Preventive Effect of Ginkgo biloba Extract (GBB) on the Lipopolysaccharide-Induced Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 via Suppression of Nuclear Factor-.KAPPA.B in RAW 264.7 Cells

Abstract

Nitric oxide (NO) which is produced by inducible nitric oxide synthase (iNOS) is a pro-inflammatory radical and an important biological mediator. 1) prostaglandin E 2 (PGE 2 ), released by arachidonic acid metabolites, is also an important mediator of acute and chronic inflammation, and it is associated with the enzyme, cyclooxygenase-2 (COX-2).2) In addition to these oxygen and arachidonic acid metabolites, tumor necrosis factor-a (TNF-a) acting as a cytokine or inflammatory mediator plays a major role in various inflammatory diseases, including septic shock and rheumatoid arthritis. 3,4) Nuclear factor-kB (NF-kB) appears to play a primary role in the transcriptional regulation of these iNOS, COX-2 and TNF-a gene expressions.5) NF-kB exists as a latent form in the cytoplasm of unstimulated cells and is bound to the inhibitory protein, IkB. 6) Phosphorylation of IkB leads to its degradation and the subsequent translocation of NF-kB to the nucleus where it activates transcriptions of target genes. 7,8) It is noteworthy that the use of medicinal plants or their crude extracts in the prevention and/or treatment of several chronic diseases has been traditionally practiced in different societies worldwide. Moreover, extracts of Ginkgo biloba LINNE (Ginkoaceae) have been used for centuries in traditional Chinese medicine. Today, a standardized extract (EGb 761) is prepared from Ginko biloba leaves and is prescribed commonly in Europe for the treatment of memory disorders, obstructive arteriosclerosis, Alzheimer's disease, ischaemic heart disease, cerebral infarction, aging, and age-related macular degeneration.9-11) Several modes of action of EGb 761 have been described: (1) its effects on the blood circulation, such as its vasoregulatory activity and rheological effects on blood (decreased viscosity, anti-platelet activating factor activity) 11) ; (2) its effects on metabolism changes, such as on neuron metabolism (increased tolerance to anoxia) 9,12,13) ; (3) its inhibition of cell membrane damage caused by free radicals 11,[13][14][15] ; and (4) its gene-regulatory effects, which suggest that it has anticancer activity. 16,17) EGb 761 contains two groups as its main active constituents: 24% flavonol glycoside (ginkgo-flavonol glycosides; quercetin, kaempferol, isorhamnetin) and 6% terpene (bilobalide and ginkgolides A, B, C).18) In the present study, we prepared a standardized Ginkgo biloba extract (GBB), i.e., an extract of Ginkgo biloba leaves standardized in terms of its total terpenes (12Ϯ3%), biflavonoid (4.5Ϯ1.5%), flavonol glycoside (Ͻ8%), and proanthocyanidine (under detection limit) content. The difference between GBB and EGb 761 is that it contains a higher level of terpene, a lower level of flavonol glycoside, and no detectable proanthocyanidine.In the present study, we compared the effects of these Ginkgo biloba extracts (GBB and EGb 761) on lipopolysaccharide (LPS)-induced NO and PGE 2 release. To further explore the possible mechanisms of these inhibitions by GBB, we investigated the expression levels...

Calcium/calmodulin‐dependent protein kinase II regulates cyclooxygenase‐2 expression and prostaglandin E2 production by activating cAMP‐response element‐binding protein in rat peritoneal macrophages

“…In response to stimulants, macrophages produce numerous pro-inflammatory cytokines and secondary mediators, which are pivotal for the innate and adaptive immune responses. 1,2 Uncontrolled expression of the substances can initiate septic shock syndrome, which is characterized as fever, hypotension, disseminated intravascular coagulation and multiple organ failure. 3,4 Among these factors, prostaglandin E 2 (PGE 2 ) is an essential mediator that contributes to vasodilatation, pain and fever.…”

Anti-Inflammatory Effect of Buckwheat Sprouts in Lipopolysaccharide-Activated Human Colon Cancer Cells and Mice

“…TNF-has been identified as the major cytokine mediator in the expression of endotoxicity. 6) LPS-treated culture cells have been used to evaluate the anti-inflammatory effects of various materials, including folk medicines such as Polygonum tinctorium, 7) Cyperus rotundus, 8) Semecarpus anacardium, 9) Ginkgo biloba, 10) and Cryptolepis buchanani, 11) and natural foods such as turmeric, 12) ginger, 13) chicory, 14) and green tea. 15) Although the mechanisms of the anti-inflammatory effects of those materials are different, a wellknown mechanism has been described as inhibition of NF-B activation and NO production caused by antioxidant active compounds.…”

Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST-Pi in rats with hepatocellular carcinoma risk

“…Bao et al [30] reported that EGb could inhibit the production of Cox-2 in myocardial ischemia/reperfusion rats. Park et al [31] found that EGb could inhibit the LPSinduced Cox-2 in macrophage cell line. Our result was inconsistent with that from the studies mentioned above.…”