School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
College of Health, Fujian Medical University, Fuzhou, Fujian Province, China.
J Ethnopharmacol. 2023 Oct 5;314:116532. doi: 10.1016/j.jep.2023.116532. Epub 2023 May 5.
Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis.
To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT).
ApoE mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays.
The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells.
In summary, our findings suggest that geniposide protects ApoE mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.
栀子是一种传统的中药，已被用于治疗各种疾病，包括通过清热解毒治疗动脉粥样硬化。京尼平苷被认为是栀子治疗动脉粥样硬化的有效化合物。
研究京尼平苷对动脉粥样硬化负担和斑块巨噬细胞极化的影响，重点关注其对血管周围脂肪组织（PVAT）中 CXCL14 表达的潜在影响。
使用载脂蛋白 E （ApoE） 小鼠喂食西方饮食（WD）来建立动脉粥样硬化模型。使用小鼠 3T3-L1 前脂肪细胞和 RAW264.7 巨噬细胞进行体外培养以进行分子检测。
结果表明，京尼平苷治疗可减少 ApoE 小鼠的动脉粥样硬化病变，这种作用与斑块巨噬细胞 M2 极化增加和 M1 极化减少相关。值得注意的是，京尼平苷增加了 PVAT 中 CXCL14 的表达，京尼平苷的抗动脉粥样硬化作用及其对巨噬细胞极化的调节作用，在体内 CXCL14 敲低后均被消除。与这些发现一致，暴露于京尼平苷处理的 3T3-L1 脂肪细胞的条件培养基（或重组 CXCL14 蛋白）增强了白细胞介素 4（IL-4）处理的 RAW264.7 巨噬细胞的 M2 极化，并且在 3T3-L1 细胞中沉默 CXCL14 后，这种作用被消除。
总之，我们的研究结果表明，京尼平苷通过增强 PVAT 中 CXCL14 的表达来诱导斑块巨噬细胞的 M2 极化，从而保护 ApoE 小鼠免受 WD 诱导的动脉粥样硬化。这些数据为 PVAT 在动脉粥样硬化中的旁分泌功能提供了新的见解，并再次证实京尼平苷是动脉粥样硬化治疗的候选治疗药物。
