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Improvement of hyperglycemia through dietotherapy/herbal remedy is an effective approach to treating diabetes. In this study, mulberry leaf, famous for silkworm’s special food and therapeutic value without any side effects, alleviated diabetes by attenuating NEFA signaling and modulating intestinal microflora. Mulberry leaf treatment significantly reduce fasting blood-glucose and HbA1c, ameliorate the blood lipid profile and improve insulin resistance in streptozotocin-induced diabetic rats. Mechanistically, we found that mulberry leaf inhibited NEFA signaling by reducing downstream signaling in the NEFA pathway, further verified by reduced PKC and improved cellular energy homeostasis based on restored expression of PGC-1α, AK2, OXPHOS and adiponectin. Mulberry leaf treatment also restored the phyla  Bacteroidetes  and  Proteobacteria  and class  Clostridia , which were associated with insulin resistance and diabetes. Our findings reveal that mulberry leaf is an edible with therapeutic potential for diabetes and may provide a novel dietotherapy/herbal remedy to the treatment of diabetes.

Mulberry leaf alleviates streptozotocin-induced diabetic rats by attenuating NEFA signaling and modulating intestinal microflora