Theaflavin attenuates cerebral ischemia/reperfusion injury by abolishing miRNA‑128‑3p‑mediated Nrf2 inhibition
and reducing oxidative stress

Li,Ronggang; Li,Xin; Wu,Haibing; Yang,Zhikun; Fei,Li; Zhu,Jianhong

doi:10.3892/mmr.2019.10755

Theaflavin attenuates cerebral ischemia/reperfusion injury by abolishing miRNA‑128‑3p‑mediated Nrf2 inhibition and reducing oxidative stress

Authors:
- Ronggang Li
- Xin Li
- Haibing Wu
- Zhikun Yang
- Li Fei
- Jianhong Zhu
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Affiliations: Department of Neurosurgery, Fudan University Huashan Hospital and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China, Department of Imaging, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, P.R. China, Department of Neurosurgery, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China
Published online on: October 17, 2019 https://doi.org/10.3892/mmr.2019.10755
Pages: 4893-4904
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Theaflavin has been proven to own strong antioxidative capacity; however, the molecular mechanism underlying its protective effect against cerebral ischemia‑reperfusion (I/R) injury remains unclear. Therefore, the present study was designed to elucidate the neuroprotective effects of theaflavin on cerebral I/R injury and its underlying molecular mechanisms. To investigate the effects of theaflavin on neurological function, neurogenesis, and oxidative stress, experiments were performed using a cerebral I/R injury rat model, and neural stem cells (NSCs) were subjected to oxygen‑glucose deprivation and reoxygenation (OGD/R). Further, the expression profiles of miRNA‑128‑3p and the regulatory function of nuclear factor (erythroid‑derived 2)‑related factor 2 (Nrf2) were evaluated in these models. We found that theaflavin treatment significantly reduced infarct volume and neuronal injury, and thus improved the impaired memory and learning ability. Furthermore, theaflavin treatment significantly enhanced the increase in NSC proliferation, reduction in the apoptotic rate and inhibition of oxidative stress. Mechanistically, theaflavin targeted miRNA‑128‑3p and further activated the Nrf2 pathway to reduce oxidative stress. In summary, theaflavin has a strong ability to attenuate cerebral I/R injury through miRNA‑128‑3p‑mediated recovery of the impaired antioxidant defense system, which suggests that it could be a potential drug candidate for ischemic stroke.

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