title: Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products, Cross-Linked Structures and Protein Thiols.
abstract: Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1), aromadendrin-8-C-glucopyranoside (2), epicatechin (3), and 2,3',4,5',6-pentahydroxybenzophenone (4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2-4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3) to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1-4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol.
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. hmafifi2013@gmail.com.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. hmafifi2013@gmail.com.
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Abdallah
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. helbassossy@kau.edu.sa.|Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. helbassossy@kau.edu.sa.
authors.forename: Hany
authors.initials: H
authors.lastname: El-Bassossy
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. gamals2001@yahoo.com.|Pharmacognosy Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt. gamals2001@yahoo.com.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Mohamed
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ahalawany2003@yahoo.com.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. ahalawany2003@yahoo.com.
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-Halawany
authors.affiliation: Departement of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia. kzalshal@yahoo.com.
authors.forename: Khalid Z
authors.initials: KZ
authors.lastname: Alshali
authors.affiliation: Departement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia. zmbanjar@yahoo.com.
authors.forename: Zainy M
authors.initials: ZM
authors.lastname: Banjar
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D002417:Cattle; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D029762:Garcinia mangostana / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D066263:Protein Aggregation, Pathological / Q000188:drug therapy*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D001577:Benzophenones; D005419:Flavonoids; D005960:Glucosides; D017127:Glycation End Products, Advanced; D010936:Plant Extracts; D013438:Sulfhydryl Compounds; C435264:garcimangosone D; D012710:Serum Albumin, Bovine; C047723:benzophenone; C080220:aromadedrin; D002392:Catechin; D005947:Glucose
keywords: advanced glycation endproducts; amadori product; aromadendrin; benzophenone; epicatechin; garcimangosone D; mangosteen