Phenolic composition, antioxidant potential and in vitro inhibitory activity of leaves and acorns of Quercus suber on key enzymes relevant for hyperglycemia and Alzheimer's disease
Introduction
Diabetes affects more than 300 million people worldwide and is expected to be the 7th leading cause of death in 2030 (Mathers and Loncar, 2006, Mai et al., 2007, Danaei et al., 2011). Type 2 diabetes (T2DM) constitute more than 90% of cases of diabetes and is associated with a variety of risk factors, including genetics and lifestyle (Mozaffarian et al., 2009). This disease is characterized by high blood glucose level caused by inherited or acquired deficiency in insulin secretion and by decreased responsiveness of the organs to secreted insulin (WHO, 1999; Yarchoan and Arnold, 2014). The inhibition of carbohydrate-hydrolysing enzymes, such as α-amylase and α-glucosidase, can significantly decrease the postprandial increase of blood glucose levels after a mixed carbohydrate diet and therefore can be an important strategy in the management of hyperglycemia linked to T2DM (Kwon et al., 2008). Examples of such inhibitors currently in clinical use are acarbose, miglitol and voglibose (Bailey, 2003). However, main drawbacks of such medications are side effects, such as abdominal distention, flatulence and meteorism (Bischoff et al., 1985). Natural inhibitors from dietary plants have been shown to inhibit both α-amylase and α-glucosidase and can be used as effective therapy for postprandial hyperglycemia with reduced side effects (Kwon et al., 2006).
Alzheimer's disease (AD) currently accounts for 60–80% of cases of dementia, has no cure and is the fourth leading cause of death in developed nations, after heart disease, cancer and stroke (Natarajan et al., 2009, Alzheimer's Association, 2010). AD affected approximately 36 million people in 2010, and it is estimated that this number may increase to 66 million by 2030 and to 115 million by 2050 (Alzheimer's Disease International, 2009). Biochemically, AD is described by a reduction of the levels of the neurotransmitter acetylcholine (ACh), which is hydrolysed primarily by AChE and secondly by BuChE (Racchi et al., 2004). The inhibition of AChE is currently the most established approach for the treatment of AD, and several AChE inhibitors (AChEI) are used to attenuate the symptoms related with this disease (e.g. tacrine, donzepil and galanthamine; Orhan et al., 2007). However, some of these AChEI show hepatotoxicity, driving the need to search for novel and safer drugs (Knapp et al., 1994).
A growing body of clinical and epidemiological research strongly suggests T2DM as a significant risk factor for developing AD (Hofman et al., 1997, Haan and Wallace, 2004, Luchsinger and Mayeux, 2004, Launer, 2005, Luchsinger et al., 2007; de la Monte and Wands, 2008; Sato and Morishita, 2014; Yarchoan and Arnold, 2014). Although the nature of the association between T2DM and AD is yet not fully understood, the possible links between the latter ailments include, for example, insulin processing, amyloid and tau protein deposition, inflammation, mitochondrial dysfunction and oxidative stress and also inadequate ACh production (Yarchoan and Arnold, 2014). Thus, it is currently accepted that AD patients might benefit from therapies presently used for the treatment of T2DM (Akter et al., 2011).
Cork oak (Quercus suber L.) is the primary source of cork, which is mainly used for the production of stoppers for wine and other alcoholic beverages and of thermal and/or acoustic insulation materials. Portugal is the world's top exporter and producer of cork, generating 157,000 tonnes annually, i.e. 50% of the world production (APCOR, 2010). Moreover, the acorns of cork oak are used as feed for free-ranging Iberian pigs, an autochthonous breed from the Iberian Peninsula. Acorns contain important nutrients, such as carbohydrates, proteins and fatty acids, and also antioxidant compounds, namely phenolic compounds and sterols (Lee et al., 1992, Mamedova et al., 1993, Cantos et al., 2003, Rakić et al., 2006, Rakić et al., 2007, Tejerina et al., 2011). Leaves from different Quercus species contain bioactive compounds, in particular phenolics (Ito et al., 2002, Bedgood et al., 2005). In a recent study we have shown that cork oak acorns collected in the Alentejo (Portugal) were a potential source of biomolecules useful for alleviating symptoms associated with AD and other neurodegenerative disorders (Custódio et al., 2013). In this work, we report for the first time a comparative evaluation of the antioxidant potential and inhibitory activity of leaf and acorn extracts of cork oak on key enzymes relevant for hyperglycemia (α-amylase and α-glucosidase) and neurodegenerative diseases (AChE and BuChE). A phytochemical characterization of the phenolic fraction of the extracts is also reported.
Section snippets
Chemicals
The chemicals used in this work were all analytical grade. Hexane was purchased from Riedel de Haën (Buchs, Switzerland), while Sigma Aldrich (Steinheim, Germany) supplied DPPH, Folin–Ciocalteu (F–C) reagent, electric eel AChE (Type-VI-S, EC 3.1.1.7), horse serum BuChE (EC 3.1.1.8), galanthamine, acetylthiocholine iodide and butyrylthiocholine chloride, 5,5′-dithio-bis(2-nitrobenzoic) acid (DTNB), gallic acid (GA), methanol, Tween 40, aluminium chloride (AlCl3) and sodium carbonate (Na2CO3).
Phytochemical characterization of the extracts
Leaves had a higher total content of phenolics and flavonoids than acorns, while tannins were present in higher amounts in the latter organ (Table 1). The higher concentration of tannins found in acorns is not strange, since those compounds are known to be astringent, which is a characteristic of acorns from different Quercus species. In leaves, the methanol extracts had the utmost TPC (211.0 mg GAE g, DW), followed by the water (61.2 mg GAE g extract, DW) and hexane extracts (2.2 mg GAE g, DW;
Conclusions
Our results suggest that both leaves and acorns from Q. suber are potential sources of antioxidant compounds, with applications in the food and pharmaceutical industries, with particular interest in the prevention of neurological diseases and diabetes (Dillard and German, 2000, Wright et al., 2006, Dai and Mumper, 2010). Taken together, our results suggest possible applications of both leaves and acorns to the pharmaceutical industry and/or as functional foods. Assays are now being conducted in
Conflict of interest
There is no conflict of interest for any of the contributing authors.
Acknowledgements
This work was partially supported by CICYT (CTQ2006-03794/BQU), Instituto de Salud Carlos III (CB06-01-0074 and PI060624), the Generalitat de Catalunya (2005SGR 00662), the Institute for Research in Biomedicine, and the Barcelona Science Park. L. Custódio would like to thanks the Portuguese Foundation for Science and Technology (Portugal) for a post-doctoral grant (grant SFRH/BPD/20736/2004).
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