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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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Berberine treatment decreased inflammation and demyelination in the lumbar spinal cord of EAE mice.Mice were subjected to histopathological assay at day 20 p.i.. Each group had six animals. Consecutive sections were analyzed for hematoxylin and eosin staining and solochrome cyanin staining to detect inflammatory infiltration and demyelination respectively. Values represent the mean±S.E.M., **P<0.01 vs. PBS-treated EAE mice.
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pone-0013489-g002: Berberine treatment decreased inflammation and demyelination in the lumbar spinal cord of EAE mice.Mice were subjected to histopathological assay at day 20 p.i.. Each group had six animals. Consecutive sections were analyzed for hematoxylin and eosin staining and solochrome cyanin staining to detect inflammatory infiltration and demyelination respectively. Values represent the mean±S.E.M., **P<0.01 vs. PBS-treated EAE mice.

Mentions: We next evaluated the lumbar spinal cords for pathological changes in EAE mice following different treatments on day 20 p.i.. Hematoxylin and eosin staining and solochrome cyanin staining were performed for evaluating inflammatory infiltration and demyelination respectively. Histological scores of the degree of inflammation and demyelination in the lumbar spinal cord of each animal were evaluated blindly, using a semiquantitative system as previously described [17]–[20].The inflammatory scores which indicated the diffuse infiltration by mixed macrophages, T and B lymphocytes into CNS white matter in the lumbar spinal cords of the PBS- and berberine-treated EAE mice were 2.67±0.17 and 1.50±0.18 respectively. Compared with PBS-treated EAE mice, berberine treatment drastically reduced inflammatory cell infiltration in EAE mice (P<0.01, Fig. 2). Solochrome cyanin staining showed the demyelinating scores of the PBS- and berberine-treated EAE mice were 2.83±0.21 and 1.83±0.20 respectively. The demyelination in the lumbar spinal cords of EAE mice was profoundly ameliorated by berberine treatment when compared with PBS treatment (P<0.01, Fig. 2). The representative sections depicting the inflammatory infiltrates and demyelination in the lumbar spinal cords of EAE mice treated by PBS and berberine were showed in Fig 3. Inflammatory infiltrates were widespread in the PBS-treated mice at day 20 p.i. (Fig. 3A) but reduced in berberine-treated mice (Fig. 3C). And a large plaque of demyelination was seen in the PBS-treated EAE mice at day 20 p.i. (Fig. 3B), but in the berberine-treated EAE mice, demyelination was markedly attenuated (Fig. 3D).


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)

Berberine treatment decreased inflammation and demyelination in the lumbar spinal cord of EAE mice.Mice were subjected to histopathological assay at day 20 p.i.. Each group had six animals. Consecutive sections were analyzed for hematoxylin and eosin staining and solochrome cyanin staining to detect inflammatory infiltration and demyelination respectively. Values represent the mean±S.E.M., **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-g002: Berberine treatment decreased inflammation and demyelination in the lumbar spinal cord of EAE mice.Mice were subjected to histopathological assay at day 20 p.i.. Each group had six animals. Consecutive sections were analyzed for hematoxylin and eosin staining and solochrome cyanin staining to detect inflammatory infiltration and demyelination respectively. Values represent the mean±S.E.M., **P<0.01 vs. PBS-treated EAE mice.
Mentions: We next evaluated the lumbar spinal cords for pathological changes in EAE mice following different treatments on day 20 p.i.. Hematoxylin and eosin staining and solochrome cyanin staining were performed for evaluating inflammatory infiltration and demyelination respectively. Histological scores of the degree of inflammation and demyelination in the lumbar spinal cord of each animal were evaluated blindly, using a semiquantitative system as previously described [17]–[20].The inflammatory scores which indicated the diffuse infiltration by mixed macrophages, T and B lymphocytes into CNS white matter in the lumbar spinal cords of the PBS- and berberine-treated EAE mice were 2.67±0.17 and 1.50±0.18 respectively. Compared with PBS-treated EAE mice, berberine treatment drastically reduced inflammatory cell infiltration in EAE mice (P<0.01, Fig. 2). Solochrome cyanin staining showed the demyelinating scores of the PBS- and berberine-treated EAE mice were 2.83±0.21 and 1.83±0.20 respectively. The demyelination in the lumbar spinal cords of EAE mice was profoundly ameliorated by berberine treatment when compared with PBS treatment (P<0.01, Fig. 2). The representative sections depicting the inflammatory infiltrates and demyelination in the lumbar spinal cords of EAE mice treated by PBS and berberine were showed in Fig 3. Inflammatory infiltrates were widespread in the PBS-treated mice at day 20 p.i. (Fig. 3A) but reduced in berberine-treated mice (Fig. 3C). And a large plaque of demyelination was seen in the PBS-treated EAE mice at day 20 p.i. (Fig. 3B), but in the berberine-treated EAE mice, demyelination was markedly attenuated (Fig. 3D).

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