Asiatic acid in Centella asiatica extract towards morphological development in an intermittent hypoxia intrauterine embryo model and molecular prediction pathway of insulin-like growth factor-1 receptor signalling

Abstract

Background: Hypoxia during pregnancy generates oxidative stress that alters the growth and development of the human fetus. Insulin-like growth factor-1 (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 (IH) zebrafish embryo model and analyze molecular docking prediction in IGF-1 receptor (IGF-1R) signaling. Methods: Embryos of zebrafish at 2 hours postfertilization (hpf) were assigned to control negative (C), 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 analyzed by a two-way analysis of variance (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 signaling in an IH animal model. Conclusion: The administration of CA extract benefits IH through the development and growth of zebrafish embryos at a dose of 2.5–5 µg/ml. Asiatic acid has a binding affinity for IGF-1R signaling.