经炎症反应减轻新生小鼠缺氧缺血性脑损伤，从而为姜黄素治疗新生儿缺氧缺血性脑病提供新的理论依据。

图形概要