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138 3. Medicinal plants in the Balkans with antimicrobial properties
Medicinal Plants as Anti-infectives
CHAPTER
4
Medicinal plants used in South
Africa as antibacterial agents for
wound healing
Samantha Rae Loggenberg
1
, Danielle Twilley
1
,
Marco Nuno De Canha
1
and Namrita Lall
1,2,3
1
Department of Plant and Soil Sciences, Faculty of Natural and Agricultural Sciences,
University of Pretoria, Pretoria, South Africa
2
School of Natural Resources, University of
Missouri, Columbia, MO, United States
3
College of Pharmacy, JSS Academy of Higher
Education and Research, Mysuru, India
Introduction
Wounds account for one of the major reasons for hospital visits in Africa each year, equating
to approximately 30%42% of hospital attendance, relating to an estimated 9% death rate each
year (
Builders & Builders, 2016). There is a concerning lack of published information regarding
the burden of wounds on South African healthcare systems; however, a study by
Lotz (2019)
aimed at determining the wound burden in a South African hospital that had limited resources.
On the day of the study, 518 inpatients were admitted of which 179 patients had wounds,
accounting for a wound burden of 34.6%, of which acute surgical wounds and burn wounds
were the most predominant, with a wound burden of 45% and 18%, respectively. Chronic
wounds were also reported, with pressure injuries (9%) and leg ulcers (9%) accounting for the
highest burden, followed by fungating wounds (3%). It was further found that 13% of all
wounds presented on the day were infected. When comparing this to patients visiting clinics
for outpatient visits, on the day of the study it was found that 63 of the 333 outpatients pre-
sented with wounds, accounting for an additional 18.9% wound burden (
Lotz, 2019).
In South Africa, it has been estimated that approximately 72% of the population rely on
traditional medicine as a source of health care, equating to an estimated R 2.9 million and
R 520 million per year in trade of traditional medicinal products and raw plant material,
139
Medicinal Plants as Anti-infectives
DOI:
https://doi.org/10.1016/B978-0-323-90999-0.00018-5 Copyright © 2022 Elsevier Inc. All rights reserved.
.
respectively (Mander, Ntuli, Diederichs, & Mavundla, 2019), which includes the use
of medicinal plants for the treatment of dermatological disorders and ailments. An eth-
nobotanical literature review by
Mabona and VanVuuren (2013) summarized that over
100 plant species in southern African were used for dermatological disorders of which
41% of the plants were used for wound treatment. Additionally, the treatment of infectious
skin diseases, which included the treatment of bacterial infections, comprised 32% of
the plant species. The treatment of sores and ulcers was categorized separately, where
approximately 25% of medicinal plants were used for these treatments, whereas treatment
of burns only comprised 10%. Furthermore,
Mabona and VanVuuren (2013) stated that
medicinal plants could potentially be used for multiple disorders, such as the use of a
plant for its wound-healing, antiinfective, and antiinflammatory properties.
According to data analysis using Web of Science, the number of publications (including
articles, literature reviews, and book chapters) within the last 510 years that include the
topics of “medicinal plants” and “wound healing” equate to 611 (
Fig. 4.1). No publications
of this nature were published between the years 2011 and 2016. However, there were
under a hundred publications that met the set requirements published in 2017, with a stea-
dy increase in the number of publications for years thereafter until 2021. Along with the
growing trend in publications between 2017 and 2021, an exponential increase in citations
was observed during this period. These data may indicate a shift towards research aimed
at investigating medicinal plants in wound healing within the last 5 years.
The gen eral shift in interest for investigating traditionally used plants for their medici-
nal value in South Africa has greatly increased within the last 5 years. There are various
foundations in South Africa that provide funding to all fields of research, with specific
focus on the investigation of South African medicinal plants. These organizations include
but are not limited to the South African Medical Research Council and the South African
FIGURE 4.1 Publications and citations relating to the use of medicinal plants for wound healing from 2017 to
2021.
140 4. Medicinal plants used in South Africa as antibacterial agents for wound healing
Medicinal Plants as Anti-infectives
Research Chairs Initiative, which focus on research developments in South Africa, as well
as foundations such as the National Research Foundation, Technology Innovation Agency,
and Department of Science and Innovation which aid in funding research outputs con-
ducted by universities and scientific institutions nation-wide. All of these foundations aim
to further the development of science, technology, medicine, and indigenous knowledge
within South Africa.
Pathophysiology of wound healing
The epidermal layer of the skin acts as the main protective barrier for the body. Lesions
and breaks in the skin may expose the internal tissues to pathogens and microbes from
the external environment, leaving soft tissue vulnerable to pathogenic infections that may
lead to adverse health conditions which may be life-threatening (
Aldridge, 2015).
The process of wound healing is a dynamic system consisting of multiple phases which
involve several factors and cellular components including hemostasis, inflammation, pro-
liferation/granulation, and remodeling/maturation (
Fig. 4.2).
Upon damage to the epidermal layer, cellular membranes are disrupted causing leakage
of cellular contents and the release of collagen into the extracellular fluid between cells.
Inactive blood plasma platelets present in the extracellular fluid interact with the exposed
collagen and become active. The activated platelets recruit red blood cells and actin fila-
ments as well as stimulate blood clot formation by facilitating the coagulation of these
molecules to the wound site (
Lynch, Colvin, & Antoniades, 1989). The formation of
a blood clot prevents further bleeding and exposure of the soft tissues to the external envi-
ronment; however, pathogens may have already entered the wound site. White blood cells
and neutrophils, also known as natural killer cells, near the wound, recognize and destroy
pathogens whilst simultaneously removing cellular debris. The identification of pathogenic
proteins activates the white blood cells to secrete fibrogenic cytokines which facilitate
the recruitment of macrophages and neutrophils to the wound site by initiating the in-
flammatory response, leading to swelling around the wound. Macrophages continue to
recruit immune cells and secrete cytokines which initiate the formation of granulation
tissue within the wound which facilitates tissue repair (
Almine, Wise, & Weiss, 2012).
FIGURE 4.2 The phases of wound healing; (A) hemostasis, (B) inflammation, (C) cell proliferation, and (D)
maturation. Source: From Servier. (2019). The phases of wound healing. Retrieved from
https://smart.servier.com/cate-
gory/anatomy-and-the-human-body/cardiovascular-system/blood/
.
141Pathophysiology of wound healing
Medicinal Plants as Anti-infectives
The granulation tissue is filled with collagen and actin filaments that dynamically contract
to promote closure of the wound and allow for the migration of newly formed tissue cells
to the center of the wound. Once the wound has closed completely, tissue remodeling and
degradation of granulation tissue around the site of injury take place to increase the tensile
strength of the tissue and allow for the formation of other structures such as hair follicles
and cell junctions (
Li et al., 2013).
Wound infection
The duration of the wound-healing process may vary depending on the size of the
wound and the severity of the tissue damage. The damaged tissue become s vulnerable
and susceptible to pathogenic infection during this period since the moist environment of
wounds provides optimal conditions for bacterial growth, which can lead to bacterial
infection. The body’s immune response limits pathogenic infection in a healthy patient;
however, immunocompromised patients are at a higher risk of infections resulting in
severe health complications (
Aldridge, 2015). If left untreated, infected wounds may lead
to bacterial overgrowth which allows the pathogen to spread into deeper tissues within
the body or disseminate into the blood, causing bacteremia (bacterial infection of the
blood). Bacteremia can lead to the spreading and infection of various tissues and organs
within the body which can overstimulate the immune response leading to septicemia
(
Zieli
´
nska-Borkowska, 2015). Septicemia involves rapid widespread inflammation through-
out infected tissue and organs to combat pathogenic infection. This abrupt inflammatory
response may cause several health complications such as sepsis, which involves the tear-
ing of tissues and in severe cases, organ failure. Depending on the preexisting health con-
dition of a patient when organ failure occurs, septicemia may result in mortality. Even
with early diagnosis and treatment, septicemia is difficult to treat due to the causative
pathogens often developing antibiotic resistance (
Churpek et al., 2017). It is therefore
important to identify antibacterial treatments suitable for dermal wounds which aid in
the prevention of bacterial infection.
Currently available treatments and products
Topical creams
Topical antibacterial treatments are produced in the form of creams, ointments, gels,
and serums which can be directly applied to dermal wounds, allowing for the diffusion of
the active compounds into the superficial layers of the skin and providing direct antibacte-
rial treatment. Aloe extracts, produced from Aloe vera and Aloe ferox, are commonly utilized
in many of these products due to their wound-healing properties and their antibacterial
effects (
Hashemi, Madani, & Abediankenari, 2015; Jia, Zhao, & Jia, 2008). Addi tionally,
transdermal drug delivery systems, such as adhesive patches, which are placed directly
onto the skin are designed to deliver an effective dose of a drug across the epidermal and
dermal layers of the skin to reach the blood circulatory system, can be used. This method
142 4. Medicinal plants used in South Africa as antibacterial agents for wound healing
Medicinal Plants as Anti-infectives
of drug delivery allows for systemic circulation of the drug whilst avoiding first-pass
metabolism which maximizes the therapeutic effects of the drug (
Ashok Kum ar,
Pullakandam, Lakshmana Prabu, & Gopal, 2010
).
Transdermal drug delivery systems
Transdermal drug delivery systems provide controlled and continuous administration of
a particular drug dosage which allows for constant plasma levels of a drug, irrespective of
its biological half-life (
Prausnitz & Langer, 2008). Transdermal patches are generally made
up of a hydrogel which is a network of polymeric chains which can retain both water and
the active compound(s) within the matrix. The polymeric matrix acts as a reservoir and
allows for the steady and continuous release of the drug for extended periods of time
(
Girard, Teferra, & Awika, 2019). Research has shown that the use of plant-derived poly-
mers in transdermal patches provided more efficient controlled release and drug perme-
ation in comparison to synthetic polymers (
Saidin, Anuar, & Affandi, 2018). Nanocarriers, a
form of transdermal drug delivery, have provided an efficient method of administration for
both lipophilic and hydrophilic drugs. Different types of nanocarriers that have been devel-
oped for transdermal drug delivery include liposomes, transfersomes, ethosomes, nio-
somes, dendrimers, lipid-based nanoparticles, polymer nanoparticles, and nanoemulsions
(
Escobar-Chavez, Diaz-Torres, & Rodriguez-Cruz, 2012). Transdermal drug delivery
patches consisting of nanoparticles that exhibit antibacterial activity have also been devel-
oped (
Ashok Kumar et al., 2010). The use of nanocarrier technology may provide efficient
drug delivery systems in the development of antimicrobial treatments against wound infec-
tion (
Escobar-Chavez et al., 2012). It is therefore important to consider research conducted
on the optimization of drug uptake and bioavailability of antibacterial compounds and
plant extracts.
Bacteria associated with infections of dermal wounds
Numerous bacteria are involved in the infection of dermal wounds; however, common
pathogens that cause wound infections include species such as Staphylococcus aureus and
Pseudomonas aeruginosa (
Bessa, Fazii, Di Giulio, & Cellini, 2015; Manzuoerh, Farahpour,
Oryan, & Sonboli, 2019
). In a case study conducted by Bessa et al. (2015), 312 swabs were
collected from infected wounds of 213 patients of which S. aureus (37%) and P. aeruginosa
(17%) were the most common pathogens detected.
Sepsis is commonly caused by adverse infections of postsurgical wounds known as nos-
ocomial infections. Nosocomial infections, also known as healthcare-associated infections,
may occur in patients, generally with pre existing health complications, which are exposed
to unsanitary healthcare facilities or equipment. The main cause of nosocomial infections
is bacterial biofilm growth on indwelling medical devices which can disseminate into the
bloodstream (
Otto, 2009). Bacterial infections in the bloodstream, leading to sepsis, may be
lethal to both healthy and immunocompromised patients due to the difficu lty in treatment
and management (
Churpek et al., 2017 ). Nosocomial infections in immunocompromi sed
143Bacteria associated with infections of dermal wounds
Medicinal Plants as Anti-infectives