Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2023-02, Vol.264, p.109501-109501, Article 109501
• Main Authors: Zakaria, Fauziahanim, Akhtar, Muhammad Tayyab, Wan Norhamidah, Wan Ibrahim, Noraini, Abu Bakar, Muhamad, Azira, Shohaimi, Shamarina, Maulidiani, Ahmad, Hafandi, Ismail, Intan Safinar, Ismail, Nor Hadiani, Shaari, Khozirah
• Format: Article
• Language: English
• Subjects: 1H NMR; Antidepressive activity; Centella asiatica; Metabolomics; Reserpine; Zebrafish
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2022.109501

Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment. [Display omitted] •C.asiatica and its triterpenoids compounds showed stress-alleviation in a reserpine-induced stress zebrafish model•8 metabolites were predicted to be responsible for the anti-stress effect of C. asiatica, including ß-hydroxyisovaleric acid, leucine, and threonine.•Valine, leucine and isoleucine biosynthesis was predicted as a metabolic pathway involved in the stress-alleviating action.