Oxymatrine ameliorates experimental autoimmune encephalomyelitis by rebalancing the homeostasis of gut microbiota and reducing blood-brain barrier disruption

Abstract

BackgroundIncreasing evidence suggests that gut dysbiosis can directly or indirectly affect the immune system through the brain-gut axis and play a role in the occurrence and development of Multiple sclerosis (MS). Oxymatrine (OMAT) has been shown to ameliorate the symptoms of MS in the classical experimental autoimmune encephalomyelitis (EAE) model of MS, but whether its therapeutic role is through the correction of gut dysbiosis, is unclear.MethodsThe effects of OMAT on intestinal flora and short-chain fatty acids in EAE model mice were evaluated by 16S rRNA sequencing and GC-MS/MS, respectively, and the function change of the blood-brain barrier and intestinal epithelial barrier was further tested by immunohistochemical staining, Evans Blue leakage detection, and RT-qPCR.ResultsThe alpha and beta diversity in the feces of EAE mice were significantly different from that of the control group but recovered substantially after OMAT treatment. Besides, the OMAT treatment significantly affected the gut functional profiling and the abundance of genes associated with energy metabolism, amino acid metabolism, the immune system, infectious diseases, and the nervous system. OMAT also decreased the levels of isobutyric acid and isovaleric acid in EAE mice, which are significantly related to the abundance of certain gut microbes and were consistent with the reduced expression of TNF-a, IL-6, and IL-1b. Furthermore, OMAT treatment significantly increased the expression of ZO-1 and occludin in the brains and colons of EAE mice and decreased blood-brain barrier permeability.ConclusionOMAT may alleviate the clinical and pathological symptoms of MS by correcting dysbiosis, restoring gut ecological and functional microenvironment, and inhibiting immune cell-mediated inflammation to remodel the brain-gut axis.

The Role of the Gut Microbiota in Neurodegenerative Diseases

“…Recent research even found a link between the development of different T cell subtypes and particular bacterial species. Polysaccharide A (PSA) molecules from Bacteroides fragilis have been found to stimulate the development of a systemic Th1 response [24]. The prevalence of neurodegenerative diseases is currently rising quickly.…”

Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“…Plant‐derived anthocyanins may prevent cognitive deficit‐related behaviors by correcting dysbiosis, restoring the intestinal ecological and functional microenvironment, and inhibiting inflammation mediated by immune cells 145 . Apart from alleviating cognitive impairment, plant root‐derived oxymatrine may alleviate clinical symptoms and pathological manifestations of multiple sclerosis by correcting microbiota dysbiosis, suppressing immune cell‐mediated inflammation, and remodeling the gut–brain axis 146 . Another natural plant antitoxin, pterostilbene, could reduce the release of inflammatory factors by decreasing lipopolysaccharide levels and modulating TLR4/NF‐κB signaling pathways in the colon and brain, thereby inhibiting oxidative stress damage, astrocyte and microglia activation, and dopaminergic neuron loss 147 .…”

“…Oxymatrine Remodel GM homeostasis Decrease BBB permeability, and ameliorate experimental autoimmune encephalomyelitis [146] Pterostilbene Increase the levels of SCFAs and maintain normal intestinal permeability Ameliorate cognitive dysfunction, and improve both memory and learning ability [147] Dimethyl itaconate…”

“… 145 Apart from alleviating cognitive impairment, plant root‐derived oxymatrine may alleviate clinical symptoms and pathological manifestations of multiple sclerosis by correcting microbiota dysbiosis, suppressing immune cell‐mediated inflammation, and remodeling the gut–brain axis. 146 Another natural plant antitoxin, pterostilbene, could reduce the release of inflammatory factors by decreasing lipopolysaccharide levels and modulating TLR4/NF‐κB signaling pathways in the colon and brain, thereby inhibiting oxidative stress damage, astrocyte and microglia activation, and dopaminergic neuron loss. 147 Natural plant‐derived active agents are promising in treating neurological disorders through the modulation of GM, providing theoretical basis for its future therapeutic value.…”

“…FMT fecal microbiota transplantation; SCFAs short-chain fatty acids (Figure created with Biore nder. com).symptoms and pathological manifestations of multiple sclerosis by correcting microbiota dysbiosis, suppressing immune cell-mediated inflammation, and remodeling the gut-brain axis 146. Another natural plant antitoxin, pterostilbene, could reduce the release of inflammatory factors by decreasing lipopolysaccharide levels and modulating TLR4/NF-κB signaling pathways in the colon and brain, thereby inhibiting oxidative stress damage, astrocyte and microglia activation, and dopaminergic neuron loss 147.…”