title: Insights into tyrosinase inhibition by compounds isolated from Greyia radlkoferi Szyszyl using biological activity, molecular docking and gene expression analysis.
abstract: Greyia radlkoferi ethanol extract and its five compounds were tested for their inhibitory activity against the mushroom tyrosinase enzyme and melanin production on melanocytes. The crude extract showed significant tyrosinase inhibition with IC50of 17.96μg/ml. This is the first report of the isolation of these 5 compounds from Greyia radlkoferi. 2',4',6'-Trihydroxydihydrochalcone showed the highest tyrosinase inhibition at 17.70μg/ml (68.48μM), with low toxicity when compared with crude extract. This compound is therefore, a key component in the crude extract, which is responsible for tyrosinase inhibitory activity. The RT-qPCR indicated that the mechanism of action is most likely post transcriptional. Further, the molecular docking study showed that tyrosinase inhibitory activity depends on interaction of the compound with Cu2+ions at the active site. This is the first report of the tyrosinase inhibitory activity of the G. radlkoferi extract and molecular insights on interaction of its compounds with Cu2+ions as the driving factor for tyrosinase inhibition. These results suggest that the extract of G. radlkoferi and the compound 2',4',6'-trihydroxydihydrochalcone have great potential to be further developed as pharmaceutical or cosmetic agents for use against dermatological disorders associated with melanin.
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Namrita
authors.initials: N
authors.lastname: Lall
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mogapi
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Marco Nuno
authors.initials: MN
authors.lastname: de Canha
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Bridget
authors.initials: B
authors.lastname: Crampton
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Mabatho
authors.initials: M
authors.lastname: Nqephe
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa; Department of Chemistry, University of Western Cape, Private Bag X17, Bellville, 7535 Cape Town, South Africa.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Hussein
authors.affiliation: Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D019684:Magnoliopsida / Q000737:chemistry*; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D014442:Monophenol Monooxygenase
keywords: Gene expression; Greyia radlkoferi; Hyper-pigmentation; Melanin inhibition; Molecular docking; Tyrosinase