Lee Aden Geonhee, Kang Sora, Im Suyeol, Pak Youngmi Kim
Phillips Exeter Academy, Exeter, NH 03833, USA.
Department of Neuroscience, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Pharmaceutics. 2022 Aug 11;14(8):1675. doi: 10.3390/pharmaceutics14081675.
Obesity is closely linked to chronic inflammation in peripheral organs and the hypothalamus. Chronic consumption of a high-fat diet (HFD) induces the differentiation of Ly6c monocytes into macrophages in adipose tissue, the liver, and the brain, as well as the secretion of pro-inflammatory cytokines. Although cinnamon improves obesity and related diseases, it is unclear which components of cinnamon can affect macrophages and inflammatory cytokines. We performed in silico analyses using ADME, drug-likeness, and molecular docking simulations to predict the active compounds of cinnamon. Among the 82 active compounds of cinnamon, cinnamic acid (CA) showed the highest score of ADME, blood-brain barrier permeability, drug-likeness, and cytokine binding. We then investigated whether CA modulates obesity-induced metabolic profiles and macrophage-related inflammatory responses in HFD-fed mice. While HFD feeding induced obesity, CA ameliorated obesity and related symptoms, such as epididymal fat gain, insulin resistance, glucose intolerance, and dyslipidemia, without hepatic and renal toxicity. CA also improved HFD-induced tumor necrosis factor-α, fat deposition, and macrophage infiltration in the liver and adipose tissue. CA decreased Ly6c monocytes, adipose tissue M1 macrophages, and hypothalamic microglial activation. These results suggest that CA attenuates the peripheral and hypothalamic inflammatory monocytes/macrophage system and treats obesity-related metabolic disorders.
肥胖与外周器官和下丘脑的慢性炎症密切相关。长期食用高脂饮食（HFD）会诱导Ly6c单核细胞在脂肪组织、肝脏和大脑中分化为巨噬细胞，并分泌促炎细胞因子。尽管肉桂可改善肥胖及相关疾病，但尚不清楚肉桂的哪些成分会影响巨噬细胞和炎性细胞因子。我们使用ADME、类药性和分子对接模拟进行了计算机分析，以预测肉桂的活性化合物。在肉桂的82种活性化合物中，肉桂酸（CA）在ADME、血脑屏障通透性、类药性和细胞因子结合方面得分最高。然后，我们研究了CA是否能调节高脂饮食喂养小鼠的肥胖诱导代谢谱和巨噬细胞相关的炎症反应。高脂饮食喂养会导致肥胖，而CA可改善肥胖及相关症状，如附睾脂肪增加、胰岛素抵抗、葡萄糖不耐受和血脂异常，且无肝肾毒性。CA还改善了高脂饮食诱导的肿瘤坏死因子-α、肝脏和脂肪组织中的脂肪沉积以及巨噬细胞浸润。CA减少了Ly6c单核细胞、脂肪组织M1巨噬细胞和下丘脑小胶质细胞的激活。这些结果表明，CA可减弱外周和下丘脑炎症单核细胞/巨噬细胞系统，并治疗肥胖相关的代谢紊乱。
