Abstract
Andrographolide is a labdane diterpene and the main active ingredient isolated from the herb Andrographis paniculata. Andrographolide possesses diverse biological effects including anti-inflammatory, antioxidant, and antineoplastic properties. Clinical studies have demonstrated that andrographolide could be useful in therapy for a wide range of diseases such as osteoarthritis, upper respiratory diseases, and multiple sclerosis. Several targets are described for andrographolide, including the interference of transcription factors NF-κB, AP-1, and HIF-1 and signaling pathways such as PI3K/Akt, MAPK, and JAK/STAT. In addition, an increase in the Nrf2 (nuclear factor erythroid 2–related factor 2) signaling pathway also supports its antioxidant and anti-inflammatory properties. However, this scenario could be more complex since recent evidence suggests that andrographolide targets can modulate glucose metabolism. The metabolic effect of andrographolide might be the key to explaining the diverse therapeutic effects described in preclinical and clinical studies. This review discusses some of the most recent evidence about the anti-inflammatory and metabolic effects of andrographolide.
Highlights
Andrographis paniculata is a traditional herb from Asian countries that has been used for relieving and reducing the severity and duration of symptoms of common colds and alleviating fever, coughs, and sore throats in uncomplicated respiratory tract infections
Andrographolide reduces RNA replication of the hepatitis C virus in a hepatic cell culture [87] and protects against the acute liver injury induced by LPS and d-galactosamine [88] by activating p 38 mitogen-activated protein kinase (MAPK) pathways and increasing nuclear factor-like 2 (Nrf2), which is mediated by the increase in the expression of heme oxygenase-1 (HO-1) [87]
Cellular metabolism plays a key role in the development of several inflammatory diseases
Summary
Andrographis paniculata is a traditional herb from Asian countries that has been used for relieving and reducing the severity and duration of symptoms of common colds and alleviating fever, coughs, and sore throats in uncomplicated respiratory tract infections. The accumulation of several cellular metabolites determines the activation/repression of signaling pathways, the epigenetic and post-transcriptional regulation of inflammatory genes, and the post-translational modification of proteins [39] Several of these pathways induced in the inflammatory process control glycolytic metabolism and could contribute to the ability of andrographolide to reduce inflammation and cancer progression [14]. By using a quantitative chemical proteomic approach, novel potential targets of andrographolide have been proposed in the fields of inflammation and immunity research, including PKM2 and LDH [52] This suggests that andrographolide could reduce the glycolytic switch induced during the joint inflammatory process. Other authors found that andrographolide inhibits TNF-α-induced IKK activation and IκBα phosphorylation in endothelial cells [62] This anti-inflammatory property has been associated with its efficacy in ameliorating ulcerative colitis, asthma, hepatic inflammation, and arthritis [14,17]. Andrographolide suppresses the proliferation of human cancer colon and multiple myeloma cells via TLR4/NF-κB inhibition [66]
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