The Traditional Chinese Medicine MLC901 inhibits inflammation processes after focal cerebral ischemia

Abstract

Inflammation is considered as a major contributor to brain injury following cerebral ischemia. The therapeutic potential of both MLC601/MLC901, which are herbal extract preparations derived from Chinese Medicine, has been reported both in advanced stroke clinical trials and also in animal and cellular models. The aim of this study was to investigate the effects of MLC901 on the different steps of post-ischemic inflammation in focal ischemia in mice. In vivo injury was induced by 60 minutes of middle cerebral artery occlusion (MCAO) followed by reperfusion. MLC901 was administered in post-treatment 90 min after the onset of ischemia and once a day during reperfusion. MLC901 treatment resulted in a reduction in infarct volume, a decrease of Blood Brain Barrier leakage and brain swelling, an improvement in neurological scores and a reduction of mortality rate at 24 hours after MCAO. These beneficial effects of MLC901 were accompanied by an inhibition of astrocytes and microglia/macrophage activation, a drastically decreased neutrophil invasion into the ischemic brain as well as by a negative regulation of pro-inflammatory mediator expression (cytokines, chemokines, matrix metalloproteinases). MLC901 significantly inhibited the expression of Prx6 as well as the transcriptional activity of NFκB and the activation of Toll-like receptor 4 (TLR4) signaling, an important pathway in the immune response in the ischemic brain. MLC901 effects on the neuroinflammation cascade induced by cerebral ischemia probably contribute, in a very significant way, in its potential therapeutic value.

The Alzheimer’s Disease THErapy with NEuroaid II (ATHENE) Study: A Double-Blind Randomized Delayed-Start Trial to Assess the Safety and Efficacy of MLC901 (NeuroAiD™II) as an add-on Treatment to Cholinesterase Inhibitors or Memantine in Patients With Mild to Moderate Alzheimer's Disease

“…Apart from β-amyloid and neuro brillary tangles, the roles of K ATP channels and neuroin ammation in the pathogenetic processes have been elucidated [47 -50]. In preclinical studies, MLC901 was demonstrated to activate K ATP channels, modulate in ammation processes and protect against glutamate-induced cell death in in vitro and in vivo studies [16,17,51].…”

The potential of MLC901 (NeuroAiD II™), a traditional Chinese medicine

“…This "bench-to-bed" approach seems not promising. Recently, studied MLC901 [9], also known as NeuroAiD II™, is one of the traditional Chinese medicine with a combination of nine herbal extracts [10]. It is the second generation of NeuroAiD™ (MLC601) with a more straightforward formula [11].…”

“…Therefore, the study done by [9] provides a credible research direction with a feasible target, signalling pathway, and assessment parameter to develop a potential therapeutic medicine for the stroke patient. demonstrated that (1) MLC901 reduced the infarction size and ischemia-induced neurological deficits, which were measured by neurological Bederson scores in the treated group [9].…”

Safety and Use of MLC601/MLC901 (NeuroAiDTM) in Primary Intracerebral Hemorrhage: A Cohort Study from the NeuroAiD Safe Treatment Registry

“…In regulating the neuroinflammation cascade, NeuroAiD modulates innate immunity by significantly reducing pro-inflammatory cytokines and chemokines [ 10 ]. Similarly, animal models in TBI demonstrated the neuroregenerative properties of NeuroAiD through the processes of neurogenesis, gliogenesis, and angiogenesis (via vascular endothelial growth factor) [ 11 ].…”