Abstract
Natural compounds derived from medicinal plants have long been considered a rich source of novel therapeutic agents. Baicalin (Ba) is a bioactive flavonoid compound derived from the root of Scutellaria baicalensis, an herb widely used in traditional medicine for the treatment of various inflammatory diseases. In this study, we investigate the effects and mechanism of action of Ba in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Ba treatment effectively ameliorated clinical disease severity in myelin oligodendrocyte glycoprotein (MOG)35–55 peptide-induced EAE, and reduced inflammation and demyelination of the central nervous system (CNS). Ba reduced infiltration of immune cells into the CNS, inhibited expression of proinflammatory molecules and chemokines, and prevented Th1 and Th17 cell differentiation via STAT/NFκB signaling pathways. Further, we showed that SOCS3 induction is essential to the effects of Ba, given that the inhibitory effect of Ba on pathogenic Th17 responses was largely abolished when SOCS3 signaling was knocked down. Taken together, our findings demonstrate that Ba has significant potential as a novel anti-inflammatory agent for therapy of autoimmune diseases such as MS.
Highlights
Approved therapies for Multiple sclerosis (MS) either have limited efficacy or pose significant safety concerns[1]
We in the present study demonstrate that Ba effectively suppressed EAE via suppressor of cytokine signaling 3 (SOCS3)-induced inhibition of Th1 and Th17 cell differentiation
While it has been suggested that Ba suppresses development of EAE in SJL/J mice and rats[18,20] by inducing IL-4 and inhibiting IFN-γ 18, as well as by promoting apoptosis of inflammatory cells in the spinal cord[20], the mechanism of Ba action in the differentiation and function of various Th cell subsets in autoimmune disease has not yet been described
Summary
Approved therapies for MS either have limited efficacy or pose significant safety concerns[1]. Research exploring novel anti-inflammatory or immunomodulatory drugs derived from medicinal plants has attracted a great deal of attention[9,10]. These plants represent a rich source of natural compounds for the identification of safe and effective candidate drugs with novel targets and/or mechanism of action in the treatment of autoimmune diseases. Preliminary evidence has linked these properties of Ba to inducing inflammatory cell apoptosis, promoting Treg cell differentiation and regulatory activity, inhibiting T-cell proliferation, suppressing IFN-γ and increasing IL-4 production[18,19,20] These results are encouraging, more direct evidence is needed on the beneficial effect and molecular mechanisms of Ba in autoimmunity.
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