Abstract
Background:
Hypoxia during pregnancy generates oxidative stress that alters the growth and development of the human fetus. Insulin-like growth factor-I (IGF-1) receptors are essential for normal fetal growth. Asiatic acid in Centella asiatica (CA) has antioxidant properties to prevent growth impairment in hypoxia.
Aims:
This study aimed to investigate the effect of asiatic acid on the morphological development of an intermittent hypoxia zebrafish embryo model and analyse molecular docking prediction in insulin-like growth factor-1 receptor (IGF-1R) signalling.
Methods:
Embryos of zebrafish at 2 hours postfertilization (hpf) were assigned to control negative (C), intermittent hypoxia (IH), and combination IH and CA extract groups consisting of 1.25 (IHCA1), 2.5 (IHCA2), and 5 (IHCA3) µg/ml. Hypoxia treatment (conducted 4 hours/day) and CA extract were administered for 3 days (2 - 72 hpf). The parameters of body length and head length were evaluated at 3, 6, and 9 days postfertilization (dpf). The data were analysed by a two-way ANOVA (P<0.05). Molecular docking was performed to explore the binding affinity of asiatic acid to IGF-1R by Molegro Virtual Docker ver.5 software.
Results:
The body length and head length of embryos in the IH and treatment groups (IHCA) were shorter than those in the control group at 3 dpf (p<0.05). However, the body length was more prolonged in the IHCA1 group, but the head length was longer in the IHCA2 group than in the IH group at 6 and 9 dpf. Molecular docking showed the reliable interaction of asiatic acid with IGF-1R signalling in an IH animal model.
Conclusion:
The administration of CA extract benefits intermittent hypoxia through the development and growth of zebrafish embryos at a dose of 2.5 to 5 µg/ml. Asiatic acid has a binding affinity for IGF-1R signalling.

Key words: Asiatic acid, Centella asiatica, Zebrafish embryo, Morphology, IGF-1R