Purification of gastroprotective triterpenoids from the stem bark of Amphipterygium adstringens; role of prostaglandins, sulfhydryls, nitric oxide and capsaicin-sensitive neurons.
In this investigation three bioactive compounds, responsible for the gastroprotective property of Amphipterygium adstringens, were purified from an active dichloromethane fraction. These compounds were 3alpha-hydroxymasticadienonic acid, beta-sitosterol and 3- epi-oleanolic acid. The latter was the most active compound (88.8 % of gastroprotection) followed by 3alpha-hydroxymasticadienoic acid and beta-sitosterol (69.8 and 42.5 % of gastroprotection, respectively). Carbenoxolone was used as positive control and it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from the active fraction, but it was unable to inhibit the ethanol-induced gastric lesions. The gastroprotection of the methanol extract was completely inhibited by the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an important role in the gastroprotection of A. adstringens methanol extract on ethanol-induced gastric mucosal lesions and that there is partial participation by prostaglandins and endogenous sulfhydryls. The effect of 3alpha-hydroxymasticadienonic acid was attenuated only by pretreatment with N-ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not participate in the gastroprotection of either the methanol extract or 3alpha-hydroxymasticadienoic acid.
Arrieta
Jesús
J
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, México D.F., México.
Benitez
Javier
J
Flores
Edith
E
Castillo
Carlos
C
Navarrete
Andrés
A
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018547:Plant Stems; D010946:Plants, Medicinal; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012855:Sitosterols / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
D005765:Gastrointestinal Agents; D010936:Plant Extracts; D011453:Prostaglandins; D012855:Sitosterols; D013438:Sulfhydryl Compounds; D014315:Triterpenes; C459620:masticadienonic acid; D009569:Nitric Oxide; D000431:Ethanol; C025473:gamma-sitosterol; D009828:Oleanolic Acid; D002211:Capsaicin