**9. Other compounds used for treatment of photoaged skin**

Apart from use of antioxidants as the treatment strategy for photoaged skin, various other compounds are also used. Among these, Retinoids and alpha-hydroxy acids (AHA) hold a significant track record. Retinoids are Vitamin A derivatives that can be naturally occurring or synthetic. Dietary forms of Vitamin A, Retinol and retinyl esters undergo transformations by enzymes alcohol dehydrogenase and microsomal retinol dehydrogenase to yield Retinaldehyde. Retinaldehyde, in turn, is converted in to Retinoic acid by suitable retinaldehyde dehydrogenases. These retinoic acids show their effects via interacting with suitable intranuclear retinoic acid receptors (RARs) [111]. Among these, all-trans-retinoic acid (Tretinoin) serves as key retinoid for treatment of photoaged skin. However due to tendency of tretinoin to cause skin irritation, there has been a switch to more effective alternatives like Adapalene which is a synthetic retinoid [112]. Adapalene has been shown to be effective against photoaging, solar lentigines and actinic keratosis treatment. A recent study has compared the efficacy of Adapalene and Tretinoin for treatment of cutaneous photoaging. Through various experiments, it was established that Adapalene 0.3% was equally effective as Tretinoin 0.05% and thus could be employed as a future treatment for moderate photoaging [113].

While the first line approach for treatment mostly involves application of topical creams, the second line approach consists of use of chemical peels. This is where AHA play a crucial role. AHAs are a group of naturally available organic acids such as glycolic acid, lactic acid, critic acid, malic acid among others where hydroxyl groups (1 or more) are attached to alpha carbon atom that in turn is bonded to first carbon atom after acid group. AHAs are employed in peels for treatment of melasma, age spots, hyperpigmentation among others. But use of AHAs for treatment of skin photo damage is still controversial. Moreover, it has been reported that AHA function may depend on concentration as well as properties of the compound used [114]. A very recent study tested the efficacy of TCA- Lactic acid chemical peels for treatment of photoaging. It showed that the peels were able to inhibit tyrosinase, collagenase and elastase activity in in-vitro experiments. Further, an increased expression of COL1A, COL3B, elastin and fibronectin genes were shown to occur when peel solution was used for 3D human skin model [115]. Another study compared the efficacy of AHA-ReT cream (double conjugated retinoid cream) with 1% retinol cream and 0.025% Tretinoin cream for treatment of photoaging. Here, they found that AHA-ReT cream was more effective in reducing wrinkles, erythema and increasing hydration coupled with less irritation on application. Thus, such methods are expected to open new avenues in photo-damaged skin treatment [116].
