Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats

Abstract

Ethnopharmacological relevance: The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico.

Aim of the study: To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats.

Materials and methods: Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion.

Results: The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG.

Conclusion: The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups and prostaglandins.

Keywords: 2′; 5′-Dideoxyadenosine (PubChem CID: 65166); Carbenexolone (PubChem CID: 636402); Chuchupate; Cimetidine (PubChemCID: 2756); DL-Propargylglycine (PubChem CID: 95575); Diazoxide (Pub ChemCID: 25014811); Diligustilide; Diligustilide (PubChem CID: 70698035); Forskolin (PubChem CID: 47936); Gastroprotection; Glibenclamide (PubChem CID: 3488); Indomethacin (PubChem CID: 3715); Ligusticum porteri; N-ethylmaleimide (PubChemCID: 4362); NaHS (PubChem CID: 16211346); Osha; Phthalides; l-NAME (PubChem CID: 135193).