Cardiovascular Journal of Africa: Vol 30 No 2 (March/April 2019)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 2, March/April 2019 100 AFRICA
endothelial cells and human umbilical vein endothelial cells.57,59
When ART-treated rats were co-treated with rooibos, the
significance compared to the control group was lost. However,
similarly, the infarct size of the ART + rooibos group also
remained unchanged compared to ART only, which excludes
pronounced infarct sparing. Although the small reduction
in infarct size when rooibos was added is unlikely to be
biologically significant, this finding, as well as the improved
baseline coronary flow observed in the ART + rooibos group
compared to ART only, warrants further investigation to explore
any possible cardio-protective properties.
ART was associated with a significant reduction in
Ach-induced aortic ring relaxation compared to the control
and co-treatment groups. The anti-relaxation effects may be an
indicator of impaired endothelial function as a result of ART,
as previously shown in humans.13,60 Although ART has been
shown to decrease markers of ED (sVCAM-1, sICAM-1, von
Willebrand factor) and increase flow-mediated dilation (FMD) in
HIV-infected individuals, the markers did not completely return
to values during no HIV infection.61,62 ART has previously been
demonstrated to induce ED in clinical and experimental models
by decreasing NO production or release through mechanistically
inhibiting eNOS expression and increasing reactive oxygen
species (ROS) production.63,64 This has mostly been observed with
PIs, but there is some evidence to suggest that some NRTIs (AZT
and abacavir) also induce ED through these mechanisms.65,66
EFV, but not TNF or FTC, has also recently been shown to
impair Ach-induced relaxation in rat thoracic aortic rings and
cause apoptosis and necrosis in EA.hy926 cells.16 However, in
contrast to our study, the drugs were administered directly to the
aortic rings in an ex vivo fashion.
Co-treatment with rooibos resulted in relaxation that was
similar to that observed in the control rings, and significantly
increased compared to the ART-treated group. This result
demonstrates that the anti-relaxation effect observed in the ART
group was attenuated when co-treated with rooibos, suggesting
that rooibos may have beneficial effects on vascular function,
possibly via antioxidant effects (not shown in the present study).
Rooibos has previously been shown to directly scavenge ROS
and inhibit inflammation.67 Aspalathus linearis has been shown
to have strong anti-HIV activity; however, scant research has
been published on its effects when co-administered with ART.25
While two-week rooibos consumption in rats was shown to
increase CYP3A4 inhibitory activity, any influence on ART
effectivity has not been shown.68,69 Therefore, to our knowledge,
the present study is the first to show that rooibos in conjunction
with ART decreased ART-induced ED.
In studies by Nakano et al.,25,26 acid polysaccharides extracted
from the leaves of A linearis suppressed the cytopathicity of
HIV (HTLV-III)-infected MT-4 cells, while polysaccharides from
Japanese green tea leaves and a hot water extract of A linearis
did not. The polysaccharide, composed of reducing sugars
(27%), neutral sugars (46%) and uronic acid (22%), also almost
completely inhibited the binding of HIV-1 to MT-4 cells.
Conclusion
The significant increase in infarct size and decrease in baseline
coronary flow observed in the hearts from the ART group was
mirrored by a decreased response to Ach-induced relaxation
in the aortic rings of the same animals. Although further
investigations are needed, our findings suggest that the specific
FDC used may have caused impaired endothelial function.
Rooibosco-treatmentprovedeffectivetoreducethedetrimental
ART-associated effects on infarct size and vasorelaxation. These
findings are novel and should be further investigated to explore
the possible future therapeutic potential of rooibos in high-risk
cardiovascular patients receiving ART.
We thank the National Research Foundation (NRF) and the Harry Crossley
Foundation for financial support, Sonia Genade for the isolated work-
ing-heart perfusions and Dee Blackhurst from the Divison of Chemical
Pathology at the University of Cape Town for the lipid and TBARS analyses.
References
1. Lopez W. HIV/AIDS: A new era of treatment. York School 2011;
8.1(Fall 2011): 11–17.
2. Kallings LO. The first postmodern pandemic: 25 years of HIV/AIDS. J
Intern Med [Internet]. 2008 Mar [cited 2018 Jul 12];263(3):218–43.
3. Schulenburg E, le Roux PJ. Antiretroviral therapy and anaesthesia Sth
Afr J Anaesth Analgesia 2008; 14: 31–38.
4. Boccara F. Cardiovascular complications and atherosclerotic manifesta-
tions in the HIV-infected population: type, incidence and associated risk
factors. AIDS 2008; 22: S19–S26.
5. Dubé MP, Lipshultz SE, Fichtenbaum CJ, Greenberg R, Schecter AD,
Fisher SD, et al. for Working Group 3. Effects of HIV infection and antiret-
roviral therapy on the heart and vasculature. Circulation 2008; 118: e36–e40.
6. Bavinger C, Bendavid E, Niehaus K, Olshen RA, Olkin I, Sundaram V,
et al. Risk of cardiovascular disease from antiretroviral therapy for HIV:
a systematic review. PLoS One 2013; 8(3): e59551.
7. Meintjes G, Black J, Conradie F, Cox V, Dlamini S, Fabian J, et al .
Adult antiretroviral therapy guidelines, by the Southern African HIV
Clinicians Society. Sth Afr J HIV Guidelines 2014; 15 (4).
8. Department of Health, Republic of South Africa. Guidelines for
expanding combination prevention and treatment options for sex work-
ers: oral pre-exposure prophylaxis (PrEP) and test and treat (T&T).
Final draft 2016. Available from:
and TT Guidelines – Final Draft – 11 May 2016.pdf.
9. Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the
toxicity of HIV medications. J Med Toxicol 2014; 10(1): 26–39.
10. Francisci D, Giannini S, Baldelli F, Leone M, Belfiori B, Guglielmini
G, et al . HIV type 1 infection, and not short-term HAART, induces
endothelial dysfunction. AIDS 2009; 23(5): 589–596.
11. Currier JS, Taylor A, Boyd F, Dezii C, Kawabata H, Burtcel B, et al .
Coronary Heart Disease in HIV Infected Individuals. J AIDS 2003; 33:
506–512.
12. Brouwer ES, Napravnik S, Eron JJ, Stalzer B, Floris-Moore M, Simpson
RJ, Stürmer T. Effects of combination antiretroviral therapies on the
risk for myocardial infarction among HIV patients. Epidemiology 2014;
25(3): 406–417.
13. Cotter BR. Endothelial dysfunction in HIV infection. Curr HIV/AIDS
Rep 2006; 3(3): 126–131.
14. Zhang C, Cai Y, Adachi MT, Oshiro S, Aso T, Kaufman RJ, Kitajima
S. Homocysteine induces programmed cell death in human vascular
endothelial cells through activation of the unfolded protein response. J
Biol Chem 2001; 276(38): 35867–35874.
15. Deanfield J, Halcox J, Rabeling TJ. Endothelial function and dysfunc-
tion: testing and clinical relevance. Circulation 2007; 115(10): 1285-1295.
16. Faltz M, Bergin H, Pilavachi E, Grimwade G, Mabley JG. Effect of the