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黄柏根提取物对小鼠胶原诱导性关节炎的抑制作用。

Inhibitory effect of the extract of Phellodendron amurense ruprecht root on collagen-induced arthritis in mice.

作者信息

Jung Hyo Won, Kim Kyung-Ho, Park Yong-Ki

机构信息

Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, 740-814, Republic of Korea.

Korean Medicine Research and Development Center, Dongguk University, Gyeongju, 740-814, Republic of Korea.

出版信息

Chin J Integr Med. 2017 Oct;23(10):755-762. doi: 10.1007/s11655-016-2094-5. Epub 2016 Jul 26.

Abstract

OBJECTIVE

To investigate whether the dried root of Phellodendron amurense Ruprecht (Phellodendri cortex; PC) extract improves arthritic symptoms through anti-inflammatory and immune-modulatory effects in collagen-induced arthritis in mice.

METHODS

Rheumatoid arthritis (RA) was induced in male DBA/1 mice by immunization with type II collagen (ColII). CIA mice were divided into 5 groups (n=10 per a group) with normal, CIA control, PC extract (50 mg/kg and 100 mg/kg)-treated, and meloxicam (50 mg/kg)-treated as the reference drug. The PC extract or meloxicam were administered orally in CIA mice once a day for 14 days after arthritis induction. Arthritic score, levels of anti-ColII IgG antibody, prostaglandin E (PGE), tumor necrosis factor (TNF)-α, and interleukin (IL)-17 in the sera of CIA mice were measured. Histopathological changes in the ankle joints of CIA mice were also analyzed by staining with hematoxylin and eosin (H and E), safranin-O and immunohistochemistry using anti-TNF-α and anti-IL-17 antibodies.

RESULTS

The arthritic score was increased in CIA mice in a time-dependent manner, as were the serum levels of anti-ColII IgG antibody, PGE, TNF-α, and IL-17. However, the oral administration of PC extract at 50 and 100 mg/kg in CIA mice significantly decreased the arthritic scores, and the serum levels of anti-ColII IgG, PGE, TNF-α, and IL-17 compared with those in the CIA group (P<0.05 or P<0.01). Furthermore, histopathological improvement of the joint architecture in CIA mice was observed after administration of PC extract. PC extract also significantly inhibited the expression of TNF-α and IL-17 in the joints of CIA mice by suppressing the expression of their mRNA and proteins.

CONCLUSION

PC extract may improve the pathological progression of RA through the inhibition of joint destruction by synovial inflammation and immune-stimulation, therefore, it would be a potential anti-arthritic agent in RA.

摘要

目的

研究关黄柏提取物是否通过对小鼠胶原诱导性关节炎的抗炎和免疫调节作用来改善关节炎症状。

方法

用II型胶原(ColII)免疫雄性DBA/1小鼠诱导类风湿性关节炎(RA)。将胶原诱导性关节炎(CIA)小鼠分为5组(每组n = 10),分别为正常组、CIA对照组、关黄柏提取物(50mg/kg和100mg/kg)处理组以及作为参比药物的美洛昔康(50mg/kg)处理组。在诱导关节炎后,每天给CIA小鼠口服关黄柏提取物或美洛昔康,持续14天。测量CIA小鼠血清中的关节炎评分、抗ColII IgG抗体水平、前列腺素E(PGE)、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-17水平。还用苏木精和伊红(H&E)染色、番红O染色以及使用抗TNF-α和抗IL-17抗体的免疫组织化学方法分析CIA小鼠踝关节的组织病理学变化。

结果

CIA小鼠的关节炎评分呈时间依赖性增加,血清中抗ColII IgG抗体、PGE、TNF-α和IL-17水平也升高。然而,给CIA小鼠口服50mg/kg和100mg/kg的关黄柏提取物,与CIA组相比,显著降低了关节炎评分以及血清中抗ColII IgG、PGE、TNF-α和IL-17水平(P<0.05或P<0.01)。此外,给药关黄柏提取物后,观察到CIA小鼠关节结构的组织病理学改善。关黄柏提取物还通过抑制TNF-α和IL-17的mRNA和蛋白表达,显著抑制了CIA小鼠关节中TNF-α和IL-17的表达。

结论

关黄柏提取物可能通过抑制滑膜炎症和免疫刺激引起的关节破坏来改善类风湿性关节炎的病理进程,因此,它可能是类风湿性关节炎中一种潜在的抗关节炎药物。

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