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.

1.
Schievink WI. Intracranial aneurysms.
N Engl J Med
. 1997 Jan;336(1):28–40.
2.
Bonita R. Cigarette smoking, hypertension and the risk of subarachnoid hemorrhage: a population-based case-control study.
Stroke
. 1986 Sep-Oct;17(5):831–5.
3.
Hashimoto T, Meng H, Young WL. Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling.
Neurol Res
. 2006 Jun;28(4):372–80.
4.
Cloft HJ, Altes TA, Marx WF, Raible RJ, Hudson SB, Helm GA, et al. Endovascular creation of an in vivo bifurcation aneurysm model in rabbits.
Radiology
. 1999 Oct;213(1):223–8.
5.
Miskolczi L, Guterman LR, Flaherty JD, Hopkins LN. Saccular aneurysm induction by elastase digestion of the arterial wall: a new animal model.
Neurosurgery
. 1998 Sep;43(3):595–600.
6.
Anidjar S, Salzmann JL, Gentric D, Lagneau P, Camilleri JP, Michel JB. Elastase-induced experimental aneurysms in rats.
Circulation
. 1990 Sep;82(3):973–81.
7.
Chalouhi N, Hoh BL, Hasan D. Review of cerebral aneurysm formation, growth, and rupture.
Stroke
. 2013 Dec;44(12):3613–22.
8.
Jayaraman T, Paget A, Shin YS, Li X, Mayer J, Chaudhry H, et al. TNF-alpha-mediated inflammation in cerebral aneurysms: a potential link to growth and rupture.
Vasc Health Risk Manag
. 2008;4(4):805–17.
9.
Chyatte D, Bruno G, Desai S, Todor DR. Inflammation and intracranial aneurysms.
Neurosurgery
. 1999 Nov;45(5):1137–46.
10.
Tracey KJ, Cerami A. Tumor necrosis factor, other cytokines and disease.
Annu Rev Cell Biol
. 1993;9(1):317–43.
11.
Han NR, Kim HM, Jeong HJ. The β-sitosterol attenuates atopic dermatitis-like skin lesions through down-regulation of TSLP.
Exp Biol Med (Maywood)
. 2014 Apr;239(4):454–64.
12.
Loizou S, Lekakis I, Chrousos GP, Moutsatsou P. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells.
Mol Nutr Food Res
. 2010 Apr;54(4):551–8.
13.
Paniagua-Pérez R, Flores-Mondragón G, Reyes-Legorreta C, Herrera-López B, Cervantes-Hernández I, Madrigal-Santillán O, et al. Evaluation of the anti-inflammatory capacity of beta-sitosterol in rodent assays.
Afr J Tradit Complement Altern Med
. 2016 Nov;14(1):123–30.
14.
Shi C, Luo X, Wang J, Long D. Incorporation of β-sitosterol into the membrane prevents tumor necrosis factor-α-induced nuclear factor-κB activation and gonadotropin-releasing hormone decline.
Steroids
. 2015 Apr;96:1–6.
15.
Hosaka K, Downes DP, Nowicki KW, Hoh BL. Modified murine intracranial aneurysm model: aneurysm formation and rupture by elastase and hypertension.
J Neurointerv Surg
. 2014 Jul;6(6):474–9.
16.
Aoki T, Kataoka H, Ishibashi R, Nakagami H, Nozaki K, Morishita R, et al. Pitavastatin suppresses formation and progression of cerebral aneurysms through inhibition of the nuclear factor kappaB pathway.
Neurosurgery
. 2009 Feb;64(2):357–65.
17.
Hashimoto N, Handa H, Hazama F. Experimentally induced cerebral aneurysms in rats.
Surg Neurol
. 1978 Jul;10(1):3–8.
18.
Nuki Y, Tsou TL, Kurihara C, Kanematsu M, Kanematsu Y, Hashimoto T. Elastase-induced intracranial aneurysms in hypertensive mice.
Hypertension
. 2009 Dec;54(6):1337–44.
19.
Gaetani P, Rodriguez y Baena R, Tartara F, Messina AL, Tancioni F, Schiavo R, et al. Metalloproteases and intracranial vascular lesions.
Neurol Res
. 1999 Jun;21(4):385–90.
20.
Kim SC, Singh M, Huang J, Prestigiacomo CJ, Winfree CJ, Solomon RA, et al. Matrix metalloproteinase-9 in cerebral aneurysms.
Neurosurgery
. 1997 Sep;41(3):642–66.
21.
Pannu H, Kim DH, Guo D, King TM, Van Ginhoven G, Chin T, et al. The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms.
J Neurosurg
. 2006 Sep;105(3):418–23.
22.
Mantovani A, Sica A, Locati M. Macrophage polarization comes of age.
Immunity
. 2005 Oct;23(4):344–6.
23.
Morgan L, Cooper J, Montgomery H, Kitchen N, Humphries SE. The interleukin-6 gene -174G[{GT}]C and -572G[{GT}]C promoter polymorphisms are related to cerebral aneurysms.
J Neurol Neurosurg Psychiatry
. 2006 Aug;77(8):915–7.
24.
Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB.
Arterioscler Thromb Vasc Biol
. 2009 Jul;29(7):1080–6.
25.
Moriwaki T, Takagi Y, Sadamasa N, Aoki T, Nozaki K, Hashimoto N. Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.
Stroke
. 2006 Mar;37(3):900–5.
26.
Toth G, Cerejo R. Intracranial aneurysms: review of current science and management.
Vasc Med
. 2018 Jun;23(3):276–88.
27.
Cummings TJ, Johnson RR, Diaz FG, Michael DB. The relationship of blunt head trauma, subarachnoid hemorrhage, and rupture of pre-existing intracranial saccular aneurysms.
Neurol Res
. 2000 Mar;22(2):165–70.
28.
Chalouhi N, Points L, Pierce GL, Ballas Z, Jabbour P, Hasan D. Localized increase of chemokines in the lumen of human cerebral aneurysms.
Stroke
. 2013 Sep;44(9):2594–7.
29.
Shen J, Yang M, Ju D, Jiang H, Zheng JP, Xu Z, et al. Disruption of SM22 promotes inflammation after artery injury via nuclear factor kappaB activation.
Circ Res
. 2010 Apr;106(8):1351–62.
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