4.7 Article

New Mechanisms of Bromelain in Alleviating Non-Alcoholic Fatty Liver Disease-Induced Deregulation of Blood Coagulation

期刊

NUTRIENTS
卷 14, 期 11, 页码 -

出版社

MDPI
DOI: 10.3390/nu14112329

关键词

bromelain; non-alcoholic fatty liver disease; blood coagulation; intrinsic pathway; extrinsic pathway; fibrinolytic system

资金

  1. Ministry of Science and Technology of Taiwan [108-2811-B-002-542, 108-2320-B-002-032-MY]

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Bromelain has anticoagulant effects on non-alcoholic fatty liver disease-induced blood coagulation deregulation by inhibiting the activation of the coagulation cascade, decreasing the stability of clots, and promoting fibrinolytic activity. The findings suggest the potential therapeutic value of bromelain for thrombosis-related diseases.
Bromelain, an enzyme extracted from the stems of pineapples, exerts anticoagulant effects; however, the regulatory mechanisms are not fully understood. Here, we aimed to investigate the effects of bromelain on non-alcoholic fatty liver disease (NAFLD)-induced deregulation of blood coagulation and the underlying molecular mechanisms. C57BL/6 mice were fed a high-fat diet (HFD), with or without bromelain (20 mg/kg/day) administration, for 12 weeks. Treatment with bromelain decreased thrombus formation in the liver and prolonged HFD-induced shortened prothrombin, activated partial thromboplastin, and fibrinogen times. Moreover, liquid chromatography-mass spectrometry/mass spectrometry and Western blot analysis showed that bromelain inhibited NAFLD-induced activation of the intrinsic, extrinsic, and common pathways by upregulating the protein expression of antithrombin III, serpin family G member 1, and alpha 1-antitrypsin, and downregulating the protein expression of fibrinogen in the liver and plasma. Bromelain also upregulated the level of plasminogen and downregulating factor XIII expression in the liver and plasma. Collectively, these findings suggest that bromelain exerts anticoagulant effects on NAFLD-induced deregulation of coagulation by inhibiting the activation of the coagulation cascade, decreasing the stability of clots, and promoting fibrinolytic activity. The present study provides new insights into the potential therapeutic value of bromelain for the prevention and treatment of thrombosis-related diseases.

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