Anti-inflammatory activity of fisetin in human mast cells (HMC-1).

Mast cells play an important role in the pathogenesis of allergic diseases through the release of inflammatory mediators such as histamine, cysteinyl leukotrienes, cytokines, and chemokines. Flavonoids, like fisetin are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. The aim of our study was to examine whether fisetin modulates inflammatory reaction in stimulated human mast cells (HMC-1). Fisetin decreased phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated gene expression and production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-4, IL-6, and IL-8 in HMC-1 cells. Fisetin inhibited PMACI-induced phosphorylation of p38 mitogen-activated protein kinase, extracellular-regulated kinase, and c-Jun N-terminal kinase. In addition, fisetin suppressed nuclear factor (NF)-kappaB activation induced by PMACI, leading to expression of IkappaB-alpha phosphorylation and degradation. Fisetin suppressed powerful induction of NF-kappaB promoter-mediated luciferase activity. These pharmacological actions of fisetin produce new suggestion that fisetin is a potential medicine for treatment of inflammatory diseases through the down-regulation of mast cell activation.     

Gastroprotective activity of Camellia sinensis black tea brew in rats

This study examined the gastroprotective potential of a black tea brew (BTB) of Camellia sinensis Linn. O. Kuntze (Theaceae) using Sri Lankan high grown Dust grade No: 1 tea in a rat ethanol-induced gastric lesion model. Three oral doses of BTB (84, 167, or 501?mg/mL) were used in evaluation of the gastroprotective activity. The results showed a strong dose dependent and significant (p?<?0.05) gastroprotective activity (in terms of number, length, and area of hemorrhagic lesions). The gastroprotective activity of BTB was superior to that of the reference drug cimetidine. The high dose of BTB (only dose tested) also offered gastroprotection in rat indomethacin- and serotonin-induced gastric lesion models. Intraperitoneal treatment of BTB and oral treatment of BTB following decaffeination suppressed its gastroprotective potential. However, indomethacin pretreatment did not reduce the gastroprotective potential of BTB in the ethanol-induced gastric lesion model. BTB also increased the gastric mucus content (by Alcian blue test), thickness of the gastric mucus layer (by histopathology), pH of the gastric contents, and possibly the gastric mucosal blood flow, and reduced the gastric acid output of the stomach. BTB also had antihistamine (by wheal test) and antioxidant activity (by the DPPH method) and impaired the gastric transit (by charcoal plug test). It is concluded that BTB of C. sinensis possesses strong oral gastroprotective action, which is mediated via multiple mechanisms. The results also justify the claim made by Sri Lankan traditional practitioners that BTB of C. sinensis has gastroprotective action.     

茶树紫芽的抗炎作用研究

该文构建了小鼠耳廓急性炎症模型、大鼠足趾肿胀炎症模型、大鼠慢性炎症模型.研究了茶树紫色芽叶提取物的抗急性、慢性炎症作用.结果 表明,茶树紫色芽叶提取物能够浓度依赖性地抑制二甲苯诱导的小鼠耳廓肿胀模型、角叉菜胶致大鼠足趾肿胀,抑制纸片诱导的大鼠肉芽肿.提示茶树紫色芽叶提取物有显著的抗炎作用.     

Modulation of hepatic cytochrome P450 activity and carcinogen bioactivation by black and decaffeinated black tea

The principal objective of this study was to compare the ability of green, black and decaffeinated black tea to modulate hepatic expression of cytochromes P450 in the rat, and the consequences on the bioactivation of some food-borne carcinogens. Furthermore, these studies allow inferences to be drawn as to the contribution of caffeine and flavanols in the tea-mediated changes in cytochrome P450 expression. Black tea is prepared from fresh tea leaf following oxidation of flavanols by polyphenol oxidases and consequently has a low content of these compounds. All three types of tea enhanced lauric acid hydroxylation but in the case of decaffeinated black tea no statistical significance was attained. Green tea and black tea, but not decaffeinated black tea, stimulated the O-dealkylations of methoxy-, ethoxy- and pentoxy-resorufin indicating upregulation of CYP1A and CYP2B. Immunoblot analysis revealed that green and black tea, but not decaffeinated black tea, elevated the hepatic CYP1A2 apoprotein levels. Hepatic microsomes from green and black tea-treated rats, but not those from the decaffeinated black tea-treated rats, were more effective than controls in converting IQ into mutagenic species in the Ames test. It is concluded that flavanols are not responsible for the effects of tea on the cytochrome P450 system, but caffeine could account for the increase in CYP1A2 and the consequent increase in the bioactivation of IQ.     

Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (2). Anti-inflammatory activity (author's transl)]

The anti-inflammatory activity and the mode of action of M73101, a new non-steroid analgesic anti-inflammatory agent, were investigated in experimental animals and compared with those of reference drugs. M73101 inhibited the increase in vascular permeability induced by acetic acid and its activity was more potent than that of phenylbutazone. M73101 showed a marked inhibitory effect against rat paw edema induced by various phlogistic agents (carrageenin, dextran, histamine, serotonin and bradykinin) and the activities were equal to or more potent than those of aminopyrine, mepirizole and tiaramide HCl. M73101 also inhibited the edema induced by mustard, scalding and anti-rat rabbit serum in rats. In addition, the anti-edematous effect of M73101 on carrageenin-induced rat paw edema was not influenced by spinalectomy or adrenalectomy, indicating that the anti-inflammatory action of M73101 was not mediated by the central nervous system and the adrenals. Local and oral administration of M73101 inhibited significantly the leucocyte migration into the fluid of CMC pouch in rats and the activity was more potent than phenylbutazone, suggesting that the anti-inflammatory effect of M73101 was due to the direct action at the inflamed site. On the other hand, M73101 did not show any marked activities on the experimental chronic inflammatory models. From these results, it is suggested that M73101 may be useful for clinical application as a basic analgesic, anti-inflammatory drug with remarkable anti-inflammatory activity in acute and subacute cases. The mechanism of the anti-inflammatory action of M73101 probably involves inhibition of an increase in vascular permeability and leucocyte migration.     

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na).

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na) were studied. Zn-PP-2Na exhibits anti-allergic action against type III and IV reactions (passive Arthus reaction in rats and tuberculin-induced footpad reaction in mice), but does not affect type I and II reactions (homologous passive cutaneous anaphylaxis in mice and reversed cutaneous anaphylaxis in rats). Zn-PP-2Na also clearly inhibits type II collagen-induced arthritis in mice. The agent inhibits general arthritis symptoms, anti-type-II collagen antibody production and type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice. Zn-PP-2Na, however, did not affect carrageenin-induced paw edema and histamine- and serotonin-induced skin reactions in rats. Zn-PP-2Na inhibits IL-1-induced mouse lymphocyte proliferation, but does not affect PMA-induced O2- generation from guinea-pig neutrophil. These results indicate that Zn-PP-2Na inhibits type II collagen-induced arthritis in mice due to the antagonism of IL-1 activity and the inhibition of DTH against type II collagen.     

Anti-inflammatory activity of propolis

Propolis (bee-glue), known as a folk medicine, is a lipophilic material found in honeybee hives. In the present study on the anti-inflammatory effect of Korean propolis, it was extracted with ethanol, and used as a test material. The LD₅₀ value with the oral administration of ethanolic extract of Korean propolis (EEKP) was higher than 2 g/kg in mice. The oral administration of the propolis extract (100 mg/kg) significantly inhibited the development of hind paw edema induced by carrageenin in rats. The oral pretreatment of the propolis extract markedly inhibited the increase in vascular permeability and the number of writhing induced by acetic acid in mice. Propolis extract, 50 and 100 mg/kg p.o. per day for 7 days, produced a significant inhibitory effect on granuloma and exudate formation in rats. This inhibitory effect was enhanced with the concomitant use of prednisolone (2.5 mg/kg). These results suggest that Korean propolis apparently has a strong anti-inflammatory activity.     

Anti-inflammatory activity of quinazolinoformazans

Eight substituted quinazolonoformazans were synthesized and evaluated for anti-inflammatory activity. The degree of protection provided by seven of these compounds, at a dose of 100 mg/kg, po, against carrageenin-induced edema in rat paw ranged from 26 to 57%. The four active substituted quinazolonoformazans (1, 2, 6, 8), on further evaluation for antiwrithmogenic activity, provided 10-80% protection against the aconitine-induced writhing response in mice. The ulcerogenic liabilities of two of the most active compounds were also determined. The doses producing ulcers in 50% of the treated rats (UD50) were 155 and 260 mg/kg, ip, for 2 and 8, respectively. The low toxicities possessed by these substituted quinazolonoformazans were indicated by their LD50 values which ranged from 600 to 1300 mg/kg, ip, in mice.     

Anti-inflammatory activity of some copper(II) complexes

Anti-inflammatory activity of some copper(II) neutral complexes and complexated salts on different animal models of inflammation has been investigated. In a preliminary screening 5 complexes were selected for a more extensive study based on their capacity inhibiting the rat hind paw edema induced by carrageenin. These selected complexes showed inhibitory action on acute and subacute inflammation with an activity degree higher than that of indometacin. They were also effective inhibitors of primary and secondary lesions in the adjuvant-induced arthritis, with an activity similar to phenylbutazone. These complexes had no topical anti-inflammatory effect.     

Anti-inflammatory activity of Seabuckthorn (Hippophae rhamnoides) leaves

Immunomodulatory activity of Seabuckthorn (SBT) leaf extract was evaluated in adjuvant induced arthritis (AIA) rat model. Inflammation was induced by injecting Complete Freund's Adjuvant (CFA) in the right hind paw of rats. SBT extract was administered intraperitoneally to treat the inflammation. The extent of inflammation and treatment response was evaluated by clinical analysis, scintigraphic visualization using technitium-99m-glutathione (Tc99m-GSH) and lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21 and 28 after creation of inflammation. The Tc99m-GSH uptake in the inflamed leg was compared with the normal contralateral leg of the same animal. The measurements were done by obtaining scintigraphic images using gamma camera and an online computer. Both qualitative and quantitative evaluation of radiotracer accumulation was considered to evaluate the anti-inflammatory response. The lymphocyte proliferation study revealed cellular immunosuppression during the early phase of the disease. Administration of SBT extract on the same day or 5 days prior to inflammatory insult into the joint, significantly reduced the inflammation as compared to the untreated animals in a dose dependent manner. These observations suggest that the SBT leaf extract has a significant anti-inflammatory activity and has the potential for the treatment of arthritis.     

Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (3). Effects on type I-type IV allergic reaction

Effects of Glyteer (GL, 5%) on Type I-Type IV allergic reactions were investigated by its topical application to rats and mice, and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), indomethacin (ID, 1%), and bufexamac (BM, 5%), which were all prepared with the same ointment base. Type I: GL showed inhibitory effects on the 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibitory activity of GL on the PCA had the same potency as that of BV (0.12%). GL also inhibited the degranulation of mast cells induced by PCA. Type II: GL did not exert an inhibitory effect on the reversed cutaneous anaphylaxis (RCA) in rats, but BM, ID and BV had an inhibitory activity on the RCA. Type III: BV markedly inhibited the direct passive Arthus reaction in rats. On the other hand, GL, BM and ID had not an inhibitory activity on it. Type IV: GL (0.2, 1 and 5%) showed a concentration-dependent inhibition on the delayed-type hypersensitivity response induced by oxazolone in mice, and the activity was stronger than those of ID and BM. From these results, it is suggested that GL applied externally possesses a potent effect as an anti-allergic drug on Type I and Type IV allergic reactions.     

Anti-inflammatory activity of ginsenoside ro

Ginsenoside Ro, an oleanane-type saponin has been screened for activity in experimental models of inflammation. Ginsenoside Ro (10,50, and 200 mg/kg, P. O.) inhibited an increase in vascular permeability in mice induced by acetic acid and reduced an acute paw edema in rats induced by compound 48/80 or carrageenin. Ginsenoside Ro did not suppress a developing adjuvant-induced edema in arthritic rats. However, ginsenoside Ro was found to be effective in hypercoagulable state, increase of connective tissue in the artery and calcium effluence from the bone in adjuvant-induced arthritic rats.     

Anti-inflammatory activity of cationic lipids

1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids.
2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-α (TNF-α).
3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge.
4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70–95%).
5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG₂₀₀₀) which blocks the interaction of cationic lipids with macrophages.
6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its induction in macrophages, was not modified in vitro or in situ by cationic lipids. The synthesis of NO and TNF-α in macrophages, both of which are PKC-dependent, was downregulated by cationic lipids.
7. These results demonstrate that cationic lipids can be considered as novel anti-inflammatory agents. The downregulation of pro-inflammatory mediators through interaction of cationic lipids with the PKC pathway may explain this anti-inflammatory activity. Furthermore, since cationic lipids have intrinsic anti-inflammatory activity, cationic liposomes should be used with caution to deliver nucleic acids for gene therapy in vivo.

     

Anti-inflammatory activity of 5,7-dimethoxyflavone

The anti-inflammatory activity of 5,7-dimethoxyflavone (5,7-DMF) has been assessed. It was found to possess a comparable effect to aspirin on the rat paw edema model, and it showed no inhibition on cotton pellet-induced granuloma formation. On the rat pleurisy model, 5,7-DMF exhibited an antiexudative effect, interfered with leukocyte migration, and markedly inhibited prostaglandin biosynthesis. In addition, 5,7-DMF caused marked lowering of the rectal temperature of rats. The results obtained from Hippocratic screening revealed that 5,7-DMF possessed a weak CNS depressant activity.     

Anti-inflammatory activity of Commiphora molmol

The petroleum ether extract of the oleo-gum resin of Commiphora molmol, at a dose of 500 mg/kg body weight, produced significant inhibition of carrageenan induced inflammation and cotton pellet granuloma. The extract also showed significant antipyretic activity in mice. Further studies on the fractionation of phytoconstituents and their mechanism of action are in progress.     

Anti-inflammatory activity of domestic papain

The influence of domestic papain to the course of experimental inflammation due to formalin, dextrane, histamine, serotonin and infectious arthritis has been studied. The domestic papain in doses of 0.325 and 0.75 mg/kg possesses strongly marked antiinflammatory activity and this ability is no less than that of butadion and indomethacin.     

Anti-inflammatory activity of hyaluronic acid

The results of in vivo experiments showed that hyaluronic acid possesses antiexudative activity comparable with that of nonsteroidal anti-inflammatory drugs. Hyaluronic acid exhibits antagonism with respect to histamine-induced inflammation.