β-Sitosterol Attenuates the Intracranial Aneurysm Growth by Suppressing TNF-α-Mediated Mechanism.

BACKGROUND

Onset of inflammation associated with increased extracellular matrix degradation of vascular walls in the neuronal area is the pathophysiology of cerebral aneurysms. It has been documented well that β-sitosterol has protective effects on various brain-related diseases independent of their lipid-lowering effects; the current work was framed to examine the effect of β-sitosterol on CA progression.

MATERIALS AND METHODS

To study whether β-sitosterol has a suppressive effect on the growth of CA, β-sitosterol administration started prior to aneurysm induction. CA was induced in Wistar male rats with or without oral administration of β-sitosterol. The expression of chemokines and inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, IL-17, IL-6, matrix metalloproteinases (MMP)-2 and -9, was elucidated by ELISA and RT-PCR.

RESULTS

Rats treated with β-sitosterol exhibited a significant reduction in aneurysmal size compared with control rats. In addition, β-sitosterol administration reduced the expression of chemokines and inflammatory cytokines, while gelatin zymography data revealed declined activity of MMP-2 and -9 in aneurismal walls. Furthermore, the levels of cytokines were significantly reduced in β-sitosterol-administered rats compared to CA rats.

CONCLUSIONS

Treatment with β-sitosterol suppresses the development of CA by inhibiting inflammatory reactions including TNF-α and thus β-sitosterol can be a suggestive candidate for the prevention of CA treatment and progression.