Abstract
Pterostilbene is a dimethyl ether derivative of resveratrol, less metabolized than its analogue, due to the substitution of two hydroxyl groups with methoxyl groups. Nevertheless, the amounts of pterostilbene phase II metabolites found in plasma and tissues are higher than those of the parent compound. The first aim of this study was to assess whether pterostilbene-4′-O-glucuronide (PT-G) and pterostilbene-4′-O-sulfate (PT-S) were able to prevent triglyceride accumulation in AML12 (alpha mouse liver 12) hepatocytes. This being the case, we aimed to analyze the mechanisms involved in their effects. For this purpose, an in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10 or 25 µM of pterostilbene, pterostilbene-4′-O-glucuronide or pterostilbene-4′-O-sulfate for 18 h. Triglycerides and cell viability were assessed by a commercial kit and crystal violet assay, respectively. Protein expression of enzymes and transporters involved in triglyceride metabolism was analyzed by immunoblot. The results showed for the first time the anti-steatotic effect of pterostilbene metabolites and thus, that they contribute to the preventive effect induced by pterostilbene on steatosis in in vivo models. This anti-steatotic effect is mainly due to the inhibition of de novo lipogenesis.
Highlights
Stilbenes have gained remarkable significance in nutrition research due to their beneficial effects on health [1]
When hepatocytes were treated with the compounds at 25 μM, a trend to reduced amounts of triglycerides was observed in the pterostilbene-40 -O-glucuronide (PT-G) group compared to that treated with the parent compound (PT-G group vs. PT group; p = 0.06; Figure 1D)
Pterostilbene presents an important advantage with regard to its analogue resveratrol, due to the presence of two methoxy groups instead of two hydroxyl groups in its chemical structure
Summary
Stilbenes have gained remarkable significance in nutrition research due to their beneficial effects on health [1]. Resveratrol (trans-3,5,4-trihydroxystilbene) is the most extensively studied example It has shown many positive biological effects against cancer, oxidative stress and inflammation [2,3]. Due to the extensive phase II metabolism that it occurs in intestine and liver [4,5,6], has prompted two interesting lines of research: analyzing the potential biological activities of its metabolites, and investigating resveratrol-derived stilbenes with higher bioavailability. With regard to the first line of research, to date little is known concerning this issue, several studies have shown that resveratrol metabolites show positive effects in cancer [7,8,9], neurodegenerative diseases [10] and type 2 diabetes mellitus [11], and that they can act as anti-inflammatory agents [12].
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