Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy

Liang，Jiayin1,2,3; Cai，Jiale1,2,3; Zhang，Yutong1; Xie，Meixia1,2,3; Li，Xiaoshi4; Hu，Tao1,2,3; Liang，Shengwang1,2,3; Xian，Minghua1,2,3; Wang，Shumei1,2,3

2022

10.1039/d2fo02367a

Food & Function   Impact Factor & Quartile

2042-6496

2042-650X

Cerebral ischemia/reperfusion (I/R) injury is the result of ischemic stroke, a serious threat to public health. I/R injury can damage the blood-brain barrier (BBB), adversely affecting the brain environment and aggravating the injury. Cyclo-(Phe-Tyr) (sparganin C, SC) is a small molecule derived from the Chinese yam Dioscorea opposita Thunb. or Sparganii rhizoma. In our previous study, SC mitigates I/R injury both in vivo and in vitro through the action of JUNB and SOX5. However, the exact pharmacological effects of SC on BBB protection after an I/R injury remain unclear. We constructed a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) injury to evaluate the therapeutic actions of SC, and the integrity of the BBB was evaluated by ELISA, western blotting, and Evans blue staining. It was found that SC significantly reduced the amount of Evans blue staining in the brain, inhibited the expression of inflammatory factors IL-6, IL-1β, IL-17, IL-23, and TNF-α as well as TIPM1/MMP proteins, and promoted the expression of the tight junction proteins occludin, ZO-1, and claudin-5. SC was found to inhibit the excess autophagy induced by I/R injury to protect BBB integrity through the PI3K/AKT/mTOR pathway, and the PI3K inhibitor LY294002 significantly reduced the SC-mediated protection. Overall, this is the first demonstration of the alleviation of BBB damage caused by I/R injury by SC and suggests a potential treatment for the effects of an ischemic stroke.

SCI

English

Others

National Natural Science Foundation of China["82004086","81473413","81274060","81773884"] ; National Major Scientific and Technological Special Project for "Significant New Drugs Development" during the Thirteenth Five-year Plan Period[2017ZX09301077] ; Science and Technology Plan Project of Guangzhou[201803010115] ; special funds for the Cultivation of Guangdong College Students' Scientific and Technological Innovation ("Climbing Program" Special Funds)[pdjh2022b0271]

Biochemistry & Molecular Biology ; Food Science & Technology

Biochemistry & Molecular Biology ; Food Science & Technology

WOS:000882033800001

ROYAL SOC CHEMISTRY

2-s2.0-85142313605

Scopus

1.Guangdong Pharmaceutical University,Guangzhou Higher Education Mega Center,Guangzhou,280 Waihuan Rd E, Guangdong,510006,China
2.Key Laboratory of Digital Quality Evaluation of Traditional Chinese Medicine,National Administration of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,Guangdong,510006,China
3.Traditional Chinese Medicine Quality Engineering and Technology Research Center of Guangdong Universities,Guangdong Pharmaceutical University,Guangzhou,Guangdong,510006,China
4.Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China

Liang，Jiayin,Cai，Jiale,Zhang，Yutong,et al. Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy[J]. Food & Function,2022.

Liang，Jiayin.,Cai，Jiale.,Zhang，Yutong.,Xie，Meixia.,Li，Xiaoshi.,...&Wang，Shumei.(2022).Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy.Food & Function.

Liang，Jiayin,et al."Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy".Food & Function (2022).