Sinomenine-glycyrrhizic acid self-assembly enhanced the anti-inflammatory effect of sinomenine in the treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease that causes cartilage and bone damage in multiple joints, ultimately leading to disability. There is an urgent need to develop multidimensional strategies to treat RA. Sinomenine (SIN) has the distinctive pharmacological activity in treating RA, but its broader clinical application is limited by its exceedingly short half-life and adverse digestive tract effects. To overcome this obstacle, a self-assembled nanohydrogel (S-G hydrogel) was designed and produced with sinomenine (SIN) and glycyrrhizic acid (GA) without carriers or catalysts through noncovalent bonding. The S-G hydrogel could promote the absorption of SIN probably by protecting SIN from releasing and degrading in the acid circumstances. Oral intake of the S-G hydrogel significantly suppressed the overactivation of neutrophil via the Nf-κb and Mapk pathways in mice with RA. Furthermore, the S-G hydrogel regulated neutrophil activity by reversing apoptosis delay and decreasing autophagy-dependent NET formation. In summary, this study presents a self-assembled hydrogel with promising potential for clinical application, and offers a novel strategy to develop new drugs from the existing patent medicine composed of compounds from traditional Chinese medicine, as well as a special insight to elucidate the herb-matching mechanism in decoction prescriptions.

Keywords: Glycyrrhizic acid; Neutrophil; Rheumatoid arthritis; Self-assembled hydrogel; Sinomenine.