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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 Ameliorates Clinical Symptoms of EAE.C57BL/6 mice were injected i.p. with PBS (●) or Ba (100 mg/kg, ○) daily (a) at the day of EAE induction, (b) day 10 p.i. (disease onset), (c) day 15 p.i. (disease peak), or (d) during the indicated time points. Results are shown as mean ± SEM (n = 5 each group). (e) Disease distribution at the end points of experiment, and (f) incidence of disease severity at the end points of experiment when treatment started at day 10 p.i. Disease severity is graded as severe (clinical score: > 3), moderate (clinical score: 1.5–3), mild (clinical score: <1.5) or none (no clinical signs). One representative of three independent experiments is shown in a, b, and c. The data in d, e, and f came from three independent experiments when Ba was injected from day 10 p.i. (n = 5–6 each group). **P < 0.01; ***P < 0.001.
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f1: Ba Ameliorates Clinical Symptoms of EAE.C57BL/6 mice were injected i.p. with PBS (●) or Ba (100 mg/kg, ○) daily (a) at the day of EAE induction, (b) day 10 p.i. (disease onset), (c) day 15 p.i. (disease peak), or (d) during the indicated time points. Results are shown as mean ± SEM (n = 5 each group). (e) Disease distribution at the end points of experiment, and (f) incidence of disease severity at the end points of experiment when treatment started at day 10 p.i. Disease severity is graded as severe (clinical score: > 3), moderate (clinical score: 1.5–3), mild (clinical score: <1.5) or none (no clinical signs). One representative of three independent experiments is shown in a, b, and c. The data in d, e, and f came from three independent experiments when Ba was injected from day 10 p.i. (n = 5–6 each group). **P < 0.01; ***P < 0.001.

Mentions: To determine the anti-inflammatory properties of Ba, we examined its effects in EAE. By testing different doses, we found that Ba at 100 mg/kg/d is optimal for suppressing EAE (Fig. s1); this dose was therefore chosen for all subsequent in vivo experiments. For the prophylactic treatment regimen, Ba administration starting from day 0 post immunization (p.i.) resulted in delayed onset and significantly decreased disease severity compared to PBS-treated control mice (P < 0.01; Fig. 1a and Table s1). In the therapeutic regimen, Ba administration starting from disease onset (day 10 p.i.) or its peak (day 15 p.i.) effectively suppressed EAE progression (Fig. 1b,c). Improvement in clinical signs was observed 1–2 days after Ba injection, and the effect persisted until the end of the experiment. To investigate the lasting effect of Ba administration, treatment was started from disease onset (day 14 p.i.) and stopped when disease development was significantly suppressed by Ba (average clinical score <1.5, day 19 p.i.). Recurrence of disease signs was observed 7–8 days after stopping Ba treatment, while re-exposure of these mice to the same treatment of Ba resulted in a significant suppression of clinical signs (Fig. 1d), suggesting the necessity for continuous daily use. Together, Ba treatment substantially reduced disease severity (Fig. 1e,f and Table s1); the majority of Ba-treated EAE mice displayed mild or moderate signs, while severe disease was only observed in PBS-treated mice (Fig. 1f). These results suggest that Ba has a significant therapeutic effect in EAE.


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 Ameliorates Clinical Symptoms of EAE.C57BL/6 mice were injected i.p. with PBS (●) or Ba (100 mg/kg, ○) daily (a) at the day of EAE induction, (b) day 10 p.i. (disease onset), (c) day 15 p.i. (disease peak), or (d) during the indicated time points. Results are shown as mean ± SEM (n = 5 each group). (e) Disease distribution at the end points of experiment, and (f) incidence of disease severity at the end points of experiment when treatment started at day 10 p.i. Disease severity is graded as severe (clinical score: > 3), moderate (clinical score: 1.5–3), mild (clinical score: <1.5) or none (no clinical signs). One representative of three independent experiments is shown in a, b, and c. The data in d, e, and f came from three independent experiments when Ba was injected from day 10 p.i. (n = 5–6 each group). **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f1: Ba Ameliorates Clinical Symptoms of EAE.C57BL/6 mice were injected i.p. with PBS (●) or Ba (100 mg/kg, ○) daily (a) at the day of EAE induction, (b) day 10 p.i. (disease onset), (c) day 15 p.i. (disease peak), or (d) during the indicated time points. Results are shown as mean ± SEM (n = 5 each group). (e) Disease distribution at the end points of experiment, and (f) incidence of disease severity at the end points of experiment when treatment started at day 10 p.i. Disease severity is graded as severe (clinical score: > 3), moderate (clinical score: 1.5–3), mild (clinical score: <1.5) or none (no clinical signs). One representative of three independent experiments is shown in a, b, and c. The data in d, e, and f came from three independent experiments when Ba was injected from day 10 p.i. (n = 5–6 each group). **P < 0.01; ***P < 0.001.
Mentions: To determine the anti-inflammatory properties of Ba, we examined its effects in EAE. By testing different doses, we found that Ba at 100 mg/kg/d is optimal for suppressing EAE (Fig. s1); this dose was therefore chosen for all subsequent in vivo experiments. For the prophylactic treatment regimen, Ba administration starting from day 0 post immunization (p.i.) resulted in delayed onset and significantly decreased disease severity compared to PBS-treated control mice (P < 0.01; Fig. 1a and Table s1). In the therapeutic regimen, Ba administration starting from disease onset (day 10 p.i.) or its peak (day 15 p.i.) effectively suppressed EAE progression (Fig. 1b,c). Improvement in clinical signs was observed 1–2 days after Ba injection, and the effect persisted until the end of the experiment. To investigate the lasting effect of Ba administration, treatment was started from disease onset (day 14 p.i.) and stopped when disease development was significantly suppressed by Ba (average clinical score <1.5, day 19 p.i.). Recurrence of disease signs was observed 7–8 days after stopping Ba treatment, while re-exposure of these mice to the same treatment of Ba resulted in a significant suppression of clinical signs (Fig. 1d), suggesting the necessity for continuous daily use. Together, Ba treatment substantially reduced disease severity (Fig. 1e,f and Table s1); the majority of Ba-treated EAE mice displayed mild or moderate signs, while severe disease was only observed in PBS-treated mice (Fig. 1f). These results suggest that Ba has a significant therapeutic effect in EAE.

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