Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA(2) activity.
The Casearia sylvestris SW (Flacourtiaceae) is utilized in folk medicine (Brazil and all Latin American) to treat several pathologic processes as inflammation, cancer, microbial infection and snake bites. Studies showed that C. sylvestris aqueous extract can inhibit many toxic effects caused by snake venoms (or caused by phospholipase A(2) isolated) from different species, mainly of Bothrops genus. Inhibition of enzymatic and myotoxic activities, decrease of edema formation and increase of the survival rate of rats injected with lethal doses of bothropic venoms are some toxic effects inhibited by C. sylvestris. In this study, four ellagic acid derivatives from aqueous extracts of C. sylvestris were isolated, characterized, and tested against effects from both total venom and PLA(2) (Asp 49 BthTX-II) from the venom of Bothrops jararacussu. The isolated compounds were as follows: ellagic acid (A), 3'-O-methyl ellagic acid (B), 3,3'-di-O-methyl ellagic acid (C), 3-O-methyl-3',4'-methylenedioxy ellagic acid (D). The inhibition constant values (Ki) for enzymatic activity, as well the IC(50) values found in the edematogenic and myotoxic activities, indicate that the ellagic acid is the best inhibitor of these activities, while compounds C and D are the substances with lowest capacity on inhibiting these same effects. Our results show that the presence of hydroxyls at position 3 or 3' (compounds A and B) increases the capacity of these derivatives on inhibiting these toxic effects. However, the presence of methoxyl groups at position 3 or 3' reduced, but did not completely inhibit the capacity of compounds C and D on inhibiting all the toxic effects studied.
Da Silva
Saulo L
SL
Campus Avançado de Divinópolis, Universidade Fed. de São João Del Rei, CEP 35501-296 Divinópolis, MG, Brazil. biomol2@hotmail.com
Calgarotto
Andrana K
AK
Chaar
Jamal S
JS
Marangoni
Sérgio
S
D000818:Animals; D000997:Antivenins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D037821:Casearia / Q000737:chemistry*; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004610:Ellagic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008956:Models, Chemical; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry
C534594:3'-O-methylellagic acid; C534595:3-O-methyl-3',4'-methylenedioxyellagic acid; D000997:Antivenins; D003435:Crotalid Venoms; D010936:Plant Extracts; D004610:Ellagic Acid; C050401:3,3'-di-O-methylellagic acid; D010741:Phospholipases A