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 beta-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 beta-sitosterol on CA progression. Materials and Methods: To study whether beta-sitosterol has a suppressive effect on the growth of CA, beta-sitosterol administration started prior to aneurysm induction. CA was induced in Wistar male rats with or without oral administration of beta-sitosterol. The expression of chemokines and inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-8, IL-1 beta, IL-17, IL-6, matrix metalloproteinases (MMP)-2 and -9, was elucidated by ELISA and RT-PCR. Results: Rats treated with beta-sitosterol exhibited a significant reduction in aneurysmal size compared with control rats. In addition, beta-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 beta-sitosterol-administered rats compared to CA rats. Conclusions: Treatment with beta-sitosterol suppresses the development of CA by inhibiting inflammatory reactions including TNF-alpha and thus beta-sitosterol can be a suggestive candidate for the prevention of CA treatment and progression.