Enriched Flavonoid Fraction from Cecropia pachystachya Trécul Leaves Exerts Antidepressant-like Behavior and Protects Brain Against Oxidative Stress in Rats Subjected to Chronic Mild Stress

Abstract

The purpose of this study was to assess the effect of an enriched C-glycosyl flavonoids fraction (EFF-Cp) from Cecropia Pachystachya leaves on behavior, mitochondrial chain function, and oxidative balance in the brain of rats subjected to chronic mild stress. Male Wistar rats were divided into experimental groups (saline/no stress, saline/stress, EFF-Cp/no stress, and EFF-Cp/stress). ECM groups were submitted to stress for 40 days. On the 35th ECM day, EFF-Cp (50 mg/kg) or saline was administrated and the treatments lasted until the 42nd day. On the 41st and 42nd days, the animals were submitted to the splash test and the forced swim test. After these behavioral tests, the enzymatic activity of mitochondrial chain complexes and oxidative stress were analyzed. EFF-Cp reversed the depressive-like behavior induced by ECM. It also reversed the increase in thiobarbituric acid reactive species, myeloperoxidase activity, and nitrite/nitrate concentrations in some brain regions. The reduced activities of the antioxidants superoxide dismutase and catalase in some brain regions were also reversed by EFF-Cp. The most pronounced effect of EFF-Cp on mitochondrial complexes was an increase in complex IV activity in all studied regions. Thus, it is can be concluded that EFF-Cp exerts an antidepressant-like effect and that oxidative balance may be an important physiological process underlying these effects.

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant‐like activity

“…LC‐QTOF analyses were performed to find out the molar mass of EFF‐ Cp flavonoids observed by HPLC/DAD and to obtain detailed structural information about minor compounds not yet identified. The chromatogram obtained (Figure ).showed minority compounds that were probably co‐eluted in separation by HPLC/DAD (Ortmann et al ., ). The major flavonoids were observed in peaks 6 and 7 as isoorientin and its isomer orientin, and isovitexin (peak 10).…”

“…To confirm if the EFF‐ Cp analyzed by LC/QTOF has antidepressant activity, as previously described (Ortmann et al, ), an acute antidepressant activity assay was also performed. The effects of the acute administration of EFF‐ Cp and imipramine on the immobility time are illustrated in Figure (A).…”

“…Studies have shown that C. pachystachya has anti‐inflammatory, cardiotonic, sedative and antioxidant properties (Aragão et al, ; Consolini, Ragone, Migliori, Conforti, & Volonté, ; Hikawczuk, Saad, Guardia, Juarez, & Giordano, ). We have been determining the potential of C. pachystachya in the central nervous system as an antidepressant‐like agent, by studying the effect of the crude extract at 200 and 400 mg/kg in mice submitted to chronic unpredictable stress (Gazal et al, ) and of EFF‐ Cp at 50 and 100 mg/kg in rats subjected to chronic mild stress (Ortmann et al, ). In fact, the achievement of an enriched flavonoid fraction allowed a reduction in the active dose, at four times, assigning technological advantages.…”

“…To obtain the crude extract (CE‐ Cp ), the plant material was dried under air flow ≤35°C, powdered and extracted by Ultra‐Turrax® T25 with ethanol 20% (1: 20, v /v; 6407.11 g ; 5 min). EFF‐ Cp was prepared as previously reported (Ortmann et al, ). CE‐ Cp was partitioned with n ‐butanol, dried under reduced pressure and stirred with Amberlite® XAD‐16.…”

“…Its crude extract, which contains phenolic constituents, particularly flavonoids as major compounds, had protective effects upon brain damage (Gazal et al, , ). These results led us to further development of an enriched C ‐glycosyl flavonoids fraction of C. pachystachya (EFF‐ Cp ) that recently was described with antidepressant‐like behavior in a chronic mild stress protocol (Ortmann et al, ).…”