Isoliquiritigenin, Liquiritigenin Rich Root Extract of Glycyrrhiza glabra Attenuates Inflammation in Macrophages and Collagen-Induced Arthritis in Rats

Abstract

Abstract The aim of this study was to evaluate the potential effect of root extract of Glycyrrhiza glabra (IVT-21), isoliquiritigenin (ISL), and liquiritigenin (LTG) present in G. glabra root extract in in-vitro anti-inflammatory activity and we also investigate the effects of IVT-21 in collagen-induced arthritis (CIA) rats. Primary peritoneal macrophage cells were used for check the anti-inflammatory effect of IVT-21. Apart from this Collagen-induced arthritis (CIA) was developed in Wistar rats. Animals were orally treated with IVT-21 at dose rate of 30,100 and 300 mg /kg for 21 days. The chemical signature of IVT-21 using HPLC analysis showed the presence of ISL and LTG as the main active ingredients. Treatment of IVT-21, ISL and LTG were able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-induced inflammation in primary peritoneal macrophages. In-vivo experimental pharmacology profile of IVT-21 against rheumatoid arthritis revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in CIA rat’s serum, and also reduced the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue of CIA rats, reduce the inflammatory mediator's gene expression in a dose-dependent manner in paw tissue of CIA rats. Further, in in-vivo safety studies of IVT-21 was found to be safe in experimental animals up to 2,000 mg/kg dose. The result of this study suggests the suitability of IVT-21 as a drug-like candidate for further investigation in the management of inflammation and rheumatoid arthritis.