Efeito do extrato aquoso e de nanopartículas poliméricas contendo sementes de Syzygium cumini sobre complicações do diabetes mellitus in vitro e in vivo

Abstract

In the long term, diabetic patients have impaired cardiovascular system, as well as an imbalance in the immune system, which leads to increased susceptibility of these in contracting fungal infections. Diabetes mellitus (DM) may also lead to a change in levels of inflammatory mediators such as those belonging to the purinergic and cholinergic systems, cytokines and nitric oxide (NO). Syzygium cumini is a medicinal plant widely used by the population in the treatment of DM, whose seeds are source of high concentrations of phytochemical compounds with relevant pharmacological actions. New drug delivery systems such as polymeric nanoparticles, can enhance the therapeutic index and improving stability of plant extracts. Considering the few studies on the interrelationship of these systems with fungal infection in DM, the use of S. cumini against DM complications and the development of new forms of use of this plant, the aim of this study was to use the aqueous seed extract of S. cumini (ASc) in the development of a polymeric nanoparticle (NPASc) and to evaluate pharmacological activities of both formulations on biochemical and inflammatory parameters of DM complications developed in vitro and in vivo, as well as to identify possible toxic effects of NPASc compared with ASc. The development of NPASc was successful, as it demonstrated characteristics compatible with nanometric systems. ASC and NPASc had a high concentration of flavonoids and phenolic compounds, besides the great antioxidant scavenger potential in the DPPH test, FRAP and against the oxidation of LDL particles, proving that the NPASc formulation was able to maintain the properties of the extract. NPASc improved ASc antifungal activity in vitro against Candida guilliermondii and C. haemulonii. No toxicity was observed for ASc, NPASc and NPB in the Artemia salina lethality test and in the analyzed parameters related to acute toxicity in mice. An increase in the biochemical parameters and proinflammatory cytokines was observed in serum and urine, in the serum activity of platelet ectonucleotidases and in NO levels, as well in ADA, DPP-IV acetylcholinesterase activities and in NO levels in lymphocytes in the groups with DM and DM followed by C. albicans infection. The same was observed compared to the activity of ADA and NO levels, TBARS and AOPP in kidney, liver and pancreatic tissues. It is noteworthy that the group of animals infected with C. albicans showed high levels of serum creatinine, pro-inflammatory cytokines and an increase in the activity of purinergic enzymes. ASc and NPASc were able to act on different routes related to the inflammatory system, such as the reduction in ectonucleotidase activities, in regulating the levels of cytokines and NO, in reducing oxidative stress and mitigating the levels of biochemical parameters in the samples. Therefore, we conclude that the changes found in diabetic rats during fungal infection may be related to inflammatory processes and both ASc as NPASc can contribute to a better understanding and applicability in the use of this plant against DM complications.