Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, No. 1035 Boshuo Road, Changchun, 130117, China.
Neurochem Res. 2018 Jul;43(7):1371-1382. doi: 10.1007/s11064-018-2552-5. Epub 2018 May 22.
Depression is a major social and health problem worldwide. Compound K (CK), an intestinal metabolite of panaxadiol ginsenosides, has been demonstrated to possess significant pharmacological effects on the central nervous system (CNS). Here, we set up this study to investigate the antidepressant effect of CK, and to explore the potential mechanisms underlying this activity. The behavioral despair model and chronic unpredictable mild stress (CUMS) model were established in mice or rats, respectively. Forced swimming test (FST), tail suspension test (TST) and locomotor activity were performed in mice, while the open-field test, food consumption and sucrose preference were assessed in rats. To investigate the underlying mechanism, the levels of endogenous noradrenaline, dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites in the prefrontal cortex (PFC) and hippocampus were detected by HPLC coupled with electron detector. The dopamine degradation enzyme (COMT and MAO) expression was measured by western blot. The BDNF and NGF expression were investigated by immunohistochemical staining analysis. The results showed CK (10, 30 mg/kg) intragastric administration for 14 days significantly shorten the immobility time in FST and TST, which could be partially reversed by a D1 receptor antagonist Sch23390. For CUMS rats, CK alleviated the depressant-like behaviors, including decreased food consumption, spontaneous locomotor activity and lower sucrose preference, while WAY-100635, a 5-HT receptor antagonist, could attenuate this effect. In addition, CK increased the levels of 5-HT, DA and their metabolites in the PFC and hippocampus of CUMS rats, and could reverse overexpression of MAO in PFC and hippocampus. CK also increased the GSH and GPx activity in the hippocampus and PFC. The IHC results revealed the BDNF and NGF expression were increased in CK-treated rats. The obtained results indicate that CK exhibits antidepressant effects in rodents, which may be due to the regulation of monoamine neurotransmitter concentration, enhancement of antioxidant capacity, as well as increase of neurotrophin expression in the CNS.
抑郁症是全球范围内一个重大的社会和健康问题。化合物 K（CK）是一种肠道代谢产物的人参二醇型皂苷，已被证明对中枢神经系统（CNS）具有显著的药理作用。在这里，我们进行了这项研究，以探讨 CK 的抗抑郁作用，并探索其潜在的作用机制。分别在小鼠或大鼠中建立了行为绝望模型和慢性不可预测轻度应激（CUMS）模型。在小鼠中进行强迫游泳试验（FST）、悬尾试验（TST）和运动活性测试，而在大鼠中评估旷场试验、食物消耗和蔗糖偏好。为了研究潜在的机制，通过高效液相色谱法与电子探测器相结合，检测前额叶皮层（PFC）和海马中的内源性去甲肾上腺素、多巴胺（DA）、5-羟色胺（5-HT）及其代谢物的水平。通过 Western blot 测量多巴胺降解酶（COMT 和 MAO）的表达。通过免疫组织化学染色分析研究 BDNF 和 NGF 的表达。结果表明，CK（10、30mg/kg）灌胃给药 14 天可显著缩短 FST 和 TST 中的不动时间，该作用可被 D1 受体拮抗剂 Sch23390 部分逆转。对于 CUMS 大鼠，CK 减轻了抑郁样行为，包括减少食物消耗、自发运动活性和降低蔗糖偏好，而 5-HT 受体拮抗剂 WAY-100635 可减弱这种作用。此外，CK 增加了 CUMS 大鼠 PFC 和海马中 5-HT、DA 及其代谢物的水平，并可逆转 PFC 和海马中 MAO 的过表达。CK 还增加了海马和 PFC 中的 GSH 和 GPx 活性。免疫组化结果显示 CK 处理的大鼠中 BDNF 和 NGF 的表达增加。研究结果表明，CK 在啮齿动物中表现出抗抑郁作用，这可能是由于调节单胺神经递质浓度、增强抗氧化能力以及增加中枢神经系统中的神经营养因子表达所致。
