Blockage of hydroxyl group partially abolishes the cholesterol-lowering activity of β-sitosterol

• β-Sitosterol (SI) effectively reduces plasma total cholesterol (TC).
• SI has a hydroxyl group (OH).
• Blockage of OH partially abolished TC-lowering activity of SI.
• OH on SI was essential for its TC-lowering activity.

β-Sitosterol (SI) is hypocholesterolemic. The present study investigated whether the blockage of its hydroxyl group would abolish its cholesterol-lowering activity. The blockage was made by methylating and ethylating the hydroxyl group on C3 position, leading to formation of β-sitosteryl 3β-methoxy (SM) and β-sitosteryl 3β-ethoxy (SE) derivatives. Male hamsters were divided into five groups (n = 8 each) and fed the non-cholesterol diet (NCD), high cholesterol diet containing 5 mmol of cholesterol (HCD), or one of the three high cholesterol experimental diets with addition of 5 mmol of SI (HCD + SI), 5 mmol of SM (HCD + SM) and 5 mmol of SE (HCD + SE), respectively, for 8 weeks. Results showed that SI could significantly reduce plasma total cholesterol (TC) by 17% (P < 0.05), while SM and SE had no effect on plasma TC. It was concluded that the hydroxyl group was essential for SI to render its cholesterol-lowering activity and its blockage abolished this ability.