Mechanism Study on Huanglian Jiedu Decoction Improving Neuronal Damage in Tau/APP/PS1 Transgenic AD Mice by Inhibiting NLRP3 Inflammasome

WANG Junli; ZHANG Huifang; XU Xinzi; WANG Rui; DU Yaming; LIU Xin; CHEN Guohua

Abstract：Objective To investigate the effects and mechanisms of Huanglian Jiedu decoction on neuronal damage in Tau/APP/PS1 transgenic Alzheimer's disease(AD)mice.Methods Tau/APP/PS1 transgenic AD mice were randomly divided into low,medium,and high-dose Huanglian Jiedu decoction intervention and model groups,with 10 mice in each group.10 male C57BL/6J mice of the same age were selected as a blank control group.After 4 weeks of drug intervention,ELISA were used to measure the levels of inflammatory factors and AD-related pathological markers such as soluble amyloid precursor protein α(sAPPα),amyloid β-protein(Aβ)40,Aβ42,and phosphorylated tau protein(p-Tau)in the hippocampal tissue of the mice.Immunofluorescence double-labeling was used to assess the expression of nod-like receptor protein 3(NLRP3)inflammasomes and microglial-specific marker ionized calcium binding adapter molecule 1(Iba1).Western blot was used to determine the activation of the NLRP3 inflammasome signaling pathway in the mice hippocampus.Results Compared to the blank control group,the model group of mice showed a significant increase in the expression of NLRP3,ASC,Caspase-1,and Iba1 in the hippocampus(P<0.05).Levels of IL-1β,IL-18,and TNF-α were significantly elevated(P<0.05),as were the levels of Aβ40,Aβ42,and p-Tau,as well as the p-Tau/Tau ratio(P<0.05),while sAPPα level decreased(P<0.05).When compared to the model group,mice in different doses of Huanglian Jiedu decoction intervention groups exhibited significant improvements in sAPPα(P<0.05),while the leveles of Aβ40,Aβ42 and p-Tau,as well as the levels of hippocampal inflammatory factors IL-1β,IL-18,and TNF-α were significantly reduced(P<0.05).Additionally,the expression of NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,and Iba1 were significantly decreased(P<0.05)in the intervention groups.Conclusion Huanglian Jiedu decoction may improve hippocampal neuronal damage by potentially inhibiting the hippocampal NLRP3 inflammasome signaling pathway,suppressing microglial activation,and reducing levels of neurotoxic pathological products such as Aβ and p-Tau.