Piperine alleviates inflammation, blood-brain-barrier and myelin
destruction
MS has numerous pathologic hallmarks as an inflammatory and autoimmune
CNS disease, such as leukocyte cells infiltration, blood-brain-barrier
(BBB) and myelin destruction.
Spinal
cords tissues were subjected to histological analysis on day 22 after
MOG’s immunization. As illustrated in Figure 6A, piperine treated-group
showed reduced leukocyte cell infiltrations by hematoxylin and eosin
(H&E) staining and less demyelination in white matter by Luxol fast
blue (LFB) staining as compared to the vehicle-treated mice.
Blood-brain-barrier (BBB) destruction is a pathologic hallmark of EAE.
We then aim to investigate the effect of piperine on BBB permeability
using a fluorescent BSA conjugate probe BSA-Cy5.5. As shown in Figure
6B, piperine significantly reduce the accumulation of BSA-Cy5.5 in the
brain as indicated by in vivo optical imaging when compared to
the vehicle treated mice, suggesting improved BBB integrity in EAE
challenge. During the pathological process of MS, destructive BBB allows
lymphocytes activated in the periphery to infiltrate the CNS, which
evoke a local immune reaction resulting in axons and myelin damages. We
next examined whether piperine treatment alleviates myelin destruction
in EAE model using a myelin-binding near-infrared dye
3,3-diethylthiatricarbocyanine iodide (DBT). DBT dye (0.3 mg/kg) were
intravenous injection to mice and the fluorescence signals were imaged.
Figure 6C shows a higher fluorescent intensity as compared to the
vehicle group, indicating reduced myelin destruction following piperine
treatment.
We also investigate the effect of piperine on EAE-related T cell
activation. As presented in Figure 6D-E, EAE challenge induce a
significantly increase of population of CD4+ and
CD8+T cell in spleen (increased from 9.35±0.17% to 13.6±0.32% for
CD4+ T cell and from 16.17±0.18% to 24.32±0.39% for
CD8+ T cell). Remarkably, piperine treatment group (30
mg/kg) shows a significantly reduction of CD4+population, when compared with the vehicle-treated mice. In addition,
reduced CD8+ proportion was also observed following
piperine administration. Taken together, these data indicate that
piperine can effectively ameliorate inflammation and protect
blood-brain-barrier and myelin in EAE mice.