Berberrubine, an Attractive derivative of berberine with multiple pharmacological activities

Berberrubine is the well-known metabolite of berberine that can be isolated from plants. It has increasingly gained attention with its biological properties that are at times more potent than berberine. Compared with berberine, the structure of berberrubine has better lipid solubility and P-gp receptor affinity, so it has better bioavailability. Equally, greater biological activity has emerged in the treatment of disease. Currently, berberrubine is mainly derived by chemical synthesis, which not only pollutes the environment but also cannot meet the market demand. In this paper, the source, pharmacokinetics, biological properties, and toxicity of berberrubine were systematically reviewed by collecting and summarizing the current relevant literature over the past few decades. Furthermore, the underlying molecular mechanism and dose–effect relationship of berberrubine and the prodrug berberine in the treatment of related diseases are also discussed to broaden the application and development prospects of berberrubine as a novel drug. Notably, the clinical studies of berberrubine are quite insufficient. Further high-quality studies are required to firmly establish the clinical efficacy of berberrubine.