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No therapeutic options currently exist for nonalcoholic fatty liver disease (NAFLD). Although commonly prescribed for cardiovascular diseases, Danshen (Salvia miltiorrhiza Bunge) has been used historically in folk medicines against chronic liver diseases, but its potential in NAFLD therapy remains uncertain. Here we reported that Tanshinone IIA (TAN-IIA), a principal constituent of Danshen, effectively ameliorated experimental NAFLD via transactivation of AMP-activated protein kinase. Using a mouse model, we established that tanshinone IIA effectively attenuated high-fat-diet induced obesity, hepatomegaly and liver steatosis. Mechanistically, we found that β2-adrenergic receptor (β2-AR) was down-regulated in liver tissues of obese mice. Tanshinone IIA might function as a β2-AR agonist, increase the intracellular cAMP levels, and turn on liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK)-acetyl-CoA carboxylase 2 (ACC2) signaling axis to promote fatty acid oxidation. Collectively, tanshinone IIA might merit investigation as a potential therapeutic agent for NAFLD especially in those patients with obesity. |
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Keywords:NAFLD; Tanshinone IIA; β2-adrenergic receptor; AMP-activated protein kinase |
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