Evaluation of antiarthritic activity of isoeugenol in adjuvant induced arthritis in murine model

Isoeugenol, a component of clover oil, possesses potent anti-inflammatory and antioxidant activity. In the present study, we investigated the effect on experimentally induced adjuvant arthritis in rats. Induction of arthritis in adjuvant exposed rats was confirmed by appearance of several physical symptoms such as redness, swelling and stiffness of paws, radiographic analysis revealing joint damage, soft tissue swelling of the footpad, histopathologic changes and expression of proinflammatory enzymes and mediators in the joint tissue. Treatment of rats with isoeugenol, however, conferred a significant protection against almost all the investigated parameters. Isoeugenol significantly and dose dependently attenuated arthritic index, paw circumference, joint stiffness and the levels of proinflammatory mediators. Exposure to isoeugenol inhibited the release of nitric oxide and proinflammatory cytokines the including PGE₂ and TNFα from lipopolysaccharide primed macrophages. Isoeugenol also showed a significant analgesic activity in acetic acid-induced writhing model. Further, unlike most antiarthritic drugs, isoeugenol had no damaging effect on gastric mucosa, which makes it a favorable antiarthritic drug. Thus, the results obtained in the present study indicate isoeugenol to possess a promising antiarthritic activity and further advocate the efficacy of natural products as antiarthritic therapeutics.     

Quantitative assessment of markers of inflammation,arthritis and pain in rats with adjuvant arthritis following the treatment with ibuprofen cream and placebo

When applied topically, nonsteroidal antiinflammatory drugs (NSAIDs) are absorbed locally and hence systemic adverse effects can be avoided due to very low plasma concentrations. In addition, direct local antiphlogistic treatment of the affected area is desirable. The present study was undertaken to assess markers of inflammation, arthritis and pain in rats with adjuvant arthritis undergoing treatment with ibuprofen cream (Dolgit cream) and placebo. Ibuprofen cream was applied (70 mg/hind paw) 3 times daily on hind paws from day 12 (after the initial signs of hind paw swelling appeared) for 3 weeks. Pain threshold, hind paw swelling, arthrogram score and serum albumin concentrations were measured in healthy controls, in rats with adjuvant arthritis and in rats treated with both placebo and active cream. Pain threshold increased in rats treated with ibuprofen cream (after 12 days of application), but this change was not significant. However, hind paw swelling significantly decreased as early as after 5 days of treatment with ibuprofen cream in comparison with both arthritic and placebo-treated rats and remained decreased throughout the study (an additional 16 days). Evaluation of the arthrogram score gave similar results. Serum albumin levels were unaffected by ibuprofen cream treatment. In conclusion, our results show that topical application of ibuprofen cream on inflamed hind paws produced significant local antiinflammatory and antiarthritic effects in rat adjuvant arthritis.     

Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs

The present study was designed to evaluate the anti-inflammatory and antiarthritic activity of the new synthetic thienopyridine analogs. The anti-inflammatory activity of thienopyridines was assayed by using carrageenan; dextran and arachidonic acid induced paw edema models (acute), cotton pellet granuloma model (Sub acute) and Freund's complete adjuvant induced arthritis (chronic) in experimental rats. The compounds BN-4, BN-14 and BN-16 have shown significant inhibition of edema in carrageenan and arachidonic acid induced paw edema model at a dose of 100mg/kg compared to the dextran induced paw edema model and also showed significant inhibition in granuloma tissue formation and Freund's complete adjuvant induced arthritis in experimental rats. These thienopyridine analogs also inhibited the proinflammatory mediators such as Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Nitric Oxide (NO) in Lipopolysaccharide (LPS) challenged murine macrophages. Ulcerogenecity study results revealed less ulcerogenic potential of BN-4, BN-14 and BN-16 compared to nonsteroidal anti-inflammatory drug (NSAID) indomethacin in rats. In conclusion, the new thienopyridine analogs were promising for the potential use as anti-inflammatory agents for both acute and chronic inflammatory disorders with low toxic effects.     

The anti-inflammatory effects of LY178002 and LY256548

LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4-thiazolidinon e) and its N-methyl analog, LY256548, inhibit the enzymatic activity of phospholipase A2, 5-lipoxygenase and fatty acid cycloxygenase. They also inhibit leukotriene B4 production from human polymorphonuclear leukocytes stimulated with the calcium ionophore A23187. Since products of the arachidonic acid cascade have been implicated as important mediators in a variety of inflammatory diseases including arthritis, LY178002 and LY256548 were studied in the Freund's Complete Adjuvant-Induced Arthritis (FCA) model in rats. The compounds were administered orally and inhibition of bone damage and paw swelling was assessed of both the injected and uninjected paws. At 50 mg/kg LY178002 inhibited soft tissue swelling in the uninjected paw by 81% while LY256548 exhibited 57% inhibition. Bone damage was also significantly inhibited by both compounds. A dose response was conducted. The minimum effective dose for LY178002 was 10 mg/kg p.o. In the established FCA model LY178002 at 50 mg/kg p.o. inhibited the uninjected paw swelling by 75% while LY256548 did not show this level of activity. These results suggest that LY178002 and LY256548 may be useful in the treatment of arthritis.     

木瓜丸对大鼠佐剂性关节炎的防治作用

目的：探讨木瓜丸对大鼠佐剂性关节炎的预防及治疗作用。方法：建立大鼠佐剂性关节炎模型，观察不同阶段给药对佐剂性关节炎的影响。结果：木瓜丸预防性给药，能抑制注射局部炎症和8d后的再肿胀，抑制对侧后肢因迟发性超敏反应引起的足肿胀；对继发病变的预防性给药，可抑制对侧足肿胀，使注射侧足肿胀明显消退，减轻再肿胀的程度；对继发病变的治疗性给药，可降低注射对侧足爪的肿胀度、前肢和尾部的病变度。结论：木瓜丸对大鼠佐剂性关节炎的原发病变和继发病变有显著的预防和治疗作用。     

Effect of Fixed Oil of Ocimum sanctum against Experimentally Induced Arthritis and Joint Edema in Laboratory Animals

The fixed oil of O. sanctum seeds was screened for antiarthritic activity using Freund's adjuvant arthritis, formaldehyde-induced arthritis and also turpentine oil-induced joint edema in rats. The oil was administered intraperitoneally for 14 days in the case of adjuvant-induced arthritis and 10 days in formaldehyde-induced arthritis. The mean changes in diameter of paw were noted at regular intervals. X-rays of paws were taken at the end of study and SGOT & SGPT levels were also estimated. The fixed oil showed significant anti-arthritic activity in both models and anti-edema activity against turpentine oil-induced joint edema.     

Antiinflammatory actions of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones

Methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones (MHSK and PHSK, resp.) upon oral administration displayed marked antiinflammatory activity in a variety of acute tests viz. carrageenan, histamine, 5-hydroxytryptamine, dextran, bradykinin and prostaglandin (PG) induced oedema in rats and carrageenan evoked swelling in mice; the activity was not altered by adrenalectomy. In subacute test of formaldehyde arthritis, they showed significant reduction in paw swelling but were less effective in granuloma tests. In chronic tests, they produced marked antiarthritic effect both in developing and established adjuvant arthritis. The compounds prevented the inflammation induced increase in serum transaminase levels and leucocyte counts. They inhibited the passive cutaneous anaphylaxis and produced reduction in ADP induced platelet aggregation. The compounds showed weaker antipyretic activity than acetylsalicylic acid in pyretic animals. MHSK showed analgesic activity using the tail clip method and antagonised acetic acid induced writhing syndrome. The compounds lacked any local anaesthetic activity. The low ulcerogenic potential of these compounds in animal models may be related to their relative inability to inhibit PG synthetase.     

芦丁对大鼠佐剂性关节炎的影响

目的观察芦丁对大鼠佐剂性关节炎(AA)的影响。方法弗氏完全佐剂制作AA大鼠模型,于造模第13天将动物随机分为空白对照组、模型组、双氯芬酸钠10mg·kg-1组及芦丁100和200mg·kg-1剂量组,空白对照组和模型组灌胃给予同体积的质量浓度为5g·L-1的羧甲基纤维素钠(CMC-Na),各组大鼠灌胃给药,每日1次,连续15d,观察药物对佐剂性关节炎大鼠原发性病变、继发性病变和体质量变化的影响,并于造模第28天乙醚麻醉处死大鼠,观察各组大鼠血生化(尿素、肌酐、总蛋白、白蛋白及白蛋白/球蛋白比)和血常规(红细胞、白细胞、血红蛋白含量)以及免疫器官(脾脏、胸腺)等指标的变化。结果芦丁100和200mg·kg-1剂量组能显著减轻模型鼠左后足关节肿胀程度(P<0.05),降低胸腺和脾脏系数(P<0.05),降低造模后大鼠血液中升高的白细胞和肌酐的含量(P<0.05)。10mg·kg-1双氯芬酸钠也表现出显著的抗炎和抗关节炎的活性(P<0.01)。结论芦丁100和200mg·kg-1剂量组对弗氏完全佐剂诱导的大鼠AA具有抗炎和改善肾脏功能的作用,且对免疫器官脾脏和胸腺具有保护作用,研究确证芦丁具有一定的抗关节炎活性。     

重组人内抑素对大鼠佐剂性关节炎继发性炎症的抑制作用

目的　观察重组人内抑素对大鼠佐剂性关节炎 (AA)继发性炎症是否有抑制作用。方法　用足容积测量仪检测足爪容积并对关节炎症程度进行目测评分 ;HE染色检测非致炎侧膝关节的病理改变。结果　福氏完全佐剂 (CFA)致炎后d 1 0 ,继发性炎症出现 ,同时给予不同剂量的内抑素(0 1、0 5、2 5mg·kg- 1 ·d- 1 ,sc) ,连续 7d。结果发现 ,内抑素 2 5mg·kg- 1 对AA大鼠的继发性足肿胀有明显的抑制作用 ;致炎后d 30病理检查显示AA大鼠的关节内滑膜增厚 ,滑膜衬层细胞增生并伴有新生血管形成 ,滑膜细胞有不同程度的脂肪变性 ;软骨及骨遭到破坏 ,且透明软骨内基质降解及新生血管形成。给予不同剂量的内抑素对AA大鼠关节组织的上述病理改变有不同程度的改善作用 ,内抑素 2 5mg·kg- 1 对AA大鼠的关节病理损伤有完全的抑制作用 ,同时可见滑膜组织内大量胶原沉积和滑膜细胞的脂肪变性。结论　重组人内抑素对大鼠佐剂性关节炎的继发性炎症有显著的抑制作用 ,并能阻止关节炎的病理改变     

The Antiinflammatory and Antiarthritic Properties of Ethanol Extract of Hedera helix

The ethanol Hedera helix plant extract was tested for its antiinflammatory properties. Intraperitoneal injections of 7.5 ml/kg wt ethanol extract showed antiinflammatory activity with 88.89% inhibition as compared to reference drug diclofenac, which showed 94.44% inhibition in formalin-induced paw oedema. As formalin-induced paw oedema closely resembles human arthritis, the antiarthritic property of ethanol extract of Hedera helix was also investigated. The visible reduction in arthritic symptoms by extract of Hedera helix suggests the potential of the plant extract against inflammation and arthritis.     

祛风息痛丸对大鼠佐剂性关节炎的治疗作用

目的观察祛风息痛丸对佐剂性关节炎的治疗作用,为其临床治疗类风湿性关节炎提供实验依据。方法建立佐剂性关节炎大鼠模型,采用玻璃容器法测定大鼠原发性和继发性足爪肿胀度。采用酶联免疫吸附试验测定血清白细胞介素1(IL-1)和肿瘤坏死因子α(TNFα)含量。结果祛风息痛丸0.26,0.78和2.34g.kg-1连续灌胃3d显著抑制佐剂性关节炎大鼠原发性足爪肿胀,对致炎后18h的肿胀抑制率分别为21.4%,36.8%和65.0%。同剂量祛风息痛丸连续灌胃30d对佐剂性关节炎大鼠继发性即非致炎侧关节肿胀具有明显的抑制作用,并可明显降低多发性关节炎病变评分,中、大剂量可明显降低血清IL-1和TNFα含量。结论祛风息痛丸对实验性佐剂性关节炎具有治疗作用。     

Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

The present work aimed to investigate the anti-rheumatism effect and the mechanism of celastrol in collagen-induced arthritis (CIA) rats. The CIA model was established in male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of celastrol for 28 days. A variety of indicators, including paw swelling and arthritis scores, were measured for anti-rheumatism effect. Celastrol treatment attenuated paw swelling and arthritis scores in CIA rats. Celastrol improved the spleen and thymus indexes in CIA rats. The increased levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ, were abolished by celastrol treatment. In addition, the weakened superoxide dismutase (SOD) activity, the increased levels of malondialdehyde (MDA), and superoxide anions, and enhanced NADPH oxidase (Nox) activity were all reversed by celastrol treatment. Nox4 overexpression reversed the attenuating effects of celastrol on paw swelling and arthritis scores in CIA rats. The celastrol-induced improvement in spleen and thymus indexes in CIA rats was inhibited by Nox4 overexpression. Nox4 overexpression reversed the abolishing effects of celastrol on the increases of TNF-α, IL-1β, IL-6, and IFN-γ levels in the serum of CIA rats. These results demonstrated that celastrol improved rheumatism in arthritis via inhibiting oxidative stress.     

Study of the anti-inflammatory activity of Populus tremula, Solidago virgaurea and Fraxinus excelsior.

Aqueous/alcoholic extracts of Populus tremula, Solidago virgaurea and Fraxinus excelsior (components of Phytodolor N) were tested individually and in 3 different combinations for anti-inflammatory activity using carrageenan induced edema and/or adjuvant induced arthritis of the rat paw. The tested combinations as well as the individual extracts significantly reduced the paw edema to varying degrees and also dose dependently inhibited the arthritic paw volume. The anti-inflammatory activity of the combinations was respectively comparable to the tested doses of diclofenac.     

Anti-inflammatory effects of LY221068 and LY269415.

LY221068, 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxy phenyl]methylene]-3-(dimethylamino)-4-thiazolidinone, and the monomethylamino analog, LY269415, are anti-oxidants and potent inhibitors of iron dependent lipid peroxidation and 5-lipoxygenase enzyme. Since oxygen radical species, lipid peroxides and products of the arachidonic acid cascade have been implicated as important mediators in a variety of inflammatory diseases including arthritis, LY221068 and LY269415 were studied in the Freund's Complete Adjuvant Induced Arthritis (FCA) model in rats. The compounds were administered orally and inhibition of bone damage and paw swelling of both the injected and uninjected paws was assessed. At 50 mg/kg p.o., LY221068 inhibited soft tissue swelling in the uninjected paw by 72% while LY269415 at 25 mg/kg p.o. exhibited 74% inhibition. Bone damage was also significantly inhibited by both compounds. In a dose response study, the minimum effective dose for LY221068 was 10 mg/kg p.o. and for LY269415 was 5 mg/kg p.o. In the established FCA model in rats, LY221068 at 50 mg/kg p.o. inhibited the uninjected paw swelling by 71% while LY269415 at 25 mg/kg p.o. inhibited 70%. These results suggest that LY221068 and LY269415 may be useful in the treatment of arthritis.     

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).     

玉屏风多糖对佐剂性关节炎大鼠T细胞亚群的影响

目的观察玉屏风多糖(Yupingfeng Polysaccharide,YPF-P)对佐剂性关节炎大鼠T细胞亚群的影响。方法采用弗氏完全佐剂(FCA)诱导大鼠AA模型。足容积法测量继发侧足肿胀度;MTT法检测刀豆蛋白(ConA)诱导的外周血淋巴细胞增殖反应;流式细胞仪检测大鼠外周血中CD4+和CD8+T细胞的变化;ELISA法检测大鼠外周血中干扰素γ(interferon-γ,IFN-γ)含量;放免法检测大鼠外周血中IL-4含量;RT-PCR法检测淋巴细胞IFN-γmRNA的表达。结果80、160mg.kg-1YPF-P给药能明显减轻关节肿胀度,不同程度地改善AA大鼠低下的外周血淋巴细胞增殖反应,明显降低CD4+/CD8+的相对比值。此外,80、160mg.kg-1YPF-P给药也能明显降低外周血IFN-γ含量和轻度提高IL-4含量,并能抑制IFN-γmRNA的表达。结论YPF-P能改善模型大鼠外周血T细胞亚群,纠正佐剂性关节炎模型大鼠Th1/Th2平衡的Th1偏移,这可能是减轻足肿胀的原因之一。     

Anti-inflammatory activities of ethanolic extract of <Emphasis Type="Italic">Carica papaya</Emphasis> leaves

The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g. In the formaldehyde arthritis model, the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves.     

芍药苷对胶原性关节炎大鼠滑膜细胞G蛋白偶联信号的调节作用

目的研究芍药苷(paeoniflorin,Pae)对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠滑膜细胞G蛋白偶联信号转导的调节作用。方法用鸡Ⅱ型胶原诱导胶原性关节炎。在免疫后d16~23,胶原性关节炎大鼠灌胃给予Pae(25、50、100mg·kg-1)。通过足爪肿胀和关节炎指数评价关节炎。采用Western blot技术检测滑膜细胞中抑制性G蛋白(Gi)表达。用放免法检测滑膜细胞中cAMP水平,用激酶发光分析法测定滑膜细胞中蛋白激酶A(PKA)的活性。结果胶原性关节炎大鼠出现明显的继发性炎症反应。滑膜细胞中Gi蛋白表达增加,而cAMP水平和PKA活性明显降低。Pae抑制胶原性关节炎大鼠的炎症应答。在100mg·kg-1,Pae抑制Gi的表达。在50mg·kg-1和100mg·kg-1剂量,Pae提高cAMP水平和PKA活性。体外研究发现,Pae(2·5、12·5、62·5mg·L-1)降低滑膜细胞中Gi的表达,而提高降低的cAMP水平和PKA活性。结论胶原性关节炎大鼠滑膜细胞中G蛋白偶联的信号转导与滑膜炎病理机制密切相关;Pae对胶原性关节炎大鼠的抗炎作用是通过调节G蛋白偶联的信号转导实现的。     

银杏叶提取物对大鼠佐剂性关节炎的治疗作用与机制

目的:考察银杏叶提取物(EGb761)对佐剂性关节炎(AA)大鼠的治疗作用,初步探讨银杏叶提取物治疗AA的作用机制。方法:将大鼠随机分为正常对照组,模型组,雷公藤多苷组,EGb761低、中、高(50,100,200 mg.kg-1)剂量组。弗氏完全佐剂致AA后d 12,大鼠出现继发性炎症,分别灌胃给予雷公藤多苷和EGb761,连续16 d;在不同的时间点检测大鼠继发侧关节肿胀度;致炎d 28处死大鼠,酶联免疫法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)含量;光学显微镜观察关节病理变化。结果:EGb761可明显减轻继发性AA大鼠足爪的肿胀度;降低大鼠血清中IL-1β和IL-6含量;升高大鼠血清中IL-4和IL-10含量。结论:EGb761对大鼠继发性AA具有显著的治疗作用,其作用机制可能与抑制促炎因子IL-1β和IL-6的产生和释放以及促进抑炎因子IL-4和IL-10的表达相关。     

Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage

The saponin astragaloside IV (AST) is one of major active components purified from Astragalus membranaceus (Fisch) Bge, which has been used in traditional Chinese medicine to treat immune disorders including rheumatoid arthritis (RA). The effects of AST on the suppression of experimental arthritis and its possible mechanisms are unknown. We measured the paw swelling of ankle joints, splenocyte proliferation, interleukin 1β (IL-1β), tumor necrosis factor α (TNFα) and nitric oxide (NO) formation by macrophages in rat adjuvant-induced arthritis (AIA). Intraarticular injection of IL-1β to rat knee joint for inducing the edema and in vitro IL-1β-stimulated cartilage impairment were examined. The results showed that oral treatment of AST (100 mg/kg/day) suppressed the joint inflammation and inhibited IL-1β, TNFα and NO production in macrophages from AIA rats. Macrophages were one of AST targeted cells, and mediated the reduced splenocyte proliferation in AIA rats. In addition, AST reduced the swelling induced by intraarticular injection of IL-1β, and protected against IL-1β-induced damage of cartilage proteoglycan synthesis and chondrocyte proliferation. We conclude that AST possesses antiarthritic effect and prevents IL-1β-induced joint inflammation and cartilage destruction. These findings suggest that AST may be used for the treatment of RA and other inflammatory joint diseases.