Geniposide Stabilized Atherosclerosis Plaque by Induced M2 Polarization via PPARγ Signaling Pathway [Letter]

作者：Haizhen Guo, Yuke Zhao, Zidong Cong · 发表于：Drug Design Development and Therapy · 年份：2025 · DOI：10.2147/dddt.s578934 · 研究领域：Peroxisome Proliferator-Activated Receptors、Cholesterol and Lipid Metabolism、Cardiovascular Disease and Adiposity

Stabilized Atherosclerosis Plaque by Induced M2 Polarization via PPAR Signaling Pathway" in Drug Design, Development and Therapy. 1 Through in vivo and in vitro experiments, the authors show that Geniposide (Gen) stabilizes atherosclerotic plaques by promoting macrophage M2 polarization via activation of the PPAR signaling pathway.These findings offer valuable, albeit preliminary, insights into the anti-atherosclerotic actions of geniposide.However, we believe that several methodological aspects would benefit from greater clarification to enhance the mechanistic support for these various findings.After carefully reading the manuscript, we feel that the reasons for choosing particular dose and treatment duration of the PPAR antagonist GW9662 need further clarification.The in vitro studies were done using only one concentration (5 M) and one pretreatment period (1 h), without testing whether the treatment affects cell viability under these conditions.Earlier findings suggest that GW9662 can be cytotoxic or exhibit off-target effects that are PPAR noninhibitory. 2 The downregulation of M2 marker expression may not only be due to specific PPAR blockade, as it cannot be excluded that drug-induced effects on cellular state also caused this downregulation through nonspecific stress responses.In addition, GW9662 was given via intraperitoneal injection in the ApoE -/ -mouse model 1 mg/kg/day.Nevertheless, the regimen was not validated by any pharmacokinetic or pharmacodynamic data.Sin...