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SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity.
J Physiol Pharmacol. 1998 Mar; 49(1):83-98.JP

Abstract

Flavonois derived from sophoradine are known to exhibit gastroprotective and ulcer healing properties but the mechanism of these actions are not fully explained. In this study we determined the effect of novel flavonoid derivative of sophoradin, SU-840, on gastric secretion, acute gastric lesions induced by acid-independent (100% ethanol) or acid-dependent ulcerogens (acidified aspirin (ASA) and stress) and on the healing of chronic gastric ulcers in rats. The number and area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using H2-gas clearance technique and the mucosal samples were excised for the measurement of PGE2 generation by radioimmunoassay. Exposure of rats to 100% ethanol or acidified ASA (100 mg/kg dissolved in 0.2 N HCl) or to water immersion and restraint stress (WRS) resulted in hemorrhagic gastric lesions accompanied by drastic fall in the GBF as compared to the values recorded in vehicle treated gastric mucosa. SU-840 (6.25-100 mg/kg i.g.) reduced dose-dependently gastric acid and pepsin secretion and gastric lesions induced by ethanol, acidified ASA and WRS, the dose inhibiting by 50% of these lesions (ID50) being 28, 17 and 95 mg/kg, respectively. This protection required much lower doses as compared to original sofalcone or sucralfate and was obtained when this sofalcone-like drug was administered via parenteral route. The protective effect of SU-840 given i.g. or i.p. was accompanied by a marked rise in the GBF and mucosal generation of PGE2. The protective activity of SU-840 showed longer duration of the action than that of sofalcone and occurred in the doses that failed to affect gastric secretion. Pretreatment with indomethacin to suppress endogenous PG reversed completely the protective and hyperemic effects of SU-840 against ethanol and stress induced damage whereas L-NNA, a potent inhibitor of NO-synthase, failed to affect protection but completely abolished the hyperemia evoked by this agent. NEM, an sulfhydryl alkylator, significantly attenuated the protective and hyperemic effects of SU-840 suggesting that endogenous sulfhydryls are involved in these effects. Seven day treatment with SU-840 accelerated significantly healing rate of chronic gastric ulcers and increased the GBF at the ulcer crater and ulcer margin. These effects were reversed by L-NNA and further restored by the addition to L-NNA of L-arginine, a substrate for NO-synthase. We conclude that SU-840 exhibits gastroprotective and hyperemic activity against acid-independent and acid-dependent irritants involving endogenous PG, sulfhydryls and hyperemia mediated by NO and 2) enhancement in gastric blood flow in the ulcer area mediated by NO appears to be essential for the acceleration of the ulcer healing by SU-840.

Authors+Show Affiliations

Department of Physiology, Jagiellonian University School of Medicine, Cracow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9594413

Citation

Brzozowski, T, et al. "SU-840, a Novel Synthetic Flavonoid Derivative of Sophoradin, With Potent Gastroprotective and Ulcer Healing Activity." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 49, no. 1, 1998, pp. 83-98.
Brzozowski T, Konturek SJ, Kwiecien S, et al. SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity. J Physiol Pharmacol. 1998;49(1):83-98.
Brzozowski, T., Konturek, S. J., Kwiecien, S., Pajdo, R., Drozdowicz, D., Sliwowski, Z., & Muramatsu, M. (1998). SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 49(1), 83-98.
Brzozowski T, et al. SU-840, a Novel Synthetic Flavonoid Derivative of Sophoradin, With Potent Gastroprotective and Ulcer Healing Activity. J Physiol Pharmacol. 1998;49(1):83-98. PubMed PMID: 9594413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity. AU - Brzozowski,T, AU - Konturek,S J, AU - Kwiecien,S, AU - Pajdo,R, AU - Drozdowicz,D, AU - Sliwowski,Z, AU - Muramatsu,M, PY - 1998/5/22/pubmed PY - 1998/5/22/medline PY - 1998/5/22/entrez SP - 83 EP - 98 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J Physiol Pharmacol VL - 49 IS - 1 N2 - Flavonois derived from sophoradine are known to exhibit gastroprotective and ulcer healing properties but the mechanism of these actions are not fully explained. In this study we determined the effect of novel flavonoid derivative of sophoradin, SU-840, on gastric secretion, acute gastric lesions induced by acid-independent (100% ethanol) or acid-dependent ulcerogens (acidified aspirin (ASA) and stress) and on the healing of chronic gastric ulcers in rats. The number and area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using H2-gas clearance technique and the mucosal samples were excised for the measurement of PGE2 generation by radioimmunoassay. Exposure of rats to 100% ethanol or acidified ASA (100 mg/kg dissolved in 0.2 N HCl) or to water immersion and restraint stress (WRS) resulted in hemorrhagic gastric lesions accompanied by drastic fall in the GBF as compared to the values recorded in vehicle treated gastric mucosa. SU-840 (6.25-100 mg/kg i.g.) reduced dose-dependently gastric acid and pepsin secretion and gastric lesions induced by ethanol, acidified ASA and WRS, the dose inhibiting by 50% of these lesions (ID50) being 28, 17 and 95 mg/kg, respectively. This protection required much lower doses as compared to original sofalcone or sucralfate and was obtained when this sofalcone-like drug was administered via parenteral route. The protective effect of SU-840 given i.g. or i.p. was accompanied by a marked rise in the GBF and mucosal generation of PGE2. The protective activity of SU-840 showed longer duration of the action than that of sofalcone and occurred in the doses that failed to affect gastric secretion. Pretreatment with indomethacin to suppress endogenous PG reversed completely the protective and hyperemic effects of SU-840 against ethanol and stress induced damage whereas L-NNA, a potent inhibitor of NO-synthase, failed to affect protection but completely abolished the hyperemia evoked by this agent. NEM, an sulfhydryl alkylator, significantly attenuated the protective and hyperemic effects of SU-840 suggesting that endogenous sulfhydryls are involved in these effects. Seven day treatment with SU-840 accelerated significantly healing rate of chronic gastric ulcers and increased the GBF at the ulcer crater and ulcer margin. These effects were reversed by L-NNA and further restored by the addition to L-NNA of L-arginine, a substrate for NO-synthase. We conclude that SU-840 exhibits gastroprotective and hyperemic activity against acid-independent and acid-dependent irritants involving endogenous PG, sulfhydryls and hyperemia mediated by NO and 2) enhancement in gastric blood flow in the ulcer area mediated by NO appears to be essential for the acceleration of the ulcer healing by SU-840. SN - 0867-5910 UR - https://www.unboundmedicine.com/medline/citation/9594413/SU_840_a_novel_synthetic_flavonoid_derivative_of_sophoradin_with_potent_gastroprotective_and_ulcer_healing_activity_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:9594413 DB - PRIME DP - Unbound Medicine ER -