Traditional Chinese medicine for the treatment of chronic inflammatory diseases: A review of inhibitors for NLRP3 inflammasome

Abstract

The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a vital part of the innate immune response, whilst its aberrant activation drives the progression of several noncommunicable diseases. It induces caspase-1 activation and the downstream substrates involved with the processing and secretion of the pro-inflammatory cytokines IL-1β and IL-18 and TNF-α. Activation of this complex often involves the adapter ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis, and play key roles in inflammation, development, and related cell death. However, the molecular mechanisms that integrate multiple inflammasome sensors to facilitate optimal host defense remain unknown; therefore, treatment is challenging. Natural medicine and small molecule-based therapies have been well-documented for their effectiveness in modulating inflammatory pathways and reestablishing the lost proteostasis inside the cells to combat several chronic diseases related to inflammation. Traditional Chinese medicines (TCMs) have potent clinical effects against NLRP3 inflammasome activation and could be used as complementary therapy. Therefore, this review summarizes various similar reports and highlights the important effects of nutraceuticals and bioactive compounds derived from medicinal plants on NLRP3 inflammasome activation and their possible mechanisms of action. Thus, TCM prescriptions, herbs, and bioactive compounds can be considered novel, practical, and accessible agents in chronic inflammatory diseases by inhibiting NLRP3 inflammasome activation.