br Epidemiological evidence There are some epidemiological a

Epidemiological evidence There are some epidemiological and clinical studies related to the myricetin on DM. Several reports state that myricetin is associated with reduced risk of DM. It was proposed that myricetin was a primitive flavonoid in Chrysobalanaceae family used for traditional medicine to control the glycemia of diabetic patients in northern Brazil [13,14]. As part of Finnish Mobile Clinic Health Examination Survey, information on habitual food consumption from a random sample of 10,054 participants suggested that the risk of type 2 mdm2 inhibitor (T2DM) might be lower due to higher intake of dietary myricetin [10]. In the United States, researchers used a composition, including myricetin, as an application for treating DM and metabolic disorders [15,16]. Nevertheless, the intake of myricetin still reveals a neutral effect. The follow-up study (333,905 person-years) of a large cohort of US middle-aged and older women in the Women\'s Health Study did not provide a strong support for the hypothesis that high intake of myricetin could protect against the development of T2DM (RR: 0.95; 95% CI: 0.81, 1.12; p for trend=0.38) [17]. These contradictory conclusions may be explained by racial and gender differences, irrational DM and diet assessment, insufficient myricetin dose, short therapeutic duration, or poor timing for supplementation initiation. Therefore, studies are still needed to address the pharmaceutical actions and mechanisms of myricetin in this regard. Although the epidemiological evidences are weak, in vitro and animal studies provide the evidence in support of the hypoglycemic effect of myricetin. In the present review, the connection between myricetin and DM is focused on the basis of current studies. The underlying mechanisms have also been discussed, which will provide possible guidance during the treatment of DM.
As mentioned above, DM is characterized by chronic hyperglycemia and the maintenance of normoglycemia is one of primary treatment goals. Increasing evidences have confirmed that myricetin can regulate glycemia in in vitro and animal studies [18–20]. It was reported that myricetin could significantly attenuate hyperglycemia through promoting glucose uptake in soleus muscle and liver, and enhancing hepatic glycogen synthase I activity and glycogen synthesis in hepatocytes of diabetic rats [18,19]. Moreover, myricetin might modulate glucose and fructose transport in Xenopus laevis oocytes by inhibiting the expression of apical, or luminal, facing-facilitated glucose transporter 2 (GLUT2), a major pathway of sugar absorption [20]. As a result, myricetin may inhibit or delay glucose absorption and can reveal substantial impact on the management of normoglycemia. These findings not only support the hypothesis that myricetin can reduce hyperglycemia and ameliorate glycogen metabolism, but also stimulate the exploration of underlying mechanisms of myricetin on anti-diabetic function.
Conclusion The rapidly increasing prevalence of DM in all parts of the world, coupled with increasing life expectancy, will continue to challenge the resourcefulness of scientists and clinicians in refining existing therapies and developing new approaches to control DM. A multitude of studies have been performed utilizing the beneficial properties of myricetin in cultured cells and diabetic animals. Based on current results and our knowledge, it is clear that myricetin has powerful effect at the cellular level and offers a great deal of promise as a novel approach for the prevention and management of DM and its complications. However, a wide diversity of questions remain open, further in vitro and animal studies are still highly desired for fully understanding of the identification of new molecular targets for protection against DM. Moreover, randomized trials should be conducted to determine whether myricetin can be recommended as a dietary strategy for reducing the risk of DM development in individuals with high-risk diabetes or as an early treatment of DM patients.