Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

Abstract

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.

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function

“… Blocking HMGB1/RAGE Signaling. [ 100 ] Intestine Rats; CLP Berberine improved compromised GVB. Modulating the ApoM/S1P pathway.…”

Sepsis-Induced Brain Dysfunction: Pathogenesis, Diagnosis, and Treatment

“…Microglia can also induce the transformation of A1 astrocytes to injury neurons [ 115 ]. In addition to secreting inflammatory cytokines [ 116 ], astrocytes also affect the release of neurotransmitters, which at last leads to neuronal injury [ 117 ]. Sepsis can dysfunction the autophagy and pyroptosis homeostasis [ 118 ] and activate ferroptosis [ 119 ] and endoplasmic reticulum stress of neurons, all of which could lead to neuronal damage [ 120 ].…”

Cytokine storm-calming property of the isoquinoline alkaloids in Coptis chinensis Franch

“…In addition to alleviating the systemic inflammatory response, BBR also significantly improved DIC and MOF caused by sepsis ( Yuan et al, 2021 ), ( Shi et al, 2021 ), ( Chen et al, 2021 ). A study has indicated that BBR and the derivatives could attenuate coagulation activation, organ dysfunction and further decreased lethality in bacterial sepsis.…”

“…The mechanism is that BBR blocked the caspase-11 inflammatory pathway by inhibiting the cytoplasmic translocation of LPS via blocking Msr1, a scavenger receptor that mediates endocytosis of LPS ( Yuan et al, 2021 ). In an experimental model of sepsis-associated encephalopathy (SAE), BBR targeted HMGB1/RAGE signaling to suppress the quantity of inflammatory events of cell factors and astrocyte activation in the cerebrum of SAE mice, thereby alleviating cognitive impairment caused by sepsis ( Shi et al, 2021 ) Moreover, septic cardiomyopathy (SCM) is the most common type of sepsis-related organ dysfunction. Chen et al (2021) found that BBR reduced myocardial injury in sepsis rats, by inhibiting sepsis-induced TLR4/NF-κB signal pathway activation and decreasing the expression levels of TNF-a, IL-1β and other inflammatory factors.…”

“…Frontiers in Pharmacology frontiersin.org SAE mice, thereby alleviating cognitive impairment caused by sepsis (Shi et al, 2021) Moreover, septic cardiomyopathy (SCM) is the most common type of sepsis-related organ dysfunction. Chen et al (2021) found that BBR reduced myocardial injury in sepsis rats, by inhibiting sepsisinduced TLR4/NF-κB signal pathway activation and decreasing the expression levels of TNF-a, IL-1β and other inflammatory factors.…”