CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 8, September 2012
AFRICA
463
population uses resources derived from traditional medicine to
control diabetes.
14
Medicinal-plant home remedies are used as
crude extracts or standard, enriched fractions in pharmaceutical
preparations.
Research summarised in a recent review
15
showed that several
southern African plant species used by rural communities as
traditionalmedicines hadhypoglycaemic effects in streptozotocin-
induced (STZ) diabetic rat. Furthermore, some species had
antihypertensive properties.
16-19
The impact on the kidney varies,
with some species being reno-protective, whereas others had
a deleterious effect on kidney function. By identifying the
bio-active compound, oleanolic acid (OA), which confers reno-
protection, we have been able to demonstrate the effectiveness of
this agent in STZ diabetic rats.
The focus of this article is to evaluate current evidence on
plant extracts used for the management of hypertension and
kidney disease in diabetes. The beneficial as well as deleterious
effects of medicinal plants in both conditions are discussed
based on reports on plants frequently used in the southern Africa
setting. Herein, a medicinal plant is defined as any plant which
provides health-promoting characteristics, temporary relief or
has curative properties.
Antihypertensive therapy and diabetic renal
disease
Diabetic complications, which include damage to large and small
blood vessels, can lead to coronary heart disease, stroke and
hypertension, the latter being a well-established major risk factor
for cardiovascular disease that contributes to end-stage renal
disease (ESRD). Reduction of blood pressure (BP) is therefore
an efficient way of preventing or slowing the progression of
ESRD. Conventionally, reno-protection is achieved through
reduction in BP with antihypertensive regimens.
20-23
Several
studies however document that antihypertensive treatment in
diabetes not only improves the quality of life,
24-27
but also reduces
renal complications.
28
The major antihypertensive drug classes widely used include
thiazide diuretics, angiotensin converting enzyme (ACE)
inhibitors, angiotensin receptor blockers (ARBs),
β
-
blockers,
central sympatholytic agents, calcium channel antagonists and
other vasodilators. However, some antihypertensive agents,
for example, thiazide diuretics and
β
-
blockers deleteriously
influence glycaemic control.
29
To date, the most effective treatments for diabetic nephropathy
(
DN) are the antihypertensive drugs, particularly those that target
the renin–angiotensin system (RAS) such as ACE inhibitors,
angiotensin-1 receptor antagonists, or their combination.
25,30,31
Although these treatments may retard the progressive decline in
renal function in diabetes, clinical trials suggest that there is no
effective treatment for DN.
8
For these reasons, novel anti-diabetic therapeutic agents
that supplement, substitute or complement the existing modern
medications to ameliorate renal function in diabetes constitute
novel therapeutic strategies for diabetes. Evidence from
biomedical literature suggests that some plant extracts have
protective effects against cardiovascular disease in diabetes.
32
The
following sections evaluate the therapeutic and pharmacological
evidence for the use of some of the medicinal plants and
their bioactive phytochemicals in cardio-renal related diabetic
complications, as well as the potential for nephrotoxicity from
other plant extracts.
Natural plants for cardiovascular disease
Several plant extracts with potential therapeutic properties
for the treatment of hypertension and complications such as
coronary heart disease, angina, arrhythmias and congestive
heart failure have been identified.
33-36
Traditional medicinal
healers in southern Africa have used
Helichrysum ceres
S Moore
[
Asteraceae] to treat kidney and cardio-respiratory disorders.
37
Recent laboratory studies suggest that the hypotensive effects of
H ceres
leaf extract in anaesthetised male Sprague-Dawley rats
could in part be attributed to the extract’s natriuretic and diuretic
properties.
38
We reported that
H ceres
ethanolic leaf extract’s
hypotensive effects were elicited in part by the direct relaxant
effects on cardiac and vascular smooth muscles.
39
The data
suggested that lowering of blood pressure was due to reduced
peripheral resistance elicited by the extract’s vasodilatatory
effects on the vascular smooth muscles, mediated in part via
the endothelium-derived factors (EDRF). This suggestion was
corroborated by the observations that
H ceres
leaf extract elicited
potent negative inotropic and chronotropic effects
in vivo
and
exhibited vasorelaxant effects in vascular tissue preparations.
We also reported that
Ekebergia capensis
Sparrm (Meliaceae)
leaf extract prevented the development of hypertension in
weanling genetically hypertensive Dahl salt-sensitive (DSS)
rats, which develop hypertension as they age.
19
The
in vivo
reduction in blood pressure by the extract occurred without
significant alterations in the heart rate, suggesting that the
in vitro
cardiovascular effects of the extract significantly
contributed to the hypotensive effects. Indeed, studies showed
that the hypotensive effect of
E
capensis
leaf extract was in
part mediated via modulation of total peripheral resistance
of the vascular smooth muscles, as evidenced by the extract’s
elicited dose-dependent vasorelaxations in endothelium-intact
and endothelium-denuded aortic ring preparations. It should
be noted that lanoxin, one of the cardiac glycosides found in a
number of plants, has specific effects on the myocardium.
Kidney function changes in diabetes mellitus
Sustained hyperglycaemia is the main cause of the changes in
kidney function in diabetes mellitus. Hyperglycaemia leads to
the increased formation of advanced glycation end-products
(
AGEs), oxidative stress, activation of the polyol pathway and
hexosamine flux, causing inflammation and renal damage.
40
AGEs result in the increased production of extracellular matrix
proteins in endothelial cells, mesangial cells and macrophages
in the kidney.
41
Additionally, AGEs have been shown to reduce
matrix protein flexibility through cross-link formation of the
extracellular matrix proteins, leading to an abnormal interaction
with other matrix components.
41
Irrespective of all the other structural and functional changes,
the mesangial alterations appear to be the main cause of declining
renal function in experimental diabetic animal models.
42
For
example, hyperfiltration, which occurs in the early stages of DN
has been attributed to increased mesangial production of vascular
permeability factors in response to stretching.
43
The subsequent
decline in glomerular filtration rate (GFR) as nephropathy
progresses may be due to expansion of the mesangial matrix,
