**7.4. Flavonoids**

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

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

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, 211].

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 infected wounds is beneficial [212].

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

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 wound contraction and increased rate of epithelialization [215].

*Martynia annua* L. is a plant that has tannins, phenols, flavonoids, carbohydrates and antho‐ cyanins as its constituents [216]. A flavonoid rich fraction and luteolin isolated from *M. annua* was shown to improve wound healing in streptozotocin induced diabetic rats. The results showed that, percent wound contraction were significantly greater for the flavonoid rich fraction and luteolin‐treated groups. Presence of matured collagen fibers and fibroblast with better angiogenesis were observed histopathologically in these groups [213].
