CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 8, September 2012
464
AFRICA
which compresses the glomerular capillaries, thereby reducing
the filtration surface area and impairing the mechanism that
maintains the normal glomerular capillary hydrostatic pressure.
42
The fall in GFR also reduces the sodium load delivered to the
macula densa cells, resulting in enhanced tubulo-glomerular
feedback (TGF).
44
In turn angiotensin II production increases
due to hyperactivation of the renin–angiotensin–aldosterone
system,
45
causing more reabsorption of sodium and an increase
in systemic blood pressure.
The accumulation of AGEs can be prevented by antioxidants
such as flavonoids or by preventing the glucose-dependent
formation of intermediate products (Amadori, Schiff bases or
Milliard products). Indeed, blocking or deleting AGEs’ receptor
(
RAGE) in experimental animals reversed atherosclerosis.
46
Amino guanidine and pyridoxamine, AGEs formation inhibitors,
had reno-protective effects in diabetic animals.
47,48
Furthermore,
inhibition of AGEs effects could be achieved through breaking of
the AGEs cross links by drugs such as alagebrium or inhibition
of AGE signal transduction.
48
Tanaka
et al
.
49
reported that the biguanide metformin, the only
example of an approved antidiabetic from a herbal source, French
lilac (
Galega officinalis
)
may be useful in the prevention of the
development of AGEs. The
Panax quinquefolium
(
Linnaeus)
[
Araliaceae] extracts, a phyto-oestrogen derived from
Vitis
vinifera
(
Linnaeus) [Vitaceae] (resveratrol), curcumin from
Curcuma longa
(
Linnaeus) [Zingiberaceae] and glycosides from
Stelechocarpus cauliflorus
(
RE Fr) [Annonaceae] have also been
reported to inhibit formation of AGEs or RAGE.
50-56
Diabetic nephropathy
Renal disease is a common and often severe complication of
diabetes, with the majority of patients with 18 years’ duration
showing signs of diabetic renal involvement.
57
In general,
about one in three patients with type 1 or 2 diabetes develops
ESRD which proceeds to DN, the principal cause of significant
morbidity and mortality in diabetes.
8
The onset of DN is
associated with a progressive rate of decline in renal function,
urinary albumin excretion and glomerular filtration rate. For
purposes of this discussion, DN is used as a generic term
referring to any deleterious effect on kidney structure and/or
function caused by diabetes mellitus.
Management of diabetic nephropathy
World Health Organisation data report age-standardised death
rate for diabetics in South Africa is 85 per 100 000 compared
with 18 in the USA and six per 100 000 in the UK.
3
The principal
reason for the high mortality rates in South Africa is renal
failure as a result of DN. Some 30 to 40% of diabetics develop
nephropathy, which is the leading cause of ESRD.
14
DN progresses through five well-defined stages.
58
Stage 1
is an increase in GFR, which progresses to the clinically silent
stage 2, in which hyperfiltration is associated with hypertrophy.
Stage 3, or initial nephropathy, is typified by microalbuminuria,
modest increases in blood pressure and a reduction in GFR.
Stage 4 sees macroalbuminuria, raised blood pressure and
progressive reductions in GFR, leading to stage 5 or ESRD when
renal-replacement therapy is required.
ESRD is managed in developed countries by renal replacement
therapy (RRT), such as dialysis and transplantation. In developing
countries, however, kidney failure rates are double those in the
West because access to RRT is severely limited by its high cost
to patients.
13
The figures are stark: 70% of patients in a Nigerian
study were able to afford dialysis for only one month, with less
than 2% having sufficient resources to remain on dialysis for
more than 12 months.
59
Access to RRT is virtually impossible
for the rural poor.
12
Current conventional diabetes therapy using blood glucose-
lowering medications has limitations in averting renal
complications. Progression towards ESRD may be slowed in
part by strict control of blood sugar levels and blood pressure,
a reduction in dietary protein intake and inhibition of the renin–
angiotensin system. Consequently, drug developmental strategy
should target these metabolic pathways for the prevention of
progression to ESRD, which proceeds to DN.
Many patients of sub-Saharan Africa however cannot afford
these expensive drugs. Hence there is an urgent need to
find affordable treatments which are effective in slowing the
progression of DN.
Medicinal plants in the management of diabetic
kidney disease
Ethno-medicinal plants have traditionally been used for the
treatment of diabetes and its complications. In fact, current
pre-clinical and clinical studies have demonstrated that many
have beneficial effects on some processes associated with
reduced renal function in experimental animals.
60-62
The active
phytochemicals responsible for their activities have also been
identified.
Our research has established the therapeutic and
pharmacological properties of a number of ethno-botanical
herbs traditionally used in the management of diabetes mellitus
by African communities.
15
Observations indicate that some
herbal extracts contain compounds that could be effective in
mild diabetes mellitus or in cases of impaired glucose tolerance
(
Fig. 1). These are likely to have a positive impact on glucose
homeostasis in diabetic patients.
Investigations from our laboratory have also examined
whether herbal extracts could lower blood pressure or improve
Fig. 1. Oral glucose tolerance test in STZ-diabetic rats
showing dose-related reduction in plasma glucose levels
following treatment with
F thonningii
bark ethanolic
extracts (FTE, 60–240 mg/kg) comparable to that induced
by metformin (500 mg/kg).
17
Statistical comparison of
the differences between the control and experimental
group means was performed using one-way analysis of
variance (ANOVA) followed by Tukey-Kramer multiple
comparison test. A value of
p
<
0.05
was considered
significant.
25
20
15
10
5
0
60
120
180
240
Glucose (mmol/l)
Time (min)
Control
FTE 240
FTE 120
FTE 60
Metformin
