Nano-Liposomal Encapsulation-Delivered Apelin-13 Attenuates Ev71 Infection-Induced Neurodegeneration by Modulating Il-6 and Tlr7

Author:

Xu Shengnan1,Cui Cheng1,Sun Manchao1,Guo Sihui1,Xu Ke1,Cui Yanan1,Gao Ziyin1,Wu Zhenqi1,Xue Jiaxin1,Ma Yucai1,He Xue1,Cai Guofeng2

Affiliation:

1. Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang Province, China

2. Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang Province, China

Abstract

Background: Enterovirus 71 (EV71) infection serves as a leading cause of hand-foot-and-mouth disease, and induces neural disorders. Apelin-13, as a neuropeptide, presents potential neuroprotective activities, but its short half-life in circulation has limited its clinical use. Objective: To explore the role of nano-liposomal encapsulation-delivered apelin-13 in the development of EV71 infection-induced neurodegeneration. Method: The liposome encapsulating apelin-13 (lipoPEG-A13) was successfully constructed and characterized in the study. The neurodegeneration measurement in an intracranially EV71-infected mouse model was performed in vivo. MTT assays, lactate dehydrogenase release assays, immunohistochemistry, and immunofluorescence staining qPCR assays, and Western blot analysis were respectively performed. Results: EV71 notably replicated and promoted apoptosis in the cerebral cortex from the EV71-infected mice but exhibited comparatively low replication and slightly regulated apoptosis in the cerebellum. Remarkably, lipoPEG-A13 was able to inhibit EV71-induced neurological injury in the murine cerebral cortex in vivo. Meanwhile, LipoPEG-A13 could attenuate EV71-caused apoptosis of the neural cell in the brain. LipoPEG-A13 decreased the Toll-like receptor 7 (TLR7) and interleukin-6 (IL-6) production in the mice. Apelin-13 inhibited the expression of TLR7 and IL-6 in the human astroglioma U251 cells. Apelin-13 could reduce the apoptosis of astrocytic cells infected with EV71. Conclusion: Nano-liposomal encapsulation-delivered apelin-13 attenuated EV71 infection-induced neurodegeneration via modulating IL-6 and TLR7 production. The finding provides new insights into how Nano-liposomal encapsulation-delivered apelin-13 modulates EV71 infection-induced neurological disorders. The Nano-liposomal encapsulation-delivered apelin-13 presents the application potential in the clinical context.

Publisher

Innovation Forever Publishing Group Limited

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