Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models.

Abstract

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.

Chios mastic treatment of patients with active Crohn’s disease

“…Even less are the data on the absorption of triterpenes. Glycyrrhetinic acid, the triterpene derivative of glycyrrhizin, has been shown to be bioactive in experimental gastric lesion models [36] and has also been detected in the serum of experimental animals [37] . In conclusion, subjecting CD patients with mild to moderate activity to mastic treatment seems to improve the clinical features of the disease and to regulate inflammation and antioxidant status.…”

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

“…[118] The anti-ulcer effects of saikosaponins have not been studied so far and in most cases the anti-ulcer properties of Bupleurum spp. appear to be attributed only to pectic polysaccharides.…”

Down-regulation of c-FLIP, XIAP and Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction of glycyrrhenitic acid derivatives in leukemia cells

“…Dandan song, 1 Yuan Gao, 2 Rui Wang, 3 Dan Liu, 2 Linxiang Zhao 2 and Yongkui Jing 3, C 12 to oleanolic acid yielded 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) which significantly increased the antitumor activities 12,13 and that methyl esterification of CDDO to methyl-2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) was found to further increase the antitumor activities. [14][15][16] Based on these discoveries, we synthesized GA derivatives by introduction of a cyano group at the position of C 2 and its methyl ester at C 30 carboxylic acid group and yielded two compounds, 2-cyano-3,11-dioxooleana-1,12-dien-30-oic acid (CDODO-11) and methyl 2-cyano-3,11-dioxooleana-1,12-dien-30-oate (CDODO-Me-11).…”