Suppression of cytokine production and neural cell death by the anti-inflammatory alkaloid cepharanthine: a potential agent against HIV-1 encephalopathy
Suppression of cytokine production and neural cell death by the anti-inflammatory alkaloid cepharanthine: a potential agent against HIV-1 encephalopathy
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DOI：
10.1016/s0006-2952(01)00692-x
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发表时间：
2001-09-15
影响因子：
5.8
通讯作者：
Baba, M
中科院分区：
文献类型：
--
作者：
Okamoto, M;Ono, M;Baba, M
炎性细胞因子和人类免疫缺陷病毒I型（HIV-1）gp 120被认为在HIV-1相关CNS疾病的发病机制中发挥重要作用。这些物质主要由HIV-1感染或激活的巨噬细胞和小胶质细胞产生。并导致神经细胞死亡千金藤素是从千金藤中分离的双乌药碱生物碱，已被证明具有抗炎、抗过敏和免疫调节活性。我们以前报道，这种化合物可以抑制肿瘤坏死因子（TNF）-α-或佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的HIV-1复制潜伏感染的U1细胞通过抑制核因子-κ B，HIV-1基因表达的有效诱导剂。在本研究中，我们证明千金藤素抑制人单核细胞培养物（包括原代单核细胞/巨噬细胞培养物）中炎性细胞因子和趋化因子（即TNF-α、白细胞介素（M）-1 β、IL-6和IL-8）的产生。千金藤素的这种作用是浓度依赖性的，在0.1 μ g/mL时观察到显著抑制。此外，该化合物还在0.04至0.2 μ g/mL的浓度下抑制TNF-α和gp 120诱导的分化的人神经母细胞瘤细胞的死亡。它能穿透血脑屏障，在日本，一种含有千金藤素作为主要成分的药物已被用于治疗慢性炎症性疾病患者。因此，千金藤素应进一步研究其在HIV-1相关CNS疾病的治疗和预防潜力。(C)2001 Elsevier Science Inc. All rights reserved.
Inflammatory cytokines and human immunodeficiency virus type I (HIV-1) gp120 are considered to play an important role in the pathogenesis of HIV-1-associated CNS disorders. These substances are produced predominantly by HIV-1-infected or activated macrophages and microglia. in the brain and induce neural cell death. Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have anti-inflammatory, anti-allergic, and immunomodulatory activities in vivo. We previously reported that this compound could inhibit tumor necrosis factor (TNF)-alpha- or phorbol 12-myristate 13-acetate-induced HIV-1 replication in latently infected U1 cells through the inhibition of nuclear factor-kappaB, a potent inducer of HIV-1 gene expression. In the present study, we demonstrated that cepharanthine suppresses the production of inflammatory cytokines and a chemokine, i.e. TNF-alpha, interleukin (M)-1 beta, IL-6, and IL-8, in human monocytic cell cultures, including primary monocyte/macrophage cultures. This effect of cepharanthine was concentration-dependent, and significant suppression was observed at 0.1 mug/mL. Furthermore, the compound also inhibited TNF-alpha- and gp120-induced death of differentiated human neuroblastoma cells at a concentration of 0.04 to 0.2 mug/mL. It penetrates the blood-brain barrier, and a medicine containing cepharanthine as a major component has been used in Japan for the treatment of patients with chronic inflammatory diseases. Thus, cepharanthine should be investigated further for its therapeutic and prophylactic potential in HIV-1-associated CNS disorders. (C) 2001 Elsevier Science Inc. All rights reserved.