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 (IGF-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-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.

Centella asiatica extract ameliorates deoxygenation-induced neurological dysfunction in zebrafish larvae

“…By shielding against damage from oxygen shortage, antioxidants are pivotal in preserving neurotransmission functions and neuroplasticity governed by BDNF and VGLUT1. Research by Ariani et al ., (2023a) , indicates that CA enhances the growth and development of hypoxia-induced zebrafish larvae, showcasing its beneficial role in neural development under hypoxic stress.…”

“…The level of hypoxia can be adjusted by altering the oxygen concentration, achieving total hypoxia for a specific duration. In this process, zebrafish embryos are exposed to deficient levels of dissolved oxygen (less than 2 mg/l) in hypoxia chambers ( Ariani et al ., 2023a ). In prior research, zebrafish embryos have been placed in hermetically sealed environments or hypoxia chambers, where the oxygen levels can be precisely controlled to induce complete hypoxia for specified durations.…”

“…In prior research, zebrafish embryos have been placed in hermetically sealed environments or hypoxia chambers, where the oxygen levels can be precisely controlled to induce complete hypoxia for specified durations. According to Ariani et al . (2023a) , the embryos are exposed to low dissolved oxygen levels (below 2 mg/l) in these chambers during this procedure.…”