Efficacy of Terpenoid in Attenuating Aortic Atherosclerosis in Apolipoprotein-E Deficient Mice: A Meta-Analysis of Animal Studies

BACKGROUND: The apolipoprotein E knockout (ApoE -/-) mouse model is well established for the study of terpenoids in the prevention of atherosclerosis. Studies investigating the clinical benefit of terpenoids in humans are scarce. This systematic review and meta-analysis evaluated the effects of terpenoid administration on atherosclerotic lesion area in ApoE -/- mice. METHODS: A comprehensive literature search using PubMed, Embase, and the Cochrane Library databases was performed to identify studies that assessed the effects of terpenoids on atherosclerosis in ApoE -/- mice. The primary outcome was atherosclerotic lesion area, and study quality was estimated using SYRCLE's risk of bias tool. RESULTS: The meta-analysis included 25 studies. Overall, terpenoids significantly reduced atherosclerotic lesion area when compared to vehicle control (P<0.00001; SMD: -0.55; 95% CI: -0.72, -0.39). In terpenoid type and dose subgroup analyses, sesquiterpenoid (P=0.002; SMD -0.93; 95% CI: -1.52, -0.34), diterpenoid (P=0.01; SMD: -0.30; 95% CI: -0.54, -0.06), triterpenoid (P<0.00001; SMD: -0.66; 95% CI: -0.94, -0.39), tetraterpenoid (P<0.0001; SMD: -1.81; 95% CI: -2.70, -0.91), low dose (P=0.0001; SMD: -0.51; 95% CI: -0.76, -0.25), medium dose (P<0.0001; SMD: -0.48; 95% CI: -0.72, -0.24), and high dose (P=0.002; SMD: -1.07; 95% CI: -1.74, -0.40) significantly decreased atherosclerotic lesion area when compared to vehicle control. PROSPERO register number is CRD42019121176. CONCLUSION: Sesquiterpenoid, diterpenoid, triterpenoid, and tetraterpenoid have potential as antiatherosclerotic agents with a wide range of doses. This systematic review provides a reference for research programs aimed at the development of terpenoid-based clinical drugs.