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International Journal of Zoology and Animal Biology Research Article 12 min read

Exploration on Traditional Uses of Herbal Medicines for Wound Healing in Different Animal Models

Dhakal I, Tiwary AK, Suhel KC, Thakur B, Regmi B and Shah MK*
* Corresponding author
ISSN: 2639-216X  10.23880/izab-16000349  Received: January 04, 2022  Published: February 15, 2022
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Keywords
Wound Healing Herbal Medicine Ethnic Group
Abstract

A wound is a bodily injury resulting in a break in the continuity of the soft tissues of animal and human beings. Wound healing is the most dynamic but complex mechanism of the body and is a continuous process. So far, various therapeutics are used to augment wound healing and organ regeneration without infection. Seemingly, ethnic groups mostly use several herbal medicines for the treatment of wounds, burns, and cuts. This review aims to elucidate the various herbal medicines that are used in-vivo or in-vitro in the experimental trial of wound healing. Moreover, herbal’s extracts have an indispensable history and successful clinical track record as indigenous drugs for wound repairmen. Because many herbal medicines show hemostasis, anti-inflammatory, antimicrobial and antioxidant properties to promote wound healing. The further scientific validation of herbal medicines with their toxicities assessment at the molecular level is necessary before it is extensively used in wound treatment.

Introduction

Skin is a multilayer organ that covers the body of all mammals. It acts as an interface between the external environment and internal organs, forming a barrier to infection. It has been also considered as a thermoregulatory organ to prevent the body from dehydration [1]. As an external organ, it is highly vulnerable to various types of injuries, burns, wounds, etc. After wounding, the body’s defense system initiates a complex cascade of biological processes toward the restoration of anatomic continuity and function. Wound healing is accomplished by several processes which involve overlapping of three phases i.e., inflammation, proliferation, and remodeling with complex series of events of repair and regeneration [2]. The healing processes are modulated up by the transforming growth factors, cytokines, mitogens, and chemotactic substances [3]. To stimulate the healing process, reduce the scar formation, and improve the strength of the new skin, several wound care products and ethno medicinal therapies have been devised and tested experimentally [3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]. Due to expensiveness, hypersensitivity reaction, the emergence of multi-resistant organisms, and a lack of newer antibiotics wound care professionals still rely on traditional and alternative medicine for wound management [13, 15]. Traditional therapies have been used in many centuries particularly by the rural populations of developing countries including Nepal.

Overview on the Mechanism of Wound Healing

Wound healing is an intricate process that involves an array of biochemical and cellular processes. Immediately after injury, the platelets enter the area and play a crucial role in hemostasis and the inflammatory phase is characterized by the influx of polymorphonuclear cells followed by infiltration of macrophages [16, 17]. Neutrophils and macrophages are the major cells that are responsible to secrete the transforming growth factor-beta (TGF-β), cytokines (interleukins, tumor necrosis factors alpha (TNF-α), and chemokines (CC-chemokine, CXC-chemokine, CX3C-chemokine, and C-chemokine) necessary for wound healing [18, 19, 20]. These complex signal networks stimulate the healing  to evolve the proliferative phase, which constitutes fibroplasia, matrix deposition, angiogenesis, and re-epithelialization [21, 22]. TGF-β regulates the proliferation of fibroblasts, collagen synthesis, production of granulation tissue (23), and differentiation of fibroblasts to myofibroblasts in granulation tissue [23, 24]. Finally, the maturation stage comprises a dynamic phase in which the new extracellular matrix composed of proteoglycans, glycosaminoglycans, factor-alpha, and collagens are continuously deposited and degraded [17, 25] (Figure 1). Fail or defects in this multifaceted biological process might destroy the delicate equilibrium of cells and soluble factors necessary for complete wound repair, resulting in fibrotic scars [26, 27].

Figure 1: Stages of wound healing. It is classically divided into four stages: (A) hemostasis, (B) inflammation, (C) proliferation, and (D) remodeling. Each stage is characterized by key molecular and cellular events and is coordinated by a host of secreted factors that are recognized and released by the cells as a wounding response. Representative subsets of major factors are depicted. CCL2, chemokine (C-C motif) ligand 2; CX3CL1, chemokine (C-X3-C motif) ligand 1; CXCL1, chemokine (C-X-C motif) ligand 1; CXCL8, C-X-C Motif Chemokine Ligand 8; EGF, Epidermal growth factor; FGF2, basic fibroblast growth factor; FGFs, fibroblast growth factors; HGF, hepatocyte growth factor; IFNs, interferons; IGFs, insulin-like growth factors; IL-1, interleukin-1; IL-1β, interleukin-beta; MMPs, matrix metalloproteinases; PDGF, platelet-derived growth factor; PDGI, platelet- derived growth inhibitor; PGF2, Prostaglandin F2; TGFα, transforming growth factor-alpha; TGFβ, transforming growth factor- beta; TIMPs, tissue inhibitor of metalloproteinases; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor (28).
Click to enlarge
Figure 1: Stages of wound healing. It is classically divided into four stages: (A) hemostasis, (B) inflammation, (C) proliferation, and (D) remodeling. Each stage is characterized by key molecular and cellular events and is coordinated by a host of secreted factors that are recognized and released by the cells as a wounding response. Representative subsets of major factors are depicted. CCL2, chemokine (C-C motif) ligand 2; CX3CL1, chemokine (C-X3-C motif) ligand 1; CXCL1, chemokine (C-X-C motif) ligand 1; CXCL8, C-X-C Motif Chemokine Ligand 8; EGF, Epidermal growth factor; FGF2, basic fibroblast growth factor; FGFs, fibroblast growth factors; HGF, hepatocyte growth factor; IFNs, interferons; IGFs, insulin-like growth factors; IL-1, interleukin-1; IL-1β, interleukin-beta; MMPs, matrix metalloproteinases; PDGF, platelet-derived growth factor; PDGI, platelet- derived growth inhibitor; PGF2, Prostaglandin F2; TGFα, transforming growth factor-alpha; TGFβ, transforming growth factor- beta; TIMPs, tissue inhibitor of metalloproteinases; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor (28).

Figure 1: Stages of wound healing. It is classically divided into four stages: (A) hemostasis, (B) inflammation, (C) proliferation, and (D) remodeling. Each stage is characterized by key molecular and cellular events and is coordinated by a host of secreted factors that are recognized and released by the cells as a wounding response. Representative subsets of major factors are depicted. CCL2, chemokine (C-C motif) ligand 2; CX3CL1, chemokine (C-X3-C motif) ligand 1; CXCL1, chemokine (C-X-C motif) ligand 1; CXCL8, C-X-C Motif Chemokine Ligand 8; EGF, Epidermal growth factor; FGF2, basic fibroblast growth factor; FGFs, fibroblast growth factors; HGF, hepatocyte growth factor; IFNs, interferons; IGFs, insulin-like growth factors; IL-1, interleukin-1; IL-1β, interleukin-beta; MMPs, matrix metalloproteinases; PDGF, platelet-derived growth factor; PDGI, platelet- derived growth inhibitor; PGF2, Prostaglandin F2; TGFα, transforming growth factor-alpha; TGFβ, transforming growth factor- beta; TIMPs, tissue inhibitor of metalloproteinases; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor (28).

The aim of wound treatment is to promote tissue repair and regeneration in a shorter time with adequate tissue perfusion and oxygenation, proper nutrition, and minimum undesired consequences (29).

Ethno-Medicinal Plants Used in Wound Healing

Ethno-medicinal plants are presumed to play a central role in remedies of wound healing since ancient times. A huge number of plants/plant extracts/decoctions or pastes are equally used by tribal and folklore traditions in Nepal, India, Bangladesh for the treatment of wounds and burns. It is important to note that about 80% of the Asian and African population still relies on the use of traditional medicine as primary health care [30]. However, the innovation of allopathic medicine retarded the utilization of ethno medicine. Due to various side effects of allopathic drugs, the uses of complementary and alternative medicines are gaining popularity for the treatment of wounds throughout the world [31]. These therapies have been proved cost-effective and efficacious for the treatment of diverse and difficult-healing wounds such as ulcers, burns, and infected wounds by stimulating the healing process and improving the strength of the new skin [32]. In this review, we elucidated the healing properties of various ethnomedicinal plants used in studies and outlined the information that might be useful to design the novel experiment for their scientific validation. Table 1 provides a general idea of the most important curative plants and their properties, with recognized effects on wound healing.

Species/
plant’s name		SchemeThe extract used
and formulation		Clinical
properties		Wound modelResultsRefer
ence
Achyranthe
saspera		An ointment
containing 5%
methanol extract		Wound healing
activity and
antioxidant
potential		Burn wound in
a rat		It exhibited wound
healing not only via
wound contraction,
fibroblast proliferation,
epidermis formation,
and collagen deposition,
but also through
the elevation of Na+,
catalase, vitamin-C, and
hydroxyl proline and
the up-regulation of the
expressions of matrix
metalloproteinases
(MMP-2 and MMP-9).		[33]
Aloe
vera		Blended fibrin/Aloe
gel film		Wound healingStreptozotocin-
induced diabetic
rats		The application
enhanced wound
healing by enhancing
hydroxyproline,
fibroblast, and collagen.		[34]
Becium
grandiflorum		5% and 10% (w/w)
ethanol leaf extract		Antibacterial,
anti-
inflammatory,
and wound
healing activity		Excision and
incision wound
models in mice		Ointments showed
an increase in wound
contraction, shorter
epithelization time,
and higher skin
tensile strength along
with considerable
deposition of collagen,
fibroblast proliferation,
and vascularization.
The plant extract
also inhibited the
inflammation.		[35]
Buteamon
osperma
(Palas)		The alcoholic
bark extract of
Buteamono sperma		Cutaneous
wound
healing and
antioxidant
properties		Excision wound
model of rat		The extract showed the
increase in DNA, total
protein, and collagen
content of granulation
tissues with more
epithelialization and
contraction.		[36]
Caesalpinia
mimosoides		Aqueous and
ethanolic extract
ointment 5%
(w/w) of shoots
and leaves		Antimicrobial,
wound
healing, and
antioxidant
activities		Circular excision
and linear
incision wound
models in adult
Wistar albino
rats		Complete wound
healing was noted with
ethanol and aqueous
extract on day 15.		[5]
Calendula
officinalis		n-hexanic and the
ethanolic extracts
from Calendula
flowers		Wound healingIn vitro studies
in human
immortalized
keratinocytes		Extracts influenced
the inflammatory
phase by activating the
transcription factor
NF-κB and by increasing
chemokine IL-8, both
at transcriptional and
protein level.		[37]
Calotropis
procera		Topical application
of 20 ml of 1.0%
sterile solution
of the latex of C.
procera twice daily		Wound healingFull-thickness
excisional
wounds of 8.0
mm diameter
were inflicted in
a guinea pig.		It resulted in wound
area reduction by
increasing collagen,
DNA, protein synthesis,
and epithelization.		[38]
Carica
papaya		Ethanol extract of
seeds (50 mg/kg/
day)		Wound-healing
activity,
antimicrobial
activity		Excision wound
model in
Sprague-Dawley
rats		The papaya seed extract
(1:1 ratio) showed 86%
wound contraction on
day 13. It also exhibited
antimicrobial activity
against Salmonella
choleraesuis and
staphylococcus aureus.		[39]
Centella
asiatica		Asiaticoside
isolated from
Centellaasiatica
gum. Topical
applications of
0.2% solution of
Asiaticoside.		Healing
activity		In-vivo study
in guinea
pig in punch
wound model
and in-vitro
study in chick
chorioallantoic
membrane
model		Asiaticoside produced
a 56% increase in
hydroxyproline, 57%
increase in tensile
strength, increased
collagen content, and
better epithelization.		[40]
Daucu
scarota		Paraffin-based
cream containing
1%, 2%, and 4%
w/w of ethanolic
extract of root
topically.		Wound healing
activity		Excision wound
model and
incision wound
model		It increased the
hydroxyproline, 57%
increase in tensile
strength, increased
collagen content,,t and
better epithelization.		[12]
Deloni
xelata		Ethanolic extract
(DSE)		Wound healing
activity		Excision,
incision, and
dead space
wound models		The complete wound
contraction was found
at 16 days. An increased
expression of Col 1α
(I) was observed in the
wound tissue treated
with DSE.		[10]
Entadap
haseoloides
(L.) Merr.		Total
Entadaphaseoloides
(L.) Merr. tannins
(TEPT) are used
topically.		Wound healing
activity		Excision wound
model in rats		It promoted the wound
shrinkage, rate and
augmented the healing
of infected wounds in
rats with antimicrobial
activity too.		[41]
Globularia
alypum		Methanolic extractBurn wound
healing
process,
inflammation,
antibacterial
and
antioxidant
activities		Burn wound of
177 mm2 area		Wound area contraction
on day 12.		[42]
Heliotropium
indicum		Ethanolic extracts
10% w/v		Wound healing
activity		Excision and
incision wound
models in rats		Complete healing of
wounds was noted at 14
days.		[43]
Hypericum
patulum		5% and 10%
w/w ointment of
methanol extract of
leaves		Wound healingExcision and an
incision wound
models in rats		Both concentrations
of ointment enhanced
wound healing.		[44]
Jatrophaneo
pauciflorapax		Two groups of
treatment: Oral
administration of
latex (250, 500,
and 750 mg/
kg) and topical
administration of
latex.		Antimicrobial,
anti-
inflammatory
activities, and
wound-healing		Anti-
inflammatory
activities in
Wistar rats		It showed higher
antioxidant activity,
anti-inflammatory
potential in oral
administration of latex,
and antimicrobial
properties to promote
wound healing.		[45]
Lavandula
aspic l.		Lavender oilAntioxidant
and wound
healing activity		Excision wound
model in rats		The biopsied skin
showed fibrous
connective tissue
regeneration on day 14.		[46]
Morinda
citrifolia l.		Ethanolic extract
of the leaf at a rate
of 150 mg /kg/day
orally		Wound healing
activity		Excision and
dead space
wound models
in rats		It enhanced wound
contraction, decreased
epithelialization
time, and increased
hydroxyproline content
and histological
characteristics.		[11]
Musa
sapientumvar.
paradisiaca		Aqueous and
methanolic extract
of Musa sapientumb
(100 mg/kg) orally.		Wound healing
activity		Excision,
Incision and
dead space
wound models
in rats		Both extracts
increased the levels
of hydroxyproline,
hexuronic acid,
hexosamine, superoxide
dismutase, reduced
glutathione in
granulation tissue, and
decreased the wound
area, scar area, and lipid
peroxidation.		[47]
Ocimum
sanctum Linn		Alcoholic and
aqueous extract 0f
400 mg/kg and 800
mg/kg body weight
of each.		Antioxidant
and wound
healing effects		Incision,
excision, and
dead space
wounds in
Wistar albino
rats		Both alcoholic and
aqueous extract
increased wound
breaking strength,
hydroxyproline,
hexuronic acid,
hexosamines,
superoxide dismutase,
catalase, reduced
glutathione, and
significantly decreased
wound contraction and
lipid peroxidation.		[48]
Pereskia
aculeate		5 % of each
methanol extract
(me) and hexane
fraction (hf) of
leaves		Wound healing
and anti-
inflammatory
potential		Excision woundHexane fraction
followed by methanol
extract markedly
accelerated the wound
closure.		[49]
Plumbago
zeylanicum		Ethanolic extracts
10% w/v		Wound healing
activity		Excision and
incision wound
models in rats		Wound completely
healed on day 18.4		[43]
Plumeria
rubralinn		0.5 % w/w
Plumeriarubralinn
(protease from the
latex) ointment
in the hydrophilic
base was applied
topically once a day		Inflammatory
activities and
wound-healing		Excision wound
model in rats		It reduced the
carrageenan-induced
edema and resulted in
81% wound contraction
at 16 days.		[50]
Pongamia
pinnata		Methanolic extracts
of leaf		Wound
healing,
antimicrobial
and
antioxidant
potential		Excision and an
incision wound
models in rats		Itdecreased the wound
size (30 mm2) on day 16.		[51]
RhuschinensisHydroalcoholic 5%
and 10% w/w leaf
extract		Wound healing
potential is
also used
to treat
hemoptysis,
inflammations,
laryngitis,
snakebite,
stomachache,
and fractures.		Incision wound,
excision wound,
and dead space
wound		10 % w/v extract had
greater wound healing
abilities than others
but less than povidone-
iodine.		[52]
Sambucu
sebulus		Alcohol preparation
of powder of leaves
and aerial parts of
plants		Wound healingFull-thickness
excision wound
model in rat		S. ebulus (2%) and
its 2% combination
enhanced wound
healing.		[53]
Stevia
rebaudiana		Aqueous crude
extract of leaves		Wound healing
potential		Excision and
incision wound
model in mice		Stevia treated mice
showed a significant
reduction in the wound
area, the faster rate of
epithelialization with
moderately higher
hydroxyproline.		[54]
Thevetiaper
uviana		Leaves hexane
extraction (lh)
and fruit water
extraction (fw)		Wound
healing with
antimicrobial,
antioxidant,
and anti-
inflammatory
potentials		Incision,
excision, and
dead space
models in rats		Complete wound
contraction was noted at
14 days.		[55]
Wedelia
chinensis		Ethanolic leaf
extract		Wound healing
activity		Excision,
incision and
dead space
wound models
in rats		Ethanolic extract
retarded the period
of epithelialization,
increased the wound
contraction, skin
breaking strength,
granulation tissue dry
weight, and breaking
strength.		[56]

Table 1: shows the medicinal plants that are used for different models of the wound healing.

Areas of Interest for Researchers

In this world, nature gifted us a huge number of plants that are being used traditionally for medicinal purposes by various ethnic groups. Since ancient times, the plants, their extracts or paste have been consistently used to treat various types of wounds and tissue-related diseases. Further validation regarding the therapeutic uses of medicinal plants for healing wounds through scientific investigation seems imperative. The study on the underlying wound healing mechanism behind the use of medicinal plants could be a novel research area. Still, the several challenges such as identification, isolation, targeting, and mechanism of action of bioactive components of the medicinal plants are underexplored for developing the suitable herbal medicine for wound healing formulations. The combination of plant extracts with allopathic medicines may have synergistic potentials to promote wound healing capability and could be of recent research interest.

Conclusion

Wound healing is a complex process of the body self- defense mechanism. The topical or oral uses of herbal medicine result in augmenting the wound contraction, epithelization rate, granulation tissue dry weight, and its breaking strength, preventing infection with proper activities of different growth factors, and collagen, etc. Although traditional and complementary medicines were used as therapeutics in the ancient period, still some ethnic groups are using them regularly. The various clinical trials in animal models, as well as in-vitro studies, proved its potentiality for wound healing purposes. The ethnomedicinal plants also possess superior wound healing abilities even in diabetic wounds. Further molecular investigations on medicinal plants are imperative for the invention of novel drugs for wound healing with minimal side effects.

Conflict of Interest

The authors declare that there is no conflict of interests.

Acknowledgment

The authors are thankful to undergraduate students who helped in the search of the relevant research articles.

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@article{dhakal2022,
  title   = {Exploration on Traditional Uses of Herbal Medicines for Wound
Healing in Different Animal Models},
  author  = {Dhakal I, Tiwary AK, Suhel KC, Thakur B, Regmi B and Shah MK},
  journal = {International Journal of Zoology and Animal Biology},
  year    = {2022},
  volume  = {5},
  number  = {1},
  doi     = {10.23880/izab-16000349}
}
Dhakal I, Tiwary AK, Suhel KC, Thakur B, Regmi B and Shah MK (2022). Exploration on Traditional Uses of Herbal Medicines for Wound
Healing in Different Animal Models. International Journal of Zoology and Animal Biology, 5(1). https://doi.org/10.23880/izab-16000349
TY  - JOUR
TI  - Exploration on Traditional Uses of Herbal Medicines for Wound
Healing in Different Animal Models
AU  - Dhakal I, Tiwary AK, Suhel KC, Thakur B, Regmi B and Shah MK
JO  - International Journal of Zoology and Animal Biology
PY  - 2022
VL  - 5
IS  - 1
DO  - 10.23880/izab-16000349
ER  -