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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 effect of berberine on brain BBB permeability in EAE mice.The integrity of BBB was detected by quantitative measurement for EB content at day 20 p.i. in six animals per group. EB is expressed as micrograms per gram of brain tissue against a standard curve. Values represent the mean±S.E.M., ** P<0.01 vs. control mice, ##P<0.01 vs. PBS-treated EAE mice.
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pone-0013489-g004: The effect of berberine on brain BBB permeability in EAE mice.The integrity of BBB was detected by quantitative measurement for EB content at day 20 p.i. in six animals per group. EB is expressed as micrograms per gram of brain tissue against a standard curve. Values represent the mean±S.E.M., ** P<0.01 vs. control mice, ##P<0.01 vs. PBS-treated EAE mice.

Mentions: The integrity of BBB of different treated animals was detected by quantitative measurement for EB content at day 20 p.i.(n = 6). 30 minutes after the intravenous injection of EB, animals were carefully perfused to remove excess dye and the content of EB in the brain tissue was measured at 610 nm using a spectrophotometer. The concentrations of extravasated EB (expressed as micrograms per gram of brain tissue) of different groups are shown in Fig. 4. In the control mice, baseline level of EB was 70.31±3.54 µg/g brain tissue. The content of EB in the brain of PBS- and berberine-treated EAE mice were 196.70±3.76 and 130.75±5.61 µg/g brain tissue, respectively. Both PBS- and berberine-treated EAE mice showed a significant increase in the content of EB in the brain when compared with the control mice (P<0.01). But the increase in the content of EB in the brain of berberine-treated EAE mice was not as remarkable as that of the PBS-treated EAE mice (P<0.01). The results showed that berebrine could prevent further injury of BBB permeability.


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 effect of berberine on brain BBB permeability in EAE mice.The integrity of BBB was detected by quantitative measurement for EB content at day 20 p.i. in six animals per group. EB is expressed as micrograms per gram of brain tissue against a standard curve. Values represent the mean±S.E.M., ** P<0.01 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-g004: The effect of berberine on brain BBB permeability in EAE mice.The integrity of BBB was detected by quantitative measurement for EB content at day 20 p.i. in six animals per group. EB is expressed as micrograms per gram of brain tissue against a standard curve. Values represent the mean±S.E.M., ** P<0.01 vs. control mice, ##P<0.01 vs. PBS-treated EAE mice.
Mentions: The integrity of BBB of different treated animals was detected by quantitative measurement for EB content at day 20 p.i.(n = 6). 30 minutes after the intravenous injection of EB, animals were carefully perfused to remove excess dye and the content of EB in the brain tissue was measured at 610 nm using a spectrophotometer. The concentrations of extravasated EB (expressed as micrograms per gram of brain tissue) of different groups are shown in Fig. 4. In the control mice, baseline level of EB was 70.31±3.54 µg/g brain tissue. The content of EB in the brain of PBS- and berberine-treated EAE mice were 196.70±3.76 and 130.75±5.61 µg/g brain tissue, respectively. Both PBS- and berberine-treated EAE mice showed a significant increase in the content of EB in the brain when compared with the control mice (P<0.01). But the increase in the content of EB in the brain of berberine-treated EAE mice was not as remarkable as that of the PBS-treated EAE mice (P<0.01). The results showed that berebrine could prevent further injury of BBB permeability.

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