Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, Singapore 117600, Singapore.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, Singapore 117600, Singapore; Immunology Program, Life Science Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Biochem Pharmacol. 2017 Sep 1;139:71-81. doi: 10.1016/j.bcp.2017.03.024. Epub 2017 Apr 2.
Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties. With this accumulated wealth of pre-clinical data, it is imperative to review and consolidate different sources of information, to decipher the major anti-inflammatory mechanisms of action in inflammatory diseases, and to provide direction for future studies. Andrographolide and its analogs have been shown to provide anti-inflammatory benefits in a variety of inflammatory disease models. Among the diverse signaling pathways investigated, inhibition of NF-κB activity is the prevailing anti-inflammatory mechanism elicited by andrographolide. There is also increasing evidence supporting endogenous antioxidant defense enhancement by andrographolide through Nrf2 activation. However, the exact pathway leading to NF-κB and Nrf2 activation by andrographolide has yet to be elucidated. Validation and consensus on the major mechanistic actions of andrographolide in different inflammatory conditions are required before translating current findings into clinical settings. There are a few clinical trials conducted using andrographolide in fixed combination formulation which have shown anti-inflammatory benefits and good safety profile. A concerted effort is definitely needed to identify potent andrographolide lead compounds with improved pharmacokinetics and toxicological properties. Taken together, andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents, and more andrographolide molecules are likely moving towards clinical study stage in the near future.
穿心莲在亚洲和斯堪的纳维亚的传统草药医学体系中一直占有一席之地。1951 年，穿心莲内酯被分离为穿心莲的主要生物活性成分，自 1984 年以来，穿心莲内酯及其类似物一直被采用现代药物发现方法来研究其抗炎特性。随着这一丰富的临床前数据的积累，有必要对不同来源的信息进行回顾和整合，以破译穿心莲内酯在炎症性疾病中的主要抗炎作用机制，并为未来的研究提供方向。穿心莲内酯及其类似物已被证明在多种炎症性疾病模型中具有抗炎作用。在研究的各种信号通路中，抑制 NF-κB 活性是穿心莲内酯发挥抗炎作用的主要机制。越来越多的证据支持通过 Nrf2 激活增强穿心莲内酯的内源性抗氧化防御。然而，穿心莲内酯激活 NF-κB 和 Nrf2 的具体途径尚未阐明。在将当前的研究发现转化为临床应用之前，需要对穿心莲内酯在不同炎症条件下的主要作用机制进行验证和共识。已经有几项使用穿心莲内酯固定复方制剂的临床试验显示出抗炎益处和良好的安全性。肯定需要齐心协力，确定具有改善药代动力学和毒理学特性的有效穿心莲内酯先导化合物。综上所述，穿心莲内酯及其类似物具有成为下一类抗炎药物的巨大潜力，在不久的将来，可能会有更多的穿心莲内酯分子进入临床研究阶段。
