ABSTRACT
OBJECTIVE: To study the anti-inflammatory mechanisms of total glycosides of Acanthopanax Giraldii (TGA). METHODS: The changes of prostaglandin E(2)(PGE(2)), tumor necrosis factor (TNF-alpha), nitric oxide (NO), and expressions of COX-1 mRNA and COX-2 mRNA in BALB/c mouse macrophages were observed by the radioimmunoassay, ELISA and nitric acid reduction and RT-PCR in the presence or absence of TGA. RESULTS: (1) TGA could significantly decrease the production of PGE(2)and NO in mouse peritoneal macrophages. The inhibitory rate to LPS-induced PGE(2)production was 87% (TGA 100 mg/L, P<0.05, vs. LPS) and 62% (TGA 20 mg/L, P<0.05, vs. LPS), respectively. The inhibitory rate of NO production in mouse peritoneal macrophages was 49% (TGA 100 mg/L, P<0.05, vs. LPS) and 21% (TGA 20 mg/L, P<0.05 vs. LPS), respectively. TGA could not inhibit LPS-induced TNF-alpha production in mouse peritoneal macrophages. (2) TGA also inhibited the expression of COX-1 and COX-2 mRNA in RAW264.7 cells. The inhibitory rate of TGA to COX-1 mRNA was 22% (TGA 100 mg/L, P<0.05, vs. blank). The inhibitory rate of TGA to COX-2 mRNA was 55% (TGA 20 mg/L, P<0.05, vs. LPS) and 100% (TGA 100 mg/L, P<0.01 vs. LPS), respectively. CONCLUSION: The anti-inflammatory mechanisms of TGA for inhibiting the production of NO and PGE(2)are through inhibiting COX-2 mRNA expression without TNF-alpha changes.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Eleutherococcus , Glycosides/pharmacology , Macrophages, Peritoneal/drug effects , Animals , Cell Line , Cyclooxygenase 1/genetics , Cyclooxygenase 2/genetics , Dinoprostone/metabolism , Female , Gene Expression Regulation, Enzymologic/drug effects , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To explore the effects of slenderstyle acanthopanax root-bark on cyclooxygenase in vivo and in vitro. METHOD: Contents of 6-keto-PGF1alpha in bovine aorta endothelial cells, PGE2 in mouse abdominal macrophages, and 6-keto-PGF1alpha in rat stomach tissue were determined. The ulcer index in rat gastric mucosa was measured. RESULT: COX-1 and COX-2 were inhibited by slenderstyle acanthopanax root-bark, and the inhibitive rate of COX-2 was higher than that of COX-1 at the same concentration. Necrotic injuries in health gastric mucosa were not produced, but the injuries previously induced by the ethanol worsened. CONCLUSION: One of the antirheumatic mechanisms of slender-root-bark might probably be mediating through inhibition of cyclooxygenase. style acanthopanax
Subject(s)
Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Drugs, Chinese Herbal/pharmacology , Eleutherococcus , Plants, Medicinal , 6-Ketoprostaglandin F1 alpha/metabolism , Animals , Aorta/enzymology , Cattle , Dinoprostone/metabolism , Drugs, Chinese Herbal/isolation & purification , Eleutherococcus/chemistry , Endothelial Cells/enzymology , Female , Gastric Mucosa/enzymology , Macrophages, Peritoneal/enzymology , Male , Mice , Plant Roots/chemistry , Plants, Medicinal/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
AIM: To investigate effects of cyclooxygenase 2 (COX-2) inhibitors on nasopharyngeal carcinoma (NPC) cells and on angiogenesis in vitro. METHODS: Human NPC cell lines (CNE1, CNE2 and SUNE) were treated with nimesulide or celecoxib. MTT assay and colony formation assay were performed to observe antiproliferation activity of COX-2 inhibitors to NPC cell lines. Cell cycle arrest and apoptosis of NPC cell strains were tested by flow cytometry assay, microscopic morphology observation, and DNA fragmentation assay. The effect of COX-2 inhibitor on angiogenesis was tested by chick chorioallantoic membrane (CAM) model. RESULTS: Nimesulide (Nim) and celecoxib (Cel) could antiproliferate NPC cell lines with IC50 182 micromol/L(Nim-SUNE), 78 micromol/L(Nim-CNE1), 175 micromol/L(Nim-CNE2), 7.2 micromol/L(Cel-SUNE), 8.1 micromol/L(Cel-CNE1), and 7.6 micromol/L(Cel-CNE2). The antiproliferation presented dose-dependent (Nim 5-400 micromol/L, Cel 0.5-80 micromol/L) and time-dependent manner (Nim IC50 562 micromol/L(24 h), 316 micromol/L(48 h), 50.1 micromol/L(240 h)). Nim and Cel arrested SUNE and CNE1 cell cycle at phase G2/M (cell aggregation rate 28.9%-45.1%(Nim 25-200 micromol-12 h-SUNE), 18.9%-26.2%(Nim 25-200 micromol-24 h-SUNE), 28.8%-35.6%(Nim 25-200 micromol-48 h-SUNE), 30.4%-16.4%(Cel 25-100 micromol-12 h-SUNE), 21.2%-19.7%(Cel 25-100 micromol-24 h-SUNE), 31.1%-19.9%(Cel 25-100 micromol-24 h-SUNE), 20.5%-34.1%(Nim25-200 micromol-12 h-CNE1), 25.2%-26.9%(Nim 25-200 micromol-24 h-CNE1), 11.5%-7.1% (Nim 25-200 micromol-48 h-CNE1)). Apoptosis shape and apoptosis strap displayed in NPC cells after treatment with Nim and Cel. Nim had a feature of anti-angiogenesis on CAM model. CONCLUSION: Nim and Cel could suppress proliferation of squamous epithelium NPC cell (SUNE, CNE1 and CNE2) through blocking cell cycle and inducing cell apoptosis. Nim could apparently suppress CAM angiogenesis induced by SUNE cell.
