Kim Eun-Kyung, Song Mi-Young, Hwang Tae-Ok, Kim Hee Jin, Moon Woo Sung, Ryu Do-Gon, So Hong-Seob, Park Raekil, Park Jin-Woo, Kwon Kang-Beom, Park Byung-Hyun
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756, Korea.
Int J Mol Med. 2008 Sep;22(3):349-56.
Although Radix clematidis has commonly been used in Chinese medicine for the treatment of arthralgia, the anti-diabetic effects of Radix clematidis have not yet been reported. In the present study, we demonstrated that Radix clematidis extract (RCE) could prevent cytokine-induced beta-cell damage and streptozotocin (STZ)-induced diabetes in mice. Treatment of RINm5F insulinoma cells with interleukin-1beta and interferon-gamma reduced cell viability; however, RCE protected the cells from this cytokine-mediated viability reduction in a concentration-dependent manner. Additionally, incubation with RCE resulted in a significant suppression of cytokine-induced nitric oxide (NO) production, which was correlated with reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein. The molecular mechanism by which RCE inhibited iNOS gene expression appeared to involve inhibition of NF-kappaB activation. Furthermore, RCE abolished the cytokine-induced increases in NF-kappaB binding activity and p65 subunit levels in the nucleus, as well as IkappaBalphadegradation in the cytosol when compared to unstimulated cells. The protective effect of RCE was further demonstrated by the observed suppression of NF-kappaB-dependent iNOS expression and normal insulin secreting responses to glucose in cytokines-treated islets. The anti-diabetic effect of RCE was even more striking in vivo, where nearly complete protection against STZ-induced diabetes was observed. Treatment of mice with STZ resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining; however, pretreatment of mice with RCE blocked the destruction of STZ-induced islets and the development of type 1 diabetes.
虽然威灵仙常用于中医治疗关节痛，但威灵仙的抗糖尿病作用尚未见报道。在本研究中，我们证明威灵仙提取物（RCE）可预防细胞因子诱导的β细胞损伤和链脲佐菌素（STZ）诱导的小鼠糖尿病。用白细胞介素-1β和干扰素-γ处理RINm5F胰岛素瘤细胞可降低细胞活力；然而，RCE以浓度依赖的方式保护细胞免受这种细胞因子介导的活力降低。此外，与RCE孵育导致细胞因子诱导的一氧化氮（NO）产生显著抑制，这与诱导型NO合酶（iNOS）mRNA和蛋白水平降低相关。RCE抑制iNOS基因表达的分子机制似乎涉及抑制NF-κB活化。此外，与未刺激的细胞相比，RCE消除了细胞因子诱导的细胞核中NF-κB结合活性和p65亚基水平的增加，以及细胞质中IκBα的降解。RCE的保护作用通过观察到的对细胞因子处理的胰岛中NF-κB依赖性iNOS表达的抑制和对葡萄糖的正常胰岛素分泌反应进一步得到证明。RCE的抗糖尿病作用在体内更为显著，在体内观察到对STZ诱导的糖尿病几乎完全的保护作用。用STZ处理小鼠导致高血糖和低胰岛素血症，免疫组织化学染色进一步证实了这一点；然而，用RCE预处理小鼠可阻断STZ诱导的胰岛破坏和1型糖尿病的发展。
