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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 2, March/April 2020

AFRICA

81

Rooibos (

Aspalathus linearis

) protects against nicotine-

induced vascular injury and oxidative stress in Wistar rats

Michelle Smit-van Schalkwyk, Shantal Windvogel, Hans Strijdom

Abstract

Background:

Rooibos (

Aspalathus linearis

) is an indigenous

South African plant, traditionally used by the local popula-

tion as a remedy against several ailments. More recently,

rooibos was shown to exhibit potent antioxidant properties,

attributed to its polyphenols. We assessed whether treat-

ment with fermented rooibos (RF), unfermented rooibos

(RUF) and melatonin (Mel), a well-documented antioxidant

included for comparison, could counter the harmful vascular

and pro-oxidant effects of nicotine.

Methods:

Vascular function, antioxidant enzyme activity and

lipid peroxidation were assessed in male adult rats treated with

nicotine (5 mg/kg body weight/day) and 2% RF, 2% RUF or

4% Mel co-administration. Nitric oxide (NO) production and

cell viability were measured in nicotine-exposed rat aortic

endothelial cells (AECs) pre-treated with RF (0.015 mg/ml).

Results:

Vascular studies showed that co-administration

with RF or Mel exerted anti-contractile and pro-relaxation

responses in aortic rings, and increased hepatic superoxide

dismutase and catalase activity in nicotine-exposed animals.

Co-treatment with Mel additionally decreased lipid peroxida-

tion in nicotine-exposed rats. RUF exerted anti-contractile

responses in aortic rings of nicotine-treated animals, while in

nicotine-exposed AECs, RF pre-treatment increased intracel-

lular NO levels.

Conclusion:

For the first time, we have shown that rooibos

co-treatment exerted beneficial vascular effects in nicotine-

exposed rats, and that this was associated with increased anti-

oxidant enzyme activity.

Keywords:

nicotine,

Aspalathus linearis

, rooibos, melatonin,

endothelial dysfunction

Submitted 4/12/18, accepted 3/9/19

Published online

Cardiovasc J Afr

2020;

31

: 81–90

www.cvja.co.za

DOI: 10.5830/CVJA-2019-052

Tobacco smoking is one of the most important risk factors for

the development of cardiovascular disease and is responsible

for approximately 12% (6.2 million) of all deaths globally.

1

It is

estimated that over five million people are current or ex tobacco

users and that over 600 000 non-smokers die from exposure

to second-hand smoke.

2

Nicotine, the addictive substance in

tobacco, is associated with the development of endothelial

dysfunction (ED) through oxidative stress. ED is an early,

reversible precursor of atherosclerosis.

3

In turn, atherosclerosis is

the underlying pathology for many cardiovascular diseases, often

resulting in myocardial infarction and stroke.

4

Nitric oxide (NO) plays an important role in protection

against the onset and progression of cardiovascular disease.

The ability of the endothelium to synthesise and release NO is

essential in regulating haemostasis, vessel tone, blood pressure

and vascular remodelling.

5

Furthermore, reactive oxygen species

(ROS) and the resultant oxidative stress are important mediators

of the pathological manifestations of ED. ROS reduce or

eliminate the protective abilities of NO, which in turn could lead

to ED.

6

Experimental and clinical data indicate that exposure to

nicotine increases oxidative stress and has the potential to

induce ED.

7

While endogenous mechanisms such as antioxidant

enzymes as well as non-enzymatic defences exist to combat

the deleterious effects of oxidative stress, they might not offer

sufficient protection against the ROS produced during nicotine

exposure.

8,9

Early endothelial changes such as ED are reversible,

10

rendering it clinically relevant to identify possible treatment

modalities such as anti-oxidant therapy, which could counter

the harmful effects of increased ROS production, and hence

restore the release of endothelioprotective NO. Protecting the

endothelium will result in reduced or delayed atherogenesis,

which lowers the risk of cardiovascular mortality. Such therapies

may include dietary supplementation with natural plant products

or chemically synthesised versions of endogenous molecules with

known antioxidant capacity.

Rooibos (

Aspalathus linearis

) is an indigenous South African

plant that is popularly consumed as a beverage and is known

to possess bio-active properties.

11

Rooibos boasts a unique

flavonoid content and contains various dihydrochalcones,

including aspalathin, a C-linked dihydrochalcone glucoside,

12,13

and aspalanin, a cyclic dihydrochalcone,

14

which are both unique

to

Aspalathus linearis

.

Both unfermented (green) and fermented (red) forms of

rooibos are commercially available. Green rooibos is immediately

dried after the cutting phase, whereas non-enzymatic oxidative

degradation of aspalathin results in the characteristic red-brown

fermented form.

15

Rooibos has been shown to exert potent anti-

oxidant, immune-modulating and chemo-protective actions,

with the additional benefit of having minimal adverse effects.

16

In addition, rooibos possesses cardioprotective properties,

including the improvement of dyslipidaemia and redox status

in human study participants,

17

as well as being able to exert

protective effects on cultured cardiomyocytes from diabetic rats.

18

Centre for Cardio-metabolic Research in Africa, Division

of Medical Physiology, Biomedical Sciences, Faculty of

Medicine and Health Sciences, Stellenbosch University,

Tygerberg, South Africa

Michelle Smit-van Schalkwyk, PhD, michelle.smitvanschalkwyk@

gmail.com

Shantal Windvogel, PhD

Hans Strijdom, PhD