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Medicinal Plants and Products
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from Traditional Medicine Systems
Contribute to Clinical Wound
Management
Tuhin Kanti Biswas , Shrabana Chakrabarti, Srikanta Pandit,
and Raj Mani
Abstract
Medicinal plants and plant products used in traditional medicine systems play
potent roles in the management of many pathological conditions by accelerating
the process of healing. The properties of plants and products are derived from
basic laboratory studies on animal models, data from clinical studi es in man are
lacking. Some notable exceptions are single medicinal plants such as Aloe vera,
Azadirachta indica, Curcuma longa, Hypericum perforatum, Centella asiatica
and Pterocarpus santalinus and products such as honey and leaves of banana
plant. Some data from clinical studies of the value of a polyherbal preparation
used in Ayurvedic medicine to irrigate wounds also exist. These are examined in
this chapter to support the argument that the medicinal plant systems valued by
Traditional Medicine systems may have untapped potential to benefit clinical
wound management. There are data driven offers from Traditional Medicine
systems from which allopathic or western medicine may benefit.
Keywords
Wound managementWound dressingsAyurvedaTraditional Chinese
Medicine
T. K. Biswas (&) S. Pandit
Department of Kayachikitsa (Medicine), J. B. Roy State Ayurvedic Medical College and Hospital,
Kolkata 700004, India
e-mail: biswastuhin@rediffmail.com
S. Chakrabarti
Chigurapati Pharmaceuticals, Hyderabad, India
R. Mani
Shanghai Jiao Tong University School of Medicine, Shanghai, China
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. Mani (ed.), Chronic Wound Management,
https://doi.org/10.1007/978-3-031-26110-7_7
117
118 T. K. Biswas et al.
Abbreviations
AYUSH Ayurveda, Yoga, Unani, Siddha, and Homeopathy
BLD Banana leaves dressings
BPPB Boiled potato peel bandage
DFU Diabetic foot ulcer
FGF Fibroblast growth factor
FPG Fasting plasma glucose
HOMA-IR Homeostasis model assessment-estimated insulin resistance
MMP Matrix metalloproteinase
PUSH Pressure ulcer scale for healing
PWAR Percentage wound area reduction
PWSR Percentage wound score reduction
QUICKI Quantitative insulin sensitivity check index
REEDA Redness, edema, ecchymosis, discharge, and approximation
TCM Traditional Chinese Medicine
TGF-a Transforming growth factor–alpha
VAS Visual analogue scale
VEGF Vascular endothelial growth factor
Introduction
Wounds are the outcome of injuries or following surgery. Healing of wounds follows a pathological process rarely needing any clinical intervention unless it
becomes complicated and/or non-healing. In most of the conditions, wounds may
heal through natural process, but it may lack quality of healing in terms of days
required, formation of scar and overgrowth of granulation tissues. Therapeutic
application of healing agents varies according to the variations of stages and condition of diverse types of wounds. The process of wound healing can be divided
broadly into two types as procedural and therapeutic. Even though there are
tremendous developments of diverse surgical procedures to manage the healing
process there are very few drugs developed from any source for their specific role in
acceleration of healing. Besides drugs of synthetic origin, there are number of natural
resources, medicinal plants, which are mentioned for their wound healing activity in
various traditional systems of medicine including Ayurveda, Yoga, Unani, Siddha,
Homeopathy, Chinese Medicine, and others in most countries. The wound healing
potential of more than one hundred and fifty medicinal plants are mentioned in
Ayurveda (Biswas and Mukherjee 2003). In the African continent about 80% of the
population depends upon the medicinal plants for primary source of medication
using forty five thousand medicinal plants under major five hundred species. This
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wide spectrum of biodiversity includes twenty-five plants of African origin as
reported in the literature for possessing wound healing properties. Equally interestingly twenty medicinal plants of African origin have been screened in the laboratory for the development of biogenic nanoparticles in combination with silver,
selenium, gold, zinc oxide and zinc sulphide with anti -in flammatory and antioxidant
properties which promote wound healing (Tyavambiza et al. 2021). In Ghana,
evidence exists of the use of one hu ndred and four medicinal plants with potential to
benefit wound healing activity. Of these, historically seventeen have been used to
treat leg ulcers caused by an infestation by the guinea worm (Dracunculus medi-
nensis) (Freiesleben et al. 2017). In the Persian system of traditional medicine
sixty-six plants are reported for their wound healing property but nine among them
have been scientifically screened for such activity which is modulated owing to the
antimicrobial, radical scavenging and anti-inflammatory properties (Hosseinkhani
et al. 2017). Much research into traditional and compleme ntary medicine has been
conducted in China under the name of traditional Chinese medicine (TCM).
Medicinal plants in TCM are broadly classified into four categories which are
Ministerial or Principal herbs that act directly to alleviate disease, Deputy or
Alternate herbs that assist Ministerial herbs, Assistant herbs that reduce adverse
effects and Envoy herbs which are used to detoxify and have a direct role in the
therapy. Most TCM product s used in wound management are polyherbal in origin
and among these two are Yunnan Paiyao and Shiunko. The evidence of the properties of these two polyherbals were based on laboratory studies using a rat model to
study fibroblast cell regeneration and angiogenesis (Chak et al. 2013).Yunnan
Paiyaois comprised Radix notoginseng (40%), Ajugaforrestiidiels (17%), Rhi-
zomadioscoreae (13%), Rhizomadioscoreaenipponicae(10%), Herbageranli &
Herbaerodii (7.2%), Dioscoreaeparviflora ting (6%), Herbainulaecappae (5%),
Borneol (1.5%) and Musk (0.3%) to control bleeding and oedem a. The formulation
behaves as Deputy herbs do. Shiunko, on the other hand is a formulation composed
with sesame oil (500 ml), Lithospermi radix (10 g), A. sinensis (10 g), lard (3 g) and
Bees wax (45 g), that acts as Principal herbs since it aids information granulation
tissue, speeding wound healing, re-epithelialization and angiogenesis (Chak et al.
2013). The Leguminosae family which comprise great many of medicinal plants
used in Ayurveda have no direct specificity of family or constituent compounds
(Biswas et al. 2016). Active constituents of various plants of this family may alleviate healing of wound by different mechanisms, for example, saponins may
enhance the synthesis of pro-collagen, tannins and flavonoids benefit anti-bacterial
and antiseptic activities which in turn help healing process (Ibrahim et al. 2018).
Medicinal plants/products may be tested for efficacy using cell culture lines to
study specific constituents, animal models or in clinical studies. Animal model
studies have in previous years, demonstrated efficacy based on controlled studies.
Investigation of such databases in English language as SCOPUS, Web of Science,
PubMed, Science Direct led to a few clinical randomized controlled studies on
specific plants and products used in Ayurveda. In this chapter, these studies are
analysed to better comprehend their potential for use in clinical wound healing.
120 T. K. Biswas et al.
What are Ideal Properties to Benefit Wound Healing?
Research with plant medicine for their wound healing efficacy gained momentum
about 3 to 4 decades ago and recent advancements included investigations of their
mechanisms of actions at molecular level. The fundamental cellular aspect of acute
wound healing involves four steps as haemostasis, inflammation, proliferation, and
matrix remodelling of wound tissues. Dur ing haemostasis, there is plugging of
platelets and formation of fibrin matrix, which stops bleeding. The process of
inflammation has beneficial roles in removal of debris as well as in the prevention of
secondary infection. The wound is closed by keratinocytes in the stage of proliferation and finally the closure of wound occurs in matrix remodelling stage when there
is formation of fibroblasts and myofibroblasts. The acute stage of wound healing is
dynamic that leads rapid healing but in the chronic stage, process of healing is
delayed due to ageing as well as absence of certain molecular factors like matrix
metalloproteinase (MMPs), FGF fibroblast growth factor (FGF), transforming
growth factor−alpha (TGF-a), vascular endothelial growth factor (VEGF), and so
on, due to excessive inflammation followed by scarring (Wilkinson and Hardman
2022). An ideal drug of plant origin should overcome all these phenomena.
Randomized Clinical Trial on Wound Dressing Agents
from Plant Origin
Objectives
A high quality of healing can only occur if the wound bed is found healthy.
Dressing of wounds appropriately may provide debridement of wound,
non-adherence of wound surface, free from toxins and allergens, if any as well as
absorb excess exudates and foul odour. Primarily the dressing of wounds is done by
conventional method with Spunbond−meltblown−spunbond (SMS) fabric (Dhinakaran et al. 2017) which is placed over a layer of adhesives. Occlusive dressings
are also in use for providing moisture in wound area followed by acceleration of
collagen synthesis, epithelialization, maintains wound pH and minimizes chances
of infection (Ghomi et al. 2019). Herbal dressing, in the form of paste or fresh juice
in a specialised process of preparation, plays a crucial role in the healing process
which may be non-toxic and having capacity of debridement of wounds.
Azadirachta Indica as Dressing Agent
Azadirachta indica L. (Family Meliaceae), commonly known in the name of Neem,
is a tall tree distributed particularly in Southeast Asian countries like India, Pakistan, Bangladesh, Myanmar, and Sri Lanka. This plant was introduced in Australia
during 1940s where it flourishes (Nishteswar and Hemadri 2013). In Ayurveda, all
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five parts of the plant viz. leaves, seed, stem bark, root and fruits are used for
various therapeutic purposes. The plant contains multiple phytochemicals such as
nimbolinin, nimbin, nimbidin, nimbidol, sodium nimbinate, gedunin, salannin and
quercetin. The leaves of the plant are widely used for different therapeutic purposes
in different forms and contain a specific alkaloids nimbin, nimbanene, nimbandiol,
nimbolide and nimbiol (Alzohairy 2016). The plant has antibacterial and antifungal
properties favouring it to be an ideal wound dressing agent as described in
Ayurveda.
The antimicrobial and antifungal activities of the aqueous extract of leaves, bark
and seed of A. Indica were screened separately in three doses 500, 1000 and
2000 µg/ml for each compared to Ciprofloxacin (5 µg/ml) and Amphotericin B
(100 µg/ml) and both these were tested against specific bacteria such as Staphy-
lococcus aureus, Pseudomonas erugi nosa, Proteus mirabilis, Enterococcus foecalis
and specific fungal infections like Aspergillus fumigates as well as Candida albicans. It was observed that leaf extract of A. Indica at the concentration of
2000 µg/ml has potent antifungal activity while bark extract exhibited significant
antimicrobial activity at the concentration of 500 µg/ml (Reddy et al. 2013). The
antimicrobial activity of A. indica in comparison with antibiotics was determined
based on the minimum inhibitory concentration (MIC) at the dilution of 500, 1000
and 2000 µg/ml in micro-tire wells. In another study it was observed that the
isolated chemical constituent of A. Indica nimonol has no antifungal activity though
the 5% aqueous extract of leaves of the plant has significant antifungal activity
against Aspergillus niger and A. flavus (Mahmoud et al. 2011).
A clinical trial was done to study with the extracts of neem (A. indica) leaves to
examine its wound irrigation properties using normal saline as a control or standardized agent in patients with diabetic foot ulcer (DFU). Patients enrolled had
DFU grade 1−3 i.e. (Localized superficial ulcer to deep ulcer with abscess,
osteomyelitis, or joint sepsis) defined using the Wagner classification (Mehraj
2018). DFU had wound areas greater than or equal to 1sq. cm. A total 246 patients
of DFU, in the age group 20 and 80 years, uncomplicated by clinical signs of
ischemia, attending in a diabetic foot ulcer care clinic in Assam, India, were
screened of which N = 46 were excluded using the inclusion/exclusi on criteria and
unwillingness to participate in the study. The patients with DFU of grade 4 or 5 as
per Wagner classification, had drug or alcohol addiction, any cognitive or mental
illness, history of prior hospitalization for DFU and were under treatment on
immunosuppressive drugs or on treatment for end stage renal disease were excluded
from the study. The remaining two hundred patients were randomized into two
groups. Each group was treated with wound dressings of either neem leaves
aqueous extract or with normal saline as irrigation twice a week for period of four
weeks. Forty patients dropped out and were lost to analysis. One hundred and sixty
patients continued the treatment with eighty patients in each group in which average
distribution of patients in two treatment groups in age groups between 41 and
60 years was maximum (62.5%) followed by age group between 61 and 80 years
(25 to 31.25%). Patients of DFU in age group between 20 and 40 years were least
(5 to 11.25%). Number of male patients in normal saline and Neem leave extract
122 T. K. Biswas et al.
irrigation treated group were 68 and 64 respectively while females were 12 and 16,
respectively.
Effects of both treatments were assessed using wound PUSH (Pressure Ulcer
Score on Healing) score (Neola Satish and Srinivasan 2021) where wound contraction size, exudation and type of tissue involved in the healing process were
assessed. Assessment of PUSH was done based on percentage wound area reduction (PWAR) and percentage wound score reduction (PWSR). The result of the
study shows that of the wound mean score in the normal saline group reduced from
12.93 to 9.14, while this reduction in neem extract group was from 11.97 to 6.7
which was highly statistically significant (p < 0.001). Mean wound area decreased
from 19.84 cm
2
to 14.31 cm2in the normal saline group and 17.14 cm2to 7.04 cm
in the neem extract group (Jayalakshmi and Thenmozhi 2021).The number of
individuals in whom ulcers achieved 50% PWAR was more in the neem leaves
group (64%) compared to 35% in the normal saline group during the four-week
study period. On the other hand, PWSR achieved 50% in 80.6% individuals of
neem group while 55.8% individuals in the saline group (Jayalakshmi and Thenmozhi 2021).The results showed the neem leaves extract have a promising role in
wound dressing.
Ayurvedic Polyherbal Formulation as Dressing Agent
In Ayurveda, detailed descriptions exist for the management of wounds. These
include procedures of cleaning of wounds, dressing, healing, maintenance of wound
area hygiene, special dietary advice for patients having wounds and so on. There are
multiple formulations of plant origin narrated in Ayurveda for their wound dressing
properties. Jatyadi Tailam is a polyherbal preparation prepared with sesame oil,
which is mentioned in Ayurvedic text Sharangadhar Samhita (Sarngadhar 2017)as
a wound dressing as well as wound healing agent. The formulation is composed of
various parts of Ayurvedic plants like Myristica fragrans, Azadirachta indica,
Tricosanthes dioica, Pongamia pinnata, Glycyrrhiza glabra, Saussure alappa,
Curcuma longa, Berberis aristata, Rubia cordifolia, Picrorhiza kurroa, Prunus
cerasoides, Symplocos racemosa, Terminalia chebula, Nelumbo nucifera, Hemidesmus indicus, Sesame indicum along with bee wax and purified copper sulphate
in different proportions. Quantitative phytochemical analyses showed presence of
phenols, proteins, tannins, sterols and terpenoids with specifically high amount of
Octadecanoic acid, a type of stearic acid. Besides, the formulation showed potent
antibacterial effect against Gram (+) bacteria like Staphylococcus aureus, Staphy-
lococcus epidermidis and Entercoccus faecalis and Gram (−) bacteria like
Escherichia coli, Pseudomonas aeruginosa, Pseudomonas mirabilis and Klebsiella
pneumonia (Mandrika et al. 2021). The formulation is widely used in Ayurveda as
dressing agent for cleaning purpose before application of any healing drug or as a
healing drug as well for the management of wounds like fissure-in ano, haemorrhoids and non-healing wounds.
2
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A randomized clinical trial was undertaken with this polyherbal formulation on
N = 30 patients with clean wounds for its wound cleaning and healing properties.
Patients were equally divided into two groups and randomly treated either with
Jatyadi tailam (an oil) or Jatyadi ointment. Randomization of the patients was done
by using special computerized software. Treatments were continued for seven
consecutive days and the effects were compared using the values of selected
parameters of Bates-Jensen Wound Assessment Tool i.e.1,2,3,7,9,10,11,12 and 13
(size, depth, edge, exudates type, skin colour surrounding wound, peripheral tissue
oedema, peripheral tissue in duration, granulation tissue, epithelialization) on
baseline, and the 8th day.
It was observed that there was significant improvement within and between the
groups in all the selected parameters of the Bates Jensen wound assessment tool. It
was predicted from the study that dressing and healing properties of oil and ointment respectively of this formulation (Jatyadi) were promising thus giving a scientific basis to textual descriptions of Ayurveda (Shindhe et al. 2020).
In another clinical study, for the management of filarial lymphoedema using an
integrated approach following the guidelines of morbidity control agenda of the
global alliance for the elimination of lymphatic filariasis (GAELF) Jatyadi tailam
was one of the components successfully used to treat the unhealthy granulation
tissues and slough at the base of the ulcer. It was reported that the Ayurvedic
component in the treatment costs was $32.5 to $107 for six months (Narahari et al.
2007).
Banana Leaves Dressings (BLD)
Banana (Musa paradisiacal Linn, family Musaceae) leaves (Fig. 1) and skin are
being used traditionally in certain countries as wound dressing agent (Hoetzenecker
et al. 2013).
An experimental study was carried out with the aqueous and methanolic extracts
of the peeled skin of the unripe banana and was applied over the excision, incision
and dead space wounds in rats using an excision model. The study revealed that
there was statistically significant reduction of wound contraction size (p < 0.001)
between 4th day to 12th days with the aqueous extract of the test sample supported
by significant generation of hydroxyproline, hexosamine as well as antioxidative
materials (Agarwal et al. 2009). In another study, a water soluble substance
extracted from leaves, skin and peels of unripe banana named as super green
(SG) was studied in streptozototin (STZ) induced diabetic excision wounds on rats
in different ratio under the ointment form and it was observed that there was
significant reduction (p < 0.05) of wound contraction size within 15 days with
concomitant potent expression of collagen I, collagen III, IL-1b, IL-6 and TNF- a in
wound tissues treated with SG ointment prepared with 1:6000 dilution (Cheng et al.
2020). However , reports of animal experimental study with banana leaf alone for
wound healing activity are limited. The banana leaf dressing (BLD) was reported to
124 T. K. Biswas et al.
Fig. 1 Banana tree (musa paradisiaca) and its leaves
be a valuable dressing for superficial burns from an RCT; also, useful to treat head
and neck injuries (Chendake et al. 2021).
Banana leaves are widely available in over hundred countries throughout the
world. Wounds treated with banana leaves healed in the same duration as wounds
treated with Vaseline gauze dressing. The most advantage of banana leaves is the
smooth and waxy surfaces which do not stick on the wound surface. Moreover,
it was estimated that BLD are 1500 to 5000-times less expensive than collagen or
biosynthetic dressings, respectively (Hoetzenecker et al. 2013).
There are some interesting clinical studies with banana leaves in diverse types of
wounds with special reference to burn wounds. In a study on N = 60 patients with
contused, lacerated, and sutured wounds over the head, neck and face regions,
comparative effects of autoclaved BLD with petroleum jelly gauze dressing were
done by assigning equal number of patients to the two groups. Effects were
observed by scoring or grading pain, status of wound bed (dry, moist, wet, saturated, and leaking). The result showed BLD treated wound fared better that the
petroleum jelly gauze treated group, the significant results being statistically significant (p < 0.01) (Chendake et al. 2021). Burn injuries are a global problem on
intense pain, long term morbidity and sometimes even loss of life. The World
Health Organization reported in 2008 that burden of burn injury falls on the world’s
poor: the vast majority (over 95%) of fire-related burns occurred in low- and
middle-income countries (Mock 2008a, 2008b). Successful management of burns
with low-cost dressing is unbelievably valuable the, BLD is a tried and tested
alternative. A pilot study on N = 38 cases of burn wounds, divided into two groups,
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were treated with banana leaf; this was prepared by cutting the midrib of the leaf,
carefully washed and dried, and then cut into pieces with average size 40 60 cm
for Group-I: Group II received a simple dressing (antimicrobial ointment, then
layers of gauze). The rate of healing in terms of outcome criteria viz. discomfort
score: it was in the group BLD 2.1 ± 1.3 compared to the 6.0 ± 1.5 in Group II;
dressing removal pain scores were 2.3 ± 1.2 and 5.9 ± 1.2 in the BLD and
Group II respectively; ease of dressing removal score was significantly lower in
BLD treated group when compared to the simple dressing group (3.5 ± 1.9 and
7.4 ± 1.2) respectively. Finally, time to complete healing in the BLD group was
8.4 ± 1.4 days compared to 13.4 ± 1.9 days in the simple dressing group. Control
of infection was favourably comparable in BLD: as evidence of signs of wound
infection (defined the presence of unpleasant odor, pus) was not found in 81.6 and
68.4% patients in the BLD and simple dressing groups. Signs of infection were
noted in 7% (BLD group) and 12% patients simple dressing or Group II) respectively. Moreover, the scoring of visual analogue scale (VAS) on the criteria like
discomfort, dressing removal pain and ease of dressing removal was favourable to
the BLD groups (Ali and Eazaym 2015).
An open controlled clinical trial of BLD versus povidone iodine ointment on
superficial partial thickness burns was done. Burns on both upper and lower
extremities treated with gauze impregnated with boiled potato peel bandage (BPPB)
on N = 30 patients and BLD. BLD and BPPB were applied in same patients on
different sites simultaneously. It was found that pain with dressing change, comfort
score and dressing handling score were parallel in both the groups. The BLD is
reported to be eleven times cheaper than BPPB. Interestingly, the boiled potato skin
used in this study was donated to the surgeon conducting the study by families in the
city. Donations of potato peels were bagged and transported free of cost to the hospital
where the potato skins were boiled before use in the study (Gore and Akoleka 2003).
The duration of area of epithelialization with number of days and mode were
also found to be better in the BLD treated group.
It was claimed that BLD is non-adherent, non-toxic, non-antigenic, cheap,
simple to prepare and easily available. It is an effective and acceptable alternative
for management of partial thickness burn wounds (Gore and Akoleka 2003). The
estimated cost of BLD for a complete treatment was estimated at INR 2000−3000
(13−38 USD).
Randomised Controlled Trial on Wound Healing Plant
Medicine
Topical Application
Most of the wound healing drugs of any origin are for topical use. The main aim
being to regenerate epithelial and granulation tissues composed of extracellular
matrix, proteoglycans, hyaluronic acid, collagen, and elastin. There are several
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