Antiinflammatory and antipyretic activity of vicolides of Vicoa indica DC.

Vicolides A,B, C and D, the sesquiterpene lactones isolated from V. indica exhibited antiinflammatory activity against cotton pellet granuloma in rats at dose level of 10 mg/kg body weight, sc. Highly significant activity was observed with vicolides C and D. They reduced the protein content, acid and alkaline phosphatase, glutamate-pyruvate transaminase and glutamate oxaloacetate transaminase activities in liver and serum. Significant reduction in ascorbic acid content in adrenals was also observed in treated animals. The highly significant antiinflammatory activity of vicolides C and D can be attributed to their chemical structures. Vicolide D has an epoxy angeloyl group while vicolide C has 3,4 epoxy group and an ester moiety in the molecule. Vicolide D possesses antipyretic activity at 250 mg/kg body weight, po dose. It may be due to the presence of epoxy angeloyl group in the molecule.     

Synthesis and pharmacological evaluation of conjugates of prednisolone and non-steroidal anti-inflammatory agents

Esters of prednisolone with ibuprofen and indomethacin were prepared by coupling the 21-hydroxy moiety of the glucocorticoid to the carboxylic group of the non-steroidal anti-inflammatory agents. The local and systemic anti-inflammatory activities of the conjugates were evaluated using the cotton pellet granuloma bioassay and their topical activity evaluated by the croton oil-induced ear edema assay, in male Sprague-Dawley rats. The results indicate that these conjugates possess greater local and topical anti-inflammatory activity than prednisolone. In the subacute ear edema bioassay, the conjugates displayed no discernible untoward systemic effects, unlike prednisolone and prednisolone acetate, which elicited significant adverse systemic effects, at equipotent doses. These findings suggest that the chemical coupling of prednisolone and non-steroidal anti-inflammatory agents produced compounds with enhanced anti-inflammatory potencies and reduced systemic toxicities, particularly when administered topically.     

Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats

The hydroalcoholic extract (HAE) of Ageratum conyzoides leaves was studied for its antiinflammatory effect on subacute (cotton pellet-induced granuloma) and chronic (formaldehyde-induced arthritis) models of inflammation in rats. The absence or presence of toxicity by prolonged use of HAE was also evaluated through biochemical and hematological analysis of rats blood samples using daily oral doses of 250 or 500 mg/kg body wt., during 90 days. The results showed that the group of rats treated with HAE (250 mg/kg body wt.; p.o.) had a 38.7% (p < 0.05) reduction in cotton-pellet granuloma. The development of chronically induced paw edema was also reduced significantly (p < 0.05) by the plant extract. The toxicity study did not show any treatment-related abnormalities in biochemical and hematological parameters. The biochemical analysis from blood samples drawn from group of rats treated orally with 500 mg/kg body wt. did, however, present 30.2% (p < 0.05) reduction of SGPT activity as compared to the corresponding control group. These results confirm the antiinflammatory properties of A. conyzoides, with no apparent hepatotoxicity.     

Anti-inflammatory activity of the epimers of N-propyl 20ξ-dihydroprednisolonamide

The epimers of a steroid carboxamide, N-propyl 20α- and 20β -dihydroprednisolonamide, were evaluated for their local and systemic effects on granuloma formation, pituitary-adrenal function and liver glycogen content in rats. When the carboxamides were administered locally, the 20β-epimer exhibited greater activity than the 20α-epimer in suppressing cotton pellet granuloma formation. Neither epimer had suppressive effects on thymus weight and plasma corticosterone levels at the dose level used. When the carboxamides were administered systemically, they were pharmacologically inactive. Furthermore, in acute pharmacological studies, the carboxamides neither increased tyrosine aminotransferase activity and glycogen deposition in the liver nor decreased plasma corticosterone levels and relative thymus weight.     

LIG抗炎,解热活性的研究

本文研究了当归提取物LIG的抗炎,解热活性.研究发现LIG(2.5,5,10 mg/kg)对角叉菜和右旋糖苷诱导的足肿胀的抑制率分别为22.2%,49.4%,76.5%和20.8%,44.2%,75.3%(P＜0.001);对棉球肉芽肿的抑制率为29.2%,44.9%,58.8%(P＜O.001);对小鼠白细胞迁移的抑制率为20.7%,35.6%,48.2%(P＜0.001).此外,LIG可降低啤酒酵母导致的高热(P＜0.001).并且,LIG的抗炎,解热作用均成剂量依赖性.以上结果显示LIG具有非常强的抗炎,解热活性.     

Novel peptides with orally active and long-lasting antihypertensive activity

A series of N-(P-substituted phosphinoyl)peptides were synthesized and their antihypertensive activities were tested in spontaneously hypertensive rats (SHR). Among them, N-(dibenzyloxyphosphinoyl)-L-Ala-L-Pro-L-Pro-OH showed the most potent and long-lasting antihypertensive activity in SHR when administered orally. Although the inhibitory activity of this peptide against the angiotensin-converting enzyme was about one-hundredth of that of Captopril, the antihypertensive activity in SHR was significantly higher and longer-lasting than that of Enalapril which has been reported to be the most potent agent among similar converting enzyme inhibitors.     

Cetilistat (ATL-962), a novel pancreatic lipase inhibitor, ameliorates body weight gain and improves lipid profiles in rats.

Cetilistat is a novel inhibitor of pancreatic lipase. The aim of this report is to evaluate the anti-obesity action of cetilistat in diet-induced obesity (DIO) rats. Cetilistat inhibited rat and human pancreatic lipase activity with an IC (50) of 54.8 nmol/l, and 5.95 nmol/l, respectively, meaning that it is 9.2 times more potent for human pancreatic lipase than for that of rat. Cetilistat was orally administered simultaneously with fat emulsion to Sprague-Dawley rats. Plasma triglyceride (TG) concentrations were measured before and after oral fat loading. The elevation in plasma triglyceride concentration by oral fat loading was reduced by cetilistat in a dose-dependent manner at 3, 10, 30, and 100 mg/kg, indicating that cetilistat reduces intestinal fat absorption in rats. Cetilistat was administered to DIO F344 rats as food admixture in a high-fat diet at 4.9, 14.9, or 50.7 mg/kg/day for three weeks. Both triglyceride and nonesterified fatty acid content in the feces were dose-dependently and drastically increased, suggesting the intestinal breakdown of fat and excretion. Body weight (BW) gain and white adipose tissue (WAT) weight were reduced in a dose-dependent manner. In addition, leptin, TG, and total cholesterol (TC) in plasma were reduced and there were no reports of oily stools. These results suggest that cetilistat ameliorates obesity and hyperlipidemia in DIO rats, a plausible animal model of the most common type of human obesity.     

Evaluation of the in vivo anti-inflammatory activity of a flavonoid glycoside from Boldoa purpurascens

The anti-inflammatory effect of 4′,5-dihydroxy-6,7-methylenedioxyflavonol 3-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-xylopyranoside, a constituent of the leaves of Boldoa purpurascens Cav. (Nyctaginaceae), was evaluated for its anti-inflammatory activity in the dextran 1% induced rat paw oedema model (acute inflammation) and the cotton pellet induced granuloma rat model (chronic inflammation). Flavonoid glycoside at doses of 2.5, 5 and 10 mg/kg, indomethacin at a dose of 7 mg/kg and the vehicle were administered orally. The compound showed significant anti-inflammatory activity in the acute phase in a dose dependent manner, most notably at the highest test dose 10 mg/kg. Also in the cotton pellet induced granuloma model, the compound showed a dose-dependent anti-inflammatory activity, with the highest effect at 10 mg/kg. In both assays, the test compound was more active than indomethacin tested at 7 mg/kg.     

Nutritional copper deficiency does not affect sponge granuloma formation in the rat

Sponge granuloma formation was compared in copper-deficient and copper-sufficient rats following feeding of respective diets for 20, 40, or 60 d. Body weight, total blood hemoglobin, and activities of ceruloplasmin and Cu, Zn-superoxide dismutase in plasma were monitored to ascertain copper deficiency. Mean granuloma weights (mg +/- SEM) in copper-deficient and copper-sufficient groups of rats, respectively, were as follows: 37 +/- 2 and 38 +/- 2 after 20 d, 22 +/- 2 and 23 +/- 2 after 40 d, and 19 +/- 1 and 21 +/- 1 after 60 d on respective diets. Thus, nutritional copper deficiency did not have an effect on sponge granuloma formation in the rat.     

Suppression of food intake is linked to enteric inflammation in nematode-infected rats

Our aim was to investigate the cause-effect relationship between intestinal inflammation induced by infection with enteric stages of Trichinella spiralis and decreased host food intake. A suppression of food intake in T. spiralis-infected rats occurred within the first 24 h postinfection (PI) and was maximized by day 6 PI. Food intake, cumulated over an 8-day PI period, decreased by 59% compared with uninfected animals. The anti-inflammatory glucocorticoid betamethasone 21-phosphate was orally administered to rats in their drinking water to suppress T. spiralis-induced jejunal inflammation. When treated with a low dose of glucocorticoid (5.2 microg/ml), food intake in infected rats was still significantly reduced, but only by 21% compared with glucocorticoid-treated, uninfected rats. At the highest glucocorticoid dose (10.4 microg/ml) administered, infection-induced reduction in food intake was not different from that of glucocorticoid-treated, uninfected counterparts. The elevation in jejunal myeloperoxidase activity caused by infection was also significantly blunted by oral glucocorticoid treatment. Our results suggest that suppressed host food intake during enteric T. spiralis infection is directly linked to intestinal inflammation.     

Cytoplasmic binding of dexamethasone and induction of tyrosine aminotransferase in neonatal rat liver

Dexamethasone administration markedly increases the activity of tyrosine aminotransferase in postnatal rat liver. The glucocorticoid fails to induce the enzyme in foetal rats when administered in utero. Dexamethasone binding activity of rat liver cytoplasm is low or absent in foetal animals but increases to adult levels 1–2 days after birth. In vitro experiments with isolated nuclei indicate that foetal nuclei have the capacity to accumulate dexamethasone but only when presented with cytosol-bound glucocorticoid.     

Antiinflammatory activity of Muktashukti bhasma.

Muktashukti bhasma (MSB), an Ayurvedic compound, consisting of pearl, Aloe vera and vinegar, inhibited acute and subacute inflammation in albino rats as induced by subplanter injection of carrageenan, histamine, 5-HT, nystatin and subcutaneous implant of cotton pellets. In all the test procedures the antiinflammatory response of 1000 mg/kg MSB was comparable to the response observed with 300 mg/kg acetylsalicylic acid (ASA). Oral premedication with MSB delayed castor oil-induced diarrhoea in rats, indicating its prostaglandin inhibitory activity. The antiinflammatory activity of the compound is attributed to its ability to cause inhibition of prostaglandins, histamine and 5-HT and also by stabilization of the lysosomal membranes. The antiinflammatory activity of MSB seems one third to half as potent as ASA.     

Antiinflammatory efficacy of extracts of latex of Calotropis procera against different mediators of inflammation

The latex of the plant Calotropis procera has been reported to exhibit potent antiinflammatory activity against carrageenin and formalin that are known to release various mediators. In the present study, we have evaluated the efficacy of extracts prepared from the latex of C procera against inflammation induced by histamine, serotonin, compound 48/80, bradykinin (BK), and prostaglandin E2 (PGE2) in the rat paw oedema model. The paw oedema was induced by the subplantar injection of various inflammagens and oedema volume was recorded using a plethysmometer. The aqueous and methanol extracts of the dried latex (DL) and standard antiinflammatory drugs were administered orally 1 hour before inducing inflammation. The inhibitory effect of the extracts was also evaluated against cellular influx induced by carrageenin. The antiinflammatory effect of aqueous and methanolic extracts of DL was more pronounced than phenylbutazone (PBZ) against carrageenin while it was comparable to chlorpheniramine and PBZ against histamine and PGE2, respectively. Both extracts produced about 80%, 40%, and 30% inhibition of inflammation induced by BK, compound 48/80, and serotonin. The histological analysis revealed that the extracts were more potent than PBZ in inhibiting cellular infiltration and subcutaneous oedema induced by carrageenin. The extracts of DL exert their antiinflammatory effects mainly by inhibiting histamine and BK and partly by inhibiting PGE2.     

Orally active factor Xa inhibitors: 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine derivatives

In our investigation of factor Xa inhibitors, a series of 1-(6-chloronaphthalen-2-yl)sulfonyl-4-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)piperazines 3a-i were synthesized. In vitro inhibitory activities of the compounds against factor Xa and coagulation are summarized. Among the compounds, 3c and 3d, possessing a carbamoyl or N-methylcarbamoyl moiety, showed potent inhibitory activities when administered orally to rats.     

The effect of spermine on the disaccharidase activities in suckling rats of different age.

The influence of the age of the rat on the maturation of disaccharidase activities induced by spermine was studied. Three-day- and 9-day-old rats were used in the experiment. Spermine was administered orally or directly into the stomach using thin tubing daily for 3 days, and disaccharidase activities in the jejunum were measured. While spermine caused maturation of not only lactase activity but also maltase and sucrase activities in 9-day-old rats, it only caused maturation of lactase activity in 3-day-old rats. Histological studies showed no significant changes in the jejunum of 3-day-old rats treated with spermine.     

Evaluation of anti-inflammatory activity of Alstonia macrophylla Wall ex A. DC. leaf extract.

Methanolic extract of dried leaves of Alstonia macrophylla Wall ex A. DC. and its fractions were investigated for its anti-inflammatory activity. The extract at a concentration of 200 mg kg(-1) and 400 mg kg(-1), p.o. and its fractions at 25 mg kg(-1) and 50 mg kg(-1), p.o. showed the significant dose dependent antiinflammatory activity in carrageenan and dextran-induced rats hind paw edema (acute models) as well as in cotton pellet-induced granuloma (chronic model) in rats. Anti-inflammatory activity of the tested extract and its fractions was comparable with that of the standard drug Indomethacin (10 mg kg(-1)).     

Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.     

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives

Several coumarin derivatives have been reported to present multiple biological activities and especially antiinflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability. Some of them were found in vitro to inhibit lipid peroxidation and to strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active compounds within the set were tested against adjuvant-induced arthritis. Compound 3 was found to significantly protect the rats from adjuvant-induced arthritis (when it is administered from the first day or when it is administered the fourteenth day, with the first symptoms of the disease). An attempt was made to delineate the possible mechanism of action of the studied compounds.     

Anti-inflammatory and analgesic activity of ononitol monohydrate isolated from Cassia tora L. in animal models

Ononitol monohydrate (OM) was isolated from Cassia tora L. leaves. The anti-inflammatory and analgesic activities of OM have been examined in male Wistar rats and mice. The efficacy of OM against inflammation was studied by using carrageenan-induced paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic activity of OM was assessed using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. In acute type inflammation models, maximum inhibitions of 50.69 and 61.06% (P < .05) were noted with 20 mg/kg of OM in carrageenan-induced hind paw oedema and croton oil-induced ear oedema, respectively. Treatment of OM (20 mg/kg) meaningfully (P < .05) reduced the granuloma tissue formation by cotton pellet study at a rate of 36.25%. OM (20 mg/kg) inhibited 53.64% of paw thickness in adjuvant-induced arthritis model. OM has also been produced significant (P < .05) analgesic activity in acetic acid-induced abdominal constriction response, formalin-induced paw licking response and in hot-plate test suggesting its peripheral and central analgesic potential. The outcomes of the present study proposed that OM influenced on the anti-inflammatory and analgesic activities.     

Anti-inflammatory activity of piperine

Piperine (1-peperoyl piperidine) was isolated from Piper nigrum Linn for the evaluation of anti-inflammatory activity in rats. Different acute and chronic experimental models like carrageenin-induced rat paw edema, cotton pellet granuloma, and croton oil-induced granuloma pouch, were employed. Simultaneously, biochemical estimations were made to elucidate the underlying mechanism of the action. Piperine acted significantly on early acute changes in inflammatory processes and chronic granulative changes. It also acted partially through stimulation of pituitary adrenal axis. Exudative changes in both acute and chronic models, however, were insignificant.