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Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway.

Zhang Y, Li X, Ciric B, Ma CG, Gran B, Rostami A, Zhang GX - Sci Rep (2015)

Bottom Line: Natural compounds derived from medicinal plants have long been considered a rich source of novel therapeutic agents.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).Taken together, our findings demonstrate that Ba has significant potential as a novel anti-inflammatory agent for therapy of autoimmune diseases such as MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Ba Treatment Reduced CNS Inflammation.Ba- or PBS-treated control EAE mice described in Fig. 1c (treatment protocol) were sacrificed at day 30 p.i., and spinal cords were harvested. Sections at lumbar level (L3) were analyzed (a) by H&E (for inflammation; left) and Luxol fast blue (LFB) (for degree of demyelination; right), and (b) pathology scores of inflammation and demyelination are expressed as mean ± SD (n = 6 each group). The absolute numbers of MNCs in the CNS of above mice were counted (n = 3 each group) (c), and expression of cytokine (d) and chemokine (e) genes was determined using real-time RT-PCR analysis, and their relative expression was calculated by log2 of −ΔΔCt values from triplicate of PCR. More than two fold changes (log2 < −1 or log2 > 1) were considered significant between groups (red dotted line). (f) The percentage of CD4+ or CD8+ in the lymphocyte gate of the CNS of the above mice was analyzed by flow cytometry. (g) Absolute numbers of CD4+ or CD8+ cells in spinal cord were calculated (n = 5 each group). (h) Splenocytes of Ba- or PBS-treated EAE mice were isolated, stimulated with MOG35–55 (25 μg/ml) or Con A (5 μg/ml) and examined for proliferation at 72 h culture using BrdU incorporation assay (n = 6 each group). Data are expressed as mean ± SEM. **P < 0.01; ***P < 0.001. One representative of three experiments is shown.
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f2: Ba Treatment Reduced CNS Inflammation.Ba- or PBS-treated control EAE mice described in Fig. 1c (treatment protocol) were sacrificed at day 30 p.i., and spinal cords were harvested. Sections at lumbar level (L3) were analyzed (a) by H&E (for inflammation; left) and Luxol fast blue (LFB) (for degree of demyelination; right), and (b) pathology scores of inflammation and demyelination are expressed as mean ± SD (n = 6 each group). The absolute numbers of MNCs in the CNS of above mice were counted (n = 3 each group) (c), and expression of cytokine (d) and chemokine (e) genes was determined using real-time RT-PCR analysis, and their relative expression was calculated by log2 of −ΔΔCt values from triplicate of PCR. More than two fold changes (log2 < −1 or log2 > 1) were considered significant between groups (red dotted line). (f) The percentage of CD4+ or CD8+ in the lymphocyte gate of the CNS of the above mice was analyzed by flow cytometry. (g) Absolute numbers of CD4+ or CD8+ cells in spinal cord were calculated (n = 5 each group). (h) Splenocytes of Ba- or PBS-treated EAE mice were isolated, stimulated with MOG35–55 (25 μg/ml) or Con A (5 μg/ml) and examined for proliferation at 72 h culture using BrdU incorporation assay (n = 6 each group). Data are expressed as mean ± SEM. **P < 0.01; ***P < 0.001. One representative of three experiments is shown.

Mentions: To assess the effects of Ba on EAE-associated CNS pathology, lumbar spinal cords were obtained from Ba-treated and control mice. Analysis of CNS tissue sections demonstrated significantly reduced inflammation and demyelination in Ba-treated animals (Fig. 2a, right) when compared with control group (Fig. 2a, left). The pathological scores of mice treated with PBS or Ba differed significantly (P = 0.031 for the infiltration score and P = 0.022 for the demyelination score) (Fig. 2b). The number of mononuclear cells (MNCs) isolated from the CNS of Ba-treated mice was markedly reduced compared with that of vehicle-treated mice (P = 0.016; Fig. 2c).


Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway.

Zhang Y, Li X, Ciric B, Ma CG, Gran B, Rostami A, Zhang GX - Sci Rep (2015)

Ba Treatment Reduced CNS Inflammation.Ba- or PBS-treated control EAE mice described in Fig. 1c (treatment protocol) were sacrificed at day 30 p.i., and spinal cords were harvested. Sections at lumbar level (L3) were analyzed (a) by H&E (for inflammation; left) and Luxol fast blue (LFB) (for degree of demyelination; right), and (b) pathology scores of inflammation and demyelination are expressed as mean ± SD (n = 6 each group). The absolute numbers of MNCs in the CNS of above mice were counted (n = 3 each group) (c), and expression of cytokine (d) and chemokine (e) genes was determined using real-time RT-PCR analysis, and their relative expression was calculated by log2 of −ΔΔCt values from triplicate of PCR. More than two fold changes (log2 < −1 or log2 > 1) were considered significant between groups (red dotted line). (f) The percentage of CD4+ or CD8+ in the lymphocyte gate of the CNS of the above mice was analyzed by flow cytometry. (g) Absolute numbers of CD4+ or CD8+ cells in spinal cord were calculated (n = 5 each group). (h) Splenocytes of Ba- or PBS-treated EAE mice were isolated, stimulated with MOG35–55 (25 μg/ml) or Con A (5 μg/ml) and examined for proliferation at 72 h culture using BrdU incorporation assay (n = 6 each group). Data are expressed as mean ± SEM. **P < 0.01; ***P < 0.001. One representative of three experiments is shown.
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f2: Ba Treatment Reduced CNS Inflammation.Ba- or PBS-treated control EAE mice described in Fig. 1c (treatment protocol) were sacrificed at day 30 p.i., and spinal cords were harvested. Sections at lumbar level (L3) were analyzed (a) by H&E (for inflammation; left) and Luxol fast blue (LFB) (for degree of demyelination; right), and (b) pathology scores of inflammation and demyelination are expressed as mean ± SD (n = 6 each group). The absolute numbers of MNCs in the CNS of above mice were counted (n = 3 each group) (c), and expression of cytokine (d) and chemokine (e) genes was determined using real-time RT-PCR analysis, and their relative expression was calculated by log2 of −ΔΔCt values from triplicate of PCR. More than two fold changes (log2 < −1 or log2 > 1) were considered significant between groups (red dotted line). (f) The percentage of CD4+ or CD8+ in the lymphocyte gate of the CNS of the above mice was analyzed by flow cytometry. (g) Absolute numbers of CD4+ or CD8+ cells in spinal cord were calculated (n = 5 each group). (h) Splenocytes of Ba- or PBS-treated EAE mice were isolated, stimulated with MOG35–55 (25 μg/ml) or Con A (5 μg/ml) and examined for proliferation at 72 h culture using BrdU incorporation assay (n = 6 each group). Data are expressed as mean ± SEM. **P < 0.01; ***P < 0.001. One representative of three experiments is shown.
Mentions: To assess the effects of Ba on EAE-associated CNS pathology, lumbar spinal cords were obtained from Ba-treated and control mice. Analysis of CNS tissue sections demonstrated significantly reduced inflammation and demyelination in Ba-treated animals (Fig. 2a, right) when compared with control group (Fig. 2a, left). The pathological scores of mice treated with PBS or Ba differed significantly (P = 0.031 for the infiltration score and P = 0.022 for the demyelination score) (Fig. 2b). The number of mononuclear cells (MNCs) isolated from the CNS of Ba-treated mice was markedly reduced compared with that of vehicle-treated mice (P = 0.016; Fig. 2c).

Bottom Line: Natural compounds derived from medicinal plants have long been considered a rich source of novel therapeutic agents.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).Taken together, our findings demonstrate that Ba has significant potential as a novel anti-inflammatory agent for therapy of autoimmune diseases such as MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.

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.

No MeSH data available.


Related in: MedlinePlus