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。     

金铁锁总皂苷抗类风湿性关节炎作用及其作用机制研究

目的:考察金铁锁总皂苷(TSPT)抗类风湿性关节炎(RA)的药理作用及作用机制。方法:建立佐剂性关节炎(AA)动物模型,观察TSPT对AA大鼠足肿胀、关节炎指数及炎性组织液中促炎细胞因子IL-1β,TNF-α水平的影响。结果:TSPT能有效抑制关节肿胀率及关节指数,降低AA大鼠炎性组织液中促炎细胞因子L-1β,TNF-α的水平。结论:TSPT具有良好的抗RA作用,其作用机制与抑制促炎细胞因子L-1β,TNF-α的水平有关。     

灵雷菌质对大鼠类风湿性关节炎作用的实验研究

 目的 考察灵雷菌质对佐剂型类风湿性关节炎（adjuvant arthritis,AA）大鼠的治疗作用。方法 建立弗氏完全佐剂(Freund’s complete adjuvant,CFA)诱导的大鼠类风湿性关节炎(rheumatoid arthritis,RA) 模型,将大鼠分为空白组、灵雷菌质高剂量给药组、灵雷菌质低剂量给药组、雷公藤多苷片给药组、模型组,连续灌胃给药2周后,检测各组大鼠的体重、关节肿胀度、关节炎指数、关节病理变化、血清肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β。结果 灵雷菌质能改善大鼠一般状况并提高AA大鼠体重,缓解AA大鼠关节红肿程度,降低其关节炎指数,改善RA大鼠的关节病理变化,显著抑制TNF-α和IL-1β的表达。结论 灵雷菌质对佐剂型关节炎有一定的治疗作用。     

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。     

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。     

Therapeutic effects and mechanisms of total flavonoids of Turpinia Arguta Seen on adjuvant arthritis in rats

AIM: To investigate the therapeutic effects and mechanisms of total flavonoids of Turpinia Arguta Seen (TFS) on adjuvant arthritis in rats. METHODS: The model of adjuvant arthritis was induced by injection of Freund's Complete Adjuvant (FCA). Secondary paw swelling of AA rats was measured with volume meter and polyarthritis index were scored. The splenocyte proliferation, (interleukin-1) IL-1 and interleukin-2 (IL-2) production were assayed by cell proliferation assay. Prostaglandin E(2) (PGE(2)) production was determined by radioimmunoassay. RESULTS: TFS (80, 160, 320 mg/kg, i.g.) could significantly inhibit secondary inflammatory reaction (secondary swelling, multiple arthritis, pathologic change of ankle arthritis) in AA rats. The results in vivo showed that the low response of splenocytes to concanavalin A (Con A) and lipopolysaccharide (LPS) and the decreased IL-2 synthesis were restored in AA rats treated with TFS (160, 320 mg/kg, i.g.), while the elevated IL-1 and PGE(2) released from peritoneal macrophages (PMphi) were also reduced. CONCLUSION: TFS has significant therapeutic effect on AA rats, which might be relate to its immunoregulatory actions.     

樱桃花青素对佐剂性关节炎大鼠自由基和炎症因子的影响

目的:观察樱桃花青素对佐剂性关节炎(AA)大鼠自由基和抗氧化功能以及炎症因子的影响.方法:将50只SD雄性大鼠随机分为5组即正常组、模型组、樱桃花青素高、中、低剂量组.对足爪肿胀进行测量,在光镜下观察各组组织形态学变化,用比色法检测了动物外周全血的谷胱甘肽过氧化物酶(GSH-PX)活性、血清超氧化物酶(SOD)活性、血清丙二醛(MDA)含量以及血清总抗氧化能力(T-AOC).用ELISA检测血清中TNF-α含量,用放射免疫法检测了足爪PGE2含量.结果:模型组和正常组相比GSH-PX,SOD活性和T-AOC能力下降,血清MDA含量升高,血清中TNF-α和足爪PGE2含量升高.樱桃花青素组能升高GSH-PX,SOD和T-AOC活力,降低血清MDA,TNF-α以及足爪PGE2含量.光镜下组织形态观察表明樱桃花青素各组能不同程度减轻滑膜增生,减少炎细胞浸润.结论:樱桃花青素能增强AA抗氧化能力,并能降低炎症细胞因子PGE2和TNF-α,从而减轻AA模型的关节炎损伤.     

Suppression of the onset and progression of collagen-induced arthritis in rats by QFGJS, a preparation from an anti-arthritic Chinese herbal formula

QFGJS is an herbal preparation, and its pronounced effectiveness in treating adjuvant-induced arthritis (AIA) has been previously demonstrated. We herein aimed to confirm its anti-arthritic effect on collagen-induced arthritis (CIA) in rats. CIA was established in female Wistar rats with intradermal injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of different doses of QFGJS beginning on the day of the induction of arthritis (day 0, the prophylactic treatment) or on the day after the onset of arthritis (day 13, the therapeutic treatment) until day 30. The results showed that prophylactic treatment with QFGJS significantly suppressed the onset of arthritis, and therapeutic treatment with QFGJS markedly reduced paw swelling and ESR levels even in the established CIA. Radiologic and histopathologic changes in the arthritic joints were also significantly reduced in the QFGJS-treated versus vehicle-treated rats. Moreover, the serum levels of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were markedly lowered in the QFGJS-treated rats. Hence, our studies demonstrate the quality, safety, and effectiveness of QFGJS as an anti-arthritic agent, which makes QFGJS a strong candidate for further clinical trials on rheumatoid arthritis (RA) patients.     

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。     

京尼平苷对类风湿性关节炎大鼠血清IL-1β和TNF-α的影响

目的:研究京尼平苷对类风湿性关节炎大鼠血清IL1β和TNFα的影响,进一步探讨该药物的作用机制。方法:建立Ⅱ型胶原蛋白诱导大鼠类风湿性关节炎模型。观察京尼平苷对实验性大鼠足肿胀的抑制作用;检测血清IL1β和TNFα的水平。结果:与模型组比较,京尼平苷可以延缓对侧肢体足肿胀发生的时间,抑制大鼠足肿胀的程度(P<0.01);用药后,中、高剂量给药组血清IL1β和TNFα水平明显低于模型组(P<0.01)。结论:京尼平苷在类风湿性关节炎大鼠中可以下调致炎因子IL1β和TNFα的水平,提示这可能与该药抑制实验性类风湿性关节炎病情进展密切相关。     

火针对类风湿性关节炎大鼠血清白介素-1和肿瘤坏死因子-α的影响

目的:观察火针对类风湿性关节炎大鼠血清白介素-1(IL-1)和肿瘤坏死因子-α(TNF-α)的影响,探讨火针治疗类风湿性关节炎的作用机制。方法:将40只雌性Wistar大鼠随机分为正常组、模型组、甲氨蝶呤(MTX)组、火针组。于大鼠右后足跖底部皮内注射0.1mL完全弗氏佐剂建立类风湿性关节炎模型。火针点刺"夹脊穴"足三里"和"阿是穴",共治疗8次。容积法测量大鼠右后足肿胀度;双抗体夹心ABC-ELISA法检测大鼠血清IL-1和TNF-α含量;光镜观察大鼠膝关节滑膜组织的病理变化。结果:模型组大鼠足部肿胀度、血清IL-1和TNF-α的含量较正常组显著升高(P<0.01);MTX组造模后33d足部肿胀度较模型组降低(P<0.01),火针组造模后19、26、33d足部肿胀度较模型组降低(P<0.01),治疗后MTX组和火针组大鼠血清IL-1和TNF-α的含量较模型组均明显降低(P<0.05,P<0.01),火针组与MTX组相比大鼠足部肿胀度、血清IL-1和TNF-α的含量明显降低(P<0.05,P<0.01)。与正常组比较,模型组大鼠滑膜组织有明显的病理改变,各治疗组均能改善膝关节滑膜组织的炎性病变,且火针对滑膜病变的改善优于MTX。结论:火针可降低类风湿性关节炎大鼠血清IL-1和TNF-α的含量,减轻关节局部肿胀度,改善滑膜病变,有效控制类风湿性关节炎的病情发展。     

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.     

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.     

加减补阳还五汤对佐剂性关节炎大鼠作用的实验研究

目的 研究加减补阳还五汤对大鼠佐剂性关节炎的影响,探讨加减补阳还五汤治疗类风湿性关节炎的作用机制.方法 建立大鼠足跖注射弗氏完全佐剂性关节炎模型,观察加减补阳还五汤对动物超敏反应性炎症血清中白细胞介素(IL-1)、肿瘤坏死因子(TNF-α)、循环免疫复合物(CIC)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性的影响.结果 加减补阳还五汤能降低模型动物的IL-1、TNF-α、CIC、MDA含量,提高SOD活性,均有显著性差异(P＜0.01).结论 加减补阳还五汤具有抗大鼠佐剂性、继发性关节炎作用,其机制与抑制自由基损伤和降低自身免疫的病理生理反应有关.     

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.     

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.     

铺灸对佐剂型关节炎大鼠白细胞介素-1和肿瘤坏死因子α、白细胞介素-10的影响

目的观察铺灸对佐剂型关节炎（AA）大鼠血清中的白细胞介素-1（IL-1）、肿瘤坏死因子α[（TNF-α）及白细胞介素-10（IL-10）的影响,初步探讨其治疗类风湿关节炎的作用机制。方法将48只Wistar大鼠随机分为空白组、模型组、药物组、铺灸组,每组12只。除空白组外,于右后足跖皮下注射弗氏完全佐剂形成从大鼠模型,造模3d后,药物组给予旭痹颗粒治疗,铺灸组给予铺灸治疗。观察大鼠造模前后及治疗后足趾肿胀度（趾围）的变化。治疗结束后股静脉采血,以放射免疫方法检测血清IL-1、TNF-α及IL-10含量。结果铺灸可减轻从大鼠足趾肿胀程度,效果优于旭痹颗粒组（P〈0．05）;显著提高从大鼠血清IL-10水平（P〈0．05）,降低血清IL-1、TNF—α水平（P〈0．05）。结论铺灸对从大鼠具有一定疗效,抑制IL-1、TNF-α的产生,提高IL-10水平可能是其机制之一。     

Immune Tolerance Effect in Mesenteric Lymph Node Lymphocytes of Geniposide on Adjuvant Arthritis Rats

Rheumatoid arthritis (RA) is a systemic, Th1 cytokine‐predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague–Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Levels of interleukin‐2 (IL‐2), IL‐4, and transforming growth factor‐β1 were tested by ELISA. The expression of β2‐AR, GRK2, and β‐arrestin‐1 and β‐arrestin‐2 was detected by western blot. Geniposide was found to relieve the secondary hind paw swelling and arthritis scores, along with attenuating histopathologic changes and decreasing IL‐2 and increasing IL‐4, transforming growth factor‐β1 in mesenteric lymph node (MLN) lymphocytes of AA rats. In addition, GE in vivo increased the expression of β2‐AR and decreased the expression of GRK2, β‐arrestin‐1 and β‐arrestin‐2, and level of cyclic adenosine monophosphate of MLN lymphocytes in AA rats. From these results, we can infer that GE on immune tolerance effects, β2‐AR desensitization, and β2‐AR‐AC‐cyclic adenosine monophosphate transmembrane signal transduction of MLN lymphocytes plays crucial roles in antiinflammatory and immunoregulatory pathogeneses of RA. Copyright © 2017 John Wiley & Sons, Ltd.