3,4-O-Isopropylidene shikimic acid

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

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

METHODS AND RESULTS:
3,4-O-Isopropylidene shikimic acid (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.
CONCLUSIONS:
ISA inhibited TNF-alpha-stimulated PMN-HUVEC adhesion and expression of ICAM-1.

Journal of Traditional Chinese Medical Sciences, 2014,1(2):120-5.

3,4-Oxo-isopropylidene-shikimic acid promotes adiopkine expression during murine 3T3-L1 fibroblast differentiation into adipocytes[Reference: WebLink]

3,4-O-Isopropylidene shikimic acid (ISA), a derivative of shikimic acid, has exhibited ameliorative effect on cognitive impairment in experimental animal models of dementia.
METHODS AND RESULTS:
This study investigated the effect of ISA on lipid accumulation and adipokine secretion during differentiation of 3T3-L1 fibroblasts to adipocytes.ISA promoted 3T3-L1 fibroblast differentiation to adipocytes and increased triglyceride content by 26%. On mechanistic levels, ISA increased expressions of C/EBP β, PPAR γ, C/EBP α, aP2 and FAS. Moreover, ISA stimulated expressions of adipokines secreted by adipocytes, including adiponectin, leptin, and resistin.
CONCLUSIONS:
These findings demonstrated that ISA promoted adipogenesis by up-regulating expressions of C/EBP β, PPAR γ, C/EBP α, aP2 and FAS, and also stimulated adipokines during adipocyte differentiation. Further study should clarify the relationship between stimulation of adipokines and cognitive enhancing effect of ISA.

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

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

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

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

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

3,4-Oxo-isopropylidene-shikimic acid (3,4-O-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.
METHODS AND RESULTS:
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.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.

Chinese Journal of Pharmacology Toxicology, 2002, 16(4):270-2.

Effect of 3,4-oxo-isopropylidene shikimic acid on brain edema and energy metabolism in rats subjected to middle cerebral artery thrombosis[Reference: WebLink]

To investigate whether the improvement effect of 3,4-O-Isopropylidene shikimic acid(ISA) on the ischemic injury is related to the improvement of energy metabolism and the abatment of brain edema.
METHODS AND RESULTS:
Adopt a middle cerebral artery thrombosis (MCAT) model induced by FeCl3 to determine the brain tissue water content, Na+, K+, -ATPase activity and energy charge, the latter was measured with HPLC. ISA was administered ig instantly after MCAT for the first time, and 1 h later for the second time. ISA 200 mg·kg-1 ig decreased the water content of brain tissue; ISA 100 and 200 mg·kg-1 ig increased the energy charge and ISA 50, 100 and 200 mg·kg-1 ig increased the Na+, K+-ATPase activity in rat brain tissue.
CONCLUSIONS:
ISA relieves the brain edema of rats subjected to MCAT by improving the energy metabolism and Na+, K+-ATPase activity in rat brain tissue.

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

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

Context 3,4-Oxo-isopropylidene-shikimic acid (3,4-O-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. To investigate the anti-inflammatory, analgesic and antioxidant activities of ISA.
METHODS AND RESULTS:
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.
CONCLUSIONS:
Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.