A review of herbal medicines in wound healing

Preparations from traditional medicinal plants are often used for wound healing purposes covering a broad area of different skin-related diseases.. Herbal medicines in wound management i

A review of herbal medicines in wound healing

Tina Maver1, MPharm , Uro
s Maver2

, PhD, MPharm , Karin Stana Kleinschek1, PhD , Dragica M Smrke3, PhD, MD , and Samo Kreft4, PhD, MPharm

Processing of Polymers, Faculty of

Mechanical Engineering, University of

Medicine, University of Maribor, Maribor,

of Pharmacy, University of Ljubljana,

Ljubljana, Slovenia

Correspondence

University of Maribor

Faculty of Medicine

Taborska ulica 8

SI-2000 Maribor

Slovenia

E-mail: uros.maver@um.si

Conflicts of interest: None.

doi: 10.1111/ijd.12766

Abstract

Herbs have been integral to both traditional and non-traditional forms of medicine dating back at least 5000 years The enduring popularity of herbal medicines may be explained

by the perception that herbs cause minimal unwanted side effects More recently, scientists increasingly rely on modern scientific methods and evidence-based medicine to prove efficacy of herbal medicines and focus on better understanding of mechanisms of their action However, information concerning quantitative human health benefits of herbal medicines is still rare or dispersed, limiting their proper valuation Preparations from traditional medicinal plants are often used for wound healing purposes covering a broad area of different skin-related diseases Herbal medicines in wound management involve disinfection, debridement, and provision of a suitable environment for aiding the natural course of healing Here we report on 22 plants used as wound healing agents in traditional medicine around the world The aim of this review is therefore to review herbal medicines, which pose great potential for effective treatment of minor wounds

Introduction

The human skin is the largest organ in the body and

rep-resents its first line of defense.1 Besides protection, the

skin has two other main functions: regulation and

sensa-tion More specifically, it provides protection from

mechanical impacts and pressure, limits the influence of

variations in temperature, fights micro-organism

infec-tions, restricts radiation effects, and prevents the entrance

of chemicals As the largest organ in the body, the skin

also plays an important role in several physiological

pro-cesses, including regulation of body temperature (via

sweat and hair) and changes in peripheral circulation and

fluid balance It is also involved in the synthesis of

vita-min D, for which it acts as a reservoir With an extensive

network of nerve cells, the skin enables detection and

relaying of changes in the environment (heat, cold, touch,

and pain) Damage to these nerve cells is known as

neu-ropathy and results in the loss of sensation in affected

areas Because of all the aforementioned and other

func-tions, the preservation of skin quality is of prime

impor-tance to maintain a healthy body.2,3

A wound is defined as the disruption of the cellular

and anatomic continuity of a tissue and may occur due to

physical, chemical, thermal, microbial, or immunological tissue trauma.4 Wounds can compromise patients’ well-being, self-image, working capacity, and indepen-dence Effective wound management is therefore neces-sary not only on the individual but also on the community level.5

The process of wound healing

Wound healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers It is reflected in a set of biochemical events

in a closely organized cascade to repair damaged tissue.6

In the human adult, wound healing is often divided into three phases, i.e., inflammatory, proliferative, and remodeling phases The inflammatory phase starts imme-diately after injury with the launch of hemostatic mecha-nisms to stop bleeding straight away.7It is characterized

by vasoconstriction and platelet aggregation to induce vasodilatation and phagocytosis, hence inflammation of the wound site The proliferative phase is characterized

by granulation, wound contraction, and epithelialization During granulation, fibroblasts form a bed of collagen, followed by the production of new capillaries.7 During 1

A wound is defined as the disruption of the cellular and anatomic continuity of a tissue and may occur due to

wound contraction, myofibroblasts decrease the size of

the wound by gripping the wound edges and contracting

using a mechanism that resembles that of smooth muscle

cells When the cells’ roles are close to complete,

unneeded cells undergo apoptosis.8 Epithelialization

involves proliferation of epithelial cells, which then

crawl atop the wound bed, covering the new tissue

Finally, the remodeling phase takes place over a period

of several months, during which the dermis responds to

injury with the production of collagen and matrix

pro-teins in an attempt to return to its pre-injury

pheno-type.9

The aim of wound treatment is to either shorten the

time required for healing or to minimize the undesired

consequences, hence scarring.10

Important activities in wound healing

management

Various physiological events can significantly affect the

course of wound healing Among the most important are

the inflammatory, antimicrobial, analgesic, and

anti-oxidant activities, regardless of the underlying

mecha-nism

The acute inflammatory response during the early

stages of injury generates factors (cytokines and

chemo-kines) essential for appropriate tissue growth and

repair.11 Prolonged inflammation can prevent the wound

from reaching the remodeling phase, as well as matrix

synthesis As a result, delays in wound closure and an

increase in pain sensation in and beside the wound

com-monly appear, leading to even more hindered healing.12

Considering the aforementioned, the anti-inflammatory

therapeutic interventions in wound care have been the

subject of extensive research, particularly in relation to

wound healing and improved patient comfort.13

Infections are known as one of the most important

factors influencing efficiency of wound healing It is

reported that a high percentage of wound-related

compli-cations and hence costs in wound care can be directly

linked to infected wounds.14 Reducing the bacterial load

may be one of the most important necessary requirements

for better wound healing, as wound infection (either

secondary or primary by opportunistic microorganisms)

can lead to reduction of local inflammation and

conse-quentially avoid tissue destruction.15 An ideal treatment

for the prevention of wound infection should act

antimi-crobially and at the same time stimulate the body’s

natu-ral immune activity without damage to surrounding

healthy tissue.16

Most wounds induce a sensation of pain Pain relates to

patient discomfort, release of stress factors, and often

reduces the patient’s quality of life Hindered mobility,

psychological issues connected with pain-induced stress, and the financial burden caused by prolonged therapy all contribute to less effective wound healing According to McGuire et al.,17chronic pain lowers the patient’s capabil-ity of healing, prolonging the overall recovery process.17,18 Suitable and effective pain management can lead to an ear-lier ambulation, adequate oxygenation, nutrition, and stress reduction All studies mentioned results in the facili-tation of wound healing, while minimizing risk for the development of chronic pain, as well as finally in lowered treatment costs.19

Inflammation also causes a coordinated influx of neu-trophils to the wound site Neuneu-trophils activate their so-called respiratory burst and produce free radicals.20,21

The presence of free radicals results in oxidative stress leading to lipid peroxidation, DNA breakage, and enzyme inactivation, including free-radical scavenger enzymes, which are known to limit the effects of reactive oxygen species Evidence for the role of oxidants in the pathogen-esis of many diseases suggests that antioxidants may be

of therapeutic use in these conditions and hence improve efficiency of wound healing.22

Important characteristics to be considered in wound healing are the wound contraction rate, granulation tissue breaking strength, as well as the collagen content.23Apart from the above-mentioned wound healing aiding activi-ties, others are also reported in the literature, i.e., astrin-gent activity, stimulated epithelization, and effective hydration of the wound site.24

Medical plants traditionally used in wound healing

Nature has been a source of medicinal treatments for thousands of years, and plant-based systems continue to play an essential role in the primary healthcare of 80% of the world’s underdeveloped and developing countries Many plants and their extracts have been used tradition-ally due to their great potential for management and treatment of wounds Natural agents induce healing and tissue regeneration through multiple connected mecha-nisms The so-called phytomedicines are affordable, and they mostly cause minimal unwanted side effects How-ever, increasing awareness of their activities, and potential and possible safety concerns, point out the need for their scientific standardization, validation, and systematic safety evaluation before efficient introduction to wound care.25In recent years, extensive research has been carried out in the area of wound healing and management through medicinal plants.25–28

Table 1 provides an overview of the most important medicinal plants and their properties, with a known or proven effect on wound healing

Azadirachta indica

Calendula officinalis

 for

Chamomilla recutita

Chromolaena odorata

Commiphora myrrha

 ,

Helianthus annuus

 for

Hydnocarpus wightiana

Hypericum perforatum

Jasminum auriculatum

Pterocarpus santalinus

Rosmarinus officinalis

 rosemary

Many plants promote the skin’s natural repair mechanisms and therefore have a huge potential for therapeutic use in wound care As our familiarity with herbal extracts and iso-lates increases and while we employ commonly used scien-tific methodology to study plants and their extracts from the physiological and pharmacological point of view, the num-ber of herbal products for wound treatment is steadily increasing Clinical proof of the therapeutic effects of herbal products has led to the study of many more herbs for their therapeutic, either curative or preventative, roles Further studies should aim at the isolation and identification of spe-cific active substances from plant extracts, which could also disclose compounds with better therapeutic value Such a combination of traditional and modern knowledge can pro-duce novel drugs for wound healing with significantly lowered unwanted side effects

Acknowledgments

The paper was co-produced within the framework of the operation entitled Centre of Open innovation and ResEarch

UM (CORE@UM) The operation is co-funded by the Euro-pean Regional Development Fund and conducted within the framework of the Operational Programme for Strengthen-ing Regional Development Potentials for the period 2007–

2013, development priority 1: Competitiveness of compa-nies and research excellence, priority axis 1.1: Encouraging competitive potential of enterprises and research excellence, contact no 3330-13-500032 The authors also acknowl-edge the financial support from the Ministry of Higher Edu-cation, Science, and Technology of the Republic of Slovenia

Questions (See answers after references)

1 What are the functions of the human skin? (multiple correct answers)

a First-line protection against infections

b Hormone secretion

c Body temperature regulation

d Pain sensation

e Water reservoir

2 Is wound healing affected if the patient suffers from pain?

a True

b False

3 Which are the main wound healing phases? (multiple correct answers)

a Infection prevention

b Inflammatory

c Proliferative

d Scarring

e Remodeling

Tridax procumbens

4 Does scarring occur in the inflammation phase of

wound healing?

a True

b False

5 What are the characteristics of an ideal medicine for

pre-vention of wound infection? (multiple correct answers)

a Antimicrobial activity

b Moisture control

c Stimulation of innate immunity

d Vasoconstriction

6 Which drugs are COMMONLY applied in wound

treatment? (mutlitple correct answers)

a Analgesics

b Astringents

c Anti-inflammatory drugs

d Antimicrobials

7 Which medical plants possess anti-inflammatory

activ-ity? (multiple correct answers)

a Achillea

b Centella asiatica

c Chamomilla recutita

d Ginko Biloba

e Rosmarinus officinalis

8 Can Angelica sinensis be used to lower the patients

sensation of pain?

a True

b False

9 Can Echinacea be used to treat Candida infections?

a True

b False

10 Which plant has been approved by FDA for food

applications? (one correct answer)

a Rosmarinus officinalis

b Pterocarpus santalinus

c Commiphora myrrha

d Azadirachta indica

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