Review Berberine: New perspectives for old remedies Micol Tillhon a , Luis M. Guama ´n Ortiz a,b , Paolo Lombardi c , A. Ivana Scovassi a, * a IGM-CNR, Via Abbiategrasso 207, 27100 Pavia, Italy b UTPL, Loja, Ecuador c Naxospharma, via Di Vittorio 70, 20026 Novate Milanese, Italy Contents 1. Introduction: Traditional Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2. Berberine: Chemical properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2.1. Clinical uses of berberine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2.2. Molecular targets of berberine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3. Berberine and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3.1. Pro-apoptotic effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3.2. Combined use with drugs and radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3.3. Effect on tumor progression and metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3.4. Induction of autophagy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 4. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 1. Introduction: Traditional Medicine Around the world, the use of plants with pharmacological properties is the main medical resource in developing countries [1,2]. This practice is known as Traditional Medicine (TM), Indigenous Medicine or Folk Medicine. According to WHO [3], TM includes knowledge, skills, and practices based on the theories, beliefs and experience typical of different situations, applied to the prevention, diagnosis, improvement or treatment of physical and mental illness. TM implies the use of mainly herbal products that contain parts of plants or active principles, according to the ethnobotany, i.e. the ‘‘science of people’s interaction with plants’’ [4] which have been used for centuries as remedies for several diseases and are still utilized as primary healthcare (PHC) in several countries [5]. About 80% of population from the developing countries of Africa and Asia uses TM for diagnosis, treatment, prevention of disease, and maintenance of good health [1,2]. TM and health practices can be a source of income, as it occurs in China and India; in South America herbal medicine is extensively used, representing an alternative to expensive Western medicine [6]. Many natural compounds from TM could serve as a good scaffold for rational drug design [7]. As reviewed by Newman and Cragg [8], they are effective as anti-inflammatory, analgesics, Biochemical Pharmacology xxx (2012) xxx–xxx A R T I C L E I N F O Article history: Received 30 May 2012 Accepted 16 July 2012 Available online xxx Keywords: Apoptosis Autophagy Berberine Cancer Isoquinoline alkaloid A B S T R A C T Chemical compounds derived from plants have been used since the origin of human beings to counteract a number of diseases. Among them, the natural isoquinoline alkaloid berberine has been employed in Ayurvedic and Chinese Medicine for hundreds of years with a wide range of pharmacological and biochemical effects. More recently, a growing body of reports supports the evidence that berberine has anticancer effects, being able to block the proliferation of and to kill cancer cells. This review addresses the properties and therapeutic use of berberine and focuses on the recent advances as promising anticancer drug lead. ß 2012 Published by Elsevier Inc. * Corresponding author. Tel.: +39 0382 546334; fax: +39 0382 422286. E-mail address: scovassi@igm.cnr.it (A.I. Scovassi). G Model BCP-11350; No. of Pages 8 Please cite this article in press as: Tillhon M, et al. Berberine: New perspectives for old remedies. Biochem Pharmacol (2012), http:// dx.doi.org/10.1016/j.bcp.2012.07.018 Contents lists available at SciVerse ScienceDirect Biochemical Pharmacology jo u rn al h om epag e: ww w.els evier.c o m/lo cat e/bio c hem p har m 0006-2952/$ – see front matter ß 2012 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.bcp.2012.07.018