Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα

Abstract

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.

A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer

“…Not surprisingly, of the 175 small molecule anti-tumor agents approved between the 1940s to 2014, almost 50% of them were derived directly from various natural products [ 28 ]. As a class of natural isoquinoline alkaloids, berberine has been shown to possess extensive pharmacological activities, such as anti-inflammatory, antioxidant, and anti-diabetes effects [ 15 , 29 , 30 ]. In addition, berberine has been of interest for years due to its anti-tumor activity of interfering with a variety of characteristics of tumorigenesis and tumor development.…”

“…Berberine, a major isoquinoline alkaloid constituent of many medicinal herbs, such as Coptidis rhizome and Berberis vulgaris , has shown great promise as an anti-cancer agent [ 15 ]. Studies have reported several important molecular mechanisms responsible for the anti-cancer effect of berberine.…”

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…Berberine has been demonstrated to have comparable effects in the treatment of T2DM with antidiabetic drugs like metformin that display multiple targets and pathways. For patients with T2DM, the main function of berberine is as a SIRT1 or AMPK agonist to mimic energy restriction [ 75 – 77 ] and to target on NF- κ B [ 78 ] to improve insulin resistance and inflammation as well as to alleviate the activation of ox-LDL-induced macrophages [ 79 ]. In addition, berberine stabilizes LDL receptor mRNA to increase the clearance rate of plasma LDL [ 80 ].…”

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

“…Studies involving animal models of LPS-induced neuroinflammation are utilized to assess in vivo activity of compounds tested for this purpose for the first time. Both of these methods may be also used with the aim of explaining the exact mechanism of action and specific effects of substances with already established neuroprotective activity [ 41 , 111 , 112 ]. The most important factors limiting the therapeutic use of these substances are often their low bioavailability in humans and not sufficient level of BBB crossing.…”