AIM AND METHODSBoth PGE2 and cAMP are important neural mediator of fever. In order to discuss if PGE2 and cAMP are involved in the antipyretic mechanism of baicalin, fever models of rats were made by i.v. injection of endotoxin (ET). The antipyretic action and effects of baicalin on contents of PGE2 and cAMP in hypothalamus were observed.

RESULTSBaicalin possessed obvious antipyretic effect on fever rats and reversed the effect of ET on contents of PGE2 and cAMP in hypothalamus. Correlation analysis showed that contents of PGE2 and cAMP in hypothalamus were positively correlated with the change of body temperature of rats.

CONCLUSIONBaicalin may exert its antipyretic effect on fever rats by inhibiting increase of contents of PGE2 and cAMP in hypothalamus.

Animals ; Cyclic AMP ; metabolism ; Dinoprostone ; metabolism ; Fever ; metabolism ; Flavonoids ; pharmacology ; Hypothalamus ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE₂, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg^-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE₂, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.
Animals ; Anti-Inflammatory Agents/pharmacology* ; Cyclooxygenase 2/chemistry* ; Dinoprostone ; Interleukin-6/metabolism* ; Iridoid Glucosides ; Mice ; Molecular Docking Simulation ; Pyridinolcarbamate

OBJECTIVE: To detect cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) release in human nasal epithelia (HNE) induced by hypoxia and/or IL-1beta of different time gradient, and to investigate their roles in nasal inflammatory pathogenesis. METHOD: Western Blot and fluorescent real time quantitative PCR were performed to detect the expression of COX-2 in HNE induced by hypoxia and/or IL-1beta. The concentrations of PGE2 were determined by enzyme immunoassay. Median comparison was statistically treated by rank sum test, and generalized linear model was used to analyze the association of hypoxia with IL-1beta. RESULT: Weak expressions of COX-2 and PGE2 were detected in normal HNE. COX-2 expression and PGE2 release increased in HNE induced by hypoxia and/or IL-1beta in time-dependent manner. Stronger expressions of COX-2 and PGE2 induced by hypoxia and/or IL-1beta than control were detected on different time (P < 0.05). The strongest inducible effect was found in hypoxia+IL-1beta group, and inducible effect decreased in hypoxia group and IL-1beta group in turn. The expressions of COX-2 and PGE2 in hypoxia+IL-1beta group were more than the sum of hypoxia group and IL-1beta group on same time. CONCLUSION Hypoxia and/or IL-1beta effectively induce COX-2 expression and PGE2 release in HNE. Synergistic effect between hypoxia and IL-1beta has been found in induction of COX-2 and PGE2 in HNE. Results indicate that the increased expressions of COX-2 and PGE2 are involved in inflammation of HNE induced by hypoxia and/or IL-1beta in vitro.
Cell Hypoxia ; Cells, Cultured ; Cyclooxygenase 2 ; metabolism ; Dinoprostone ; metabolism ; Humans ; Interleukin-1beta ; pharmacology ; Nasal Mucosa ; cytology ; metabolism

Effect of antiatherogenic high density lipoprotein (HDL) and apolipoprotein AI (apoAI) on production of prostaglandin E2 (PGE2) by human monocyte-derived macrophages was investigated. Macrophages were loaded with acetylated low density lipoprotein followed by incubation with HDL3 or apoAI. PGE2 produced and secreted in culture supernatant was quantified by enzyme immunoassay. HDL3 induced production of PGE2 by macrophages in a time-dependent manner. 24 h after incubation, PGE2 production by HDL3-treated macrophages increased 3.7-fold of that by control cells. ApoAI also induced PGE2 secretion to 2.1-fold, which was significantly less than HDL3. The data indicate that both HDL3 and lipid-free apoAI enhance PGE2 synthesis and secretion by human macrophages and this may further contribute to the protection from atherosclerosis.
Apolipoprotein A-I ; pharmacology ; Arteriosclerosis ; prevention & control ; Culture Media, Conditioned ; Dinoprostone ; biosynthesis ; Humans ; Lipoproteins, HDL ; pharmacology ; Lipoproteins, HDL3 ; Macrophages ; cytology ; metabolism ; Monocytes ; metabolism

OBJECTIVETo investigate the influence of the prostaglandin E2 on the proliferation of the melanocytes in the full-thickness skin graft.

METHODSSixty-eight guinea-pigs were divided into experimental-1 group (skin graft), experimental-2 group (skin graft + diclofenac), and control groups. After the full-thickness skin graft, the dynamic changes of the prostaglandin E2 were measured and the proliferation of the melanocyte with its density was also evaluated by using histochemical and autoradiographic methods.

RESULTSIn the experimental-1 group, the content of PGE2 was increasing in seven days after the operation, continued to the one month, and then returned to the base level. The labelling indices of 3H-MC-TdR of the group was also increasing postoperatively between the second day and the fourteenth day, and reach a second peak after one month, then came to the normal level. The density of the melanocytes was decreasing rapidly 3 days after the surgery, then began to increase and exceeded over the normal level 21 days after the operation. However, in the experimental-2 group, the content of PGE2 decreased in two days after the surgery, and then showed the inclination similar to the experimental-1 group with the different points in narrower range. The number of melanocytes labelled by 3H-TdR began to increase at the first day after the surgery, which appeared earlier than the experimental-1 group and was similar in the changing tendency with a less extent. The density of MC showed the similar tendency to the experimental-1 group in a narrower changing range with both of increasing and decreasing. The density of the MC was much lower in 21 after the operation than the experimental-1 group and normal control group.

CONCLUSIONThe increased PGE2 in the earlier stage of the skin grafting could enhance the inflammatory reaction to the tissue, as well as the melanocytes. It may stimulate the proliferation of the MC with the result of increasing their density. The use of the diclofenac might reduce the inflammation and suppress the proliferation of melanocytes, and result in the skin with light color due to decreasing the number of MC in the epidermis of the graft.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Cell Count ; Cell Proliferation ; Diclofenac ; pharmacology ; Dinoprostone ; metabolism ; Epidermis ; Guinea Pigs ; Melanocytes ; cytology ; Skin ; Skin Transplantation ; Time Factors

Sesquiterpenoid is a kind of compound widely distributed in nature, which has a wide range of biological activities, such as anti-inflammatory, anti-tumor and immunomodulatory activities. This paper would review the anti-inflammatory mechanism of sesquiterpenoid. The mechanism is mainly by inhibiting the activation of nuclear factor (NF-κB), mitogen-activated protein kinase (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways and down-regulating the inflammatory gene expression including tumor necrosis factor- (TNF-), prostaglandin E₂ (PGE₂), nitric oxide (NO), interleukin-1(IL-1), IL-6, IL-8 and other inflammatory factors. Thereby, the production and release of inflammatory cytokines are reduced to exert anti-inflammatory effect. This review is intended to provide reference for related research.
Anti-Inflammatory Agents ; pharmacology ; Dinoprostone ; Humans ; Interleukins ; MAP Kinase Signaling System ; NF-kappa B ; Nitric Oxide ; STAT Transcription Factors ; Sesquiterpenes ; pharmacology ; Signal Transduction ; Tumor Necrosis Factor-alpha

OBJECTIVE: To explore the effect of insulin-like growth factor (IGF-1) on the concentration of NO and PGE(2) in the supernatant of rabbit articular chondrocytes induced by IL-1, and to explore the mechanism of IGF-1 in the development of osteoarthritis (OA). METHODS: The samples were divided into 7 groups: IL-1beta 10 microg/L group, IL-1beta 10 microg/L+IGF-1 1 microg/L group, IL-1beta 10 microg/L+IGF-1 10 microg/L group, IL-1beta 10 microg/L+IGF-1 50 microg/L group, IL-1beta 10 microg/L+IGF-1 100 microg/L group, IGF-1 50 microg/L group, and a blank control group. The chondrocytes from the articular cartilage of 2 month old rabbits were cultivated and identified, and then co-cultured in the second filial generation chondrocytes on plates with or without recombinant human IGF-1 or IL-1. The concentration of NO was detected by nitrate reductase kit, and that of PGE(2) by enzyme-linked immunosorbent assay (ELISA). The results were analyzed by statistical method. RESULTS: The average value of NO and PGE(2) was (89.971+/-10.224) micromol/L and (22.028+/-8.731) micromol/L in the IL-1beta 10 microg/L group, and (12.404+/-8.809) micromol/L and (1.900+/-0.227) ng/L in the blank control group. The concentration of NO and PGE(2) in IL-1beta 10 microg/L group was significantly higher than that in the blank control group (P<0.05). At the same concentration of 10 microg/L, IGF-1 could dose-dependently decrease the increase of NO and PGE(2) concentration induced by IL-1beta in the chondrocytes supernatant in vitro, and the optimum concentration of IGF-1 was 50 microg/L. CONCLUSION IL-1 can significantly increase the concentration of NO and PGE(2), and IGF-1 can dose-dependently decrease the concentration of NO and PGE(2) in the chondrocytes supernatant in vitro. The optimum concentration of IGF-1 was 50 microg/L.
Animals ; Cartilage, Articular ; cytology ; metabolism ; Cells, Cultured ; Chondrocytes ; drug effects ; metabolism ; Dinoprostone ; metabolism ; Insulin-Like Growth Factor I ; pharmacology ; Interleukin-1 ; pharmacology ; Nitric Oxide ; metabolism ; Osteoarthritis ; metabolism ; Rabbits

PURPOSE: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. MATERIALS AND METHODS: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Omega, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). RESULTS: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05). CONCLUSION: EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
Adult ; Aspirin/pharmacology ; Cell Proliferation/*radiation effects ; Collagen/metabolism ; Dinoprostone/metabolism ; *Electromagnetic Fields ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Intervertebral Disk/*pathology/radiation effects ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Tetrazolium Salts/pharmacology ; Thiazoles/pharmacology ; omega-N-Methylarginine/pharmacology

OBJECTIVETo explore the mechanisms of muscovite gastric mucosal protective effect.

METHODRat model of chronic gastritis were used. After gastric mucosal injury was induced, the rats were divided into 6 groups and were treated with different drugs. 2 weeks later, the tissue and blood samples were obtained and measured.

RESULTThe general conditions, the observations under macroscopy, microscope and electron microscope of the middle and high dose of muscovite groups resembled those of the normal group. Their PH levels were higher than those of the model group, and the rates of intestinal metaplasia were lower, but the PGE2 level of the middle dose of muscovite group was the highest.

CONCLUSIONMuscovite can be adsorbed on the surface of the gastric mucosa. It has gastric mucosal protective effect by improving excretion of mucus and synthesis of PGE2 in gastric mucosa, restraining gastric acid, reversing of intestinal metaplasia and decreasing inflammation cells.

Aluminum Compounds ; pharmacology ; Animals ; Dinoprostone ; blood ; Gastric Juice ; chemistry ; Gastric Mucosa ; pathology ; ultrastructure ; Gastritis ; blood ; chemically induced ; pathology ; Hydrogen-Ion Concentration ; Materia Medica ; pharmacology ; Microscopy, Electron, Scanning ; Potassium Compounds ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Silicates ; pharmacology ; Sodium Salicylate

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid into prostanoids which participate in various cellular functions including apoptosis, mitogenesis, inflammation, immune modulation and differentiation. Moreover, the synthetic glucocorticoid, dexamethasone has immune modulating and anti-inflammatory effects in vivo. Recently, dexamethasone was found to enhance retinoic acid-induced neuronal differentiation. In this study, we investigated the mechanisms of dexamethasone-mediated neuronal differentiation. Immunoblotting and morphological analysis demonstrated that dexamethasone induced neuronal differentiation through COX 1 induction. This phenomenon was inhibited by indomethacin, a COX inhibitor. In addition, the addition of exogenous prostaglandin E2 (PGE2), a substance produced by the COX-mediated pathway, triggered neurite outgrowth of cells treated with COX inhibitor. Taken together, COX 1 appears to play an important role in dexamethasone-mediated neuronal differentiation.
Animals ; Anti-Inflammatory Agents/pharmacology ; Cell Differentiation/*drug effects ; Cyclooxygenase Inhibitors/pharmacology ; Dexamethasone/*pharmacology ; Dinoprostone/metabolism ; Enzyme Induction ; Hybrid Cells ; Indomethacin/pharmacology ; Isoenzymes/*biosynthesis ; Mice ; Prostaglandin-Endoperoxide Synthase/*biosynthesis ; Rats ; Tumor Cells, Cultured