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

Abstract

Three main inflammatory signaling pathways include nuclear factor-κB (NF-κB), Janus kinases/Signal transducer and activator of transcriptions (JAKs/STATs), and mitogenactivated 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

Research Progress on Autophagy Regulation by Active Ingredients of Traditional Chinese Medicine in the Treatment of Acute Lung Injury

“…Berberine is a quaternary ammonium salt isoquinoline alkaloid isolated from the Coptidis rhizome (Huanglian) that has antibacterial, anti-inflammatory and antioxidant effects. 100 Oxyberberine has a stronger anti-inflammatory effect and is safe. 101 In mice with LPS-induced ALI and lung epithelial A549 cells, oxyberberine treatment significantly improved pulmonary oedemaedema, neutrophil infiltration and inflammatory factor expression, inhibited apoptosis and ROS production in A549 cells, and inhibited mitophagy induced by LPS in A549 cells.…”

Exploring the mechanism of three herb pairs for the treatment of atherosclerosis through network pharmacology and molecular modeling

“…EGFR (Epidermal growth factor receptor, degree = 57) inhibition significantly reduced T cell infiltration in the AS process [37], and alkaloids in Huanglian-Gualou reduced the proliferation and migration of VSMCs induced by EGFR [38]. CASP3 (Caspase-3, degree=55) is expressed as an apoptotic protease in atherosclerotic plaques [39], and oxyberberine inhibited the expression of pro-apoptotic protein CASP3 [40]. Moreover, PPARG (Peroxisome proliferatoractivated receptor gamma, degree =50) affected lipid metabolism in macrophage foam cells and induced inflammatory response associated with AS [41].…”

“…Alkaloids and triterpenoids haved been reported to downregulate the expression of the downstream target MMP9 by interacting with MAPK3, and significantly reduced the thickness of carotid intima in mice fed with high cholesterol diet [43]. Oxyberberine reduced the expression of AGEs and RAGE, and regulated the downstream MAPK signal pathway,inhibiting the expression of pro-apoptotic protein CASP3 [40]. Therefore, we hypothesised that the Huanglian-Gualou pair showed clearing heat and resolving phlegm against AS by modulating the MAPK and AGE-RAGE pathways.…”

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

“…NF-κB (nuclear factor-kappaB)由 Sen [33] 于 1986 年发 现, 是调节小鼠 B 淋巴细胞中 κ 轻链表达的转录因子, 已被发现可以调控大量基因的表达, 有 5 个成员: [8,34] .…”

“…越来越多的体外和体内实验模型表明, BBR 还能在免疫 系统中发挥调节作用. 因而可以认为 BBR 是一种多效 分子, 可同时靶向多种炎症相关信号分子 [8] . 但由于其 存在抗炎活性较低、生物利用度低等问题, 严重限制了 它的使用, 因而关于原小檗碱类生物碱的全合成、抗炎 机制与抗炎构效关系的分析成为了研究重点.…”