**8. Fats and oils with wound healing properties**

Several unsaturated fatty acids such as oleic, linoleic, eicosapentanoic and arachidonic acids are among the natural ligands for perosisome proliferative activator receptors (PPAR) which are involved in wound healing. These PPAR are nuclear hormone receptors and are up regulated in keratinocytes after injury and have been found to be important regulators of re‐ epithelialization [217, 218]. Also ω‐3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect the synthesis and activity of proinflammatory cytokines which to a large extent initiate the inflammatory stage of wound healing [219, 220]. It can therefore be said that the presence of these fatty acids in plant extracts and other compounds could contribute to the survival and differentiation of keratinocytes through the activation of PPAR. Also they may promote the recovery of the epidermal barrier, skin homeostasis and anti‐inflammatory activity to the skin during the wound healing process.

### **8.1. Eucalyptus oil (Dinkum oil)**

Procyanidin C1 inhibits nitric oxide production and the release of pro-inflammatory cytokines (IL-6 and TNF-α). Additionally, the potent anti-inflammatory effect of procyanidin C1 occurs through inhibition of mitogen-activated protein kinase and NF-κB signaling pathways. These two factors play a major role in controlling inflammation in the wounds [206]. In wound healing, procyanidin C1 activity presents a novel and effective means of inflammation control. Procyanidin dimers and trimers extracted from grape seeds are also known to exhibit higher

Flavonoids are a chemically defined group of polyphenols that have a basic structure of two aromatic rings (A and B) linked through three carbons that usually form an oxygenated heterocycle (C ring). The chemical characteristics of the C ring define the various subgroups of flavonoids by providing different arrangements of hydroxy, methoxy, and glycosidic

An important effect of flavonoids is the scavenging of oxygen-derived free radicals, reduction of liquid peroxidation, anti-inflammatory and wound healing activities. A drug that inhibits lipid peroxidation is believed to increase the viability and strength of collagen fibers and prevents cell damage by promoting DNA synthesis Flavonoids prevent or delay the onset of

Several flavonoids, including quercetin, result in a reduction in ischemia-reperfusion injury through the activity of constitutive nitric-oxide synthase which is important in maintaining the dilation of blood vessels [209]. Quercetin, in particular, inhibits both cyclooxygenase and lipoxygenase activities, thus diminishing the formation of their inflammatory metabolites [210,

Certain flavonoids, notably diosmin and hesperidin, have been used routinely in Europe for many years to treat varicose veins, hemorrhoids, and the edema that accompanies chronic venous insufficiency. These flavonoids have now been employed in the treatment of wounds. Purified micronized flavonoid fraction, comprising 90% diosmin and 10% hesperidin, is basically used as a phelebotonic and vasculoprotector agent. It also has anti-inflammatory and anti-edematous actions. In a clinical study, groups with infected wounds that were orally and topically treatment, accelerated wound healing when compared to the untreated control group. This was confirmed with surface area measurements and histopathological evaluation. This study showed that oral or topical administration of micronized flavonoid fraction in

A flavonoid rich fraction of *Martynia annua* L. has also been shown to induce mature collagen fibers and promote fibroblasts with improved angiogenesis in an *in vivo* model [213]. Isovitexin and vitexin are the major flavonoid constituents of *Jatropha multifida* L. which is used commonly

Flavonoids from *Vernonia arborea* and *Pentas lanceolata* have been reported to promote wound healing by their astringent and antimicrobial properties, which seems to be responsible for

growth-promoting activity than the monomer on hair epithelial cells *in vivo* [207].

groups, and the bonding with other monomers [208].

510 Wound Healing - New insights into Ancient Challenges

cell necrosis and also improve vascularity to the wounded area [179].

**7.4. Flavonoids**

211].

infected wounds is beneficial [212].

for the treatment of infected wounds and skin [214].

wound contraction and increased rate of epithelialization [215].

This oil is obtained by steam distillation of fresh leaves of *Eucalyptus globules* which belongs to the family Myrtaceae. It is indigenous to Australia and Tasmania. It is cultivated in United States, Spain, Portugal and India. It contains eucalyptol, pinene, camphene, phellandrene, citronellal and geranyl acetates. In skin care, it is used to treat burns, blisters, herpes, cuts, wounds, skin infections and insect bites [221].
