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Different gentian preparations are used as traditional remedies for internal pain control in: Persian traditional medicine (PTM), Chinese traditional medicine (CTM) and Ancient Greek medicine (AGM) from the time of the Roman Empire. Objective: To present a survey of the ethnopharmacological applications of gentians recorded as being used in Eastern and Western traditional medical systems (PTM, CTM and AGM) and their pharmacological effects, chemical composition as well as an in silico investigation of the possible active component/s for the alleviation of internal pain via molecular docking studies. Major traditional medicine literature (PTM, CTM and AGM, 50 AD- 1770) and ethnobotanical studies for the application of gentians were reviewed. Nine European species representing 5 of the 13 sections currently attributed to Gentianawere selected. Chemical compounds and pharmacological activity data of these species were gathered from different databases including Google Scholar, PubChem, PubMed and Web of Science (between 1972 and 2020). The possible active constituents of gentians on visceral pain receptors were investigated, in silico. In all investigated literature, traditional uses of gentian were indicated to have anti-nociceptive effects on visceral pain and possess diuretic action. According to our computational study, acylated flavonoid glycosides, viz. trans-feruloyl-2"-isovitexin (33), trans-feruloyl-2"-isovitexin-4ʹ-O-β-D-glucoside (34), iso-orientin-4'-O-glucoside (38), trans-caffeoyl-2"-iso-orientin-4ʹ-O-β-D-glucoside (39), iso-orientin-2"-O-β-D-glucoside (40) and isoscoparin (41), might be responsible for visceral pain reduction by interacting with the purinergic receptor (P2X3) and vanilloid receptor 1 (TrpV1). This finding shows a good correlation with different traditional gentian uses in Persian, Chinese and European ethnomedicine for visceral pain control.

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