Effect of Centella asiatica ethanol extract on zebrafish larvae ( Danio rerio) insomnia model through inhibition of Orexin, ERK, Akt and p38 [version 2; peer review: 2 approved, 1 approved with reservations]

• Published in: F1000 research Vol. 13; p. 107
• Main Authors: Afif, Zamroni, Eddy Santoso, Mochammad Istiadjid, Nurdiana, ., Khotimah, Husnul, Satriotomo, Irawan, Kurniawan, Shahdevi Nandar, Sujuti, Hidayat, Iskandar, Dheka Sapti, Hakimah, Annisatul
• Format: Journal Article
• Language: English
• Published: F1000 Research Ltd 01.01.2024
• Subjects: Akt; Centella asiatica; eng; ERK; Insomnia; Orexin; p38; Centella asiatica; Akt; p38; Insomnia; Orexin; ERK
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.141064.2

Background: Insomnia is difficulty initiating or maintaining sleep for at least three nights a week or more and lasting for at least 3 months. One of the molecules that play a role in the circadian rhythm of arousal system is hypocretin/orexin. Orexin activates the p38-MAPK signaling pathway and increases phosphorylated ERK1/2 levels. Centella asiatica (CA) has a role in the signal work of the MAPK/ERK, Akt, and p38 path in many various diseases. Methods: The research method used is true laboratory experimental. The research approach used was randomized control group post-test only. Zebrafish embryos aged 0-7 dpf were used in this study. The treatment group consisted of 5 groups: normal, insomnia, insomnia + 2.5 μg/mL CA, insomnia + 5 μg/mL CA, and insomnia + 10 μg/mL CA. The locomotor motion of zebrafish larvae was observed using Basler cameras on days five-, six- and seven-day post fertilization (dpf), then analyzed by using Western Blot method. Results: The results proved that exposure to CA extract was able to reduce the expression of orexin (91963 ± 9129) and p38 (117425 ± 6398) as an arousal trigger in the sleep-wake cycle, with the most optimal concentration of CA 5 μg/mL. Exposure to CA extract was also able to reduce the expression of ERK (94795 ± 30830) and Akt (60113.5 ± 27833.5) with an optimum concentration of CA 2.5 μg/mL. Conclusion: Exposure to CA extract was able to improve the sleep activity of zebrafish larvae insomnia model by extending the total inactivity time ( cumulative duration) and shortening the duration of first sleep ( latency to first) in light and dark phases through inhibition of orexin, ERK, p38, and Akt.