Neuroprotective and anti-inflammatory effects of Yingqiao San on epileptogenesis are mediated by inhibiting HMGB1 translocation and regulating the HMGB1/TLR4 signaling pathway

Abstract Background: Epileptogenesis was the latency period of epilepsy. Neuronal damage and subsequent inflammatory response were the basic mechanisms of epileptogenesis. From now on, there was still no effective drugs to prevent the process of epileptogenesis. Yingqiao San, a famous classic prescription over 400 years in China, was widely used in sorts of infectious disease. In preclinical study of childhood epilepsy complicated with upper respiratory tract infections, we found that YQS can not only reduce the frequency of respiratory tract infections, but also decrease the frequency and duration time of seizures, and can alleviate sterile inflammation to some extent. HMGB1, an important late mediator in sterile inflammation, has been seem as a potential target of epileptogenesis. So we hypothesized that YQS had effect of antiepileptogenic, may be related to inhibit the translocation of HMGB1 and modulate neuroinflammation.Methods: The pilocarpine-induced status epileptic model was adopted to induce brain injury model in mice. Observation and sampling were performed at 7 days, 14 days and 28 days. The number of seizures, duration time of seizures, mortality rate and the appearance of brain were employed to determine the anti-seizure effects of YQS. The Nissl staining, FJB staining were employed to determine the neuroprotective of YQS. The double immunofluorescent staining were employed to observe inflammatory response and the location of HMGB1 in glia cells. The Western blot and immnuohistochemical staining were used to calculate the quantitative and qualitative of HMGB1 to detect the translocation of HMGB1 and the expression of HMGB1/TLR4 signaling pathway. Results: It was found that YQS can effectively decrease the frequency of seizures, shorten duration time of seizures, reduce the mortality of mice and alleviate brain edema. YQS can significantly attenuate neuronal damage and inhibit the activation and proliferation of microglia and astrocytes with time-dependent. Moreover, YQS can modulate the subsequent inflammatory response by inhibiting HMGB1 translocation and regulating the expression of HMGB1/TLR4 signaling pathway.Conclusions: YQS can prevent the process of epileptogensis. Its neuroprotective and anti-inflammatory effects on epileptogenesis may mediate by inhibiting HMGB1 translocation and modulating neuroinflammation. It can still be used as an adjunctive therapy for treatment of epilepsy.