title: Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, Singapore 117600, Singapore.
authors.forename: W S Daniel
authors.initials: WSD
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, Singapore 117600, Singapore.
authors.forename: Wupeng
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, Singapore 117600, Singapore.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhou
authors.affiliation: 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. Electronic address: phcwongf@nus.edu.sg.
authors.forename: W S Fred
authors.initials: WSF
authors.lastname: Wong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D003872:Dermatitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D004224:Diterpenes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006505:Hepatitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D015507:Drugs, Investigational; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051267:NF-E2-Related Factor 2; D052002:NF-kappa B p50 Subunit; C495635:NFE2L2 protein, human; C489548:NFKB1 protein, human; D020011:Protective Agents; C030419:andrographolide
keywords: Asthma; Autoimmune; Hepatitis; NF-κB; Neurodegeneration; Nrf2