2 Mechanisms of Chinese medicines and formulae
2.1 NF-κB signaling pathway
By modulating the expression of KLF2 and the NF-κB signaling pathway in HUVECs, Yiqi-Huoxue granule can inhibit PAI-1 and TF, exhibiting considerable antithrombotic action(Wu et al., 2019). Xiao-Zhi formula can reduce atherosclerotic plaques(Li et al., 2021c), control blood lipid levels and serum TMAO levels, and increase reverse cholesterol transport in macrophages by increasing the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1(Mao et al., 2012; Gao et al., 2018), thus suppressing inflammation. Through MAPK, ERK5/STAT3, and AKT/NF-κB p65 signaling pathways, Taoren Honghua drug mitigate atherosclerosis and exert anti-inflammatory effects(Wang et al., 2020b). By reducing the expression of the AP-1 and AKT/NF-κB signaling pathways, Suxiao Jiuxin Pill suppresses CD137(L i et al., 2011). The Shexiang Baoxin Pill can decrease lipid absorption and increase lipid outflow. Shenmai Fang decreases the mRNA and protein expressions of IL-1, IL-6, TNF-α, and intercellular adhesion molecules and reduces lactate dehydrogenation enzyme content in the supernatant of lipopolysaccharide-injured cardiac microvascular endothelial cells to play an anti-inflammatory role.
2.2 NRF2 pathway
BuYangHuanWu decoction promotes revascularization in HLI db/db mice by targeting antioxidant, anti-inflammatory, and angiogenesis via the AKT/GSK3β/NRF2 pathway(Liu et al., 2020a; Bao et al., 2021).Salvia miltiorrhiza extract stimulates HO-1 expression via the PI3K/Akt-MEK1-Nrf2 pathway(Lee et al., 2012), which lowers intracellular ROS generation and protects cells from oxidative stress-induced cell damage(Guo et al., 2021). The alcohol extract of Schisandra chinensis decreased the aortic plaque area, adjusted blood lipid levels, increased antioxidant enzyme activity, reduced malondialdehyde levels, up-regulated the expressions of Nrf-2 and HO-1, and decreased oxidized LDL, endothelin-1, and thromboxane B2 levels while increasing 6-ketoprostaglandin F1 levels(Chen et al., 2018).
2.3 ABCA1 pathway
The PPAR-LXR-ABCA1 pathway is involved in lipid regulation and inflammatory activity in Fufang Guanxinkang. Hirudo nipponicaextraction can significantly reduce endothelial cell inflammatory injury and the development and death of macrophage foam cells by regulating the LOX-1/LXR-α/ABCA1 pathway(Lu et al., 2019a), avoiding atherosclerosis. Polypeptides in Hirudo nipponica could be the active ingredients(Xiong et al., 2015; Lu et al., 2019b).
TABLE 2 | Mechanisms of Chinese medicines and formulae