Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway  

作　　者：Dan MU Huaguang QIN Mengjie JIAO Shaogui HUA Tingzhe SUN 

机构地区：[1]School of Life Sciences,the Province Key Laboratory of the Biodiversity Study and Ecology Conservation in Southwest Anhui,Anqing Normal University,Anqing 246133,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2021年第2期123-135,共13页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(Nos.31971185 and 31800316);the Key Projects of Support Program for Outstanding Young Talents in Colleges and Universities of Anhui Province(Nos.gxyq ZD2020031 and gxyq2018034);the Key Project of the Education Department of Anhui Province,China(No.KJ2017A359)。

摘　　要：Ischemic stroke presents a leading cause of mortality and morbidity worldwide.Theaflavic acid(TFA)is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect.However,the dynamic properties of TFA-mediated protection remain largely unknown.In the current study,we evaluated the function of TFA in the mitochondria apoptotic pathway using mathematical modeling.We found that TFA-enhanced B-cell lymphoma 2(Bcl-2)overexpression can theoretically give rise to bistability.The bistability is highly robust against parametric stochasticity while also conferring considerable variability in survival threshold.Stochastic simulations faithfully match the TFA dose response pattern seen in experimental studies.In addition,we identified a dose-and time-dependent synergy between TFA and nimodipine,a clinically used neuro-protective drug.This synergistic effect was enhanced by bistability independent of temporal factors.Precise application of pulsed doses of TFA can also promote survival compared with sustained TFA treatment.These data collectively demonstrate that TFA treatment can give rise to bistability and that synergy between TFA and nimodipine may offer a promising strategy for developing therapeutic neuro-protection against ischemic stroke.

关 键 词：Theaflavic acid(TFA) NIMODIPINE Ischemic stroke APOPTOSIS SYNERGY 

分 类 号：R285[医药卫生—中药学]