Astragaloside IV Attenuates Experimental Autoimmune Encephalomyelitis of Mice by Counteracting Oxidative Stress at Multiple Levels

Abstract

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

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“…To determine the permeability of BBB, the Evans blue (EB) dye extravasation method was used, according to He et al (2013). Briefly, the mice were i.p.…”

Astragaloside IV Alleviates Early Brain Injury Following Experimental Subarachnoid Hemorrhage in Rats

“…However, the potential mechanism underlying astragaloside IV-induced neuroprotective effect still remains obscure. According to the results of previous literatures and our investigations, we speculated that the positive effect may due to the factors as following: Firstly, oxidative stress induced by SAH was the key factor that leads to brain injury57, and numerous studies have shown that astragaloside IV could inhibit oxidative damage by scavenge free radicals and enhance antioxidant system 21, 25, 26, 58, and this process may associate with Nrf2 signaling pathway59. In terms of our understanding, the anti-oxidative stress ability of astragaloside IV may play a vital role in alleviating SAH-induced injury.…”

Astragalosides from Radix Astragali benefits experimental autoimmune encephalomyelitis in C57BL /6 mice at multiple levels

“…EAE induction was performed in 6-weeks-old female C57BL/6 mice as described previously [25]. Each mouse received 100 μl of complete Freund’s adjuvant emulsified with 300 μg MOG 35–55 and 400 μg of heat-inactivated Mycobacterium tuberculosis H37RA via subcutaneous injection.…”