Zhang Hualin, Li Zhong, Zhou Zhongliu, Yang Hongyan, Zhong Zhiyong, Lou Caixia
School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang 524048, China.
Neurology Department, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China.
Pharmacol Biochem Behav. 2016 Jan;140:17-26. doi: 10.1016/j.pbb.2015.10.018. Epub 2015 Oct 31.
Ginsenoside Rb3 has been proved to have antidepressant-like effects, which possesses 1 xylose and 3 glucose moieties with 20(S)-protopanaxadiol (PPD) as the aglycone. However, it is commonly accepted that orally ingested ginsenosides can be deglycosylated or partially deglycosylated into active derivatives by the intestinal bacteria. To identify potential antidepressant drug candidates, we compared the antidepressant-like activities between ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K (C-K), and PPD. Effects of acute (1-day), short chronic (7-days), and longer chronic treatments (14-days) with these ginsenosides (50 and 100mg/kg, p.o.) on the behavioral changes in the forced swim test (FST), tail suspension test (TST) and open field test were investigated. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels and mouse brain monoamine neurotransmitters 5-HT, NA and DA levels were measured using commercially available competitive enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, C-K showed antidepressant-like activities similar to that of Rb3, and Rg3 displayed antidepressant-like effects at lower dosage and faster time, indicating it has better effects than Rb3, whereas Rh2 and PPD failed to show any effect. Our results also showed, unlike the positive control fluoxetine, Rb3, Rg3 and C-K significantly increased the NA levels in the brain regions of mice exposed to FST but did not affect the 5-HT and DA levels. Moreover, treatment with Rg3 could reverse swim stress-induced increased levels of serum ACTH and corticosterone. These results suggest that C-K and Rg3 are the active deglycosylated derivatives, especially the latter compound, which is more potent than Rb3 and exerts antidepressant-like effects by regulating NA, ACTH and corticosterone levels.
人参皂苷Rb3已被证明具有抗抑郁样作用，它含有1个木糖和3个葡萄糖部分，苷元为20(S)-原人参二醇（PPD）。然而，人们普遍认为口服摄入的人参皂苷可被肠道细菌去糖基化或部分去糖基化成为活性衍生物。为了鉴定潜在的抗抑郁药物候选物，我们比较了人参皂苷Rb3与其四种去糖基化衍生物Rg3、Rh2、化合物K（C-K）和PPD的抗抑郁样活性。研究了这些人参皂苷（50和100mg/kg，口服）急性（1天）、短期慢性（7天）和长期慢性治疗（14天）对强迫游泳试验（FST）、悬尾试验（TST）和旷场试验行为变化的影响。使用市售的竞争性酶联免疫吸附测定（ELISA）试剂盒测量血清皮质酮和促肾上腺皮质激素（ACTH）水平以及小鼠脑单胺神经递质5-HT、NA和DA水平。有趣的是，C-K显示出与人参皂苷Rb3相似的抗抑郁样活性，Rg3在较低剂量和更短时间内表现出抗抑郁样作用，表明它比Rb3效果更好，而Rh2和PPD未显示出任何作用。我们的结果还表明，与阳性对照氟西汀不同，人参皂苷Rb3、Rg3和C-K显著增加了暴露于FST的小鼠脑区中的NA水平，但不影响5-HT和DA水平。此外，用Rg3治疗可逆转游泳应激诱导的血清ACTH和皮质酮水平升高。这些结果表明，C-K和Rg3是活性去糖基化衍生物，尤其是后一种化合物，它比Rb3更有效，并通过调节NA、ACTH和皮质酮水平发挥抗抑郁样作用。
