The Combination of Natural Molecules Naringenin, Hesperetin, Curcumin, Polydatin and Quercetin Synergistically Decreases SEMA3E Expression Levels and DPPIV Activity in In Vitro Models of Insulin Resistance.
Emanuele Salvatore ScarpaChiara GiordaniAntonella AntonelliMassimiliano PetrelliGiancarlo BalerciaFrancesca SilvettiAlessio PieroniJacopo SabbatinelliMaria Rita RippoFabiola OlivieriGiulia MatacchionePublished in: International journal of molecular sciences (2023)
Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen ® , Mivell, Italy) synergistically decreases expression levels of the pro-inflammatory gene SEMA3E in insulin-resistant HepG2 cells and synergistically decreases DPPIV activity in insulin-resistant Hep3B cells, indicating that the combination of these five phytochemicals is able to inhibit pro-inflammatory and insulin resistance molecular mechanisms and could represent an effective innovative complementary approach to T2DM pharmacological treatment.
Keyphrases
- insulin resistance
- glycemic control
- type diabetes
- skeletal muscle
- adipose tissue
- high fat diet
- metabolic syndrome
- polycystic ovary syndrome
- high fat diet induced
- poor prognosis
- anti inflammatory
- induced apoptosis
- oxidative stress
- weight loss
- drug delivery
- copy number
- combination therapy
- drug induced
- dna methylation
- replacement therapy