Berberine: A multipotent remedy with unknown cellular target?

Abstract

Recently, Shen et al. (2010) reported that berberine influences the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide in broiler chickens. We speculate here that the effects of the berberine could be partly explained by its interaction with aryl hydrocarbon receptor (AhR)-cytochrome P450 CYP1A signaling pathway. Berberine, a quaternary isoquinoline alkaloid, is extensively used as traditional medicine or as a component of numerous food supplements and dietary products. Berberine exerts a plethora of biological activities and therapeutic effects, including antibacterial, antimotility, antifungal, antisecretory, antimalarial, antiinflammatory, anticancer, antiproliferative, antidiabetic, neuroprotective, and many other activities (Baird et al., 1997; Vrzal et al., 2005; Bhadra and Kumar, 2010). Although berberine was reported to interact with multiple cellular targets, such as cyclooxygenase-2, activator protein-1, α2-adreno receptors, hepatocyte nuclear factor 4α, and telomerase, the true target responsible for particular biological activities is not known yet. It was demonstrated that berberine is an activator of human AhR in human hepatoma cells HepG2 and rat hepatoma cells H4IIE (Vrzal et al., 2005). Aryl hydrocarbon receptor has various cellular functions; among them, it is an important regulator of immune response, cell cycle, and detoxification and it is involved in chemically induced carcinogenesis (Harper et al., 2006; Esser et al., 2009). Activation of AhR in vivo resembles the Dr. Jekyll and Mr. Hyde story. Synthetic exogenous AhR activators such as dioxins, polyaromatic hydrocarbons, or polychlorinated biphenyls cause endocrine and metabolic disruptions and cancers. Several natural products including resveratrol or flavonoids modulate AhR transcriptional activity, resulting in positive effects on lipid metabolism. In contrast, sustained activation of AhR by endogenous activators such as indirubin or eicosanoids is necessary for cell survival, differentiation, development, and immune functions. We suggest here that many of the biological effects of berberine in humans could be mediated via transcriptional activation of AhR by berberine. Consequently, it could be of value to examine the involvement of AhR while studying in vitro biological effects of berberine.