The School of Pharmaceutical Engineering and Life Science, Changzhou University, Jiangsu 213164, China.
The School of Pharmaceutical Engineering and Life Science, Changzhou University, Jiangsu 213164, China; The School of Medicine, the University of Southampton, Southampton SO16 6YD, UK.
Int Immunopharmacol. 2018 Dec;65:511-521. doi: 10.1016/j.intimp.2018.10.039. Epub 2018 Nov 5.
Rheumatoid arthritis (RA) is an autoimmune disease and characterized by the excessive cell proliferation, abnormal cell cycle of lymphocytes and synovial cells. The therapeutic effects of curcumin in active RA patients were reported, but limited by its insolubility and rapid systemic elimination. Dimethyl curcumin (DiMC) is a metabolically stable analogue of curcum with anti-inflammatory property. In this study, liposomes encapsulated dimethyl curcumin (Lipo-DiMC) was prepared to improve the bioavailability and metabolic-stability; collagen induced arthritis (CIA) rat model was employed to investigate the effects of Lipo-DiMC treatments during CIA progress. Physical assessments and routine-blood-test were performed. Fresh spleen lymphocytes were isolated from normal, CIA and Lipo-DiMC-treated CIA rats; flow-cytometry for cell-cycle analysis, western-blotting for intracellular signal pathway protein expressions, gelatin-zymography for matrix-metalloproteases 2/9 (MMP-2/9) and GF-AFC for dipeptidyl-peptidase I (DPPI) activity assay. Compared with untreated CIA rats, Lipo-DiMC treatments relieved paw-swellings, suppressed the increments of immunocytes numbers and inhibited DPPI and MMP-2/9 over-activity in blood. Lipo-DiMC adjusted CIA-induced cell cycle dysfunction at G0/G1-phase and S-phase of spleen lymphocytes for CIA rats. The intracellular expression-trends of P38, P21, Bcl-2, JNK-1 and DPPI of spleen lymphocytes were observed during CIA progress with and without Lipo-DiMC administrations. Lipo-DiMC exhibited its therapeutic functions by attenuating CIA development in rats, associated with down-regulating CIA-induced lymphocytes numbers, inhibiting over-expressed of DPPI and MMP-2/9, and adjusting cell cycles. These findings provide a new insight into the mechanism of Lipo-DiMC treatment in CIA rat model and suggest that Lipo-DiMC could be considered as a potential drug for RA treatment.
类风湿关节炎（RA）是一种自身免疫性疾病，其特征为淋巴细胞和滑膜细胞过度增殖、细胞周期异常。已有研究报道姜黄素对活动期 RA 患者具有治疗作用，但由于其不溶性和快速的全身消除，其应用受到限制。二甲基姜黄素（DiMC）是一种具有抗炎作用的姜黄素代谢稳定类似物。本研究制备了包载二甲基姜黄素的脂质体（Lipo-DiMC）以提高其生物利用度和代谢稳定性；并采用胶原诱导关节炎（CIA）大鼠模型，研究 Lipo-DiMC 在 CIA 进展过程中的作用。进行了体格评估和常规血液检查。从正常、CIA 和 Lipo-DiMC 治疗 CIA 大鼠中分离新鲜脾淋巴细胞；流式细胞术进行细胞周期分析，Western blot 检测细胞内信号通路蛋白表达，明胶酶谱法检测基质金属蛋白酶 2/9（MMP-2/9）和 GF-AFC 法检测二肽基肽酶 I（DPPI）活性。与未治疗的 CIA 大鼠相比，Lipo-DiMC 治疗可缓解足肿胀，抑制免疫细胞数量的增加，并抑制血液中 DPPI 和 MMP-2/9 的过度活性。Lipo-DiMC 可调节 CIA 诱导的脾淋巴细胞 G0/G1 期和 S 期细胞周期功能障碍。观察到 CIA 进展过程中以及给予 Lipo-DiMC 后，脾淋巴细胞中 P38、P21、Bcl-2、JNK-1 和 DPPI 的细胞内表达趋势。Lipo-DiMC 通过减轻 CIA 大鼠的发病机制，降低 CIA 诱导的淋巴细胞数量，抑制 DPPI 和 MMP-2/9 的过度表达，以及调节细胞周期，发挥其治疗作用。这些发现为 Lipo-DiMC 治疗 CIA 大鼠模型的机制提供了新的见解，并表明 Lipo-DiMC 可作为治疗 RA 的潜在药物。
