Shi Jian, Xu Huan, Cavagnaro María José, Li Xingmei, Fang Jia
Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Hematology and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2021 Nov 15;12:760186. doi: 10.3389/fphar.2021.760186. eCollection 2021.
As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.
作为一种由宿主对感染的免疫反应失调引起的危及生命的多器官功能障碍，脓毒症通常是全球众多传染病严重预后和死亡的常见途径。脓毒症相关脑病（SAE）常伴有脓毒症情况，是脓毒症患者死亡率增加和预后不良的最重要原因之一，这仍然是一个亟待解决的临床问题。在本研究中，阐述了小檗碱在治疗方面显著的转化应用发现。结果显示，小檗碱治疗可显著恢复脓毒症小鼠的认知障碍。小檗碱治疗组小鼠海马中TNF-α、IL-1α和C1qA的表达水平降低，同时还发现脓毒症小鼠海马中新生神经元数量减少、小胶质细胞和星形胶质细胞活化的减弱效应。此外，研究发现小檗碱通过抑制HMGB1信号传导来抑制小胶质细胞应激的A1星形胶质细胞，进而阐明了HMGB1/RAGE信号传导抑制导致SAE取得更好预后的分子机制。综上所述，本研究表明小檗碱靶向HMGB1/RAGE信号传导以抑制小胶质细胞应激的A1星形胶质细胞和新生神经元减少，从而减轻脓毒症诱导的认知障碍。总体而言，小檗碱可能作为潜在的治疗药物，而HMGB1/RAGE信号传导将成为治疗SAE药物开发的新靶点。
