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.     

Paeoniflorin inhibits function of synoviocytes pretreated by rIL-1α and regulates EP4 receptor expression

Ethnopharmacological relevance

To investigate the effect of the Paeoniflorin (Pae), a main active component of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora, on regulation of synoviocytes cultured from rats collagen-induced arthritis (CIA) in vitro.

Materials and methods

CIA was induced in male Sprague-Dawley rats immunized with chicken type II collagen (CCII) in Freund's complete adjuvant. The levels of interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), prostaglandin E₂ (PGE₂) and cyclic adenosine monophosphate (cAMP) were measured by radioimmunoassay. The proliferation responses was determined by the 3-(4,5-2dimethylthiazal-2yl) 2,5-diphenyltetrazoliumbromide (MTT) assay. Expression of E-prostanoid (EP₄) receptor was detected by Western blotting technique.

Results

Treatment of Pae (2.5, 12.5, 62.5 μg/ml) significantly decreased the production of IL-1 and TNF-α. Recombinant interleukin-1 (rIL-1α) (10 ng/ml) apparently stimulated synoviocyte, thymocyte and splenocyte proliferation, and Pae (12.5, 62.5 μg/ml) inhibited abnormal proliferation responses stimulated by rIL-1α. Moreover, rIL-1α time- and concentration-dependently increased production of PGE₂. The production of PGE₂ produced by synoviocytes from CIA rats significantly inhibited by administration of Pae (12.5, 62.5 μg/ml). rIL-1α (10 ng/ml) decreased cAMP of synoviocytes cells treated for 24 h. Similarly rIL-1α (0.1, 1, 10 ng/ml) induced a concentration-dependent decrease in the production of cAMP at 24 h. Pae (12.5, 62.5 μg/ml) increased the production of cAMP in synoviocytes. The immunoblot, Pae (12.5, 62.5 μg/ml) apparently increased the expression of EP₄ receptor in synoviocytes stimulated by rIL-1α (10 ng/ml).

Conclusions

The present study indicates that Pae might exert its anti-inflammatory effects through suppressing synoviocytes function and regulating immune cells responses in CIA rats, which might be associated with its ability to up-regulate the E-prostanoid (EP₄) receptor protein expression and modulate intracellular cAMP level.     

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。     

The expression change of β-arrestins in fibroblast-like synoviocytes from rats with collagen-induced arthritis and the effect of total glucosides of paeony

Aim of the study

To investigate the expression of β-arrestins in fibroblast-like synoviocytes (FLS) from collagen-induced arthritis (CIA) rats and the effect of total glucosides of paeony (TGP).

Materials and methods

TGP and glucosides of tripterygium wilfordii (GTW) were intragastriclly administrated to collagen-induced arthritis (CIA) rats after immunization. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index and histopathological changes. Antibodies to type II collagen (CII) were determined by enzyme-linked immunosorbent assay (ELISA). Synoviocyte proliferations were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of β-arrestins in synoviocytes from CIA rats was measured by western blot.

Results

The administration of TGP (25, 50, 100 mg/kg) depressed hind paw swelling and decreased the arthritis scores of CIA rats. TGP improved the pathologic manifestations of CIA. Serum anti-CII antibodies level increased significantly in CIA rats, while TGP had no effect on it. Fibroblast-like synoviocytes (FLS) proliferation was inhibited by TGP (50, 100 mg/kg). On d14, d28 after immunization, β-arrestins expression greatly up-regulated in synoviocytes from CIA rats and then returned to baseline levels on d42 after immunization. TGP (50, 100 mg/kg) significantly reduced the expression of β-arrestins.

Conclusion

An inflammatory process in vivo induces an up-regulation of β-arrestins in synoviocytes from CIA rats while TGP can inhibit this change, which might be one of the important mechanisms for TGP to produce a marked therapeutic effect on RA.     

白芍总苷对大鼠胶原性关节炎及其免疫功能的影响

 目的研究白芍总苷(TGP)对大鼠胶原性关节炎(CIA)及其免疫功能的影响。方法采用鸡Ⅱ型胶原诱导大鼠CIA模型,关节评分法检测关节炎发生情况,ELSIA法检测大鼠血清中抗CⅡ抗体的水平,MTT法检测T细胞和B细胞增殖反应,IL-1、IL-2活性的测定采用小鼠淋巴细胞增殖法。结果大鼠于致炎后第14天开始出现多发性关节炎症状,体重减轻,血清中抗CⅡ抗体水平升高,TGPig给药,连续14d,能够明显抑制CIA大鼠的AI,促进大鼠体重的恢复,降低血清中抗CⅡ抗体水平。进一步研究表明,TGP体内、外给药均能抑制CIA大鼠增高的T、B淋巴细胞增殖反应,还能显著降低刀豆蛋白A(ConA)诱导的CIA大鼠脾淋巴细胞产生IL-2的能力以及脂多糖(LPS)诱导的腹腔巨噬细胞产生IL-1的能力。结论TGP对CIA大鼠具有治疗作用,其机制可能与其调节CIA大鼠异常的免疫功能,平衡细胞因子的产生有关。     

中药熏蒸疗法对II型胶原诱导型关节炎大鼠滑膜细胞IL-1β mRNA表达的影响

目的 观察中药熏蒸疗法对II型胶原诱导型关节炎(CIA)大鼠关节滑膜细胞IL-1β mRNA表达水平的影响,以探讨中药熏蒸疗法治疗类风湿性关节炎(RA)的机理.方法 建立CIA模型,将雄性Wistar大鼠40只随机分为正常组、模型组、水熏组、低熏组、高熏组,观察各组大鼠膝关节滑膜细胞IL-1β mRNA的表达.结果 熏蒸各组大鼠滑膜细胞中IL-1β mRNA的表达量明显低于模型组,具有非常显著差异(P＜0.01);而各熏蒸组组间比较,高、低熏组明显低于水熏组,均有非常显著差异(P＜0.01);高熏组明显低于低熏组,亦具有显著差异(P＜0.01).结论 中药熏蒸疗法能明显抑制CIA大鼠滑膜细胞IL-1β mRNA表达,并推测中药熏蒸疗法抗炎机制与其抑制IL-1β的表达相关.     

二仙除痹汤对大鼠胶原诱导型关节炎的影响

目的探讨二仙除痹汤对大鼠胶原诱导型关节炎（CIA）的作用及机制。方法取健康Wistar大鼠,随机分为正常组、模型组及二仙除痹汤低、高剂量组,除正常组外其余各组建立大鼠CIA模型。二仙除痹汤低、高剂量组于造模后第7日起分别给予二仙除痹汤8、16 g/kg灌胃,每日1次,连续4周。评估发病率及临床积分,观察关节组织病理形态和放射学改变,检测关节组织匀浆上清和血清中促炎细胞因子白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α以及血清炎症介质前列腺素（PG）E2的含量变化。结果模型组大鼠CIA发病率100%,关节炎最高临床积分8.2,踝关节出现明显的炎症细胞浸润、血管翳形成、软骨和骨破坏等组织病理学变化以及关节间隙狭窄或增宽、关节面虫蚀样破坏等影像学改变,关节和血清中IL-1β、TNF-α、IL-6以及血清PGE2含量明显升高。与模型组相比,二仙除痹汤低、高剂量组可显著降低关节炎的发病率（分别为60%、40%）、临床积分（分别为5.7、3.8）和改善关节组织病理学改变,二仙除痹汤高剂量组还能明显抑制骨破坏程度,降低关节和血清中IL-1β、TNF-α、IL-6及PGE2的含量,二仙除痹汤低剂量组的亦显著抑制血清中IL-1β、IL-6以及关节中IL-6的含量。结论二仙除痹汤能控制大鼠CIA病情的发生发展,其机制可能与对系统和关节局部促炎细胞因子和炎症介质的有效抑制有关。     

芍芪多苷对大鼠胶原性关节炎的治疗作用

 目的研究芍芪多苷(SQDG)对大鼠胶原性关节炎(CIA)的治疗作用,并初步探讨其作用机制。方法在建立鸡Ⅱ型胶原诱导的大鼠关节炎模型基础上,通过检测足爪容积、关节炎评分和未致炎侧大鼠的足爪压痛观察和评价关节炎症的发生情况;观察胸腺指数、脾脏指数的变化;MTT法检测T、B细胞增殖反应;小鼠淋巴细胞增殖法检测IL-1、IL-2活性;ELISA法检测血中抗Ⅱ型胶原抗体。结果大鼠免疫后第14天出现足爪红肿,继发性炎症高峰期在第22天,炎症在第26天后开始减轻。SQDG(21.25,42.5,85mg·kg^-1)、白芍总苷(TGP,50mg·kg^-1)、黄芪总皂苷(ASTs,7mg·kg^-1)ig给药能不同程度的减轻CIA大鼠的关节炎症,使增高的大鼠胸腺指数和脾脏指数降低;进一步研究表明,SQDG、TGP、ASTs能使CIA大鼠升高的ConA诱导的T细胞增殖和LPS诱导的B细胞增殖反应下降;下调升高的脾细胞IL-2水平和升高的腹腔巨噬细胞IL-1水平;并使CIA大鼠血清中升高的抗CⅡ抗体下降。结论SQDG对大鼠CIA具有较好的治疗作用,其机制与其调节异常免疫功能有关。     

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.     

Suppression of lipopolysaccharide-induced of inducible nitric oxide synthase and cyclooxygenase-2 by Sanguis Draconis, a dragon's blood resin, in RAW 264.7 cells

Sanguis Draconis (SD) is a kind of dragon's blood resin that is obtained from Daemomorops draco (Palmae). It is used in traditional medicine and has shown anti-inflammatory activity in some diseases. In this study, we examined the effects of Sanguis Dranonis ethanol extract (SDEE) on LPS-induced inflammation using RAW 264.7 cells. Our data indicated that SDEE inhibits LPS-stimulated NO, PGE2, IL-1 beta and TNF-alpha release, and iNOS and COX-2 expression. Furthermore, SDEE suppressed the LPS-induced p65 expression of NF-kappa B, which was associated with the inhibition of I kappa B-alpha degradation. We also found that the expression of HO-1 was significantly increased in RAW 264.7 cells by SDEE. These results suggest among possibilities of anti-inflammation that SDEE inhibits the production of NO and PGE2 by the down-regulation of iNOS and COX-2 gene expression via the suppression of NF-kappaB (p65) activation. SDEE can induce HO-1 over-expression in macrophage cells, which indicates that it may possess antioxidant properties. This result means that SEDD its anti-inflammatory effects in macrophages may be through a novel mechanism that involves the action of HO-1. Thus, SD could provide a potential therapeutic approach for inflammation-associated disorders.     

通痹合剂乙酸乙酯部位调节CIA大鼠细胞免疫的作用机制研究

目的评价通痹合剂乙酸乙酯部位(TBHJ)对胶原诱导型关节炎(CIA)大鼠的影响,揭示其抗炎抗风湿的作用机制。方法牛Ⅱ型胶原混合弗氏完全佐剂于Wistar大鼠尾根部注射造模,随机分为模型组,甲氨蝶呤(MTX)组和TBHJ治疗组,容积法评价后肢肿胀度;给药后30 d,乳腺钼靶机大鼠四肢摄片,计分法评价各组大鼠X光片四肢96块骨侵蚀和100个关节间隙变化;处死动物,取后肢踝关节苏木素-伊红染色,观察中性粒细胞、淋巴细胞和浆细胞浸润,滑膜细胞增生和软骨破坏的情况;免疫组化法观察关节内IL-17和CD28表达;RT-PCR法比较CD28 mRNA表达。结果 CIA大鼠出现严重的关节炎症和破坏,TBHJ给药后7 d即可明显抑制CIA大鼠关节肿胀;给药后30 d,TBHJ和MTX可明显抑制大鼠关节肿胀和关节破坏,与模型组比较有统计学差异(P<0.01);TBHJ可明显抑制CIA大鼠中性粒细胞、淋巴细胞、浆细胞的浸润、滑膜增生和软骨破坏(P<0.05),MTX可抑制滑膜增生和软骨破坏;CIA大鼠IL-17,CD28 mRNA和蛋白表达明显增加,TBHJ可明显抑制IL-17和CD28。结论 TBHJ具有抑制关节免疫炎症和关节破坏的作用,其机制可能是通过抑制T细胞第二信号分子CD28的表达,减少IL-17的产生实现的。     

白芍总苷对佐剂关节炎大鼠足爪组织病理的影响及MMP-9蛋白表达的抑制作用

目的:探讨白芍总苷(total glucosides of paeonia:TGP)对佐剂关节炎大鼠足爪组织中基质金属蛋白酶-9(MMP-9)蛋白表达的抑制作用和对大鼠足爪组织病理改变的影响及血清中血管内皮生长因子(VEGF)和白介素-1β(IL-1β)含量的影响。方法:建立Ⅱ型胶原诱导的佐剂关节炎大鼠模型,用免疫组化染色法检测足爪组织中MMP-9蛋白的表达,病理切片观察不同剂量的TGP对佐剂关节炎大鼠的治疗效果,用ELISA法检测佐剂关节炎大鼠血清中VEGF和IL-1β的含量。结果:白芍总苷中(50 mg/kg)、大(100 mg/kg)剂量组的胞浆内MMP-9的阳性表达比模型对照组明显降低,TGP中、大剂量治疗组与地塞米松组能明显改变佐剂关节炎大鼠皮下组织细胞排列、炎性细胞浸润及血管增生现象,TGP 25 mg/kg组对改善佐剂关节炎大鼠足部皮肤的病理状况无明显作用。中、大剂量的TGP组和地塞米松组血清VEGF和IL-1β的含量明显降低。结论:TGP对佐剂关节炎大鼠炎症的抑制作用,可能与其下调MMP-9蛋白的表达,抑制炎性细胞浸润及血管增生,降低炎性细胞因子VEGF和IL-1β的产生有关。     

Protective effect of Astragali radix extract on interleukin 1beta-induced in fl ammation in human amnion

The aim of this study was to investigate the effect of Astragali radix extract on interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha production and prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) release from IL-1beta-stimulated human amnion. Primary monolayer cultures of amnion cells were established from women undergoing elective caesarean section before the onset of labour. Production of both IL-6 and TNF-alpha was stimulated in a concentration-dependent manner by proinflammatory cytokine IL-1beta (0.01-10 ng/mL). Astragalus extract inhibited IL-6 production by approximately 75% from cells under IL-1beta-stimulated conditions. Treatment of amnion cells with IL-1beta (0.01-10 ng/mL) resulted in a significant increase in PGE(2) release. Incubation of the cells with the extract for 24 h significantly inhibited IL-1beta-induced PGE(2) production. A concentration-dependent increase in LTC(4) production by amnion cells occurred in response to IL-1beta. Astragalus extract blocked the effect of IL-1beta in LTC(4) production in human amnion. These results indicate that Astragali radix has a broad antiinflammatory effect in human amnion and may be considered a promising agent to protect preterm labour.     

柴胡注射液对LPS发热大鼠解热机制的研究

目的:研究柴胡注射液对LPS发热模型大鼠血清中细胞因子和下丘脑中升温介质的影响。方法:腹腔注射LPS(100ug/kg)建立大鼠发热模型,监测不同时间点柴胡注射液对LPS发热模型大鼠体温影响;模型升温峰值时收集指标,ELISA法检测血清中细胞因子(TNF-α、IL-1β、cAMP、PGE2)、下丘脑中升温介质(cAMP、PGE2)含量变化。结果:柴胡注射液(5ml/kg、2.5ml/kg、1.25ml/kg)能显著降低LPS发热模型大鼠的体温,且量效关系较显著;柴胡注射液各剂量组能显著抑制发热模型大鼠血清中IL-1β、TNF-α、cAMP、PGE2增加和下丘脑中cAMP、PGE2的释放。结论:柴胡注射液对LPS发热模型大鼠有较好的解热作用,其解热效果可能与其抑制外周IL-1β、PGE2增加和下丘脑cAMP、PGE2释放有关。     

白芍总苷长期给药对胶原诱导型关节炎大鼠和正常大鼠肠道菌群影响的纵向研究

目的纵向观察不同剂量白芍总苷(total glucosides of paeony,TGP)给药12周过程中对胶原诱导型关节炎(collagen-induced arthritis,CIA)大鼠以及正常大鼠肠道菌群(简称"菌群")的影响,发现白芍总苷长期给药重点调控的菌群及其代谢功能,以探究其通过影响菌群治疗类风湿关节炎(rheumatoid arthritis,RA)的机制。方法将雄性SD大鼠随机分为正常组、模型组、正常及模型给药白芍总苷(948、474、158 mg·kg^-1)剂量组。于模型复制后给药0周(给药前)以及给药4、8、12周后收集大鼠粪便样本,利用Illumina Miseq平台进行高通量测序,采用相应软件进行操作分类单元(operational taxonomic unit,OTU)、Alpha多样性指数测定,进行Beta多样性分析、基于图形系统发育分析(graphical phylogenetic analysis,GraPhlAn)、偏最小二乘判别分析(partial least squares discriminant analysis, PLS-DA)与线性判别分析(linear discriminant analysis effect size,LEfSe)等的菌群群落结构相似性分析。同时借助数据库进行菌群不同水平分类学组成分析以及PICRUSt(phylogenetic investigation of communities by reconstructing unobserved states)菌群功能的预测。每组先进行不同时间点上述指标的动态变化分析,再进行各组间扣除相同变化后的比较,筛选出白芍总苷对胶原诱导型关节炎和正常大鼠或2个以上剂量调节作用相同的菌群及菌群代谢功能。结果 (1)白芍总苷3个剂量均可影响胶原诱导型关节炎大鼠菌群OTU的经时变化,仅低剂量可影响正常大鼠该指标的经时变化。(2)白芍总苷中、高剂量影响胶原诱导型关节炎大鼠菌群Alpha多样性指数的经时变化,而3个剂量均不影响正常大鼠该指标的经时变化。(3)综合Beta多样性分析以及GraPhlAn、PLS-DA、LEfSe分析,对胶原诱导型关节炎大鼠菌群的影响白芍总苷低、高剂量强于中剂量,对正常大鼠则白芍总苷中、高剂量强于低剂量。Coprococcus属是白芍总苷给药后胶原诱导型关节炎和正常大鼠共同的优势菌属,Akkermansia、Sutterella、Bacteroides、Parabacteroides、SMB53属是不同剂量白芍总苷给药后共同的菌群差异贡献者。(4)不同剂量白芍总苷对胶原诱导型关节炎大鼠各水平分类学组成分析影响呈剂量依赖性,对正常大鼠则作用相近;白芍总苷低、中剂量对胶原诱导型关节炎和正常大鼠菌群影响均不同,而高剂量对两者的Peptococcaceae科、Coprococcus属影响明显。(5)胶原诱导型关节炎大鼠升高的Biosynthesis of Other Secondary Metabolites菌群代谢功能(以下简称"功能"),可被中剂量白芍总苷降低;3个剂量白芍总苷均明显升高胶原诱导型关节炎大鼠Endocrine System功能,中、高剂量均明显升高Immune System功能,低、高剂量均明显降低Cardiovascular Diseases、Cellular Processes and Signaling功能。高剂量白芍总苷降低正常和胶原诱导型关节炎大鼠中Immune System Diseases功能。结论白芍总苷对胶原诱导型关节炎大鼠的菌群调节作用强于正常大鼠。上述白芍总苷长期给药稳定和重点调节的菌群和菌群代谢功能解释了其对类风湿关节炎的疗效,不同剂量白芍总苷明显影响的菌群和菌群代谢功能不同。     

电针“足三里”“三阴交”穴对胶原性关节炎大鼠滑膜细胞分泌功能的影响

目的:观察电针"足三里"三阴交"对胶原性关节炎(collagen-induced arthritis,CIA)大鼠的治疗作用,并探讨该疗法调节CIA大鼠滑膜细胞分泌功能的部分机制。方法:36只Wistar大鼠随机分为正常对照组、模型对照组和电针治疗组。模型对照组和电针治疗组采用牛Ⅱ型胶原在大鼠背部正中线作多点皮内注射诱发CIA模型。电针治疗组选取"足三里"三阴交"穴进行电针刺激,频率2Hz,强度2mA,时间30min,连续治疗30d。处理前后分别观察CIA大鼠足跖肿胀度、痛阈;采用ELISA法检测大鼠膝关节滑膜细胞培养上清液中前列腺素E2(PGE2)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)水平。结果:模型对照组大鼠足跖肿胀度,滑膜细胞培养上清中PGE2浓度和TNF-α、IL-1β含量均高于正常对照组大鼠,差异有统计学意义(P<0.05,P<0.01),痛阈低于正常对照组大鼠,差异有统计学意义(P<0.05)。与模型对照组比较,电针治疗组大鼠足跖肿胀度减小,痛阈升高,关节滑膜细胞培养上清中PGE2浓度下降,TNF-α和IL-1β含量降低,差异有统计学意义(P<0.05)。结论:电针"足三里"三阴交"穴对胶原性关节炎大鼠具有良好的治疗作用,该作用可能与抑制关节滑膜细胞的分泌功能有关。     

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.     

Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice

Chelidonium majus L. has multiple applications in Korean traditional medicine because of its anti-tumoral, cytotoxic, anti-inflammatory and anti-microbial activities and has long been known to have anti-inflammatory effects. However, no study on the anti-arthritic activity of Chelidonium majus has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN), and spleen, using ELISA and competitive RT-PCR. DBA/1J mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CME orally at 400, 40mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Administration of CME significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-6 in spleen and lymph node. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CME. In conclusion, our results demonstrates that CME significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-alpha, IL-6, IFN-gamma, B cells, gammadelta T cells (in spleen) and increased proportion of CD4+CD25+ regulatory T cells in vivo. In the serum of CME-treated mice, the levels of IgG and IgM RA factor were decreased.