Hibiscus sabdariffa Linn. Extract Increases the mRNA Expression of the Arcuate Nucleus Leptin Receptor and is Predicted in silico as an Anti-obesity Agent

Background: Leptin is predominant in regulating body weight by stimulating energy expenditure through its neuronal action in the brain. Moreover, it is projected to adipose tissue and induces adipocyte browning by activating the β3-adrenergic receptor (β3AR). However, the expression of leptin receptor (Lep-R) and β3AR in people with obesity is downregulated. Aim: We hypothesized that Hibiscus sabdariffa Linn. extract (HSE) would increase hypothalamus arcuate nucleus (ARC) Lep-R and white adipose tissue (WAT) β3AR mRNA expression in DIO rats. This study also analyzed the potency of H. sabdariffa bioactive compounds as activators of Lep-R and β3AR by an in-silico experiment. Methods: Twenty-four male Sprague-Dawley rats were divided into four groups: Control (standard food), DIO (high-fat diet), DIO-Hib200 (HFD+HSE 200 mg/kg BW), and DIO-Hib400 (HFD+HSE400 mg/kg BW). HSE was administered orally for five weeks, once a day. Results: HSE administration significantly (p <0,05) increased the ARC Lep-R expression. The Lee index significantly decreased to the normal range (≤ 310) with p <0,001 for DIO-Hib200 and p <0,01 for DIO-Hib400. Among 39 bioactive compounds, 5-O-caffeoyl shikimic acid exhibited high free binding scores (-8,63) for Lep-R, and myricetin_3_arabinogalactoside had high free binding scores (-9,39) for β3AR. These binding predictions could activate Lep-R and β3AR. Conclusion: This study highlights that HSE could be a potential therapeutic target for obesity by increasing LepR mRNA and leptin sensitivity, enhancing energy expenditure, and reducing obesity.