Maneenet Juthamart, Monthakantirat Orawan, Daodee Supawadee, Boonyarat Chantana, Chotritthirong Yutthana, Kwankhao Pakakrong, Pitiporn Supaporn, Awale Suresh, Chulikhit Yaowared
Graduate School of Pharmaceutical Science, Khon Kaen University, Khon Kaen 40002, Thailand.
Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Pharmaceuticals (Basel). 2021 Jul 9;14(7):659. doi: 10.3390/ph14070659.
Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of , fruit, and the petals of . According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.
重度抑郁症（MDD）是一种常见且使人衰弱的精神疾病，其特征为持续情绪低落、缺乏精力、活动减退、快感缺失、性欲减退以及认知和社交功能受损。然而，由于涉及基因与环境之间的复杂相互作用，MDD的多因素病因在很大程度上仍不明确。Kleeb Bua Daeng（KBD）是一种泰国传统草药配方，一直用于促进大脑健康。它由[植物名称1]地上部分、[植物名称2]果实和[植物名称3]花瓣按1:1:1的比例组成。根据各药用植物的药理活性，KBD具有治疗MDD的良好潜力。本研究在不可预测的慢性轻度应激（UCMS）小鼠模型中研究了KBD的抗抑郁活性。每日给UCMS小鼠施用KBD，通过增加2%蔗糖摄入量改善了快感缺失，并通过减少强迫游泳试验（FST）和悬尾试验（TST）中的不动时间改善了绝望行为，且对运动活动没有任何影响。KBD的作用机制是多模式的。KBD通过上调额叶皮质和海马中脑源性神经营养因子（BDNF）和环磷酸腺苷反应元件结合蛋白（CREB）的mRNA表达来促进神经发生。每日用KBD治疗可通过上调糖皮质激素受体（GR），同时下调血清和糖皮质激素诱导激酶1（SGK1）和FK506结合蛋白5（FKBP5）的mRNA表达，显著逆转UCMS诱导的下丘脑-垂体-肾上腺（HPA）轴失调。KBD治疗还使包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β和IL-6在内的促炎细胞因子表达恢复正常。KBD及其成分提取物在体外对单胺氧化酶（MAO）A和B也表现出抑制作用。KBD的多种抗抑郁作用强调了其作为MDD有效新型治疗方法的潜力。
