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.

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.

Obesity has become one of the most important health problems worldwide requiring urgent need for efficient control. Pleurotus citrinopileatus (P. citrinopileatus)—a type of edible mushroom with abundant bioactive molecules—is a promising source for achieving this goal. In the present study, we evaluated the anti‐obesity and hypolipidemic effect of P. citrinopileatus water extract (PWE) using a series of biochemical assays in randomized high‐fat diet‐induced obese (DIO) C57BL/6J mice, which were gavaged daily with low or high levels of PWE (400 or 800 mg/kg of body weight, respectively) in addition to high‐fat diet for 12 weeks. Results showed that PWE significantly reduced the weight gain, fat accumulation, and food intake of DIO mice within 12 weeks. PWE also decreased the serum triglycerides, cholesterol and low‐density lipoprotein, aspartate transaminase, nonesterified fatty acid, and creatinine, but increased high‐density lipoprotein. Additionally, PWE improved the glucose tolerance of mice fed with high fat. From above, we conclude that PWE has great potential as functional foods for management of obesity and/or associated metabolic disorders.