3-4-oxoisopropylideneshikimic-acid and Disease-Models--Animal

Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid (SA). SA is extracted from the dry fruit of Illicium verum Hook. f. (Magnoliaceae), which has been used for treating stomachaches, skin inflammation and rheumatic pain. Objective To investigate the anti-inflammatory, analgesic and antioxidant activities of ISA. Materials and methods Analgesic and anti-inflammatory activities of ISA were evaluated using writhing, hot plate, xylene-induced ear oedema, carrageenan-induced paw oedema and cotton pellets-induced granuloma test, meanwhile the prostaglandin E2 (PGE2) and malondialdehyde (MDA) levels were assessed in the oedema paw tissue. ISA (60, 120 and 240 mg/kg in mice model and 50, 120 and 200 mg/kg in rat model) was administered orally, 30 min before induction of inflammation/pain. Additionally, ISA was administered for 12 d in rats from the day of cotton pellet implantation. The active oxygen species scavenging potencies of ISA (10(-3)-10(-5) M) were evaluated by the electron spin resonance spin-trapping technique. Results ISA caused a reduction of inflammation induced by xylene (18.1-31.4%), carrageenan (7.8-51.0%) and cotton pellets (11.4-24.0%). Furthermore, ISA decreased the production of PGE2 and MDA in the rat paw tissue by 1.0-15.6% and 6.3-27.6%, respectively. ISA also reduced pain induced by acetic acid (15.6-48.9%) and hot plate (10.5-28.5%). Finally, ISA exhibited moderate antioxidant activity by scavenging the superoxide radical and hydroxyl radical with IC50 values of 0.214 and 0.450 μg/mL, respectively. Discussion and conclusion Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Carrageenan; Cotton Fiber; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Granuloma, Foreign-Body; Hot Temperature; Hydroxyl Radical; Indomethacin; Male; Malondialdehyde; Mice, Inbred ICR; Pain; Rats, Sprague-Dawley; Shikimic Acid; Superoxides; Time Factors; Xylenes

Cerebral ischemia-reperfusion (I/R) injury is a secondary injury caused by oxidative stresses and inflammatory responses after recovery from cerebral ischemia. Brain protective drugs were used to reduce the injury. In order to improve the distribution in brain and enhance the brain-protective efficacy, some pharmaceutical technologies were used to achieve brain targeting delivery.. To investigate the physiological disposition of ISA liposome, and provide references for the further study about high-efficacy brain-protective preparations for I/R injury.. Comparative studies were carried out. The pharmacodynamics in t-MCAO model rats were studied first, and then the pharmacokinetics and brain distribution of the two preparations were determined.. At the same dose, the efficacy of ISA liposome was better (P < 0.05). The efficacy was dose dependent, with significant difference of 20 mg/kg (P < 0.01) and indistinctive difference of 10 mg/kg (P = 0.22), compared with vehicle-treated rats. The parameters, T(1/2β), MRT and AUC were different significantly between the two preparations. The enhancement of brain distribution for ISA in the liposome was obvious, with the maximum concentration 7.18 μg/g, while close to zero for the solution group.. ISA liposome could increase the distribution in brain and enhance the efficacy significantly. The results revealed that the liposomal DDS was potential as a novel strategy for the treatment of cerebral I/R injury. In addition, further targeted modification, such as PEG-modified liposomes, which possess a long circulating property in the bloodstream, would further improve the targeting delivery to the brain and lead to more significant efficacy.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Half-Life; Injections, Intravenous; Liposomes; Male; Neurons; Neuroprotective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Shikimic Acid; Tissue Distribution

3,4-Oxo-isopropylidene-shikimic acid (ISA) is a derivative of shikimic acid (SA). SA is extracted from Illicium verum Hook.fil., which has been used in traditional Chinese medicine and used for treating vomiting, stomach aches, insomnia, skin inflammation, and rheumatic pain.. To investigate the effects and the protective mechanism of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats.. Colitis in rats was induced by colonic administration with TNBS. ISA (50, 100, and 200 mg/kg) was administered for 12 days to experimental colitis rats. The inflammatory degree was assessed by macroscopic damage score, colon weight/length ratios (mg/cm), and myeloperoxidase (MPO) activity. Malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS) activities were measured with biochemical methods.. ISA significantly ameliorated macroscopic damage, reduced colon weight/length ratios and the activity of MPO, depressed MDA and NO levels and iNOS activity, and enhanced GSH level, and GSH-Px and SOD activities in the colon tissues of experimental colitis in a dose-dependent manner. Moreover, the effect of ISA (200 mg/kg) was as effective as sulfasalazine (500 mg/kg).. The findings of this study demonstrate the protective effect of ISA on experimental colitis, probably due to an antioxidant action.

Topics: Animals; Colitis, Ulcerative; Colon; Disease Models, Animal; Drug Evaluation, Preclinical; Glutathione; Glutathione Peroxidase; Male; Malondialdehyde; Neutrophil Infiltration; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Shikimic Acid; Superoxide Dismutase; Trinitrobenzenesulfonic Acid

To study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) against arteriovenous shunt and middle cerebral artery thrombosis (MCAT) in rats.. Arteriovenous shunt model was adopted to measure thrombus weight; The neurologic deficit (ND) and the infarct size (IS) of the middle cerebral thrombosis (MCAT) model induced by FeCl3 were observed; The effect of ISA on platelet aggregation rate of rat and rabbit by giving ISA in vivo and in vitro was studied.. ISA 25, 50, 100 and 200 mg.kg-1 ig was shown to reduced the weight of thrombus in arteriovenous shunt model; ISA 50, 100 and 200 mg.kg-1 ig for 2 times in 24 hours, attenuated the ND of rats subjected to MCAT; ISA 100 and 200 mg.kg-1 reduced IS of rats after MCAT by 27.8% and 31.6%, respectively; ISA 50, 100 and 200 mg.kg-1 ig inhibited platelet aggregation of normal rats; ISA 10(-3)-10(-5) mol.L-1, inhibited rabbit platelet aggregation in vitro.. ISA inhibited thrombosis by anti-platelet-aggregation.

Topics: Animals; Brain; Disease Models, Animal; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Male; Platelet Aggregation; Rabbits; Random Allocation; Rats; Rats, Wistar; Shikimic Acid