7β-Hydroxysitosterol crosses the blood-brain barrier more favored than its substrate sitosterol in ApoE-/- mice.

Abstract In this study, we compare the distribution of intraperitoneally injected sitosterol, 7β-hydroxysitosterol or vehicle only (control) for 28 days in male ApoE−/− mice. Furthermore we examine its impact on surrogate markers of cholesterol biosynthesis and sterol absorption rate in plasma, brain and liver tissues from these animals. Injection of sitosterol revealed a 32.1% ( P  = 0.013) lower plasma total cholesterol compared with control. Cholesterol corrected plasma and absolute brain and liver levels of sitosterol are 4.1-, 1.7-, and 7.2-fold ( P P  = 0.018) together with a 24.1% ( P  = 0.047) lower concentration of hepatic lathosterol. After injection of 7β-hydroxysitosterol the concentrations of 7β-hydroxysitosterol in plasma, brain and liver are 21.0-, 65.8- and 42.7-fold ( P P  = 0.001 and −24.5; P  = 0.004) as well as lower absolute liver cholestanol levels (−31.9%; P Intraperitoneally injected sitosterol and 7β-hydroxysitosterol differently influence cholesterol metabolism in plasma and liver. We conclude that the polar 7β-hydroxysitosterol compound can pass the blood brain barrier with higher efficacy than its substrate, sitosterol. Though present in higher amounts in the brain, both, sitosterol and 7β-hydroxysitosterol do not influence cholesterol metabolism in the brain as proven by our surrogate markers.