The combined treatment of NAD+ and atorvastatin ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Huanhuan Sun; Jueqiong Wang; Li Guo; Ying Wang; Jing Zhang; Jinli Wang; Moyuan Quan; Bin Li

doi:10.1016/j.jneuroim.2020.577429

The combined treatment of NAD⁺ and atorvastatin ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

J Neuroimmunol. 2020 Oct 24:350:577429. doi: 10.1016/j.jneuroim.2020.577429. Online ahead of print.

Authors

Huanhuan Sun¹, Jueqiong Wang², Li Guo², Ying Wang², Jing Zhang², Jinli Wang², Moyuan Quan², Bin Li³

Affiliations

¹ Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
² Department of Neurology, Neurological Laboratory of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
³ Department of Neurology, Neurological Laboratory of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China. Electronic address: jack511@163.com.

PMID: 33176238
DOI: 10.1016/j.jneuroim.2020.577429

Abstract

Multiple sclerosis (MS) is a demyelinating and degenerating disorder of the central nervous system impacting many patients worldwide. Due to the complex pathogenesis of MS, drugs to treat MS often show partial effectiveness. Earlier experiments have demonstrated that both atorvastatin and nicotinamide adenine dinucleotide (NAD⁺⁾ may ameliorate experimental autoimmune encephalomyelitis (EAE), which is known as a classical model of MS, via different protective mechanisms. Since combination therapy can exhibit more beneficial effects than monotherapy, we observed the protective effects of combined treatment of atorvastatin and NAD⁺ in EAE mice. Our results showed that the combined treatment of these two drugs at half of their optimal dosages had synergistic effect to alleviate the severity of EAE in mice than treatment with each alone. The combined treatment of EAE mice with atorvastatin plus NAD⁺ relieved the clinical signs and histologic changes, increased the proportion of Treg cells, attenuated IL-17 production, reduced proinflammatory cytokine secretion of Th17 cells, and increased cytokine secretion of Treg cells. In addition, the combined treatment also diminished phosphorylation of both P38 MAPK and ERK, while elevated SIRT1 expression. Taken together, these data suggested that combined treatment with NAD⁺ and atorvastatin could attenuate the progression of EAE by synergistic immune regulation.

Keywords: Atorvastatin; Combined treatment; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Nicotinamide adenine dinucleotide; SIRT1 and P38 MAPK/ERK.