Xiaowei Fei1, Chen Chen2, Sun Kai2, Xiaojun Fu2, Weitao Man3, Boyun Ding2, Chongwu Wang4, Ruxiang Xu5. 1. Department of Neurosurgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China, Chengdu 610072, China.; Dapartment of Physiology, Dalian Medical University, Dalian 116044, China.; Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. 2. Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China. 3. Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China. 4. Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China.. Electronic address: darklordwcw@163.com. 5. Department of Neurosurgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China, Chengdu 610072, China.; Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, China.. Electronic address: 524727684@qq.com.
Abstract
BACKGROUND: Intracranial hemorrhage (ICH) is one of the most common brain traumas, and inflammation caused by ICH seriously affects the quality of life and prognosis of patients. Eupatilin has been shown to have anti-inflammatory effects in various diseases. However, only one paper has reported that Eupatilin has a therapeutic effect on the inflammatory response caused by ICH and the underlying mechanism needs to be studied. METHODS: We used erythrocyte lysis stimulation (ELS) to induce mouse microglia BV2 as the inflammation model. CCK-8 and Transwell assays were used to detect cell viability and migration. RT-PCR, western blotting, and ELISA were used to detect the secretion of inflammatory factors and the expression of related mechanism proteins. HE staining was used to detect cell edema and death. RESULT: We found that ELS significantly increased protein and mRNA levels and secretion of inflammatory factors IL-1β and TNF-α, which Eupatilin attenuated through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway. The anti-inflammatory effect of Eupatilin was significantly attenuated after siRNA was used to reduce TLR4 expression. The experimental results and mechanism were also verified in TLR4 knockout mice in vivo. CONCLUSION: Eupatilin has a therapeutic effect on inflammation caused by ICH. The underlying mechanism may be related to TLR4/MyD88, which brings new hope for clinical patients to improve symptoms and prognosis.
BACKGROUND:Intracranial hemorrhage (ICH) is one of the most common brain traumas, and inflammation caused by ICH seriously affects the quality of life and prognosis of patients. Eupatilin has been shown to have anti-inflammatory effects in various diseases. However, only one paper has reported that Eupatilin has a therapeutic effect on the inflammatory response caused by ICH and the underlying mechanism needs to be studied. METHODS: We used erythrocyte lysis stimulation (ELS) to induce mouse microglia BV2 as the inflammation model. CCK-8 and Transwell assays were used to detect cell viability and migration. RT-PCR, western blotting, and ELISA were used to detect the secretion of inflammatory factors and the expression of related mechanism proteins. HE staining was used to detect cell edema and death. RESULT: We found that ELS significantly increased protein and mRNA levels and secretion of inflammatory factors IL-1β and TNF-α, which Eupatilin attenuated through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway. The anti-inflammatory effect of Eupatilin was significantly attenuated after siRNA was used to reduce TLR4 expression. The experimental results and mechanism were also verified in TLR4 knockout mice in vivo. CONCLUSION:Eupatilin has a therapeutic effect on inflammation caused by ICH. The underlying mechanism may be related to TLR4/MyD88, which brings new hope for clinical patients to improve symptoms and prognosis.
Authors: Jiwon Jang; Jong Sub Lee; Young-Jin Jang; Eui Su Choung; Wan Yi Li; Sang Woo Lee; Eunji Kim; Jong-Hoon Kim; Jae Youl Cho Journal: Biomolecules Date: 2020-05-10