Available online at www.sciencedirect.com Use of natural products in gastrointestinal therapies Stuart M Brierley 1,2,3 and Olaf Kelber 4 Altered motility, discomfort and pain are common debilitating symptoms of patients with functional gastrointestinal disorders. However, these conditions represent a significant and unmet need for mainstream medical treatment, particularly after high profile therapeutic drug withdrawals due to safety concerns. As such an increasing number of sufferers are turning to alternative medicines in an effort to seek relief from their symptoms. Alternative medicines have traditionally been looked at by mainstream medicine with cynicism. However, new evidence demonstrates that the active components in natural products have actions on specific ion channels and receptors, many of which are located in sensory systems distributed throughout the body. These findings may not only explain the symptomatic benefit of these alternative medicines but also provide novel therapeutic targets for mainstream drug development. As such natural products represent a wealth of untapped potential which is waiting to be unlocked. Addresses 1 Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia 2 Department of Gastroenterology & Hepatology, Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia 3 Discipline of Physiology, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia 4 Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany Corresponding author: Brierley, Stuart M (stuart.brierley@adelaide.edu.au) Current Opinion in Pharmacology 2011, 11:604–611 This review comes from a themed issue on Gastrointestinal Edited by L Ashley Blackshaw and Qasim Aziz Available online 11th October 2011 1471-4892/$ – see front matter # 2011 Elsevier Ltd. All rights reserved. DOI 10.1016/j.coph.2011.09.007 Introduction Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS) are highly prevalent functional gastrointestinal dis- orders affecting up to 30% of the population. Although their aetiologies are different, altered motility, discomfort and pain are common symptoms, as are a lack of effective mainstream medical therapies. Increased recognition by patients of the current limits of conventional mainstream medicine has helped drive growing interest in alternative natural product therapies. However, such therapies are viewed by many in mainstream medicine with scepticism. There are many reasons for this including a historical lack of rigorous clinical trials and a perception that these ‘natural therapies’ are just non-specific actions. However, over the last decade an enormous amount of evidence in a variety of fields has indicated that natural products are a valuable source of pharmacological tools, as they have actions on specific ion channels and receptors, and are therefore potentially useful leads in the development of new human therapeutics. Selectivity of natural products Natural products comprise compounds that have been extracted from botanical sources through to all manner of organisms (for probiotics see review by Eamon Quigley in this edition). Such compounds have allowed major mechanistic breakthroughs in physiology and disease in other fields. For example, recent advances in taste mod- alities, a fundamental process we take for granted every- day, reveal complex mechanisms whereby several distinct classes of specific taste receptors and taste receptor cells are required to distinguish between sweet, sour, bitter, umami (savoury) and salty compounds [1  ]. By contrast, more brutal natural products have evolved for prey capture and defence. Cone snails, snakes, spiders and scorpions utilise venoms containing diverse bioactive compounds to immobilise or kill their prey. In fact, many of these venom peptides have been shown to act on specific ion channels (particularly voltage-gated sodium/potassium/calcium channels) and other cellular receptors to impair their normal functioning [2  ,3]. Such studies have utilised high-throughput screening methods to identify venoms with a desired activity to allow subsequent isolation of bioactive molecules [4  ]. The successfulness of this approach has led to several different venom peptide deriva- tives receiving FDA approval for clinical use in hyperten- sion (Captopril), unstable angina (Eptifibatide), Type 2 diabetes mellitus (Exenatide) and highly selective use in chronic pain (Ziconotide) [4  ]. These drug treatments are synthetic versions of active compounds identified from the pit viper (Bothrops jararaca), rattle snake (Sistrurus miliarius barbouri), Gila monster (Heloderma suspectum) and cone snail (Conus magus), respectively. In the GI field we have yet to scratch the surface of mechanistic insight to be gleamed from these developing venomous compounds. To date the best insight has been gained from the neurotoxin tetrodotoxin (TTX; isolated from the puffer fish) where animal studies have shown that sodium currents that are TTX-resistant (thought to be mediated by Na V 1.8) are enhanced in gut innervating sensory neurons in inflammatory, nematode or bacterial Current Opinion in Pharmacology 2011, 11:604–611 www.sciencedirect.com