Kobayashi Y, Miyazawa M, Araki M, Kamei A, Abe K, Hiroi T, Hirokawa T, Aoki N, Ohsawa T and Kojima T
Study background: Hypercholesterolemia causes arteriosclerosis, a risk factor for cerebral or myocardial infarctions. Prevention of hypercholesterolemia by improving dietary habits has recently attracted attention in many countries. It has been reported that the leaves of the mulberry plant, Morus alba L., which is commonly used for tea in Asian countries, can ameliorate hypercholesterolemic conditions.
Method: To determine its mechanism of action, we performed gene expression profiling of the liver of mice fed a high-cholesterol diet and a polyphenol-rich mulberry leaf extract containing abundant quercetin and kaempferol for 4 weeks.
Results: The levels of total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in plasma, and level of total cholesterol in the liver were significantly lower in the mice treated with the mulberry leaf extract than that in the control group mice. DNA microarray analysis revealed that mulberry extract downregulated the expression of genes involved in cholesterol biosynthesis, including hydroxymethylglutaryl-CoA reductase gene, and upregulated the transcription of peroxisome proliferator-activated receptor (PPAR)α and γ, transcriptional factors known to regulate lipid metabolism or immunity, and their target genes. Additionally, the mulberry extract stimulated both innate and acquired immunity, including the induction of scavenger and Toll-like receptors and the activation of pathways in various lymphocytes, such as macrophages, eosinophils, neutrophils, natural killer cells, B cells, and T cells.
Conclusion: The results obtained in this study suggest that quercetin and kaempferol in the mulberry leaf induce the activation of PPARα and PPARγ, transcription of Ppara and Pparg genes, and stimulation of PPAR signaling pathways. These phenomena ultimately lead to the reduction of cholesterol synthesis and immunostimulation.
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