3,4-O-Isopropylidene shikimic acid

Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.[Pubmed:27609150]

Pharm Biol. 2016 Oct;54(10):2282-7.

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 mug/mL, respectively. Discussion and conclusion Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.

Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.[Pubmed:22476587]

Dig Dis Sci. 2012 Aug;57(8):2045-54.

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The findings of this study demonstrate the protective effect of ISA on experimental colitis, probably due to an antioxidant action.

[Experimental studies on the anti-thrombosis effect of 3,4-oxo-isopropylidene-shikimic acid].[Pubmed:12579816]

Yao Xue Xue Bao. 2002 Apr;37(4):245-8.

AIM: To study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) against arteriovenous shunt and middle cerebral artery thrombosis (MCAT) in rats. METHODS: 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. RESULTS: 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. CONCLUSION: ISA inhibited thrombosis by anti-platelet-aggregation.

3,4-oxo-isopropylidene-shikimic acid inhibits adhesion of polymorphonuclear leukocyte to TNF-alpha-induced endothelial cells in vitro.[Pubmed:14769217]

Acta Pharmacol Sin. 2004 Feb;25(2):246-50.

AIM: To examine the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) on human polymorphonuclear leukocyte (PMN) adhesion to human umbilical vein endothelial cells (HUVEC) and explore its mechanism. METHODS: Adhesion of PMN to HUVEC was measured by rose bengal staining assay. Cell-ELISA and RT-PCR methods were used to examine the expression of adhesion molecules ICAM-1. Cell viability was detected with MTT assay. RESULTS: ISA (1-100 micromol/L) effectively reduced PMN adhesion to TNF-alpha-induced HUVEC with the inhibitory rate from 17.2 % to 53.5 %, and exerted no effect on PMN adhesion to normal HUVEC. Adhesion molecule ICAM-1 surface protein and mRNA expression induced by TNF-alpha (400 kU/L) were significantly inhibited by ISA. In addition, the cell viability of HUVEC was unchanged 48 h after treatment with ISA. CONCLUSION: ISA inhibited TNF-alpha-stimulated PMN-HUVEC adhesion and expression of ICAM-1.