Melatonin receptor agonist Piper betle L. ameliorates dexamethasone‑induced early life stress in adult zebrafish

Abstract

Early life exposure to stress has been suggested to be a crucial factor for the development of the brain and its functions. It is well documented that childhood stress is a risk factor for sleep problems in adulthood. Piper betle L. leaf extract (PB) has been used in several traditional medicines to cure various ailments. Recently, PB has been proved to have antidepressant activity. The literature suggests that antidepressants affect the synthesis and release of melatonin through several mechanisms. Thus, this study investigated the potential role of PB for the treatment of sleep disruption after early life stress exposure. Firstly, dexamethasone (DEX) (2 and 20 mg/l for 24 h) was administered to zebrafish larvae on the 4th day post-fertilization (dpf) to induce early life stress. The effects of stress on behaviour during adulthood, melatonin level and stress-related gene expression (nfkb) in the brain were then studied. Next, the possible role of PB (10 and 30 mg/Kg) was studied by measuring its effect on behaviour and by quantifying the expression levels of several melatonin-related (MT1, MT2, aanat1, aanat2) and stress-related (nfkb) genes by qPCR. DEX-treated zebrafish exhibited anxious behaviour, along with a lower level of melatonin and a higher mRNA expression of nfkb. After treatment with PB, a similar effect on behaviour and gene expression levels as the melatonin treatment group (10 mg/kg; positive control) was seen in adult zebrafish. These molecular confirmations of the observed behavioural effects of the PB indicate a possible role in the treatment of early life stress-induced sleep disruption.

Occurrence, Fate, Effects, and Risks of Dexamethasone: Ecological Implications Post-COVID-19

“…DEXAtreated adult zebrafish exhibited anxious behavior, lower melatonin, and higher mRNA expression of the nkfb gene compared to the control. Further, results showed increased MT 2 expression during exposure and the suppression of aanat 2; however, no changes in MT 1 and aanat 1 expressions were observed [102]. Hence, exposure to DEXA in the environment may perturb the expression of genes in, e.g., anti-inflammatory, immunity, and molecular aspects in fish.…”

“…The anti-inflammatory molecule results demonstrated that the immune gene expression of il-1β, cxcl-8, tnf α, and crp was downregulated following DEXA injection on crucian carp (Carassius auratus) [101]. A study by Kumari et al [102] examined the levels of melatoninrelated genes (MT 1, 2, aanat 1, and aanat 2) and the stress-related (nfkb) gene after exposure of adult zebrafish to DEXA at early life and then treatment with Piper betle L. (PB). DEXAtreated adult zebrafish exhibited anxious behavior, lower melatonin, and higher mRNA expression of the nkfb gene compared to the control.…”

Betelvine (Piper betleL.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes

“…The results showed improved levels of melatonin‐related behavioural gene expression (MT1, MT2, aanat1 and aanat2) and stress‐related gene expression (NF‐kB) similar to positive control melatonin. 124 …”

Light Exposure’s Effects on Inactive State Duration and Sleep Latency in Zebrafish (Danio Rerio) Larvae Insomnia Model

“…Light can be used as a continuous stimulus for 24 hours without a dark phase or with 18 hours of light exposure and 6 hours of flashes of light during the dark phase with 2 x 2 minutes (light x dark) or 4 x 1 minute (light x dark) to disturb the fish's sleep. 17 . The light exposure device consisted of an on and off switch, an adapter, a setting button for dark and light, and a light intensity control button.…”