羟基积雪草苷对小鼠抑郁行为和大鼠不同脑区单胺氧化酶活性的影响

目的:研究羟基积雪草苷(madecassoside, MC)对实验小鼠抑郁行为及对大鼠不同脑区单胺氧化酶(monoamine oxidase,MAO)活性的影响.方法:以丙咪嗪为阳性对照药,采用小鼠强迫游泳实验和利舍平拮抗实验,观察MC对小鼠游泳不动时间和利舍平诱导的小鼠体温降低的影响;分别以吗氯贝胺和帕吉林为阳性对照药,测定急性(3 d)和慢性(21 d)给予大鼠MC对不同脑区单胺氧化酶A (monoamine oxidase-A,MAO-A)和单胺氧化酶B(monoamine oxidase-B,MAO-B)活性的影响.结果:(1) MC高、中、低剂量(10、20、40 mg/kg)均可显著减少小鼠的游泳不动时间(P<0.01).(2)低剂量(10 mg/kg)和中剂量(20 mg/kg)均能显著拮抗利舍平诱导的小鼠体温降低(P<0.05),但高剂量(40 mg/kg)对利舍平诱导的小鼠体温降低无显著性影响(P>0.05).(3)急性给药,MC高、中、低剂量均显著降低大鼠海马MAO-A活性(P<0.01),高剂量显著降低下丘脑MAO-A活性(P<0.01),对皮质MAO-A活性无显著性影响(P>0.05);慢性给药,MC对皮质和下丘脑MAO-A 的活性没有显著影响(P>0.05),MC高剂量可显著增加海马MAO-A的活性(P<0.01).(4)急性给药,MC低、中剂量可显著降低大鼠大脑皮质MAO-B的活性(P<0.05),MC低剂量可显著降低下丘脑MAO-B的活性(P<0.05),而MC中剂量显著增加海马MAO-B的活性(P<0.01); 慢性给药,MC高、中、低剂量对不同脑区MAO-B的活性均没有显著影响(P>0.05).结论:MC具有抗抑郁作用,其作用可能与降低脑内MAO的活性有关,急性给药比慢性给药对MAO的影响更为显著,引起这种差异的原因尚需作进一步研究.

Effect of madecassoside on depression behavior of mice and activities of MAO in different brain regions of rats

OBJECTIVE: To evaluate the effects of madecassoside (MC) on the depression behavior of mice and the activities of monoamine oxidase (MAO) in different rat brain regions. METHODS: Imipramine as the positive contrast medicine, effects of MC on the depression behavior of mice were observed by forced swimming test and reserpine antagonist test. Moclobemide and pargyline as the positive controlled medicines, the activities of monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) in different rat brain regions were determined after intragastric administration of MC in 3 different dosages for 3 days or 21 days. RESULTS: (1) The low, middle and high dosages of MC (i.g.) significantly reduced the immobility time of mice in forced swimming test (P<0.05). (2) MC in dosages of 10 mg/kg and 20 mg/kg prevented the lowering of temperature induced by reserpine (P<0.05), while 40 mg/kg had no significant effects on it (P>0.05). (3) With acute administration (3 days), the low, middle and high dosagey of MC (i.g.) significantly inhibited the activity of MAO-A in hippocampus (P<0.01), and the high dosage significantly inhibited the activity of MAO-A in hypothalamus (P<0.01), while the 3 dosages had no significant effects on the activity of MAO-A in cortex (P>0.05). With chronic administration (21 days), MC in 3 dosages had no significant effects on the activities of MAO-A in cortex and hypothalamus (P>0.05), and the high dosage (40 mg/kg) significantly enhanced the activity of MAO-A in hippocampus (P<0.01). (4) With acute administration, MC in dosages of 10 mg/kg and 20 mg/kg significantly inhibited the activity of MAO-B in cortex (P>0.05), and MC in dosage of 10 mg/kg significantly inhibited the activity of MAO-B in hypothalamus (P<0.05), and MC in dosage of 20 mg/kg significantly enhanced the activity of MAO-B in hippocampus (P<0.01). With chronic administration, MC of 3 dosages produced no significant effects on the activities of MAO-B in 3 different rat brain regions (P>0.05). CONCLUSION: These results support the idea that MC produces antidepressant effects through MAO inhibition in rat brain, which seems stronger with acute administration than chronic administration, while its mechanism remains to be further studied.