Antioxidant, acetylcholinesterase inhibitory activity and cytotoxicity assessment of the crude extracts of Boophane disticha

Abstract

1. Introduction
Alzheimer’s disease (AD) is the most common
neurodegenerative disease and is characterized by
memory impairment, cognitive dysfunction, behavioral
disturbances and deficits in daily living (Konrath et al,
2012). Approaches to enhance cholinergic function in
AD have included stimulation of cholinergic receptors
or prolonging the availability of acetylcholine (ACh)
released into the neuronal synaptic cleft by inhibiting
ACh hydrolysis through the use of acetylcholinesterase
(AChE) inhibitors (Howes and Houghton, 2003). Tacrine
was the first widely used AChE inhibitor (Summers,
2006). Second generation AChE inhibitors with longer
half-lives than tacrine, such as donepezil, galanthamine
and rivastigmine, have since been developed and are
currently in use (Shah et al, 2008). In addition, several
lines of evidence indicate that reactive oxygen species
are associated with the pathogenesis of AD, as some
cellular characteristics of this disease are either causes
or effects of oxidative stress (Zhu et al, 2004; Sultana et
al, 2006; Konrath et al, 2012). Generally, the
physiological role of antioxidant compounds is to
attenuate the oxidation chain reactions by removing

free-radical intermediates (Liu and Nair, 2010). Since a
large amount of evidence demonstrates that oxidative
stress is intimately involved in age-related
neurodegenerative diseases, there have been a number
of studies which have examined the positive effects of
antioxidants in reducing or blocking neuronal death
occurring in the pathophysiology of these disorders
(Ramassamy, 2006). Consequently, the use of
antioxidants has been explored in an attempt to slow
AD progression and neuronal degeneration (Howes and
Houghton, 2003).
Toxicity testing is an essential requirement for the
development of modern pharmaceutical compounds.
Medicinal plants are assumed to have low toxicity due
to their long-term consumption by humans and animals
(Luseba et al, 2007; Verschaeve and van Staden, 2008;
Aremu et al, 2011). However, several studies have
shown that many plants used as food or medicine, have
potential toxic effects (Du Plooy et al, 2001; Barlow and
Schlatter, 2010). Almost all known AChE inhibitors have
several drawbacks, such as hepatotoxicity, short
duration of biological action, low bioavailability,
adverse cholinergic side effects in the periphery and
narrow therapeutic windows (Lee et al, 2011). Some
common synthetic antioxidants including butylated
hydroxyanisole (BHA) and butylated hydroxytoluene
(BHT) have been reported to be toxic (Aremu et al,
2011). Therefore, the search for new AChE inhibitors
and antioxidants, particularly from natural products,
with low toxicity and higher efficacy continues.
Many plants are reputed to have ‘anti-ageing’ or
‘memory-enhancing’ effects and are used traditionally
to treat several neurodegenerative diseases (Howes and
Houghton, 2003). One such plant, Boophane disticha
(L.f.) Herb. belongs to the family Amaryllidaceae. It is an
attractive, deciduous bulbous plant with a thick
covering of dry scales above the ground and is widely
distributed in Africa, ranging from Sudan in the north to
the Western Cape Province in the south (Wrinkle,
1984). Decoctions of bulb scales are given to sedate
violent, psychotic patients while bulb infusions are
reported to be used to treat mental illness (van Wyk
and Gericke, 2000; Sobiecki, 2002). Bulb decoctions are
also used in the treatment of headaches, abdominal
pain, weakness, sharp chest pains and persistent
bladder pains, as well as treatment of varicose ulcers,
relief of urticaria, and cancer (Botha et al, 2005). This
study was aimed at evaluating the AChE inhibitory and
antioxidant activity of the bulbs and roots of B. disticha
to partially justify its traditional use in treatment of
neurodegenerative diseases. The safety of using this
plant in traditional medicine was also investigated by
assessing its toxicity using the MTT and neutral red
assays.