Ahmed Hanan H, Essam Reham M, El-Yamany Muhammed F, Ahmed Kawkab A, El-Sahar Ayman E
Department of Pharmacy, Al-Noor University College, Nineveh, Iraq.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo, University, Cairo, Egypt.
Food Funct. 2023 Oct 16;14(20):9265-9278. doi: 10.1039/d3fo02222f.
Depression is a widespread neuropsychiatric illness whose etiology is yet mysterious. Lactoferrin (LF), an iron-binding glycoprotein, is reported to promote neuroprotection through its role in the modulation of oxidative stress and inflammation. The objective of the present research was to evaluate the efficacy of LF against chronic restraint stress (CRS)-induced depressive behavior in rats. Depression was evidenced by a reduced grooming time in the splash test and an increased immobility time in the tail suspension test (TST) and forced swimming test (FST). This effect was also accompanied by reduced GSH and serotonin levels and elevated lipid peroxidation and corticosterone levels in the hippocampus. Additionally, an exaggerated hippocampal inflammatory response was also shown by a rise in NF-κB (p65) and TNF-α levels and a reduced IL-10 level. Moreover, CRS substantially reduced the BDNF content as well as the protein levels of PI3K, Akt, and mTOR while boosting the GSK3β content. Interestingly, LF therapy significantly improved CRS-induced behavioral and biochemical aberrations, an effect which was suppressed upon pretreatment with LY294002 (PI3K inhibitor). This suggests that the antidepressant potential of LF may be mediated through the modulation of the PI3K/Akt/mTOR signaling pathway. Furthermore, LF succeeded in restoring 5-HT and corticosterone levels, diminishing oxidative stress and ameliorating the inflammatory cascades. Therefore, and for the first time, LF might serve as a promising antidepressant drug through targeting the PI3K/Akt/mTOR pathway.
抑郁症是一种广泛存在的神经精神疾病，其病因尚不明确。乳铁蛋白（LF）是一种铁结合糖蛋白，据报道它通过调节氧化应激和炎症发挥神经保护作用。本研究的目的是评估LF对慢性束缚应激（CRS）诱导的大鼠抑郁行为的疗效。在溅水试验中梳理时间减少，在悬尾试验（TST）和强迫游泳试验（FST）中不动时间增加，证明了抑郁状态。这种效应还伴随着海马中谷胱甘肽（GSH）和血清素水平降低，脂质过氧化和皮质酮水平升高。此外，核因子κB（p65）和肿瘤坏死因子-α（TNF-α）水平升高以及白细胞介素-10（IL-10）水平降低也表明海马炎症反应加剧。此外，CRS显著降低了脑源性神经营养因子（BDNF）含量以及磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B（Akt）和哺乳动物雷帕霉素靶蛋白（mTOR）的蛋白水平，同时提高了糖原合成酶激酶-3β（GSK3β）含量。有趣的是，LF治疗显著改善了CRS诱导的行为和生化异常，而用LY294002（PI3K抑制剂）预处理后这种效应受到抑制。这表明LF的抗抑郁潜力可能是通过调节PI3K/Akt/mTOR信号通路介导的。此外，LF成功恢复了5-羟色胺（5-HT）和皮质酮水平，减少了氧化应激并改善了炎症级联反应。因此，LF首次可能通过靶向PI3K/Akt/mTOR途径成为一种有前景的抗抑郁药物。
