Efeito da suplementação com o extrato aquoso de Aloysia gratissima (Gillies & Hook.) Tronc. e Rutina em ratos machos e fêmeas com comportamento tipo depressivo: avaliação de parâmetros bioquímicos, oxidativos e inflamatórios

Abstract

The pathophysiology of depression is extremely complex and not yet fully elucidated, but it is known that it interacts with oxidative stress, neurotransmitters, mainly amines, and inflammatory parameters, which are altered in depressed patients and are normalized after treatment. Therefore, the present work aimed to investigate the antidepressant potential of Aloysia gratissima extract (Gillies & Hook.) Troncoso and the flavonoid rutin, as well as a co-treatment of both, both in their acute and subacute administration, in a model of LPS-induced depressive-like behavior in adult Wistar rats, analyzing behavioral, antioxidant, neurotransmitter and inflammatory effects, as well as treatment safety. For this, male and female animals were divided into 6 groups, the depressivelike behavior was induced by a single intraperitoneal administration of LPS (1mg/kg), and they differed in terms of treatment, the negative control received saline (C) , the positive control was given the first choice antidepressant, fluoxetine at a dose of 1mg/kg (F), two groups received different doses of rutin, 50mg/kg (R50) or 100mg/kg (R100), one group was treated with the aqueous extract of A. gratissima 100mg/kg (AG) and the co-treatment received 50mg/kg of extract and 10mg/kg of rutin (AG+R) by gavage for 15 days. Behavioral tests were performed 24h after LPS administration and repeated 24h after the first treatment in both sexes, with only AG showing antidepressant effects in males (p=0.0021, when compared to the previous result itself) in its acute administration. . In females, behavioral tests were still repeated on days 7 and 15 of treatment, at the end of which only R100 showed antidepressant potential (p=0.0296). After 15 days of repeated treatment, oxidative stress parameters were quantified in the blood plasma of females, which demonstrated the antioxidant effect of R100 (p=0.0296) and AG+R (p<0.0001) when compared to F in the test of Carbonyl and R50 (p=0.0130), AG (p=0.0162) and AG+R (p=0.0236) when compared to C in TBARS. The levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8, TNF-α and hsCRP quantified in the hippocampus of guinea pigs were significantly high in C, all treatments were effective in reducing them, highlighting the AG+R, which proved to be as efficient as F in the levels of IL-1β, IL-8, IL-10 and hsCRP and significantly higher in IL-6 (p=0.0046) and TNFα (p< 0.0001). The values of dopamine and serotonin neurotransmitters quantified in the hippocampus were also significantly low in group C, which was remedied by all treatments (p>0.0001), showing a possible antidepressant effect. As for the safety of the treatments, the values found in the leukocyte differential of the animals were not altered in any group, whereas in the print made with the liver of the animals, the values of monocytes found in AG (p<0.0001 for males and females) , AG+R (p<0.0001 for males and females) and R100 (p<0.0001) and R50 (p=<0.0005), only for males, was significantly lower than in C, a trend that followed in the values of inflammatory infiltrates, with AG+R having significantly lower values than C for both males and females (p<0.0001 and p=0.0007), showing a hepatoprotective effect. Therefore, it can be suggested that both the aqueous extract of A. gratissima and the flavonoid rutin, and the joint use of both, have a potential antidepressant-like effect in subacute administrations, given their antioxidant, anti-inflammatory and on the visualized neurotransmitters, in addition to being safe.