Laboratório de Avaliação de Substâncias Bioativas, Departamento de Ciências Naturais, Universidade Regional de Blumenau, Blumenau, Santa Catarina, Brazil.
Behav Pharmacol. 2020 Jun;31(4):397-406. doi: 10.1097/FBP.0000000000000549.
The pathophysiology of depression includes glucocorticoids excess, glutamatergic excitotoxicity, and oxidative stress impairment. Previous study demonstrated Morus nigra L. leaves extract and syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid), its major phenolic compound, administered orally for 7 days, decreased the immobility time in the tail suspension test, without locomotor alteration. Therefore, the purpose of this study was to investigate the antidepressant-like effects, antioxidant effects, and neuroprotective effects of M. nigra leaves extract and syringic acid in an animal model of depression induced by corticosterone. Herein, corticosterone administered in male Swiss mice, 60-90 days of age, at 20 mg/kg, once a day, for 21 days, was effective to induce depressive-like phenotype. This alteration was accompanied by the increase of oxidative stress markers (lipid peroxidation, nitrite, and protein carbonyl) and the decrease in nonprotein thiols level, besides impairment in the hippocampus. Conversely, the treatment with M. nigra leaves extract (10 mg/kg), syringic acid (1 mg/kg), or fluoxetine (10 mg/kg), administered once a day for the last 7 days of the corticosterone treatment, was able to abolish the behavioral alterations elicited by corticosterone, reinforcing evidence of the M. nigra leaves extract and syringic acid having antidepressant-like effect. Both treatments also exerted antioxidant property in the mice's brain, reducing the amount of oxidative stress and abolishing the corticosterone-induced damage in the hippocampal slices. In addition, the treatments protected the hippocampus against the damage induced by the association between corticosterone administration and glutamate excess. In conclusion, M. nigra leaves extract and syringic acid revoke depressive-like behavior induced by corticosterone via inhibition of oxidative stress and hippocampal damage.
抑郁症的病理生理学包括糖皮质激素过多、谷氨酰胺能兴奋毒性和氧化应激损伤。先前的研究表明，桑树叶提取物和丁香酸（4-羟基-3,5-二甲氧基苯甲酸），其主要的酚类化合物，口服给药 7 天，可以减少悬尾试验中的不动时间，而不会改变运动能力。因此，本研究旨在探讨桑树叶提取物和丁香酸在皮质酮诱导的抑郁动物模型中的抗抑郁作用、抗氧化作用和神经保护作用。在此，将皮质酮以 20mg/kg 的剂量每天一次施用于 60-90 天大的雄性瑞士小鼠，共 21 天，有效诱导了类似抑郁的表型。这种改变伴随着氧化应激标志物（脂质过氧化、亚硝酸盐和蛋白质羰基）的增加和非蛋白巯基水平的降低，以及海马损伤。相反，桑树叶提取物（10mg/kg）、丁香酸（1mg/kg）或氟西汀（10mg/kg）治疗，每天一次，在皮质酮治疗的最后 7 天给药，能够消除皮质酮引起的行为改变，进一步证明了桑树叶提取物和丁香酸具有抗抑郁作用。两种治疗方法还在小鼠大脑中发挥了抗氧化作用，减少了氧化应激的数量，并消除了皮质酮诱导的海马切片损伤。此外，这些治疗方法还保护了海马免受皮质酮给药和谷氨酸过多引起的损伤。总之，桑树叶提取物和丁香酸通过抑制氧化应激和海马损伤，逆转了皮质酮诱导的类似抑郁的行为。
