Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF‐κB, JAK/STAT, and MAPK signaling pathways

Three main inflammatory signaling pathways include nuclear factor-κB (NF-κB), Janus kinases/Signal transducer and activator of transcriptions (JAKs/STATs), and mitogen-activated protein kinases (MAPKs) play crucial roles in inducing, promoting, and regulating inflammatory responses in the immune system. Importantly, the breakdown of mechanisms that tightly regulate inflammatory signaling pathways can be the underlying cause of uncontrolled inflammatory responses and be associated with the generation and development of several inflammatory diseases. Hence, therapeutic strategies targeting inflammatory signaling pathways and their downstream components may promise to treat inflammatory diseases. Studies over the past two decades have provided important information on the polytrophic pharmacological and biochemical properties of berberine (BBR) as a naturally occurring compound, such as antioxidant, antitumor, antimicrobial, and antiinflammatory activates. Interestingly, the modulatory effects of BBR on inflammatory signaling cascades, which lead to the inhibition of inflammation, have been widely investigated in several in vitro and in vivo studies. For the first time, herein, this comprehensive review attempts to put together these studies and provide important insight into the modulatory effects of BBR on NF-κB, JAKs/STATs, and MAPKs signaling pathways in vitro in various types of immune cells and in vivo in several experimental inflammatory diseases. As the second achievement of this review, we also explore the therapeutic efficacy and antiinflammatory effects of BBR regarding its modulatory action.