Huotan Jiedu Tongluo Formula Inhibits Atherosclerotic Vulnerable Plaques Via the Autophagy-NLRP3 Inflammasome Signaling Pathway

Context: Huotan Jiedu Tongluo Formula (HJTF) has been widely used in the clinic to treat atherosclerotic vulnerable plaques (VP). However, the mechanism of HJTF is not clear. Objective: This study examine the inhibitory effect and potential mechanisms of HJTF against VP in vivo and vitro experiments. Materials and methods: In vivo experiments, given a carotid collar and high-cholesterol diet to establish the ApoE-/- VP model and gave the mice (n=12) HJTF (12.103 g/kg/d) gavaged or Evolocumab Injection (18.2 mg/kg/2w) subcutaneous injection for eight weeks. The Sham group (n=12) and Model group (n=12) were given equivalent volumes of distilled water by gavage. Histological examination of the intimal condition of mouse carotid arteries. ELISA to clarify the expression of inflammatory factors in mouse serum. qRT-PCR and Western blot to clarify NLRP3 inflammasome with autophagy-related indicators in mouse carotid artery tissues. In vitro experiments, applied lipopolysaccharide (LPS) induced inflammatory injury models in RAW 264.7 cells to observe the protective effect of HJTF and its effect on the autophagy-NLRP3 inflammasome signaling pathway in vitro. Result: HJTF could reduce body weight (P<0.05) and blood lipids (P<0.01) in mice with VP. HJTF also inhibited intimal hyperplasia (P<0.001) and collagen fibril deposition (P<0.01) in mice's carotid arteries and reduced the content of MMP-9 (P<0.001). HJTF reduced the content of inflammatory factors IL-1β (P<0.01) and TNF-α (P<0.05) in mice serum and increased the level of autophagy in mice carotid arteries to inhibit the expression of NLRP3 inflammatory vesicles. In vitro experiments demonstrated similar results. Conclusion: HJTF has the potential to inhibit the VP through the autophagy-NLRP3 inflammasome signaling pathway.