Investigating the efficacy of bioactive compounds of the bitter orange plant on uremic pruritus using molecular docking study

Uremic pruritus is a frequent symptom in patients with chronic kidney disease, which affects about one-third of dialysis patients and greatly reduces their quality of life. Using drugs derived from natural plants can be an alternative way to limit and treat uremic pruritus in kidney patients. This research was conducted to evaluate the antipruritic potential of bioactive compounds of Bitter orange. A molecular docking simulation was performed on the nine natural components of Bitter orange against the active binding sites of four protein receptors related to the itching mechanism. The results showed that the selected compounds could inhibit kappa-opioid receptors 4DJH, 6VI4, 6B73, and G protein-coupled receptor 5ZTY well and have a stronger inhibitory effect compared to the anti-itch drug Gabapentin. According to the binding scores (DS) ranging from -8.72 to -4.88, and inhibition constants (Ki), the best antipruritic activities belong to Nobiletin, Caryophyllene, Naringenin, and Tangeretin ligands. The binding results showed that the natural compounds of orange could be considered a valuable source for inhibiting uremic pruritus.