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On-line Access: 2021-02-07

Received: 2020-09-11

Revision Accepted: 2020-11-08

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Tingzhe SUN


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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.2 P.123-135


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

Author(s):  Dan MU, Huaguang QIN, Mengjie JIAO, Shaogui HUA, Tingzhe SUN

Affiliation(s):  School of Life Sciences, the Province Key Laboratory of the Biodiversity Study and Ecology Conservation in Southwest Anhui, Anqing Normal University, Anqing 246133, China

Corresponding email(s):   confucian007@126.com

Key Words:  Theaflavic acid (TFA), Nimodipine, Ischemic stroke, Apoptosis, Synergy

Dan MU, Huaguang QIN, Mengjie JIAO, Shaogui HUA, Tingzhe SUN. Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway[J]. Journal of Zhejiang University Science B, 2021, 22(2): 123-135.

@article{title="Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway",
author="Dan MU, Huaguang QIN, Mengjie JIAO, Shaogui HUA, Tingzhe SUN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway
%A Dan MU
%A Huaguang QIN
%A Mengjie JIAO
%A Shaogui HUA
%A Tingzhe SUN
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 2
%P 123-135
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000540

T1 - Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway
A1 - Dan MU
A1 - Huaguang QIN
A1 - Mengjie JIAO
A1 - Shaogui HUA
A1 - Tingzhe SUN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 2
SP - 123
EP - 135
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000540

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.




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