Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.
Korean J Physiol Pharmacol. 2013 Oct;17(5):393-403. doi: 10.4196/kjpp.2013.17.5.393. Epub 2013 Oct 17.
Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.
黄芩素（BA）是一种源自黄芩根的植物源性活性黄酮类化合物，已广泛用于治疗与应激相关的神经精神疾病，包括抑郁症。先前的研究表明，反复束缚应激会破坏下丘脑-垂体-肾上腺（HPA）轴的活性，导致抑郁症。BA 对抑郁症影响的行为和神经化学基础仍不清楚。本研究使用强迫游泳试验（FST）和脑神经递质水平的变化来确认 BA 对反复束缚应激诱导的大鼠行为和神经化学变化的影响。雄性大鼠在每日暴露于反复束缚应激（2 h/天）之前 30 分钟接受 10、20 或 40 mg/kg BA（ip）。通过测量血清皮质酮水平和下丘脑促肾上腺皮质释放因子的表达来确认 HPA 轴对反复束缚应激的激活。每日 BA 给药可显著缩短 FST 中的不动时间，增加蔗糖消耗，并使应激相关的海马多巴胺浓度降低恢复到接近正常水平。BA 可显著抑制应激诱导的腹侧被盖区神经元酪氨酸羟化酶免疫反应性和海马脑源性神经营养因子（BDNF）mRNA 表达的降低。综上所述，这些发现表明，在反复束缚应激之前给予 BA 可显著改善无助行为和抑郁症状，可能是通过防止多巴胺和 BDNF 表达的降低。因此，BA 可能是治疗或缓解与抑郁症相关的复杂症状的有效药物。
