Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in rats

Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall. The present study was carried out to investigate the effects of TGP on adjuvant arthritis (AA) of rat and its possible mechanisms. AA was induced by metatarsal footpad injection with complete Freund's adjuvant in male Sprague-Dawley rats. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index. Activity of interleukin-1 (IL-1) was detected by Con A-induced thymocytes proliferation of C57BL/6J mice assay. The tumor necrosis factor alpha (TNFalpha), prostaglandin E(2) (PGE(2)) and cyclic adenosine monophosphate (cAMP) levels in synoviocytes were assessed by radioimmunoassay (RIA). PGE(2) receptors, EP2 and EP4, were analyzed by Western blot analysis. The level of IL-6 was measured by ELISA. Intragastric administration of TGP (50,100 mg/kg) significantly decreased secondary inflammatory reaction in AA rats. Suppressing the activity of IL-1 and TNFalpha, decreased PGE(2) and increased cAMP levels in synoviocytes of AA rats were observed after administration of TGP. In the immunoblot analysis, TGP could up-regulate the expression of EP2 and EP4. These results showed TGP significantly inhibited the progression of AA, and the inhibitory effects might be associated with its ability to mediate the level of cAMP and inhibit the production of IL-1, TNFalpha, IL-6 and PGE(2) from activated synoviocytes.     

Therapeutic effects of daphnetin on adjuvant-induced arthritic rats

AIM OF THIS STUDY: Daphnetin was regarded as the mark compound for quality control of Zushima-Pian, a traditional Chinese medicine tablet for treating rheumatoid arthritis (RA). However, no in vivo study on the therapeutic effects of daphnetin for RA has been reported. MATERIALS AND METHODS: The adjuvant arthritic (AA) rat model was developed to evaluate the anti-arthritic effects of daphnetin. After immunized with Freund's complete adjuvant (FCA), the rats were treated with daphnetin (2.25 and 4.5mg/kg) for three weeks. We determined the change of secondary paw swelling and the arthritis scores of these tested rats. The severity of arthritis in the knee joints was evaluated by histological assessment of cartilage destruction. The levels of IL-1, TNF-alpha and MIF in the serum were measured by ELISA. RESULTS AND CONCLUSIONS: Our results showed that daphnetin significantly reduced paw swelling and decreased the arthritis scores. The pathological examination demonstrated that articular cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in AA rats were suppressed by daphnetin. There was significant reduction in production of interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and macrophage migration inhibitory factor (MIF) in serum of AA rats treated with daphnetin except the low dose group (2.25mg/kg) on TNF-alpha. In conclusion, we demonstrates that daphnetin is highly effective on preventing and suppressing the development and progression of adjuvant-induced arthritis and provides direct evidences that daphnetin is one of the active principle of Zushima-Pian for treating rheumatoid arthritis.     

马钱子总碱囊泡凝胶对AA大鼠的治疗作用

目的:观察马钱子总碱囊泡凝胶对佐剂性关节炎(AA)大鼠的治疗作用及其机制。方法:SD大鼠随机分为9组:正常组、AA模型组、马钱子总碱囊泡凝胶高、中、低剂量(25,12.5,6.25 mg·kg-1)组、马钱子总碱药物凝胶高、中、低剂量(25,12.5,6.25 mg·kg-1)组和扶他林对照组(双氯芬酸二乙胺乳胶剂,50 mg·kg-1)。除正常组外,其余各组均以弗氏完全佐剂(FCA)每鼠左后足跖皮内注射0.1 mL致炎,各给药组在大鼠足趾部分均匀涂抹药物并用油纸包裹。足容积法测量继发侧足肿胀度,进行疼痛评分和多发性关节炎评分,HE染色观察关节病理损伤,酶联免疫吸附测定法(ELISA)测定白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、前列腺素(PGE2)、白细胞介素6(IL-6)和血管内皮细胞生长因子(VEGF)的表达。结果:与模型组相比,囊泡凝胶和药物凝胶可明显减轻AA大鼠的继发侧足爪肿胀度(17～21 d)。马钱子总碱囊泡凝胶和药物凝胶可有效抑制大鼠多发性关节炎指数,减轻关节病理学损伤,马钱子总碱囊泡凝胶还可降低滑膜组织匀浆上清液IL-1,TNF-α,PGE2,IL-6水平和提高VEGF水平。结论:马钱子总碱囊泡凝胶可拮抗大鼠AA发展,其作用机制与抑制炎症介质的生成密切相关。     

Therapeutic effect of tripterine on adjuvant arthritis in rats

AIMS OF THE STUDY: Tripterygium wilfordii Hoog f., a perennial vine, is used in traditional Chinese medicine for treatment of rheumatoid arthritis. This study was to determine whether tripterine, isolated from Tripterygium wilfordii Hoog f., had therapeutic effects on adjuvant arthritis. MATERIALS AND METHODS: Adjuvant arthritis (AA) was induced in rats on day 0. Tripterine 5, 10 and 20 mg kg(-1)day(-1), or prednisone 10 mg kg(-1)day(-1) was given to rats intragastrically from day 19 to day 24. RESULTS: Tripterine significantly inhibited paw swelling and bone destruction in AA rats. Serum level of IgG anti-Mycobacterium tuberculosis antibodies and delayed-type hypersensitivity (DTH) induced by Mycobacterium tuberculosis were also decreased by tripterine. The effects of tripterine were associated with decreased interleukin-1beta (IL-1beta) mRNA expression in ankle joint synovial membrane and tumor necrosis factor-alpha (TNF-alpha) mRNA expression in homogenized paws from adjuvant-induced arthritic rats. CONCLUSIONS: These findings suggested that tripterine had a therapeutic effect on adjuvant arthritis.     

加味木防己汤抗大鼠实验性关节炎的研究

目的探讨加味木防己汤对大鼠实验性佐剂关节炎（adjuvant arthritis,AA）的作用及其机制。方法应用弗氏完全佐剂注射诱发大鼠产生实验性关节炎,第18天开始给予加味木防己汤灌胃,39天测量AA大鼠体重,脾及胸腺指数,足肿胀度。HE染色观察大鼠踝关节组织病理学变化,ELISA法测定大鼠血清中白细胞介素-1β（IL-1β）,肿瘤坏死N子-α（TNF—α）的含量。结果加味木防己汤能缓解AA病情,使足肿胀度下降,体重及脏器指数改善,关节水肿减轻,淋巴细胞浸润明显减少,滑膜增生受抑制。血清IL-1β,TNF—α的含量明显下降。结论加味木防己汤对AA大鼠的治疗作用,可能与其下调IL-1β,TNF—α的含量有关。     

野菊花总黄酮对佐剂性关节炎大鼠氧自由基代谢的影响

目的:探讨野菊花总黄酮(total flavonoids of Chrysanthemum indicum,TFC)对佛氏完全佐剂诱导的佐剂性关节炎(AA)大鼠模型的继发性肿胀作用及自由基代谢和免疫调节的影响.方法:用佛氏完全佐剂(FCA)建立大鼠的佐剂性关节炎模型,用足趾容积测量仪检测大鼠的继发性肿胀,观察TFC对其的治疗作用;采用试剂盒检测佐剂性关节炎大鼠的血清和腹腔巨噬细胞培养上清中的SOD活性、MDA含量以及NO水平;采用ConA诱导测定大鼠脾淋巴细胞增殖反应,采用小鼠脾细胞增殖法测定IL-2活性.结果:与模型组比较,TFC能改善佐剂性关节炎大鼠的继发性足趾肿胀,能降低血清和腹腔巨噬细胞中MDA和NO含量,升高SOD活性,同时促进脾淋巴细胞增殖和IL-2活性.结论:TFC可以抑制佐剂性关节炎大鼠的继发性足趾肿胀,其机制可能与其抗氧化作用和免疫调节有关.     

湿迪胶囊对大鼠佐剂性关节炎作用机制的研究

目的：观察湿迪胶囊对大鼠佐剂性关节炎(AA)的作用并初步探讨其作用机制。方法：SD大鼠,雄性,随机分为正常组(0.5% CMC-Na溶液)、模型组(0.5% CMC-Na溶液)、地塞米松组(0.45 mg·kg_-1)、白芍总苷组(150 mg·kg_-1)以及湿迪胶囊(以生药计)高(5 400 mg·kg_-1)、中(2 700 mg·kg_-1)、低(1 350 mg·kg_-1)剂量组；除正常组外,其余各组采用大鼠右后足跖皮内注射氟氏完全佐剂建立AA模型,并分别给予灌胃治疗,观察各组的足跖肿胀度,测定炎性肿胀足前列腺素E₂(PGE₂)含量及血清中丙二醛(MDA)、超氧化物歧化酶(SOD)含量,测定脾及胸腺指数,并观察踝关节的病理组织学变化。结果：湿迪胶囊高、中、低剂量组可剂量依赖性显著抑制大鼠右后足跖的原发性肿胀和左后足跖的继发性肿胀；与模型组比较,湿迪胶囊高、中、低剂量组SOD总活力明显升高,MDA含量明显下降,PGE₂含量降低；与模型组比较湿迪3个剂量组的胸腺和脾脏指数均有所提高,差异有显著意义；湿迪高、中、低剂量组均可明显减轻AA大鼠的病理变化。结论：湿迪胶囊能明显抑制滑膜组织的炎症,减轻细胞的损伤程度,因而对AA大鼠具有一定的治疗效果。     

赤雹根总皂苷对类风湿性关节炎大鼠血清细胞因子的影响

目的研究赤雹根总皂苷对类风湿性关节炎大鼠血清IL-1β、IL-6、TNF-α的影响。方法以弗氏完全佐剂诱导大鼠佐剂性关节炎,将造模成功50只大鼠随机分为模型组,赤雹根总皂苷160,80,40 mg/(kg·d)组和雷公藤12 mg/(kg·d)组,另取10只正常大鼠作正常对照。连续灌胃给药21 d。观测各组大鼠继发关节肿胀度和关节炎指数;给药后第22天,处死大鼠,用酶联免疫吸附法(ELISA)检测血清IL-1β、IL-6、TNF-α含量。结果赤雹根总皂苷能明显降低佐剂性关节炎大鼠继发侧的关节肿胀度和关节炎指数(P<0.01);与正常对照组相比,模型组大鼠血清IL-1β、IL-6、TNF-α含量明显升高(P<0.01);赤雹根总皂苷灌胃治疗后,各组大鼠血清IL-1β、IL-6、TNF-α含量较模型组明显降低(P<0.01)。结论赤雹根总皂苷对大鼠类风湿性关节炎有治疗作用,且该作用与抑制IL-1β、IL-6、TNF-α的合成有关。     

通痹灵对大鼠佐剂性关节炎滑膜细胞功能的影响

目的：研究通痹灵（ＴＢＬ）对佐剂性关节炎（ＡＡ）大鼠滑膜成纤维增殖及滑膜细胞分泌白细胞介素１（ＩＬ－１），肿瘤坏死因子α（ＴＮＦ－α）和前列腺素Ｅ２（ＰＧＥ２）的影响。     

Immunomodulatory activity of the aqueous extract from rhizome of Smilax glabra in the later phase of adjuvant-induced arthritis in rats

Our previous paper has reported that the aqueous extract from Rhizoma Smilacis Glabrae (RSG) remarkably inhibited the primary inflammation of adjuvant arthritis (AA) in rats. In the present study, we further examined the activity of RSG and its mechanism on the secondary inflammation of AA. The administration of RSG (400 and 800 mg/kg) during the later phase significantly inhibited the swelling of the adjuvant-non-injected footpad of AA rats. The lipopolysaccharide-induced production of IL-1, TNF and NO by peritoneal macrophages was significantly reduced. In contrast, the extract significantly recovered the decrease in weight gain of the AA rats and Concanavalin A-induced T lymphocyte proliferation and IL-2 production by their splenocytes, while prednisolone (10mg/kg) showed a significant aggravation. Furthermore, RSG significantly recovered the picryl chloride-induced delayed-type hypersensitivity to almost normal levels from the higher or lower levels induced by different treatments of cyclophosphamide with a normalization of CD4/CD8 ratio. These results suggest that RSG exhibit an improvement on AA through down-regulating over-activated macrophages and up-regulating the dysfunctional T lymphocytes during the later phase of arthritis. Such characteristics of RSG on AA may be advantageous to the long-term treatment of clinical rheumatoid arthritis.     

六味地黄汤对佐剂性关节炎大鼠免疫功能的影响

目的：研究六味地黄汤对佐剂性关节炎（AA）大鼠的作用特点。方法：观察六味地黄汤对AA大鼠细胞免疫、体液免疫功能的作用,并与环磷酰胺（CY）和环孢素A（CsA)进行比较。结果：六味地黄汤口服给药对AA大鼠的关节肿胀具有明显的抑制作用,对AA大鼠的免疫功能紊乱也具有治疗作用。可使AA大鼠低下的淋巴细胞增殖水平恢复正常,而环磷酰胺（CY）与环孢素A（CsA) 则使AA大鼠低下的淋巴细胞水平进一步降低。结论：六味地黄汤AA大鼠的治疗作用与免疫抑制剂CY、CsA不同,其作用不是通过免疫抑制而是通过调节免疫平衡来实现的。     

侗族传统抗风湿药对大鼠佐剂性关节炎的治疗作用

目的:研究了侗族传统抗风湿药对佐剂性关节炎(adjuvant arthritis,AA)大鼠的治疗作用。方法:采用大鼠足跖皮内注射弗氏完全佐剂诱发大鼠AA模型。足容积法测量继发侧足肿胀度,进行疼痛评分和多发性关节炎评分。结果:侗族传统抗风湿药2000mg.kg-1.d-1剂量组于第14d开始不同程度降低AA大鼠继发侧足肿胀度、关节疼痛评分、多发性关节炎指数(P<0.05)。结论:侗族传统抗风湿药对佐剂性关节炎大鼠有明显的抗炎治疗作用。     

Inhibitory effects of the root extract of Litsea cubeba (lour.) pers. on adjuvant arthritis in rats

Ethnopharmacological relevance

The dried root of Litsea cubeba (Lour.) Pers. (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in southwestern China.

Aim of the study

This study investigated the preventive efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model.

Materials and methods

Arthritis was induced in male Wistar rats by immunization with CFA. Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at 50 mg/kg and 200 mg/kg were orally administered from a day after the induction of arthritis. Paw swelling, arthritic score, body weight growth rate, index of thymus and spleen were observed, and the production of TNF-α, IL-1β, IL-6 and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase were also measured by enzyme-linked immunosorbent assay. Moreover, histological changes in the ankle joint were analyzed in AA rats.

Results

Both EELC and WELC significantly suppressed paw swelling and arthritic score, increased the loss in body weight and decreased the index of thymus. Histopathological improvement in joint architecture was also observed in EELC, WELC-treated AA rats. The expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF-α, IL-1β and IL-6 were remarkably attenuated in serum of all Litsea cubeba-treated rats, however, IL-10 was markedly increased at doses of 50 mg/kg of EELC and WELC.

Conclusions

These results indicate that extract of Litsea cubeba root significantly attenuates adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing of IL-10 in serum as well as down-regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This suggests that Litsea cubeba root might be used as a therapeutic agent for the treatment of human arthritis.     

益肾蠲痹丸对类风湿性关节炎的药效学研究

目的：使用弗氏完全佐剂制作大鼠关节炎模型,评价益’肾蠲痹丸对类风湿性关节炎的药效。方法：使用弗氏完全佐剂造模后,测量益肾蠲痹丸对对侧足爪肿胀和脏器指数的影响：ELISA法检测其对血清肿瘤坏死因子Ⅱ（TNF-Ⅱ）,白介素1β（IL—1β）,白介素-6（IL-6）的影响;分光光度法测量总一氧化氮合酶（tNOS）和诱导型一氧化氮合酶（iNOS）活性：并用Westernblot法检测益肾蠲痹丸对凋亡蛋白Bcl-2表达的影响。结果：益肾蠲痹丸可有效抑制大鼠佐剂性关节炎所引起的足跖肿胀,且对胸腺脾脏指数无明显影响。益肾蠲痹丸可有效抑制血清中TNF-Ⅱ,IL-1β,IL-6含量：抑制血清中iNOS活性;下调Bcl-2在滑膜组织中的表达。结论：益肾蠲痹丸的抗类风湿关节炎的作用与其调节主要炎症因子,下调炎症部位Bcl-2蛋白表达有关。     

痛风颗粒浸膏粉对大鼠痛风性关节炎和佐剂性关节炎的影响

目的:研究痛风颗粒浸膏粉对大鼠急性痛风性关节炎(Acute Gouty Arthritis)和佐剂性关节炎(Adjuvant Arthritis,AA)的影响。方法:将大鼠分为正常对照组、模型对照组、痛风颗粒浸膏粉高剂量组(8.75g/kg)、低剂量组(4.375 g/kg),观察痛风颗粒浸膏粉灌胃给药对大鼠尿酸钠致急性痛风性关节炎模型的足肿胀率的影响,并观察其对佐剂性关节炎模型踝关节肿胀度及其病理改变的影响。结果:对急性痛风性关节炎,痛风颗粒浸膏粉8.75g/kg对足肿胀有明显的改善(P<0.01),4.375g/kg较之于模型组有改善但无统计学意义,起效剂量为8.75g/kg。对佐剂性关节炎,痛风颗粒浸膏粉高剂组、低剂量组对大鼠右足踝关节肿胀程度以及继发的对侧足踝关节肿胀程度均有改善,并抑制踝关节组织病理学改变(P<0.01或P<0.05),起效剂量为4.375 g/kg,在4.375g/kg～8.75g/kg剂量范围,受试物对佐剂性关节炎具剂量依赖性的抑制作用。结论:痛风颗粒浸膏粉不仅对实验性大鼠痛风性关节炎有较好的治疗作用,其对佐剂关节炎也作用明显。     

雷公藤多苷联合来氟米特对佐剂性关节炎 大鼠的治疗及机制研究

目的: 研究雷公藤多苷联合来氟米特普配伍使用对佐剂性关节炎(AA)大鼠的治疗效果及其可能的作用机制。方法: 建立AA大鼠关节炎模型,分为对照组、模型组、来氟米特组、雷公藤多苷组和雷公藤多苷联合来氟米特配伍组;来氟米特20 mg ·kg^-1 ig,1次/d;雷公藤多苷组:雷公藤多苷20 mg ·kg^-1 ig,1次/d;配伍组:来氟米特20 mg ·kg^-1 ig,8 h后,雷公藤多苷20 mg ·kg^-1 ig,1次/d均于造模后14 d开始给药,连续处理21 d。治疗后,观察AA大鼠足爪肿胀程度及关节炎指数(AI),采用放射免疫法检测血清中白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达水平,酶联免疫吸附法(ELISA)检测血清中干扰素-γ(IFN-γ)、IL-4和前列腺素E₂(PGE₂)含量。结果: ① 相较于AA模型组,来氟米特组、雷公藤多苷组和配伍组中大鼠足爪肿胀程度及AI评分均显著下降(P均<0.01),其中以配伍组大鼠关节炎症状改善最为明显(P<0.05)。② 模型组大鼠血清IL-1β,TNF-α,IL-6和PGE₂水平明显高于正常对照组(P<0.01),而经过治疗后血清中各细胞因子含量均发生不同程度的下降,且以配伍组降低最为显著(P<0.01或P<0.05);③ 模型组大鼠血清中IFN-γ表达水平明显高于正常对照组,而IL-4含量明显低于对照组(P<0.01),治疗后各组中AA大鼠血清中IFN-γ水平显著降低,而IL-4水平明显升高(P<0.05),其中以配伍组变化最为明显(P<0.01)。结论: 雷公藤多苷和来氟米特联合使用可显著降低血清中炎症因子水平,减少关节破坏,减轻AA大鼠的关节炎症状。     

逐痹胶囊对大鼠佐剂性关节炎的影响

目的:观察逐痹胶囊对大鼠佐剂性关节炎(adjuvantarthritis,AA)的影响及作用机制。方法:用福氏完全佐剂(CFA)诱导大鼠AA模型,MTT法检测脾淋巴细胞增殖能力,免疫组织化学方法检测踝关节滑膜白细胞介素1(IL-1),白细胞介素6(IL-6)含量,并且测量原发及继发性关节肿胀程度。结果:生药52,26,13g·kg^-1体重灌胃大鼠,逐痹胶囊显著抑制AA大鼠原发及继发踝关节炎性肿胀;降低脾淋巴细胞增殖能力及踝关节滑膜内IL1,IL-6含量。结论:逐痹胶囊对大鼠AA有一定抑制作用。     

葛根汤对大鼠佐剂性关节炎防治作用研究

探讨葛根汤对佐剂性关节炎的防治作用。结果表明,葛根汤8．2,16．4g/kg致炎前3d灌胃给药,可显著抑制大鼠佐剂性关节炎急性足爪肿胀,对于继发性的足肿胀也有明显的抑制作用。可降低继发性关节炎关节液中的PGE2的含量。提示葛根汤具有防治佐剂性关节炎的作用。     

葛根汤对大鼠佐剂性关节炎防治作用研究

探讨葛根汤对佐剂性关节炎的防治作用。结果表明 ,葛根汤 8 2 ,16 4 g/kg致炎前 3d灌胃给药 ,可显著抑制大鼠佐剂性关节炎急性足爪肿胀 ,对于继发性的足肿胀也有明显的抑制作用。可降低继发性关节炎关节液中的PGE2 的含量。提示葛根汤具有防治佐剂性关节炎的作用