Efeitos do extrato rico em polifenois da folha de SYZYGIUM CUMINI (L.) SKEELS sobre o diabetes induzido por estresse oxidativo

Abstract

Oxidative stress contributes to the development and progression of diabetes complications. Natural antioxidants such as polyphenols can reduce or prevent the oxidative damage caused to the pancreatic islets through the attenuation of oxidative stress. Syzygium cumini (L.) Skeels (Myrtacea) is a imported specie from the Indian subcontinent and cultivated throughout the Brazilian territory that has high concentration of polyphenols in its different parts. Among its medicinal properties are: anti-inflammatory, cardioprotective, anti-neoplastic, anti-hyperglycemic activity, among others, mainly described for its seeds. For your terapeutical potential, S. cumini has been used over about 130 years for the control of diabetes, however, there are controversies its efficacy of S. cumini in in-vivo trials. Thus, the objective of this work was to evaluate the antidiabetic and antioxidant effects of the Polyphenol-Rich extract (PESc) from S. cumini leaves. Initially, we report different mechanisms responsible for the cardiometabolic properties of S.cumini as inhibition of HMG-CoA, stimulation to insulin secretion, increase of the expression of GLUT-4 are described for polyphenols. Next, we prepare the ERP from the leaves of S .cumini. These were submitted to maceration using alcohol: water (7: 3) resulting in the crude hydroalcoholic extract (EHB). The EHB was partitioned with increasing polarity solvents (chloroform and ethyl acetate). The acetate phase was concentrated and lyophilized generating the PESc. Rattus norvegicus adults (60 days) received alloxan (150 mg / kg, ip) for induction of type 1 diabetes. These were radominated and divided into 3 groups (control, treated prior to alloxan injection and treated before and after treatment alloxan). After the treatment with PESc (50 mg / kg), the animals presented a marked reduction in glycemic and lipidemic levels, as well as a reduction in insulin resistance, especially in the previously treated group. Then we quantified total phenols by Prussian Blue method and flavonoids by the aluminum chloride method. The polyphenol content was 71.78 ± 8.57 GAE / 100 g and the flavonoid concentration was 8.21 ± 0.42 QE / 100 g. To verify which polyphenols were associated with the anti-diabetic effects observed with the treatment using S.cumini we determined the chemical profile of the PESc by HPLC-MS employing gradient elution. Five phenolic compounds were identified in PESc: gallic acid, myricetin 3-α-arabinopyranoside, myoxycetin deoxyhexoside, myricetin and quercetin. PESc showed significant antioxidant activity in the inhibition assays of DPPH•, ABTS•+ and lipoxygenase (LOX) (IC50 values: 3.88 ± 1.09, 5.98 ± 1.19, 27.63 ± 8.47 μg / mL, respectively). DPPH• and lipoxygenase, the antioxidant activity of ERP was equivalent to that exhibited by the standards tested (gallic acid, myricetin and quercetin). PESc also stimulated insulin secretion in β-cells (INS-1E) non-toxic. We have also collected literature results showing that polyphenols (most abundant components in S.cumini) are promising lipid-lowering agents by partially inhibiting hepatic microsomal triglyceride transfer protein (MTP), a chaperone resident in the endoplasmic reticulum that plays a key role in the assembly and secretion of VLDL. Thus, we suggest in this work that the route of inhibition of hepatic MTP may be responsible for the ati-hypertriglyceridemic effect of S.cumini. Together, the data obtained in this study reinforce the anti-diabetic, antioxidant and hypolipidemic potential of S.cumini.