Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Metabolic Profiling and Gene Expression Analyses of Purple-Leaf Formation in Tea Cultivars (Camellia sinensis var. sinensis and var. assamica).

Purple-leaf tea cultivars are known for their specific chemical composition that greatly influences tea bioactivity and plant resistance. Some studies have tried to reveal the purple-leaf formation mechanism of tea by comparing the purple new leaves and green older leaves in the same purple-leaf tea cultivar. It has been reported that almost all structural genes involved in anthocyanin/flavonoid biosynthesis were down-regulated in purple-leaf tea cultivars when the purple new leaves become green older leaves. However, anthocyanin/flavonoid biosynthesis is also affected by the growth period of tea leaves, gradually decreasing as new tea leaves become old tea leaves. This leads to uncertainty as to whether the purple-leaf formation is attributed to the high expression of structural genes in anthocyanin/flavonoid biosynthesis. To better understand the mechanisms underlying purple-leaf formation, we analyzed the biosynthesis of three pigments (chlorophylls, carotenoids, and anthocyanins/flavonoids) by integrated metabolic and gene expression analyses in four purple-leaf tea cultivars including Camellia sinensis var. sinensis and var. assamica. Green-leaf and yellow-leaf cultivars were employed for comparison. The purple-leaf phenotype was mainly attributed to high anthocyanins and low chlorophylls. The purple-leaf phenotype led to other flavonoid changes including lowered monomeric catechin derivatives and elevated polymerized catechin derivatives. Gene expression analysis revealed that 4-coumarate: CoA ligase (4CL), anthocyanidin synthase (ANS), and UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT) genes in the anthocyanin biosynthetic pathway and the uroporphyrinogen decarboxylase (HEME) gene in the chlorophyll biosynthetic pathway were responsible for high anthocyanin and low chlorophyll, respectively. These findings provide insights into the mechanism of purple-leaf formation in tea cultivars.