Atividade antidiabética da 4-Metoxichalcona isolada e nanoencapsulada

Abstract

Diabetes mellitus, a metabolic disorder resulting from defects in insulin secretion or production, has become a serious public health problem worldwide. Given the implications of metabolic alterations caused by diabetes on society, economy, and quality of life, the search for new therapeutic alternatives for this disease is of utmost importance. In this context, the present study aimed to evaluate the antidiabetic activity of isolated 4-methoxychalcone (MPP) and its nanoencapsulated formulation (NC), through in silico, in vitro, and in vivo assays. Initially, MPP was synthesized using the Claisen-Schmidt condensation reaction and subsequently characterized and quantified by NMR and mass spectrometry. The nanoencapsulation of MPP resulted in a stable and sustained release formulation with favorable characteristics, including a monomodal distribution with a size of 187±3.85 nm, zeta potential of -19.9 ± 0.72 mV, polydispersity index of 0.21 ± 0.007, and conductivity of 0.041 ± 0.004 mS. This formulation demonstrated stability over a wide range of temperatures (10 ˚C to 80 ˚C) and pH (1 to 5). MPP showed promising results, demonstrating no toxicity both in vitro and in vivo. Furthermore, it exhibited hypoglycemic effects in both healthy and diabetic mice during the oral glicose tolerance test (TTOG), although it did not have the same effect in the oral sucrose tolerance test (TTOS). Oral administration of both isolated MPP and its nanoencapsulated formulation demonstrated hypoglycemic effects in diabetic mice after 7 weeks of treatment. The glycemia levels obtained with the MPP-containing nanocapsule (NC10 = 166±58) at a dose of 10 mg/kg bw, metformin (MET200 = 199±64), and MPP (MPP200 = 123±44) at a dose of 200 mg/kg bw were statistically equivalent to the non-diabetic group (GN = 121±15), indicating that nanoencapsulation potentiated the antidiabetic effect of MPP by 20 times. Additionally, an antiglycation effect was observed in vitro, and these results were confirmed by the reduction of HbA1c levels (%) in the MET200, MPP200, and NC10 groups, reaching levels comparable to the non-diabetic group (GN). Importantly, glycemic control was achieved without causing hepatic damage, as evidenced by the low malondialdehyde concentrations (µmol/g) and liver histology. These results are of great significance, as MPP is a low-cost and readily available molecule. The development of an active nanoformulation containing this molecule proves to be an excellent therapeutic option for diabetes treatment. Thus, this study significantly contributes to the search for new pharmacological approaches in the fight against this chronic metabolic disease. However, further investigations and clinical trials are necessary to fully validate the therapeutic potential and safety of this nanoformulation, enabling its clinical application and potential as an effective medication for diabetes mellitus treatment.Diabetes mellitus, a metabolic disorder resulting from defects in insulin secretion or production, has become a serious public health problem worldwide. Given the implications of metabolic alterations caused by diabetes on society, economy, and quality of life, the search for new therapeutic alternatives for this disease is of utmost importance. In this context, the present study aimed to evaluate the antidiabetic activity of isolated 4-methoxychalcone (MPP) and its nanoencapsulated formulation (NC), through in silico, in vitro, and in vivo assays. Initially, MPP was synthesized using the Claisen-Schmidt condensation reaction and subsequently characterized and quantified by NMR and mass spectrometry. The nanoencapsulation of MPP resulted in a stable and sustained release formulation with favorable characteristics, including a monomodal distribution with a size of 187±3.85 nm, zeta potential of -19.9 ± 0.72 mV, polydispersity index of 0.21 ± 0.007, and conductivity of 0.041 ± 0.004 mS. This formulation demonstrated stability over a wide range of temperatures (10 ˚C to 80 ˚C) and pH (1 to 5). MPP showed promising results, demonstrating no toxicity both in vitro and in vivo. Furthermore, it exhibited hypoglycemic effects in both healthy and diabetic mice during the oral glicose tolerance test (TTOG), although it did not have the same effect in the oral sucrose tolerance test (TTOS). Oral administration of both isolated MPP and its nanoencapsulated formulation demonstrated hypoglycemic effects in diabetic mice after 7 weeks of treatment. The glycemia levels obtained with the MPP-containing nanocapsule (NC10 = 166±58) at a dose of 10 mg/kg bw, metformin (MET200 = 199±64), and MPP (MPP200 = 123±44) at a dose of 200 mg/kg bw were statistically equivalent to the non-diabetic group (GN = 121±15), indicating that nanoencapsulation potentiated the antidiabetic effect of MPP by 20 times. Additionally, an antiglycation effect was observed in vitro, and these results were confirmed by the reduction of HbA1c levels (%) in the MET200, MPP200, and NC10 groups, reaching levels comparable to the non-diabetic group (GN). Importantly, glycemic control was achieved without causing hepatic damage, as evidenced by the low malondialdehyde concentrations (µmol/g) and liver histology. These results are of great significance, as MPP is a low-cost and readily available molecule. The development of an active nanoformulation containing this molecule proves to be an excellent therapeutic option for diabetes treatment. Thus, this study significantly contributes to the search for new pharmacological approaches in the fight against this chronic metabolic disease. However, further investigations and clinical trials are necessary to fully validate the therapeutic potential and safety of this nanoformulation, enabling its clinical application and potential as an effective medication for diabetes mellitus treatment.