Macrocystis angustifolia is a potential source of enzyme inhibitors linked to type 2 diabetes and dementia Kannan R. R. Rengasamy & Mutalib A. Aderogba & Stephen O. Amoo & Wendy A. Stirk & Johannes Van Staden Received: 10 July 2013 /Revised and accepted: 24 September 2013 /Published online: 10 October 2013 # Springer Science+Business Media Dordrecht 2013 Abstract In continuation of the screening of South African seaweeds to identify potential candidates for the development of pharmaceutically active functional foods, we investigated the inhibitory effects of a crude 80 % methanol extract, solvent fractions and isolated compounds from the kelp Macrocystis angustifolia against enzymes involved in type 2 diabetes and dementia. Repeated column fractionation of the ethyl acetate fraction of the crude extract of M . angustifolia afforded two phenol derivatives identified by spectroscopic analyses (1D and 2D NMR): 4-(2-hydroxyethyl)phenol (tyrosol) (1 ) and 4-(1,2-dihydroxyethyl)phenol (2 ). These compounds were isolated from a marine alga for the first time. The ethyl acetate (IC 50 =14.08±1.21 μg mL −1 ) and butanol (IC 50 =77.94±11.69 μg mL −1 ) fractions exhibited potent inhibition against α-glucosidase and acetylcholines- terase (AChE) enzymes, respectively. Tyrosol (1 ) and its derivative, 4-(1,2-dihydroxyethyl)phenol (2 ), showed potent inhibition against both α-glucosidase and AChE enzymes. Based on in silico evaluation, these two compounds are antici- pated to possess sufficient oral bioavailability in accordance to the Lipinski Rule of Five without any toxicity risk. Natural α-glucosidase and AChE inhibitors from M . angustifolia offer a novel approach to control type 2 diabetes and dementia. Keywords 4-(1,2-Dihydroxyethyl)phenol . Acetylcholinesterase . α-Glucosidase . Drug-likeness . Lipinski Rule of Five . Tyrosol Introduction Diabetes mellitus (DM) is one of the most expensive and troublesome chronic diseases and is recognized as a con- dition that is increasing to epidemic proportions through- out the world (King et al. 1998). The World Health Organization (WHO) estimated that diabetes affects 347 million people worldwide with more than 80 % of deaths due to diabetes occurring in low- and middle-income countries (WHO 2013). A therapeutic approach for treating diabetes is to decrease postprandial hyperglycaemia by the inhibition of enzymes such as α-glucosidase that hydrolyse carbohydrates. Synthetic α-glucosidase inhibitors such as acarbose, miglitol and voglibose are widely used for the management of type 2 diabetes as oral antidiabetic drugs (Van de Laar et al. 2005). However, they also cause various side effects such as flatulence, diarrhoea and abdominal discomfort (Suzuki et al. 2009). Alzheimer's disease (AD), another major health problem, is known to be the most common cause of dementia. Alzheimer's disease is estimated to affect 1 in 85 people globally by 2050 (Brookmeyer et al. 2007). The inhibition of acetylcholinesterase (AChE) is one of the most common approaches for the treatment of AD, senile dementia, ataxia, myasthenia gravis and Parkinson's disease (Mukherjee et al. 2007). The inhibition of AChE plays a critical role in enhancing cholinergic neurotransmission in the brain and decreasing β-amyloid formation in order to protect the neu- rons from neurodegeneration (Hodges 2006). Recently, re- searchers proposed a strong association between diabetes and AD and found that the management of diabetes and cholesterolaemia reduced the risk of AD by 12–13 % (Greener 2013). Application of marine biotechnological tools to develop bioactive compounds from marine products to be used as K. R. R. Rengasamy : M. A. Aderogba : S. O. Amoo : W. A. Stirk : J. Van Staden (*) Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa e-mail: rcpgd@ukzn.ac.za J Appl Phycol (2014) 26:1557–1563 DOI 10.1007/s10811-013-0171-8