Immunoregulatory Material Research Center, Korea Research Institute of Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 56212, Korea.
Division of Biotechnology and Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan-si, Korea.
Molecules. 2019 Nov 7;24(22):4042. doi: 10.3390/molecules24224042.
Portulaca oleracea is as a medicinal plant known for its neuroprotective, hepatoprotective, antidiabetic, antioxidant, anticancer, antimicrobial, antiulcerogenic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of P. oleracea extract (95% EtOH) remain unknown. Here, we hypothesized that alkaloids, the most abundant constituents in P. oleracea extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-22) using nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and screened their effects on NO production in lipopolysaccharide (LPS)-induced macrophages. Compound 20, 1-carbomethoxy-β-carboline, as an alkaloid structure, ameliorated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and proinflammatory cytokines associated with the mitogen-activated protein kinase (MAPK) pathways, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Subsequently, we observed that compound 20 suppressed nuclear translocation of nuclear factor κB (NF-κB) using immunocytochemistry. Moreover, we recently reported that compound 8, trans-N-feruloyl-3', 7'-dimethoxytyramine, was originally purified from P. oleracea extracts. Our results suggest that 1-carbomethoxy-β-carboline, the most effective anti-inflammatory agent among alkaloids in the 95% EtOH extract of P. oleracea, was suppressing the MAPK pathway and nuclear translocation of NF-κB. Therefore, P. oleracea extracts and specifically 1-carbomethoxy-β-carboline may be novel therapeutic candidates for the treatment of inflammatory diseases associated with the activation of MAPKs and NF-κB.
马齿苋是一种药用植物，具有神经保护、肝保护、抗糖尿病、抗氧化、抗癌、抗菌、抗溃疡和抗炎活性。然而，负责马齿苋提取物（95%乙醇）个别药理作用的特定活性化合物仍然未知。在这里，我们假设生物碱是马齿苋提取物中最丰富的成分，是其抗炎活性的原因。我们使用核磁共振（NMR）和电喷雾电离质谱（ESI-MS）研究了其植物化学成分替代物（化合物 1-22），并筛选了它们对脂多糖（LPS）诱导的巨噬细胞中一氧化氮（NO）产生的影响。作为生物碱结构的化合物 20，1-甲氧基-β-咔啉，改善了一氧化氮（NO）的产生、诱导型一氧化氮合酶（iNOS）和与丝裂原活化蛋白激酶（MAPK）途径相关的促炎细胞因子，p38、细胞外信号调节激酶（ERK）和 c-Jun N-末端激酶（JNK）。随后，我们观察到化合物 20 通过免疫细胞化学抑制核转录因子κB（NF-κB）的核易位。此外，我们最近报道化合物 8，反式-N-阿魏酰-3'，7'-二甲氧基酪胺，最初是从马齿苋提取物中分离出来的。我们的结果表明，在马齿苋 95%乙醇提取物的生物碱中，最有效的抗炎剂 1-甲氧基-β-咔啉，通过抑制 MAPK 途径和 NF-κB 的核易位来抑制炎症。因此，马齿苋提取物，特别是 1-甲氧基-β-咔啉，可能是治疗与 MAPKs 和 NF-κB 激活相关的炎症性疾病的新型治疗候选药物。
