Synthesis of cholesterol analogues and comparison on their effect on plasma cholesterol with β-Sitosterol

Abstract

The application of plant sterols in the treatment of hypercholesterolemia is promising. We hypothesize that plant sterols can reduce blood cholesterol because they have a side chain of at least three branches. Three cholesterol analogues were synthesized: CA0 (no side chain), CA3 (a 3‑carbon chain with one branch), and CA14 (a 14‑carbon side chain with two branches), and then compared their effect on blood cholesterol with that of β-sitosterol. Structurally, β-sitosterol has a 10‑carbon side chain with three branches. Results demonstrated that β-sitosterol could effectively reduce plasma total cholesterol (TC) by 20.3%, whereas CA0, CA3 and CA14 did not affect plasma TC in hypercholesterolemia hamsters. β-Sitosterol was absent in the plasma and liver, indicating it was not absorbed. We concluded that β-sitosterol with three branches had plasma TC-lowering activity. In contrast, cholesterol analogues with a side chain of two or fewer branches did not affect plasma cholesterol.