Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria; African Centre of Excellence for Drug Research, Herbal Medicine Development and Regulatory Science (ACEDHARS), University of Lagos, Nigeria.
Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria; African Centre of Excellence for Drug Research, Herbal Medicine Development and Regulatory Science (ACEDHARS), University of Lagos, Nigeria.
Neurochem Int. 2022 Sep;158:105379. doi: 10.1016/j.neuint.2022.105379. Epub 2022 Jun 17.
Gymnosporia heterophylla (synonym Maytenus) is widely used in folk medicine for the treatment of various illness including neurological diseases. This study presents the antidepressant-like and anxiolytic-like effects of novel bioactive constituents; 3,4-seco-1-hydroxy-21-oxoolean-3,11-olide (A2), 1β,2β-diacetoxy-9β-benzoyloxy-6α-nicotinoyloxy-β-dihydroagarofuran (A5) as well as known 3-acetoxy-1β-hydroxyLupe-20(29)-ene (selective COX-2; A4) from the aerial parts of G. heterophylla. The antidepressant-like effect was studied using the forced swim test (FST) while the elevated plus maze test (EPMT) and open field test (OFT) were employed for anxiolytic-like effect. Acute treatment with A4 and A5 (0.5, 5 or 10 mg/kg) significantly reduced the duration of immobility and immobile episodes with prolongation of immobility latency in the FST with peak effects observed at 10 and 0.5 mg/kg, respectively. Moreover, antidepressant-like effect of A4 and A5 were relatively better than that of fluoxetine. Conversely, the pretreatment of mice with prazosin (1 mg/kg, α-adrenoceptor antagonist), yohimbine (1 mg/kg; α-adrenoceptor antagonist), or sulpiride (50 mg/kg; dopamine D-receptor antagonist) reversed antidepressant-like effect of A4 and A5 but not WAY 100635 (10 mg/kg, i.p., selective 5-HT receptor antagonist), GR 127935 (5 mg/kg, i.p., selective 5-HT receptor antagonist), metergoline (4 mg/kg, i.p, non-selective 5-HT receptor antagonist), ketanserin (5 mg/kg, i.p., a selective 5-HT receptor antagonist) or p-chlorophenylalanine (pCPA) (100 mg/kg, i.p., tryptophan hydroxylase inhibitor) in the FST. Interestingly, A2, A4 and A5 significantly increased the time spent in the open arms of the EPM suggestive of anxiolytic-like action. Findings from this study showed that the novel β-dihydroagarofuran sesquiterpene alkaloid and triterpenes possesses antidepressant-like and anxiolytic-like effects through enhancement of monoaminergic signaling.
异叶 Gymnosporia（别名 Maytenus）在民间医学中被广泛用于治疗各种疾病，包括神经疾病。本研究介绍了新型生物活性成分；3,4-seco-1-hydroxy-21-oxoolean-3,11-olide（A2）、1β,2β-二乙酰氧基-9β-苯甲酰氧基-6α-烟酰氧基-β-二氢沉香呋喃（A5）以及来自 Gymnosporia heterophylla 地上部分的已知 3-acetoxy-1β-hydroxyLupe-20(29)-ene（选择性 COX-2；A4）的抗抑郁和抗焦虑样作用。使用强迫游泳试验（FST）研究抗抑郁样作用，而高架十字迷宫试验（EPMT）和旷场试验（OFT）用于抗焦虑样作用。急性给予 A4 和 A5（0.5、5 或 10mg/kg）可显著缩短 FST 中的不动时间和不动时间，并延长不动时间潜伏期，其峰值作用分别在 10 和 0.5mg/kg 时观察到。此外，A4 和 A5 的抗抑郁样作用相对优于氟西汀。相反，用哌唑嗪（1mg/kg，α-肾上腺素受体拮抗剂）、育亨宾（1mg/kg；α-肾上腺素受体拮抗剂）或舒必利（50mg/kg；多巴胺 D 受体拮抗剂）预处理小鼠可逆转 A4 和 A5 的抗抑郁样作用，但 WAY 100635（10mg/kg，ip，选择性 5-HT 受体拮抗剂）、GR 127935（5mg/kg，ip，选择性 5-HT 受体拮抗剂）、麦角乙脲（4mg/kg，ip，非选择性 5-HT 受体拮抗剂）、酮色林（5mg/kg，ip，选择性 5-HT 受体拮抗剂）或对氯苯丙氨酸（pCPA）（100mg/kg，ip，色氨酸羟化酶抑制剂）则不能逆转 A4 和 A5 的抗抑郁样作用。有趣的是，A2、A4 和 A5 显著增加了 EPM 中开放臂的停留时间，提示具有抗焦虑样作用。这项研究的结果表明，新型β-二氢沉香呋喃倍半萜生物碱和三萜类化合物具有抗抑郁和抗焦虑样作用，通过增强单胺能信号。
