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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 6, November/December 2015
AFRICA
225
Most drugs originated from or are derived from herbs.
However, dosages and usable forms of the drugs must be
investigated with expensive clinical trials before they become
commercialised.
14,16
Although there are conflicting reports, herbal
products, while they still have risks, may be safer for prophylaxis
and the treatment of diseases. In addition, they are inexpensive
and readily available.
17
The quality and quantity of herbal
products may vary depending on seasonal and regional growing
conditions, and may therefore have different effects.
18
Supervision
and quality control should therefore be required during their
production.
Ginseng is a commonly studied therapeutic herbal
product.
18
The protective role of ginseng extracts with several
metabolic mechanisms has been reported in cardiovascular
events.
19
It has been hypothesised that ginseng extracts may
protect the cardiovascular system by acting as an antioxidant,
antihypertensive, antidiabetic and antinociceptive agent.
15,19
The protective effects of acetylsalicylic acid and clopidogrel
bisulfate on ischaemia–reperfusion injury have been previously
described.
6,7,20,21
In addition, similar findings have been reported
for ginsenosides.
22
However, to our knowledge, there has been
no definitive comparison of these three agents in the literature.
In this study, the systemic, cardiac and renal protective
effects of the well-known anti-aggregant agents acetylsalicylic
acid and clopidogrel bisulfate were compared with ginsenoside
Rb
1
(Panax) against oxidant stress in a peripheral ischaemia–
reperfusion model.
MDA serves as a biomarker for detection of peroxidative
damage in reperfused organs; it is a product of enzymatic and
oxygen radical-induced lipid peroxidation.
9
Reduced MDA
levels have previously been reported with acetylsalicylic acid- or
clopidogrel-treated patients in ischaemia–reperfusion studies.
23,24
Although, PON-1 is mainly produced by the liver, it has been
identified in other tissues such as the kidney, heart and brain.
25
An inverse relationship was reported between PON-1 activity
and antiplatelet agents.
26
Prolidase is a marker for collagen metabolism that is related
to increased levels of nuclear hypoxia-inducible factor-1 alpha
(HIF-1).
9,27
Increased prolidase levels were reported in acute
ischaemic events.
27
In the current study, the serum MDA levels were partially
improved in the clopidogrel bisulfate and ginsenoside Rb
1
groups, while the serum PON1 levels were markedly decreased
in all three groups. Renal PON1 levels were only significantly
expressed in the clopidogrel bisulfate group. Renal prolidase
levels were significantly decreased in all groups compared to the
control I/R group. Cardiac prolidase levels were significantly
decreased in the clopidogrel bisulfate and ginsenoside Rb
1
groups. According to our results, it appears that ginsenoside Rb
1
had a beneficial effect on the oxidative stress induced by I/R by
antioxidant mechanisms.
Mannaa
et al
. reported that Panax had a neuroprotective
effect in acrylamide-induced neurotoxicity.
15
In another study,
Basha
et al
. reported the renoprotective effects of ginsenosides
against oxidative stress in streptozotocin-induced diabetic
nephrotoxicity in mice.
22
In addition, it has been reported
that ginsenosides can play a protective role in decreasing lipid
peroxidation and ameliorating oxidative damage.
28
Kim reported that ginsenosides have possible protective
mechanisms in cardiovascular events.
19
He described these
mechanisms as follows:
•
Ginsenosides inhibit Ca
2+
entry, and therefore may ameliorate
cardiac function.
19
However, acetylsalicylic acid can stimulate
the Ca
2+
entry pathways.
29
•
Ginseng normalises blood pressure and improves blood circu-
lation.
19
Previous reports noted that acetylsalicylic acid and
clopidogrel can alter blood flow in tissues.
30
•
Ginsenoids can protect against myocardial damage via nitric
oxide-mediated cardiac protection, antioxidant and intracel-
lular calcium homeostasis, and attenuation of calcineurin
activation.
19
Similarly, some literature has suggested that
clopidogrel and acetylsalicylic acid improve endothelial nitric
oxide.
31,32
•
Ginseng saponin has a protective role on endothelial cells via
a cellular signalling pathway.
19
Similar cellular mechanisms
were reported for clopidogrel and acetylsalicylic acid.
33,34
•
Ginseng has a cardiovascular protective role in inhibiting
oxidative damage due to the prevention of reactive oxygen
species generation.
19
Also, the anti-oxidant effects of clopi-
dogrel and acetylsalicylic acid have been described in previous
reports.
7,
34
There are some limitations that need to be addressed in this
study. An experimental I/R model was created for this study in
healthy rats. Therefore, our results are pertinent only to the rat
model and these results should be confirmed in human subjects.
The other limitation is that only oxidative markers were studied
and PCR and Western blot analysis were not applied. Because of
this, our findings are lacking in cellular reflections.
Conclusion
Herbal medicine is still important for the majority of the world’s
population. Traditional ginseng extracts may have beneficial
effects on ischaemia–reperfusion injury. However, we caution
that herbs should not replace traditional drugs. Ginseng can be
beneficial as a drug supplement when controlled by healthcare
organisations. In addition, future cardiovascular studies are
needed to clarify the drug interactions and the proper dose of
ginseng extracts.
We are grateful to Dicle University DUBAP for their sponsorship of the
English editing of this manuscript.
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