Short communicationEvaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells
Introduction
A body of evidence suggests that prostaglandins (PGs) and nitric oxide (NO) are involved in various pathophysiological processes including inflammation and carcinogenesis, and inducible isoforms of cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) are mainly responsible for the production of large amounts of these mediators (Schmidt and Walter, 1994, Simon, 1999).
Two isoforms of COX, designated COX-1 and COX-2, have been known, and catalyze the biosynthesis of PGs from arachidonic acid (Vane et al., 1998). COX-1 is constitutively expressed in most tissues and seems to be responsible for housekeeping roles for normal physiological functions. In contrast, COX-2 is not detectable in most normal tissues, but is induced by pro-inflammatory cytokines, growth factors, oncogenes, carcinogens, and tumor promoters, implying a role for COX-2 in both inflammation and control of cell growth (Dean et al., 1991, Oshima et al., 1996, Subbaramaiah et al., 1996). Thus, compounds that inhibit the activity or expression of COX-2 might be an important target for cancer chemoprevention or antiinflammation.
Nitric oxide synthase (NOS) is another important enzyme involved in regulation of inflammation, vascular tone, neurotransmission, tumor cells and other homeostasis of human body. Nitric oxide (NO) is generated via oxidation of the terminal guanidine nitrogen atom of l-arginine by NOS. NO is released during a variety of pathophysiological responses including circulatory shock, inflammation and carcinogenesis (Ohshima et al., 1994, Mordan et al., 1993). NO has also been proposed to be an important mediator of tumor growth. For example, endogenously formed NO appeared to cause the neoplastic transformation of mouse fibroblasts (Mordan et al., 1993). Overexpressed NOS has also been detected in several human tumors (Thomsen et al., 1995, Radomski et al., 1991, Gallo et al., 1998). Thus, along with selective inhibitors of COX-2 or iNOS enzyme activity, a rational enable to address to develop more selective agents for suppression of these genes that might be overexpressed during the inflammation or carcinogenic process. In the present study, therefore, the methanolic extracts of natural products were primarily screened to discover new lead compounds in suppression of corresponding enzyme expression with the assay system of inhibition of prostaglandin E2 accumulation, or inhibition of NO production in LPS-stimulated RAW264.7 cell, a murine macrophage cell line.
Section snippets
Chemicals
Lipopolysaccharide (LPS, E. coli 0111: B4), bovine serum albumin, and sodium bicarbonate were purchased from Sigma Chemical Co. (St. Louis, MO, USA). Fetal bovine serum (FBS), Dulbecco's modified eagle's medium (DMEM), penicillin–streptomycin and trypsin–EDTA were from GIBCO-BRL (Gaithersburg, MD, USA). Prostaglandin E2 (PGE2) and PGE2-acetylcholineesterase conjugate were from Cayman Co. (Ann Arbor, MI, USA).
Preparation of test materials
Natural products including Korean medicinal plants were purchased from herbal markets
Results and discussion
Several studies have suggested that overexpression of either inducible cyclooxygenase (COX-2) or nitric oxide synthase (iNOS) might be intimately involved in the pathogenesis of diseases including inflammation, cancer, multiple sclerosis, Parkinson's syndrome, and Alzheimer's disease. Thus, there are many efforts to develop enzyme inhibitors or repressors of enzyme formation that are selective for the inducible forms of these enzymes and do not affect the desirable activity of their respective
Acknowledgements
This work was supported in part by the grant of HMP-00-O-21600-0010 funded by the Ministry of Health and Welfare, Korea.
References (15)
- et al.
Suppression of intestinal polyposis in APCΔ716 knockout mice by inhibition of prostaglandin endoperoxide synthase-2 (COX-2)
Cell
(1996) - et al.
NO at work
Cell
(1994) Role of regulation of cyclooxygenase-2 during inflammation
American Journal of Medicine
(1999)- et al.
Evaluation of COX-2 inhibitor for potential chemopreventive properties in colon carcinogenesis
Cancer Research
(1996) - et al.
TIS 10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue
Journal of Biological Chemistry
(1991) - et al.
Macrophage deactivating factor and transforming growth factors-ß1, -ß2 and -ß3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ
Journal of Immunology
(1990) - et al.
Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer
Journal of National Cancer Institute
(1998)
Cited by (202)
Ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological profile of Morus alba L.: A comprehensive review
2023, South African Journal of BotanyCeylon cinnamon: a versatile ingredient for futuristic diabetes management
2022, Journal of Future FoodsClove (Syzygium aromaticum) phenolics: Extraction, compositions, and biological activities
2022, Clove (Syzygium aromaticum): Chemistry, Functionality and ApplicationsEnvironmental Contaminants and Medicinal Plants Action on Female Reproduction
2022, Environmental Contaminants and Medicinal Plants Action on Female ReproductionGenus Pterocarpus: A review of ethnopharmacology, phytochemistry, biological activities, and clinical evidence
2021, Journal of EthnopharmacologyHepatoprotective effect of the hydroalcoholic extract of Cichorium intybus in a rat model of obstructive cholestasis
2021, Arab Journal of GastroenterologyCitation Excerpt :In agreement with the results of the present study, Conforti et al. [35] showed that the tocopherol ingredient of C. intybus inhibits NO production. In addition, Hong et al. [36] reported that C. intybus reduces the production of inducible nitric oxide synthase in cultured mouse macrophage cells. In conclusion, the current study confirms that the hydroalcoholic extract of C. intybus protects the liver against obstructive cholestasis-induced injury.