• Archives of Pharmacal Research
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• v.26 no.5
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• Environmental Mutagens and Carcinogens
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• v.25 no.4
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• pp.143-149
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• 2005

The identification of COX-2 (cyclooxygenase-2) has led to potential novel insights on disease pathogenesis (atherosclerosis, cancer, Alzheimer's disease) and the regulation of normal organ function. The present in vivo study with estrogen or soy-isoflavones has provided evidence for the association between COX-2 and ICAM-1 (Intercellular adhersion molecule-1). In the system of mature female rats, soy-isoflavones exerted more pronounced effect on ICAM-1 inhibitory and COX-2 stimulatory effect than estrogen. In the system of ovariectomized estrogen deficient rats, the down-regulatory properties of soy-isoflavones on ICAM-1 was less evident, whereas estrogen exerted the inhibitory activity. These results demonstrate that COX-2 limits adhersion molecule expression on rat aorta cells and suggest that COX-2 may play a protective role in cardiovascular system in mature female rats. Soy-isoflavones appear to have beneficial effect on vascular systems through modulation of ICAM-1 and COX-2, and these molecules appeared to be closely associated.

• YAKHAK HOEJI
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• v.42 no.6
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• pp.558-566
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• 1998

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitlitively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the beneficial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. Therefore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDS. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural products were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of Prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandins by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera. inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a con-centration of 1${\mu}$g/ml.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.133-134
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• 2001

Abnormal regulation of the inducible form of cyclooxygenase (COX-2) has been often observed in various types of cancerous and transformed cells. Recently, targeted inhibition of COX-2 is recognized as one of the promising strategies for the prevention or treatment of cancer as well as inflammation, As part of a program to evaluate the cancer chemopreventive potential of anti-inflammatory phytochemicals, we initially determined the COX-2 inhibitory activity of some naturally occurring diarylheptanoids structurally related to curcumin.(omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.88-92
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• 2006

Genistein was tested for chemopreventive potential against breast cancer by measuring the effect on proliferation of human breast cancer cells, human placental aromatase activity and cyclooxygenases-2 (COX-2) expression and activity, Genistein inhibited the growth of estrogen-independent MDA-MB-231 human breast cancer cell. However, there is no inhibitory effect of genistein on human placental aromatase activity. The expression of COX-2 was inhibited by genistein in Western blot analysis. Genistein significantly inhibited COX-2 activity at the concentrations of 10 (p<0.05), 25 (p<0.05) and 50 ${\mu}M$ (p<0.01). These results suggest that genistein may have breast cancer chemopreventive potential by inhibiting the growth of human breast cancer cell and expression and activity of COX-2.

• Natural Product Sciences
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• v.3 no.1
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• pp.19-28
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• 1997

Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible cyclooxygenase (COX-II) is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions such as inflammation. We have evaluated the inhibitory effects of solvent fractionated extracts of natural products on the activities of COX-I and COX-II. Oxygen uptake COX assay was performed, as a primary screening from the tissue extracts of bovine seminal vesicles (BSV), by monitoring the initial rate of oxygen uptake using an oxygen electrode. Additionally, we evaluated plant extracts for the inhibitory effects of COX-I (in HEL cells) and COX-II (in lipopolysaccharide activated J774A.1 macrophages) using thin layer chromatography of prostanoids produced from $^{14}C-labelled$ arachidonic acid (AA). The use of such models of COX-I and COX-II assay will lead to the identification of specific inhibitors of cyclooxygenases with presumably less side effects than present therapies. Inhibitory effects of 50 kinds of plant extracts on the COX-I and COX-II activities were determined and the active fractions were found in the ethyl acetate fractions of Dryopteris crassirhizoma (roots), Amomum cardamomum (roots), Triticum aestivum (seeds), Perilla sikokiana (leaves), Anemarrhena asphodeloides (roots). Especially, the ethyl acetate fraction of Dryopteris crassirhizoma (roots), which exhibited the strong inhibition against BSV COX $(IC_{50},\;65.4\;{\mu}g/ml)$, COX-I $(IC_{50},\;8.5\;{\mu}g/ml)$, and COX-II $(IC_{50},\;17.2\;{\mu}g/ml)$, is under investigation to isolate active principles using activity-guided fractionation method.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1061-1066
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• 2003

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for treating pain, rheumatic arthritis and inflammation. The present investigation was carried out to determine the in vivo and in vitro anti-inflammatory activity of AP using several animal models of inflammation. The 70% ethanol extract of the fruit of AP significantly inhibited acetic acidinduced, vascular permeability in a dose dependent manner (23%, 38%, and 41 % inhibition at doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg, respectively). This effect was maintained in AP water-soluble fraction (APW). The APW fraction also showed significant inhibitory activity against the rat paw edema induced by a single treatment of carrageenan. In vitro experiments were performed to demonstrate the inhibitory activities of APW (100 $\mu$ g/ml) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production. The results showed that APW dose-dependently suppressed LPS-induced NO production in RAW 264.7 macrophages without a notable cytotoxic effect and also decreased inducible NO synthase (iNOS) protein expression. APW also showed a significant inhibitory effect in LPS-induced $PGE_2$ production and cyclooxygenase-2 (COX-2) expression.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.37-45
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• 2005

In the present study, we examined the effect of crude methanolic extract (CME) from Euonymus alatus (Thunb.) Sieb on arachidonic acid (AA) cascade in SKBR3 human breast cancer cell line. CME had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a $Ca^{2+}$ ionophore. The inhibition was concentration-dependent, with the 50 value of about 5 M. CME had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, CME concentration-dependently inhibited the conversion of AA to $PGE_2$ in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, CME inhibited the activities of both constitutive COX (COX­I) and inducible COX (COX-2) in a concentration-dependent manner, with the 50 values of about 0.8 and 2M, respectively. Lineweaver-Burk plot analysis indicated that CME competitively inhibited the activities of both COX-l and -2. This study is a first demonstration that CME directly inhibits COX activity.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.311-315
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• 2001

The root of Astragalus membranaceus Bunge (Leguminosae), which has been used for the treatment of hypertension, chronic hepatitis, duodenal ulcers, chronic nephritis and promotion of immunity in folk remedies. Cyclooxygenase (COX-2) is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. Thus, a logical approach to the treatment of inflammatory disease should involve the inhibitors of COX-2. To develop new COX-2 inhibitors from natural products, Astragali Radix was screened by inhibiting prostaglandin $E_2(PGE_2)$ generation in the culture medium using enzyme immunometric assay. Two isoflavone glycosides, $7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-{\beta}-D-glucoside$ and $calycosin-7-O-{\beta}-D-glucoside$ isolated from Astragali Radix inhibited COX-2 activity.

• Natural Product Sciences
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• v.4 no.4
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• pp.263-267
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• 1998

From the dried flower-buds of Syzygium aromaticum Merr. et Perry (Myrtaceae), seven compounds, i.e., eugenol (1), oleanolic acid (2), kaempferol 7-O-metylether (3), 3,3',4-tri-O-methylellagic acid (4), maslinic acid (5), ${\beta}-sitosterol-3-O-glucoside$ (6), and isorhamnetin 3-O-glucoside (7) were isolated. Compound 1 showed cyclooxygenase-2 (COX-2) inhibitory activity.