Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia. Electronic address: https://twitter.com/zenab_aldurrah.
Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
Comp Biochem Physiol C Toxicol Pharmacol. 2023 Sep;271:109678. doi: 10.1016/j.cbpc.2023.109678. Epub 2023 Jun 8.
Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p < 0.0001) compared to the CUS group. A significant increase in total distance travelled, and contact duration was observed only in the fluoxetine-treated group (t-test, p = 0.0007) and (t-test, p = 0.0207), respectively. A significant increase in highly mobile duration was observed in both treatment groups. Andrographolide (50 mg/kg, i.p.) acute treatment showed a significant reduction in freezing duration (p = 0.0042), duration in a dark area (p = 0.0338) and cortisol level (p = 0.0156) and increased total distance travelled (p = 0.0144). Twenty-six compounds were tentatively characterized by LC-MS/MS method, and andrographolide content is 0.042 μg/g. According to cortisol analysis, A. paniculata's LC is 627.99 mg/L, while andrographolide's EC was determined as 26.915 mg/kg. Further assessment of the cellular and molecular underpinnings of the anti-depressive effect of andrographolide is strongly recommended to evaluate the potential as an antidepressant.
穿心莲（A. paniculata）在啮齿动物模型中显示出抗抑郁作用。斑马鱼最近已成为抗抑郁药物发现研究的一种有价值的补充转化模型。本研究调查了穿心莲提取物和穿心莲内酯在慢性不可预测应激（CUS）-斑马鱼模型中的抗抑郁作用。将四组斑马鱼（每组 10 条，n = 10/组），即对照组、CUS（应激，未处理）、CUS + 穿心莲（100mg/L）和 CUS + 氟西汀（0.01mg/L），在开放场和社会互动测试中进行评估，治疗后 24 小时。在提取物筛选后，评估了穿心莲内酯（5、25 和 50mg/kg，ip）和氟西汀（10mg/kg，ip）的行为和皮质醇分析。在行为研究之前，使用 UHPLC-ESI-MS/MS 对穿心莲提取物进行了急性毒性和表征。与 CUS 组相比，穿心莲（t 检验，p = 0.0234）和氟西汀治疗组（t 检验，p < 0.0001）的冻结持续时间明显减少。仅在氟西汀治疗组中观察到总行进距离和接触持续时间显著增加（t 检验，p = 0.0007）和（t 检验，p = 0.0207）。两个治疗组的高迁移持续时间均显著增加。穿心莲内酯（50mg/kg，ip）急性治疗可显著减少冻结持续时间（p = 0.0042）、在暗区的持续时间（p = 0.0338）和皮质醇水平（p = 0.0156），并增加总行进距离（p = 0.0144）。通过 LC-MS/MS 方法初步鉴定了 26 种化合物，穿心莲内酯含量为 0.042μg/g。根据皮质醇分析，穿心莲的 LC 为 627.99mg/L，而穿心莲内酯的 EC 为 26.915mg/kg。强烈建议进一步评估穿心莲内酯抗抑郁作用的细胞和分子基础，以评估其作为抗抑郁药的潜力。
