Literature‐Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji‐Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo
Ga‐Ram Yu, Seungjun Lee, Da-Hoon Kim, Dong‐Woo Lim, Hyuck Kim, Won‐Hwan Park, Jai‐Eun Kim
Abstract
Relatively high proportions of proinflammatory M1‐like macrophages in tissues may lead to vascular impairment and trigger numerous diseases including atherosclerosis‐related cardiovascular disease (CVD). Jisil Haebaek Gyeji‐tang (JHGT), a polyherbal decoction, is traditionally used to treat various human ailments including chest pain, angina, and myocardial infarction. In the present study, we investigated the anti‐inflammatory effects of JHGT on lipopolysaccharide‐ (LPS‐) stimulated M1 macrophage polarization generated via the mitogen‐activated protein kinases (MAPKs) pathway in RAW 264.7 mouse macrophages. The reducing power of JHGT was also investigated using DAF‐FA DA in a zebrafish model. JHGT significantly reduced inflammatory mediator levels, including iNOS, COX2, TNF‐ α , IL‐6, and IL‐1 β , as compared with LPS‐stimulated controls in vitro and ex vivo. Furthermore, JHGT suppressed the ERK1/2, JNK, and p38 MAPK pathways and reduced p‐I κ B α levels and the nuclear translocation of NF‐ κ B in RAW 264.7 cells. In addition, treatment with JHGT significantly reduced the NO levels in LPS‐treated zebrafish larva ex vivo. Our findings show the potent anti‐inflammatory properties of JHGT are due to its suppression of MAPK signaling, NF‐ κ B translocation, and M1 macrophage polarization.