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Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice.

Ma X, Jiang Y, Wu A, Chen X, Pi R, Liu M, Liu Y - PLoS ONE (2010)

Bottom Line: Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects.These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration.We think that berberine might be a potential therapeutic agent for MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Background: Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects. However, there are no reports about the effects and mechanisms of berberine in experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS).

Methodology/principal findings: Female C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with berberine at the day of disease onset and medication was administered daily until mice were sacrificed. Blood-brain barrier (BBB) permeability and the alteration of matrix metalloproteinase-2 (MMP-2, 72 kDa) and matrix metalloproteinase-9 (MMP-9, 92 kDa) in the brain and cerebrospinal fluid (CSF) of EAE mice were detected by quantitative measurement for Evan's blue (EB) content, Western blot and gelatin zymography respectively. The results showed that berberine attenuated clinical and pathological parameters of EAE, reduced the permeability of BBB, inhibited the activity and expression of MMP-9 but not MMP-2 in the CSF and brain of EAE mice.

Conclusions/significance: These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration. We think that berberine might be a potential therapeutic agent for MS.

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The gelatinolytic activities of MMP-2 and MMP-9 in the CSF of different treated mice.CSF was obtained by puncture of the cisternamagna to detect gelatinase activity at day 20 p.i.. Each group had seven animals. Values represent the mean± S.E.M., **P<0.01, *P<0.05 vs control mice, ##P<0.01 vs PBS-treated EAE mice.
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pone-0013489-g006: The gelatinolytic activities of MMP-2 and MMP-9 in the CSF of different treated mice.CSF was obtained by puncture of the cisternamagna to detect gelatinase activity at day 20 p.i.. Each group had seven animals. Values represent the mean± S.E.M., **P<0.01, *P<0.05 vs control mice, ##P<0.01 vs PBS-treated EAE mice.

Mentions: CSF of control mice, PBS- and berebrine-treated EAE mice were obtained by puncture of the cisternamagna (n = 7). To determine the activities of MMP-2 and MMP-9 in CSF, zymography was performed. The changes in MMP-2 and MMP-9 activity were well in line with the expression of protein in the brain. There was a marked increase of MMP-2 and MMP-9 activity in CSF in PBS-treated EAE mice compared to the control mice (P<0.05 for MMP-2 and P<0.01 for MMP-9, respectively). Treatment with berberine reduced MMP-9 zymographic activity in CSF compared to PBS-treated EAE mice (P<0.01). There was not significantly difference of the activity of MMP-2 between the PBS- and berberine-treated EAE mice. (P>0.05, Fig. 6).


Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice.

Ma X, Jiang Y, Wu A, Chen X, Pi R, Liu M, Liu Y - PLoS ONE (2010)

The gelatinolytic activities of MMP-2 and MMP-9 in the CSF of different treated mice.CSF was obtained by puncture of the cisternamagna to detect gelatinase activity at day 20 p.i.. Each group had seven animals. Values represent the mean± S.E.M., **P<0.01, *P<0.05 vs control mice, ##P<0.01 vs PBS-treated EAE mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957444&req=5

pone-0013489-g006: The gelatinolytic activities of MMP-2 and MMP-9 in the CSF of different treated mice.CSF was obtained by puncture of the cisternamagna to detect gelatinase activity at day 20 p.i.. Each group had seven animals. Values represent the mean± S.E.M., **P<0.01, *P<0.05 vs control mice, ##P<0.01 vs PBS-treated EAE mice.
Mentions: CSF of control mice, PBS- and berebrine-treated EAE mice were obtained by puncture of the cisternamagna (n = 7). To determine the activities of MMP-2 and MMP-9 in CSF, zymography was performed. The changes in MMP-2 and MMP-9 activity were well in line with the expression of protein in the brain. There was a marked increase of MMP-2 and MMP-9 activity in CSF in PBS-treated EAE mice compared to the control mice (P<0.05 for MMP-2 and P<0.01 for MMP-9, respectively). Treatment with berberine reduced MMP-9 zymographic activity in CSF compared to PBS-treated EAE mice (P<0.01). There was not significantly difference of the activity of MMP-2 between the PBS- and berberine-treated EAE mice. (P>0.05, Fig. 6).

Bottom Line: Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects.These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration.We think that berberine might be a potential therapeutic agent for MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Background: Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects. However, there are no reports about the effects and mechanisms of berberine in experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS).

Methodology/principal findings: Female C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with berberine at the day of disease onset and medication was administered daily until mice were sacrificed. Blood-brain barrier (BBB) permeability and the alteration of matrix metalloproteinase-2 (MMP-2, 72 kDa) and matrix metalloproteinase-9 (MMP-9, 92 kDa) in the brain and cerebrospinal fluid (CSF) of EAE mice were detected by quantitative measurement for Evan's blue (EB) content, Western blot and gelatin zymography respectively. The results showed that berberine attenuated clinical and pathological parameters of EAE, reduced the permeability of BBB, inhibited the activity and expression of MMP-9 but not MMP-2 in the CSF and brain of EAE mice.

Conclusions/significance: These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration. We think that berberine might be a potential therapeutic agent for MS.

Show MeSH
Related in: MedlinePlus