*4.1.2.6. Other oils*

Other less well-known essential oils with a proven beneficial effect on wound healing include the bark oil of *Santiria trimera* (a member of the frankincense family) [101], oils from *Hypericum perforatum* (St. John's Wort) and *Calendula arvensis* [102], oils extracted from *Cinnamomum zeylanicum* (cinnamon) bark [103], and the extract from *Chromolaena odorata* (Siam weed) [104].

An overview of the main chemical components of the above described essential oils is depicted in **Figure 4**.

### *4.1.3. Other compounds with wound healing properties*

of another commercially available tea tree oil-based cream against different bacteria and con-

Thyme (*Thymus vulgaris*) is an aromatic plant, commonly used in preparation of several dishes, whereas its essential oil has been widely reported to contribute to the healing of burns [82]. Thyme essential oil is derived from the steam distillation of the leaves, stems and flowers of the plant. One of such is the study by Dursun et al., who investigated the impact of thyme oil on the formation of nitric oxide, which is an important inflammatory mediator [92]. They studied the effect of thyme oil on burn wound in rats and showed that it not only decreased the amount of nitric oxide produced in response to the burn, but also facilitated wound healing [92]. Several other studies were conducted in regard of the potential antimicrobial activity of the thyme oil. For example, Bozin et al. showed an effective antibacterial and antifungal activity *in vitro* [93]. Their results are in agreement with another study that was performed by Shin and Kim, who determined a significant inhibitory action of thyme oil against both antibiotic-susceptible and resistant strains of *Streptococci, Staphylococcus aureus* and *Salmonella typhimurium* [94]. With the aim to evaluate the thyme oil's potential antifungal action, Giordani et al. combined it with amphotericin B and showed that it significantly potentiated the effectiveness of the latter [95]. Finally, Komarcevic discussed the available evidence showing that topically applied thyme oil increased collagen deposition, angiogenesis and keratinocyte migration, all together significantly contributing to the efficiency of wound healing [96].

Orafidiya et al. performed two studies regarding the potential use of ocimum oil derived from the leaves of *Ocimum basilicum* L. in wound healing applications [97]. First, they studied its potential effect on the healing of full-thickness excisional and incisional wounds in an animal model [97]. They found and improved wound healing performance in wounds treated with the essential oil in comparison with the control [97]. In the second study, Orafidiya et al. demonstrated a significant antiseptic effect of a 2% solution of ocimum oil against strains and isolates from boils, wounds and acne [98]. This group was not the only one testing the potential effect of basil extract. Another similar study was performed by Singh and Majumdar, who studied the potential anti-inflammatory action of ocimum oil. They found a significant inhibition of vascular permeability and leucocyte migration in animal studies [99]. Singh conducted another study, in which he determined that the anti-inflammatory activity of ocimum oil could be related to a blockading of the enzymes cyclooxygenase and lipoxygenase in the

Other less well-known essential oils with a proven beneficial effect on wound healing include the bark oil of *Santiria trimera* (a member of the frankincense family) [101], oils from *Hypericum perforatum* (St. John's Wort) and *Calendula arvensis* [102], oils extracted from *Cinnamomum zeylanicum* (cinnamon) bark [103], and the extract from *Chromolaena odorata* (Siam weed) [104].

firmed its effectiveness against *Staphylococcus aureus* and *Escherichia coli* [91].

*4.1.2.4. Thyme oil*

130 Herbal Medicine

*4.1.2.5. Ocimum oil (basil)*

arachidonic acid metabolism [100].

*4.1.2.6. Other oils*

Research on plant-derived compounds with potential use in wound healing drugs is a developing area in modern biomedical sciences. Scientists who are trying to develop newer drugs from natural resources are looking towards different regions, where there is a strong evidence of plant in traditional medicine (India, Africa, etc.) [105]. Most of these herbal medicines are not isolated compounds, but rather extracts composed of several constituents, which synergistically aid the wound healing process [106]. Not many have been screened scientifically for the evaluation of their wound healing activity in different pharmacological models and patients, but the potential of most remains unexplored [107]. The most important groups of compounds were described above, whereas we briefly review some of the less commonly used compounds and groups.

**Figure 4.** An overview of chemical structures of the above mentioned essential oils.

#### *4.1.3.1. Alkaloids*

Alkaloids are heterocyclic compounds that contain a nitrogen atom in at least one of the heterocycles [108]. They usually have various potent biological activities and are of bitter taste [109]. Some synthetic compounds of similar structure are also termed alkaloids. They are not that common in the plant kingdom, are represented by diverse chemical structures, and almost all show interesting properties for therapeutic use [110]. Alkaloids are produced also by other organisms including bacteria, fungi and animals [109]. Although alkaloids are not the first choice of chemicals to be used in relation to wound treatment, there are still some interesting plants that need further analysis due to their already proven potential for this purpose. Among the plants that produce alkaloids with potential beneficial effects on wound healing are the *Papaveraceae* (poppy family) and *Berberidaceae* (barberry family) families [111]. Both produce isoquinoline alkaloids that possess a range of biochemical effects relevant for medical use (e.g. inhibition of pain, growth inhibition of cancer cell growth, and growth of bacterial cells) [111]. Among other indirectly related beneficial properties are also the stimulation of bone marrow leucocytes, which modulate the inflammation phase of wound healing [112].

sooner rather than later prescribed as antimicrobial drugs, and the public is becoming increasingly aware of problems with the over prescription and misuse of traditional antibiotics [123]. It is reported that, on average, two or three antibiotics derived from microorganisms are launched each year [124]. Phytochemicals with an antimicrobial activity can be divided into several categories, most of which were already described above. These include phenolics, terpenoids, essential oils and alkaloids [123]. Among the other ones, we will briefly review also

Plant-Derived Medicines with Potential Use in Wound Treatment

http://dx.doi.org/10.5772/intechopen.72813

133

First antimicrobial peptides were reported back in 1942 [123]. Mostly, these compounds are positively charged and include disulphide bonds in their structure [125]. One of the known possible mechanism of actions involves the formation of ion channels in the microbial membrane [125], while the other is related to a competitive inhibition of adhesion of microbial proteins to host polysaccharide receptors [126]. Some of the most important subgroups of antimicrobial peptides include thionins, which are toxic to yeasts and Gram-negative and

Polyacetylenes are another group of potential antimicrobial compounds with interesting properties. The compound 8S-heptadeca-2(Z),9(Z)-diene-4,6-diyne-1,8-diol was shown to be effective against *S. aureus* and *B. subtilis* but not to Gram-negative bacteria or yeasts [127]. In Brazil, acetylene compounds and flavonoids derived from single plant extracts traditionally

Many plants and their extracts have great potential for the management and treatment of wounds. Natural agents induce healing and regeneration of the lost tissue by multiple mechanisms. The so-called phytomedicines are affordable and they cause minimal adverse effects. However, there is need for scientific standardization, validation and safety evaluation of plants of traditional medicine before these can be recommended for wound healing [49]. Therefore, an extensive research has been carried out in the area of wound healing and man-

The following paragraphs outline some medicinal plants and their properties that exhibit

*Achillea millefolium* (Family: *Asteraceae*)*.* Yarrow (a common name of the plant) has been known and used due to its healing effects by many cultures for hundreds of years [129]. Among its proven beneficial effects in wound healing are a good antibacterial activity against *Shigella dysenteriae* [130], moderate activities against *Streptococcus pneumoniae, Clostridium perfringens* and *Candida albicans,* and a weak antibacterial activity against *Mycobacterium smegmatis, Acinetobacter* 

*Aloe vera* (Family: *Liliaceae)*. *Aloe vera* has been used for medicinal purposes in several cultures for millennia: Greece, Egypt, India, Mexico, Japan and China [133]. 3500 years ago, Egyptians used this herb in treating burns, infections and parasites [134]. Its gel has the ability to heal different kinds of wounds including ulcers and burns by forming a protective coating on the

*lwoffii* and *Candida krusei* [131]. Yarrow also has a proven anti-inflammatory effect [132].

**5. Plants with beneficial effect on wound healing, approved by the** 

the lectins and polypeptides, as well as polyacetylenes.

are used for treatment of malaria fever and liver disorders [128].

**Committee on Herbal Medicinal Products (HMPC)**

Gram-positive bacteria [125].

agement through medicinal plants [38].

wound healing activity.

#### *4.1.3.2. Resins*

This group of plant-derived compounds presents a complex mixture of lipid-soluble chemicals [113]. These can be both non-volatile (e.g. diterpenoid and triterpenoid compounds) and volatile (mono- and sesquiterpenoids) [114]. Resins are most commonly found in nature as part of various wood-derived structures, although they are also present in herbaceous plants [115]. Among their common properties are a general stickiness, whereas their fluidity depends on the contents of volatile compounds [115]. When exposed to air they harden. Among their beneficial biological activities for wound healing are the antimicrobial activity, but their actions depend on the composition of the chemical mixture. Resins are generally safe, but contact allergy may occur [116].

The common structural precursor of terpenoids is the five-carbon building block isoprene [117]. Monoterpenoids are formed of two isoprene units, whereas sesquiterpenoids consist of three units. Both mentioned groups are commonly denoted as low-molecular-weight terpenoids, which are one of the most varied groups of plant products that include more than 25,000 compounds [118]. The phenylpropanoid group of terpenoids is less common and is based on a nine-carbon skeleton, whereas their synthesis pathway differs from the other terpenoids [119]. Compounds of all three mentioned groups have often strong odours and flavours, which is related to their properties (e.g. the lipophilicity and volatility) [120]. Since they exhibit various biological activities, they are found in several herbal remedies [121]. Of particular importance in relation to wound healing are their antibacterial and antiviral effects, whereas they possess also other activities like the antineoplastic activity, as well as stimulation gastrointestinal tract [118]. They are not toxic unless they are concentrated as volatile oils [122]. The plant family best known for these compounds is *Lamiaceae* (thyme family).
