Messeha Samia S, Zarmouh Najla O, Mendonca Patricia, Kolta Malak G, Soliman Karam F A
College of Pharmacy and Pharmaceutical Science, Florida A & M University, Tallahassee, FL 32307, USA.
College of Pharmacy and Pharmaceutical Science, Florida A & M University, Tallahassee, FL 32307, USA.
J Neuroimmunol. 2017 Dec 15;313:129-137. doi: 10.1016/j.jneuroim.2017.09.007. Epub 2017 Sep 20.
Activated microglial cells produce the pro-inflammatory mediators such as nitric oxide (NO) and cytokines. The excessive release of these mediators can lead to neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Inhibition of the release of these pro-inflammatory molecules may prevent or halt the progression of these diseases. Plumbagin (PL), a naphthoquinone compound in the roots of the traditional medicinal plant Plumbago zeylanica L., showed anti-inflammatory effects on macrophages. However, PL effects on activated microglia remain unknown. In the present study, PL has been examined for its anti-inflammatory effect on LPS - activated microglial BV-2 cells. In this study, NO and iNOS expression were investigated in BV-2 microglial cells in the presence of PL or the selective iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). The results obtained indicate that PL was >30-fold potent than L-NIL in inhibiting NO production with an IC of 0.39μM. Our immunofluorescence study confirmed the ability of PL to significantly inhibit iNOS expression in the activated microglia. Furthermore, the extracellular microglial pro-inflammatory cytokine expression in the presence of 2μM of PL was detected, quantified, and validated using cytokine antibody protein arrays and quantitative ELISA. The results obtained showed that PL significantly downregulated the expression of many cytokines including IL-1α, G-CSF, IL-12 p40/p70, MCP-5, MCP-1, and IL-6. In conclusion, PL potency in attenuating multiple pro-inflammatory agents indicates its potential to be used for neurodegenerative diseases.
活化的小胶质细胞会产生促炎介质，如一氧化氮（NO）和细胞因子。这些介质的过度释放会导致神经退行性疾病，如阿尔茨海默病（AD）和帕金森病（PD）。抑制这些促炎分子的释放可能会预防或阻止这些疾病的进展。白花丹素（PL）是传统药用植物白花丹根中的一种萘醌化合物，对巨噬细胞具有抗炎作用。然而，PL对活化小胶质细胞的作用尚不清楚。在本研究中，检测了PL对脂多糖（LPS）激活的小胶质BV-2细胞的抗炎作用。在本研究中，在有PL或选择性诱导型一氧化氮合酶（iNOS）抑制剂L-N6-（1-亚氨基乙基）赖氨酸（L-NIL）存在的情况下，研究了BV-2小胶质细胞中NO和iNOS的表达。所得结果表明，PL在抑制NO产生方面的效力比L-NIL高30倍以上，半数抑制浓度（IC）为0.39μM。我们的免疫荧光研究证实了PL能够显著抑制活化小胶质细胞中iNOS的表达。此外，使用细胞因子抗体蛋白阵列和定量酶联免疫吸附测定（ELISA）检测、定量并验证了在存在2μM PL的情况下细胞外小胶质细胞促炎细胞因子的表达。所得结果表明，PL显著下调了包括白细胞介素-1α（IL-1α）、粒细胞集落刺激因子（G-CSF）、白细胞介素-12 p40/p70、单核细胞趋化蛋白-5（MCP-5）、单核细胞趋化蛋白-1（MCP-1）和白细胞介素-6（IL-6）在内的多种细胞因子的表达。总之，PL在减弱多种促炎因子方面的效力表明其具有用于神经退行性疾病的潜力。
