Abstract:
Diabetes
is one of the major risk factors for cataract. Aldose reductase has been
reported to play an important role in sugar-induced cataract. In this study, we
conducted pharmacological investigations upon experimental rat lenses using
extracts of the fruits of Litchi chinensis (Sapindaceae). Of the extracts and
organic fractions of L. chinensis tested, a MeOH extract and an EtOAc fraction
were found to be potent inhibitors of rat lens aldose reductase (RLAR) in
vitro--their IC(50) values being 3.6 and 0.3 microg/mL, respectively. From the
active EtOAc fraction, four minor compounds with diverse structural moieties
were isolated and identified as D-mannitol (1), 2,5-dihydroxybenzoic acid (2),
delphinidin 3-O-beta-galactopyranoside-39,59-di-O-beta-glucopyranoside (3), and
delphinidin 3-O-beta- galactopyranoside-39-O-beta-glucopyranoside (4). Among
these, 4 was found to be the most potent RLAR inhibitor (IC(50) = 0.23
microg/mL), and may be useful in the prevention and/or treatment of diabetic
complications.
Introduction
Cataract, the leading cause of blindness worldwide, is
associated with several risk factors, a major one of which is considered to be
diabetes. Various pharmacological intervention strategies aimed at the
prevention of diabetes are currently being investigated. Among these, aldose
reductase inhibitors (ARIs) have received considerable attention owing to the
proposed involvement of aldose reductase (AR) in the pathophysiology of
diabetic complications, including cataract [1]. A vast literature exists
demonstrating that cataract progression can be slowed or prevented by the use
of natural therapies, and particularly by the use of plants having high flavonoid
contents, which have exhibited considerable in vivo AR inhibitory
effects [2].
Litchi (Litchi chinensis Sonn., Sapindaceae) is a
tropical to subtropical crop that originated in South-East Asia. With the
gradual consumer acceptance of litchi fruits for their delicious taste and
attractive red skin, there has been a steady increase in litchi production over
recent decades, with increasing exports into Europe and North America from
production areas in both the Southern and Northern hemispheres. Litchi fruit
pericarp (LFP) accounts forapproximately 15% by weight of the whole fresh fruit
and comprises significant amounts of flavonoids. Consequently, litchi LFP
tissues may be a potentially important source of AR-inhibiting compounds [3].
Previous pharmacological and phytochemical studies on litchi have revealed the
fruit to be a rich source of anthocyanins [4] and several flavone glycosides
[5]. Duan et al. (2007) reported that anthocyanins from LFP tissues strongly
inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical
scavenging activity against diphenylpicrylhydrazyl (DPPH) radicals, superoxide
anions, and hydroxyl radicals. Wang et al. [6] reported that an LFP extract
exhibited potential in vitro and in vivo anticancer activity against
hepatocellular carcinoma. Furthermore, the LFP extract exhibited a
dose-dependent, time-inhibitory effect on cancer cell growth. The anticancer activity
of LFP water-soluble crude ethanolic extract might result, at least in part,
from the inhibition of DNA synthesis, proliferation, and apoptosis induction in
cancer cells [7].
However, the biological activity of LFP has not been
investigated in detail. From this perspective, various inhibitors, such as the
inhibitors of rat lens aldose reductase (RLAR), are presently being developed
as novel potential therapeutic agents. Therefore, we have screened LFP for its
ability to inhibit RLAR in vitro.
In our continuing search for the bioactive principles from crude
plant extracts, we have evaluated the extracts and fractions of L. chinensis,
particularly in relation to their inhibitory effects on RLAR. Here, the effects
of compound isolate
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