Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model

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 andrographo...

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Published in:	Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 271; p. 109678
Main Authors:	Aldurrah, Zenab, Mohd Kauli, Farah Syazwani, Abdul Rahim, Nurhidayah, Zainal, Zurina, Afzan, Adlin, Al Zarzour, Ragdhaa Hamdan, Muhamad Salhimi, Salizawati, Che Zain, Mohamad Shazeli, Zakaria, Fauziahanim
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-09-2023
Subjects:	Andrographis Andrographis paniculata Andrographolide Animals Antidepressive Agents - pharmacology Behavioural test Chromatography, Liquid Chronic unpredictable stress Cortisol analysis Fluoxetine - pharmacology Hydrocortisone Plant Extracts - pharmacology Tandem Mass Spectrometry Toxicity test Zebrafish CUS Cortisol analysis UHPLC-ESI-MS/MS Chronic unpredictable stress Behavioural test Andrographis paniculata Toxicity test OFT Andrographolide HPLC ICH SIT
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Summary:	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 LC50 is 627.99 mg/L, while andrographolide's EC50 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. [Display omitted] •A. paniculata extract and andrographolide reduce stress in CUS zebrafish model•Andrographolide (50 mg/kg, i.p.) acute treatment significantly reduce cortisol level in whole-body CUS zebrafish.•EC50 of single administration andrographolide (i.p.) determined as 26.915 mg/kg, based on cortisol analysis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1532-0456 1878-1659
DOI:	10.1016/j.cbpc.2023.109678