Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Abstract

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

HuNoV Non-Structural Protein P22 Induces Maturation of IL-1β and IL-18 and N-GSDMD-Dependent Pyroptosis through Activating NLRP3 Inflammasome

“…Berberine (BBR), a natural isoquinoline alkaloid isolated from several traditional Chinese herbal plants, is traditionally used to treat diarrhea and gastroenteritis [ 28 , 37 ], and it was reported to inhibit the activation of the NLRP3 inflammasome [ 38 ]. Here, we intended to investigate whether BBR could inhibit NLRP3 inflammasome activation caused by HuNoV and found that BBR treatment reduced the secretion of IL-1β and IL-18 and suppressed N-GSDMD-driven pyroptosis through inhibiting the activation of NLRP3 inflammasome caused by HuNoV and P22, suggesting that BBR has the potential to treat HuNoV-induced acute gastroenteritis through inhibiting the inflammatory response and pyroptosis.…”

Natural biomolecules and derivatives as anticancer immunomodulatory agents

“…Berberine also inhibited AMPK-dependent autophagy in adipose tissue macrophages, which reduced palmitate-induced inflammasome activation, IL-1β release, insulin resistance ( 125 ). Beneficial effects of berberine-mediated inflammasome inhibition have been reported in Parkinson’s disease, endovascular injury, drug-induced hepatotoxicity and diabetic nephropathy (by suppressing epithelial to mesenchymal transition (EMT) ( 126 ). Given the inhibitory effects of berberine on inflammasome activation and the importance of this pathway in radiation-induced injury, we propose that berberine may protect patients from radiation-induced lung and abdominal injury ( 112 , 113 ) by inflammasome inhibition.…”

Research Progress on the Synthesis of Protoberberine Skeleton and Its Anti-inflammatory Activity

“…图 2 小檗碱对典型炎症通路的抑制作用 Figure 2 Inhibitory effect of berberine on canonical inflammatory pathways 2.2 NLRP3 炎性小体 NLRP3 (NOD-, LRR-, and pyrin-domain containing protein 3)是一种多蛋白复合物 [37] : [38] . NLRP3 作为目前研究最为广泛的炎 性小体, 其确切的下游抗炎机制尚未完全发掘, 其抑制 剂仍处于临床, 有待进一步探索 [39] .…”