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Biochemical and Molecular Actions of Nutrients

Mulberry (Morus alba L.) Leaves and Their Major Flavonol Quercetin 3-(6-Malonylglucoside) Attenuate Atherosclerotic Lesion Development in LDL Receptor-Deficient Mice¹

Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Izumo City, Shimane 693-8501 and ^* Shimane Institute for Industrial Technology, Matsue City, Shimane 690-0816, Japan

²To whom correspondence should be addressed. E-mail: shiwaku{at}med.shimane-u.ac.jp.

The effects of dietary consumption of mulberry (Morus alba L.) leaves and their major flavonol glycoside, quercetin 3-(6-malonylglucoside) (Q3MG), on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidative modification, was studied in LDL receptor-deficient (LDLR–/–) mice. Male mice aged 8 wk were randomly assigned to 4 groups (control, quercetin, Q3MG, and mulberry). The control group was fed an atherogenic-diet containing 3 g cholesterol and 15 g cocoa butter/100 g. The other experimental groups were fed the same atherogenic diet supplemented with 0.05 g quercetin/100 g for the quercetin group, 0.05 g Q3MG/100 g for the Q3MG group, and 3 g dried mulberry-leaf powder/100 g for the mulberry group. The mice were fed their respective diets for 8 wk. The susceptibility of LDL to oxidative modification was significantly decreased in the Q3MG- and mulberry-treated mice, as evidenced by the 44.3 and 42.2% prolongation of the lag phase for conjugated diene formation compared with that of the control mice. The atherosclerotic lesion area in both the Q3MG- and mulberry-treated mice was significantly reduced by 52% compared with that of the controls. However, in the quercetin group, no protective effects were observed against LDL oxidation or atherosclerotic lesion formation. In conclusion, mulberry leaves attenuated the atherosclerotic lesion development in LDLR–/– mice through enhancement of LDL resistance to oxidative modification, and these antioxidative and antiatherogenic protective effects were attributed mainly to Q3MG, the quantitatively major flavonol glycoside in mulberry leaves.

KEY WORDS: • mulberry • quercetin 3-(6-malonylglucoside) • LDL oxidation • atherosclerosis • LDLR–/– mice

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