Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Eur J Pharmacol. 2013 Sep 5;715(1-3):230-7. doi: 10.1016/j.ejphar.2013.05.016. Epub 2013 May 24.
Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF.
冬凌草甲素是一种从冬凌草中提取的具有药理活性的药物，具有很强的抗炎作用。然而，目前尚不清楚冬凌草甲素是否影响 B 细胞激活因子（BAFF）的表达，从而对 BAFF 相关自身免疫性疾病（如系统性红斑狼疮（SLE））的治疗产生有益作用。因此，本研究旨在探讨冬凌草甲素在调节 BAFF 和改善 SLE 中的作用。在体外，我们研究了冬凌草甲素对小鼠巨噬细胞中 BAFF 表达和产生的影响。此外，我们利用自发性小鼠 SLE 模型，通过测量狼疮症状、肾脏损伤、BAFF 表达和 B 细胞亚群的变化，研究了冬凌草甲素递送来治疗 MRL(lpr/lpr)狼疮样疾病的作用。结果表明，冬凌草甲素通过抑制其启动子的转录激活，显著抑制了小鼠巨噬细胞中 BAFF 的表达。体内给予冬凌草甲素可有效改善 MRL(lpr/lpr)小鼠的血清学和临床 SLE 表现，提高生存率、降低蛋白尿水平、减少特异性自身抗体的产生、减轻肾脏损伤，与 BAFF 下调以及 B 细胞成熟和分化率降低有关。因此，冬凌草甲素通过抑制 BAFF 可能成为治疗 SLE 的一种新的天然治疗策略。
