Fufang Zhenzhu Tiaozhi (FTZ) suppression of macrophage pyroptosis: Key to stabilizing rupture-prone plaques.

BACKGROUND: Research on the Chinese herbal formula Fufang Zhenzhu Tiaozhi (FTZ) has demonstrated its effectiveness in treating hyperlipidemia and glycolipid metabolic disorders. Additionally, FTZ has shown inhibitory effects on oxidative stress, regulation of lipid metabolism, and reduction of inflammation in these conditions. However, the precise mechanisms through which FTZ modulates macrophage function in atherosclerosis remain incompletely understood. Therefore, this study aims to investigate whether FTZ can effectively stabilize rupture-prone plaques by suppressing macrophage pyroptosis and impeding the development of M1 macrophage polarization in ApoE-/- mice. METHODS: To assess the impact of FTZ on macrophage function and atherosclerosis in ApoE-/- mice, we orally administered FTZ at a dosage of 1.2 g/kg body weight daily for 14 weeks. Levels of interleukin-18 and interleukin-1ß were quantified using ELISA kits to gauge FTZ's influence on inflammation. Total cholesterol content was measured with a Cholesterol Assay Kit to evaluate FTZ's effect on lipid metabolism. Aortic tissues were stained with Oil Red O, and immunohistochemistry techniques were applied to assess atherosclerotic lesions and plaque stability. To evaluate the effects of FTZ on macrophage pyroptosis and oxidative damage, immunofluorescence staining was utilized. Additionally, we conducted an analysis of protein and mRNA expression levels of NLRP3 inflammasome-related genes and macrophage polarization-related genes using RT-PCR and western blotting techniques. RESULTS: This study illustrates the potential therapeutic effectiveness of FTZ in mitigating the severity of atherosclerosis and improving serum lipid profiles by inhibiting inflammation. The observed enhancements in atherosclerosis severity and inflammation can be attributed to the suppression of NLRP3 inflammasome activity and M1 polarization by FTZ. CONCLUSION: The current findings indicate that FTZ provides protection against atherosclerosis, positioning it as a promising candidate for novel therapies targeting atherosclerosis and related cardiovascular diseases.

The Chinese herbal medicine Fufang Zhenzhu Tiaozhi protects against diabetic cardiomyopathy by alleviating cardiac lipotoxicity-induced oxidative stress and NLRP3-dependent inflammasome activation.

BACKGROUND: Fufang Zhenzhu Tiao Zhi (FTZ) formula is a Chinese herbal preparation used in the clinical treatment of disorders of glucolipid metabolism. Given its effective actions on the regulation of lipid dysfunction and its anti-inflammatory and antioxidative effects, we designed this study to investigate the cardioprotective effect and possible mechanism of FTZ in diabetic cardiomyopathy (DCM) mice. METHODS: FTZ was administered to diabetic mice by oral gavage daily at a dose of 1.2 g/kg or 2.4 g/kg bodyweight for 8 weeks. Doppler echocardiography, H&E, and WGA staining were used to evaluate cardiac function and structure in the mice. The levels of proinflammatory cytokines and lipids in serum were detected with corresponding commercial kits. Immunofluorescence staining and flow cytometry were used to detect oxidation damage and pyroptosis in myocardial cells. RT-PCR and western blotting were used to analyze the protein and mRNA expression levels of NLRP3 inflammasome-related genes. RESULTS: Our study indicated that FTZ improved cardiac function, attenuated heart hypertrophy, improved serum lipid and proinflammatory cytokine levels, and restrained oxidative stress and NLRP3 inflammasome-induced inflammatory activities in diabetic mouse hearts. The in vitro data suggested that FTZ suppressed intercellular lipid accumulation as well as palmitic acid (PA)-induced oxidative stress and NLRP3 inflammasome-dependent pyroptosis in cardiomyocytes. CONCLUSION: Our present findings indicate that FTZ inhibits DCM by inhibiting both oxidative stress and NLRP3 inflammasome activation induced by cardiac lipotoxicity.