|
[PMID]: | 29203373 |
[Au] Autor: | Preciado LM; Rey-Suárez P; Henao IC; Pereañez JA |
[Ad] Endereço: | Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. |
[Ti] Título: | Betulinic, oleanolic and ursolic acids inhibit the enzymatic and biological effects induced by a P-I snake venom metalloproteinase. |
[So] Source: | Chem Biol Interact;279:219-226, 2018 Jan 05. | [Is] ISSN: | 1872-7786 |
[Cp] País de publicação: | Ireland |
[La] Idioma: | eng |
[Ab] Resumo: | Betulinic acid (BA), Oleanolic acid (OA) and Ursolic acid (UA), are pentacyclic triterpenoids with widespread occurrence throughout the plant kingdom, these compounds are widely recognized by their pharmacological and biological properties, such as, anti-tumoral, anti-inflammatory, anti-microbial and hepatoprotective activity. In this work we determined the inhibitory ability of these compounds on the enzymatic, hemorrhagic, myotoxic and edema-inducing activities of Batx-I, a P-I metalloproteinase isolated from Bothrops atrox venom. BA, UA and OA inhibited the proteolytic activity of Batx-I on gelatin with IC values of 115.3, 223.0 and 357.3 µM, respectively. Additionally, these compounds showed inhibition of the hemorrhagic activity of Batx-I in skin with IC 345.7, 643.5 and 1077.0 µM for BA, UA and OA in preincubation experiments. In studies with independent-injection, in which Batx-I was injected and then, at the same site, a concentration of 600 µM of each compound were administered at either 0, 5 or 10 min, BA showed a significant reduction of hemorrhage at 0 and 5 min. In addition, these compounds inhibited myotoxicity and edema-forming activity of Batx-I at 600 µM concentration. Molecular docking studies suggested that these compounds could occupy part of the substrate binding cleft of the enzyme affecting its catalytic cycle. In this manner, triterpenic acids are candidates for the development of inhibitors for the prevention of local tissue damage in snakebite envenomation. |
[Mh] Termos MeSH primário: |
Venenos de Crotalídeos/enzimologia Metaloproteases/metabolismo Ácido Oleanólico/farmacologia Triterpenos/farmacologia
|
[Mh] Termos MeSH secundário: |
Animais Bothrops/fisiologia Edema/induzido quimicamente Edema/prevenção & controle Hemorragia/induzido quimicamente Hemorragia/prevenção & controle Metaloproteases/genética Camundongos Estrutura Molecular Doenças Musculares/induzido quimicamente Doenças Musculares/prevenção & controle Ácido Oleanólico/química Triterpenos/química
|
[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Crotalid Venoms); 0 (Triterpenes); 4G6A18707N (betulinic acid); 6SMK8R7TGJ (Oleanolic Acid); EC 3.4.- (Metalloproteases); P3M2575F3F (ursolic acid) |
[Em] Mês de entrada: | 1801 |
[Cu] Atualização por classe: | 180103 |
[Lr] Data última revisão:
| 180103 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171206 |
[St] Status: | MEDLINE |
|
|
|