Abstract
This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA.
Highlights
Because of the unwanted side effects of current drugs used for rheumatoid arthritis (RA) treatment, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years’ experience in treating patients [1]
We found that in RA fibroblast-like synoviocytes (RAFLS), COX-2 effects can be mainly mediated by thromboxane A2 (TxA2), and the mRNA expression of COX-2 is regulated by TxA2 action [11]
Because COX-2derived TxA2 is not the molecular target of non-steroidal antiinflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs), the limitations and negative side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway, which coupled with the positive role of the COX-2/TxA2 pathway in pathogenesis of RA suggests that the pharmacological approaches targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy of RA (Figure 3)
Summary
Because of the unwanted side effects of current drugs used for rheumatoid arthritis (RA) treatment, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years’ experience in treating patients [1]. Analysis of patents on anti-RA therapies issued in China revealed that traditional Chinese Medicine may provide substantial new information for anti-RA drugs development [2]. GL is readily hydrolyzed to glycyrrhetinic acid (GA) in human body [5]. Following oral administration in humans as well as in rats, GL is metabolized in the gastrointestinal tract by glucuronidases into GA, which can be totally absorbed [6]
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