Anti-inflammatory,analgesic, antipyretic and related properties of meloxicam,a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs.With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenaninduced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration.Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain.In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeastinduced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid.Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm.Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam.The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.     

Synthesis of some thiophene, imidazole and pyridine derivatives exhibiting good anti-inflammatory and analgesic activities

A series of thiophene derivatives 1a-d & 2a-c were synthesized by condensation of 5-nitro-2-thiophene carboxaldehyde with mono and diamines respectively. Various imidazole derivatives 3a-c were obtained by condensing 4-(2-ethylamino)-1H-imidazole with 4-acetylpyridine, 2-acetylpyridine and 4-acetylbenzonitrile respectively. Pyridine derivatives 4a-e were synthesized by condensing 2-hydrazino-pyridine with various carbonyl compounds; 5a-c by condensing 2, 6-pyridine dicarbonyl dichloride with various aryl sulfonylhydrazides; 6, 7 by condensing 2, 6-dialdehyde pyridine with 2-hydrazinopyridine and anthranilonitrile respectively and compound 8 by condensing 2, 5-thiophene dialdehyde with hydrazinopyridine. All the compounds were characterized by IR, (1)HNMR, Mass spectra and elemental analysis. Compounds 1a-d; 2a-c; 3a-c; 4a-e; 5a-c, 6, 7 and 8 were screened for anti-inflammatory and analgesic activities. Compounds 1b and 2c exhibited good anti-inflammatory (26.5% and 33.4% at 50mg/kg p.o. respectively) and 3a, 3c good analgesic (100% and 75% at 100 mg/kg p.o. respectively) activities.     

双向发酵对草乌中乌头碱类成分含量影响及菌质抗炎镇痛作用的初步研究

目的观察中药草乌被10种药用真菌（菌株代号为A、O、V、D、E、F、H、SW、O^①、 ）发酵后,乌头碱、中乌头碱、次乌头碱含量变化及HPLC指纹图谱的差异及发酵菌质镇痛、抗炎方面的作用。方法将草鸟作为“药性基质”,控制一定条件,草乌被药用真菌双向固体发酵,并以草乌中的主要成分乌头碱、中乌头碱和次乌头碱为分析对象,分析革乌菌质中乌头碱类成分含量变化;并利用扭体痛证模型、耳廓肿胀模型试验研究草乌菌质各组（发酵空白组,草乌＋O^①组,草乌＋A组,草乌＋v组,草乌＋F组）的药效。结果草乌＋v,草乌＋A菌质中乌头碱、中乌头碱及次乌头碱含量与生药材比较有明显的降低,且有新的成分产生;与发酵空白组比较,草乌＋A组、草乌＋v组对抑制化学刺激所致的小鼠疼痛反应有显著性差异（P〈0．05）。结论双向发酵后部分“药性菌质”中乌头碱、新乌头碱和次乌头碱含量明显降低,镇痛作用增强,提示双向发酵是生物技术在中医药领域中运用的有益尝试。     

Evaluation of anti-inflammatory and analgesic properties ofl-glutamine

It was established thatl-glutamine, an aminoacid, has marked anti-inflammatory activity and moderate analgesic activity. The drug was effective orally in suppressing various experimentally induced inflammatory reactions and did not show any gastric irritation in anti-inflammatory doses. It is observed that the anti-inflammatory effect ofl-glutamine is not due to counter irritant action. It is suggested that it may partially mediate its anti-inflammatory activity by interfering with the action and/or synthesis of prostaglandins. Its anti-inflammatory activity is comparable to that of phenylbutazone and merits further study.     

Capillarosclerosis of the lower urinary tract in analgesic (phenacetin) abuse

Summary The ultrastructural appearances in Capillarosclerosis of the lower urinary tract in analgesic abuse are reported. The capillaries show thickened basement membranes consisting of numerous thin basement membrane lamellae. Between the newly formed basement membrane lamellae, masses of empty vacuoles (fat vacuoles) and a variety of membranous and vesicular structures are present. The pathogenesis of this alteration in the basement membrane is unknown. A common pathogenetic mechanism may be operative in the discoloration of renal papillae and mucous membranes of lower urinary tract on the one hand and capillarosclerosis on the other.     

筋骨活络抗炎镇痛作用研究

本文报告筋骨活络的两种给药途径的镇痛、抗炎实验。结果表明,无论是口服药粉混悬液还是外搽酒剂,筋骨活络均能产生明显的镇痛抗炎作用。     

The morphologic diagnosis of analgesic (phenacetin) abuse.

A number of different morphologic characteristics were examined to determine their relative values in establishing a purely morphologic diagnosis of phenacetin abuse. These included hyperpigmentation of the skin, the costal cartilages, the liver, and the renal tubules, and capillarosclerosis of the lower urinary tract. Hyperpigmentation of the skin, liver, and renal tubules cannot be used in the diagnosis of phenacetin abuse. Massive brown pigmentation of the costal cartilages in patients under 60 years of age suggests phenacetin abuse, but even this morphologic parameter, when used alone, is insufficient to establish a definite diagnosis. Capillarosclerosis in the lower urinary tract does, however, permit one to diagnose phenacetin abuse with certainty, as it is found exclusively in this condition.     

Acute and Subchronic Toxicity of Chantaleela Recipe in Rats

Acute and subchronic toxicities of Chantaleela recipe were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 females, 5 males) did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 600, 1,200 and 2,400 mg/kg body weight for 90 days (10 females, 10 males). No signs of abnormalities were observed in the test groups as compared to the controls. The test and control groups (on the 90^th day) and the satellite group (on the 118^th day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The results suggest that Chantaleela recipe did not cause acute or subchronic oral toxicities to female and male rats.     

Molecular targets of dietary polyphenols with anti-inflammatory properties

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.     

Evaluation of analgesic and anti-inflammatory activity of diospyros cordifolia extract

In this study we evaluated the analgesic and anti-inflammatory activities of the methanol extract of stem bark of Diospyros cordifolia (MEDC) Roxb. The analgesic effects of the stem bark of the plant was assessed in mice using the tail-flick method while carrageenan, histamine and dextran induced paw oedema was used to study the antiinflammatory effects in rats. The MEDC exhibited significant (p<0.01) analgesic effects comparable to the reference drug diclofenac sodium. MEDC also was evaluated for its anti-inflammatory potential against carrageenan, histamine and dextran induced rat paw edema. The methanol extract (25 and 50 mg / kg body weight) exhibited significant (p<0.01) activity against all phlogistic agents used in a dose dependent manner. All these effects were compared with reference drug phenylbutazone (100 mg/kg body weight).     

The possibility of scar formation due to intrarenal reflux in analgesic nephropathy

Summary Using an autopsy case of a 59-year-old man with analgesic nephropathy, papillary necrosis, and nephrolithiasis, it is shown that analgesic nephropathy may be complicated by damage resulting from intrarenal urine reflux. The morphologic alterations characteristic of intrarenal and/or pyelointerstitial reflux are caused by high intrapelvic pressure values during episodes of renal colic. Bacterially infected and possibly also sterile urine is then forced into the interstitium, directly within the papillary defect or indirectly via the tubular system after rupture of the tubule. The result is a severe interstitial process with inflammation, destruction, and scarring.     

Acute and Subchronic Toxicity Study of Tud-Rak-Ka-Sai-Puu Recipe in Rats

Acute and subchronic toxicities of Tud-Rak-Ka-Sai-Puu (TR) recipe were studied in male and female rats. After 14 days of a single oral administration of test substance (5,000 mg/kg body weight), measurement of the body and organs weights, necropsy and health monitoring were performed. No signs and differences in the weights and behavior were observed relative to the control rats, suggesting that TR recipe in the dose of 5,000 mg/kg body weight does not produce acute toxicity. The subchronic toxicity was determined by oral feeding in male and female rats daily with the test substance at 2, 20, 200 and 2,000 mg/kg body weight for 90 days. No defects of animal behavior were observed in the test groups. Both test and control groups (on the 90^th day) as well as the satellite group (on the 118^th day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry, and microanatomy. These results together with the information of signs, behavior and health monitoring can lead to a conclusion that an oral administration of TR recipe at 2, 20, 200 and 2,000 mg/kg body weight for 90 days did not cause subchronic toxicity.     

The topical anti-inflammatory and analgesic properties of bromfenac in rodents

Bromfenac [2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium slat sesquihydrate] is an anti-inflammatory/analgesic agent that possesses potent topical activity in rats, guinea pigs, and mice. In rat models of acute (carrageenan paw edema) and chronic (adjuvant arthritis) inflammation, preparations of bromfenac at concentrations as low as 0.01–0.32% (0.01–0.32 mg bromfenac) produced significant anti-inflammatory activity when applied to the injected paw or to the backs of rats. In the acute paw edema test, topical bromfenac was more potent than indomethacin or hydrocortisone and about as active as triamcinolone acetonide. Bromfenac, at concentrations of 0.1–0.32%, showed topical analgesic more potent than indomethacin (24.9×), more potent than ketoprofen (14.9×), and superior to piroxicam. In the guinea pig UV-erythema test, bromfenac was active (26.1×indomethacin) when applied to the UV-exposed site, but not when applied away from the site. The results suggest that bromfenac has activity topically because of a local and a systemic effect. Test results obtained with a long (4–7 hr) pretreatment time (paw edema, adjuvant arthritis, abdominal constriction) are due in great part to a systemic effect of topically applied bromfenac, while the UV-erythema test (1-hr treatment time) clearly indicates a local effect.     

Phillygenin exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes

Context: Phillygenin (PHI) is an intestinal metabolite of phillyrin from the genus Forsythia. Although the regulatory activity of Forsythia on immune system has been investigated, the effect of PHI on activated lymphocytes is poorly understood.

Objective: This study was aimed to discuss the possible anti-inflammation potential of PHI on mitogen-activated stimulated lymphocytes in vitro.

Methods: Mice spleen lymphocytes were incubated with PHI for 4?h, and then stimulated with concanavalin A (Con A) or phorbol 12-myristate 13-acetate/ionomycin (PMA?+?Ion). Cell viability was assayed by cell counting kit-8 (CCK-8). The expression of CD69 and CD25, proliferation, cell cycle, intracellular Ca²⁺ concentration, apoptosis, mitochondrial inner membrane potential (ΔΨm), mitochondrial permeability transition (MPT), interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were analyzed by flow cytometry. The expression of cyclin B1, cyclin D1, Cyclin E, and the phosphorylation of c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (Erk1/2) and p38 were assayed by western blotting.

Results: The results showed that PHI inhibited the proliferation of Con A-activated lymphocytes and induced a G₀/G₁ phase arrest by suppressing cyclin D1 and cyclin E. Meanwhile, PHI antagonized Con A-induced T cells activation through blocking intracellular Ca²⁺ overload and suppressing the phosphorylation of JNK and Erk1/2. Both Con A and PMA?+?Ion-induced secretion of IL-2, IFN-γ, and TNF-α were attenuated by PHI. PHI enhanced Con A-induced lymphocytes apoptosis through decreasing ΔΨm and increasing MPT.

Conclusion: These results suggest that PHI exhibits its anti-inflammatory activity through modulating multiple cellular behaviors, leading to the suppression of the adaptive immune response.     

Anti-Diarrheal Activity and Toxicity of Learng Pid Samud Recipe

Learng Pid Samud (LPS) recipe is a traditional remedy in Thai folk medicine to ease the common diarrhea. The anti-diarrheal potential of LPS recipe was herein examined in vitro using a guinea-pig ileum model. The LPS exerted an inhibitory effect on acetylcholine-induced smooth muscle contraction in the guinea pig ileum. Significantly, not only did the LPS reduce the total amount of feces in the induced diarrhea rats, but also the intestinal transit in the charcoal meal test. A single oral administration with the recipe at 5,000 mg/kg did not cause acute toxicity and the daily oral administration (1,000, 2,000 and 4,000 mg/kg) for 90 days in rats did not produce any toxic signs and symptoms. In conclusion, the Learng Pid Samud recipe remedy is evidently safe and effective for the anti-diarrheal treatment which supports its therapeutic uses in the alternative medicine.     

Antioxidant and anti-inflammatory activities of selenomethylene blue

The selenium derivative of methylene blue, has been compared with the parent compound. Unlike some organic selenium compounds neither of the compounds affected macrophage chemiluminescence nor did they catalyse the glutathione-dependent breakdown of hydroperoxidesin vitro. However, both inhibited iron-induced hepatic lipid peroxidation,in vitro andex vivo, the selenium derivative being 3-fold more active in this respect. Both compounds inhibited inflammatory paw oedema in the rat, selenomethylene blue being the more active. Selenomethylene blue, thus, does not exhibit a different anti-oxidant/anti-inflammatory profile from that of the parent sulphur compound, but exhibits increased inhibitory activity.

     

Lesions of the renal papilla induced by paracetamol

The acute nephrotoxic effects of paracetamol in the uninephrectomized homozygous Gunn rat are different from those of aspirin. Both compounds induce renal papillary necrosis but paracetamol produces accumulation of non-cellular material in the interstitial space, less damage to interstitial cells, more damage to tubular epithelium, and more severe necrosis of proximal convoluted tubules. In both cortex and papilla only a small fraction of the cells at risk are affected. It is concluded that the findings are consistent with a synergistic nephrotoxic effect between the two compounds, but that the lesions are not sufficiently severe for the natural history of analgesic nephropathy to be wholly explicable by such synergism.     

尼尔样1型生长因子通过促进软骨生成及抗炎作用来治疗骨关节炎的潜力

背景:骨关节炎是一种复杂的全关节疾病,主要影响的关节是膝关节,其次是手和髋关节,治疗上主要以缓解疼痛症状为基础,但令人遗憾的是,到目前为止还没有有效的药物可以阻止疾病的进展.最近,一种具有促软骨形成、抗炎、抗脂肪、促血管化等特性的成骨蛋白——尼尔样1型生长因子(Nel-like molecule 1,Nell-1)进入...     

Atherosclerosis: anti-inflammatory and immunomodulatory activities of statins

Large clinical trials have demonstrated that HMG-CoA reductase inhibitors or 'statins' greatly reduce cardiovascular-related morbidity and mortality. The beneficial effects of statins were first assumed to result from their ability to reduce cholesterol synthesis and improve serum lipid profiles. In recent years, however, numerous pleiotropic effects of statins on atherosclerotic lesions have been described. In this review, we summarize the actions of statins on different aspects of atherosclerotic plaque development. These include endothelial dysfunction, leukocyte recruitment and inflammation, smooth muscle cell activation/proliferation, and finally plaque rupture and thrombosis.