Arshad Laiba, Jantan Ibrahim, Bukhari Syed N A, Fauzi Mh Busra
Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia.
School of Pharmacy, Taylor's University, Lakeside campus, 47500 Subang Jaya, Selangor, Malaysia.
Curr Pharm Biotechnol. 2018;19(6):468-482. doi: 10.2174/1389201019666180703092723.
3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has previously been shown to manifest potent immunosuppressive effects on the in vitro phagocytosis process of human neutrophils.
In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors.
Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction.
BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH.
These findings suggest the potential of BBP as a potent immunosuppressive agent.
3,5-双[4-(二乙氧基甲基)亚苄基]-1-甲基-哌啶-4-酮（BBP），一种新型合成姜黄素类似物，先前已被证明对人中性粒细胞的体外吞噬过程具有强大的免疫抑制作用。
在本研究中，研究了BBP对由不同体液和细胞免疫因子介导的体内固有免疫和适应性免疫反应的影响。
雄性Balb/c小鼠口服给予BBP（5、10和20mg/kg），持续14天，并在第0天用绵羊红细胞（sRBC）免疫，以测定适应性反应。测定BBP对从处理/未处理动物血液中分离的中性粒细胞吞噬过程的影响。还监测了血清铜蓝蛋白和溶菌酶水平以及血浆髓过氧化物酶（MPO）水平。通过评估其对T和B淋巴细胞增殖、T淋巴细胞亚群CD4+和CD8+以及Th1/Th2细胞因子分泌以及血清免疫球蛋白（IgG、IgM）和迟发型超敏反应（DTH）的影响，进一步探讨其作用机制。
BBP对中性粒细胞迁移、Mac-1表达、吞噬活性和活性氧（ROS）产生具有显著的剂量依赖性降低作用。与致敏对照组相比，观察到淋巴细胞增殖呈剂量依赖性抑制，同时效应细胞表达下调和细胞因子释放减少。此外，BBP处理小鼠的血清铜蓝蛋白、溶菌酶和免疫球蛋白水平以及MPO血浆水平在统计学上显著降低。BBP还剂量依赖性地抑制DTH中绵羊红细胞（sRBC）诱导的小鼠爪肿胀率。
这些发现表明BBP作为一种强大的免疫抑制剂具有潜力。
