Bromelain Ameliorates Atherosclerosis by Activating the TFEB-Mediated Autophagy and Antioxidant Pathways

Bromelain, a cysteine protease found in pineapple, has beneficial effects in the treatment of inflammatory diseases; however, its effects in cardiovascular pathophysiology are not fully understood. We investigated the effect of bromelain on atherosclerosis and its regulatory mechanisms in hyperlipidemia and atheroprone apolipoprotein E-null (apoe(-/-)) mice. Bromelain was orally administered to 16-week-old male apoe(-/-) mice for four weeks. Daily bromelain administration decreased hyperlipidemia and aortic inflammation, leading to atherosclerosis retardation in apoe(-/-) mice. Moreover, hepatic lipid accumulation was decreased by the promotion of cholesteryl ester hydrolysis and autophagy through the AMP-activated protein kinase (AMPK)/transcription factor EB (TFEB)-mediated upregulation of autophagy- and antioxidant-related proteins. Moreover, bromelain decreased oxidative stress by increasing the antioxidant capacity and protein expression of antioxidant proteins while downregulating the protein expression of NADPH oxidases and decreasing the production of reactive oxygen species. Therefore, AMPK/TFEB signaling may be crucial in bromelain-mediated anti-hyperlipidemia, antioxidant, and anti-inflammatory effects, effecting the amelioration of atherosclerosis.

Automated summary

Bromelain, a cysteine protease found in pineapple, has been found to have beneficial effects in the treatment of inflammatory diseases. In this study, the effects of bromelain on hyperlipidemia and atherosclerosis in mice were investigated. It was found that daily administration of bromelain improved hyperlipidemia, reduced aortic inflammation, and slowed down the progression of atherosclerosis. The mechanisms underlying these effects involve the promotion of cholesteryl ester hydrolysis, autophagy, and antioxidant capacity through the AMPK/TFEB signaling pathway.