In vivo evaluation of piperine and synthetic analogues as potential treatments for vitiligo using a sparsely pigmented mouse model

Background Piperine and its analogues have been reported to stimulate melanocyte replication in vitro and may be useful in treating the depigmenting disease, vitiligo. Objective To investigate the ability of piperine (PIP) and three analogues to stimulate pigmentation in a strain of sparsely pigmented mice. Methods The test compounds were PIP [5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylpiperidine], tetrahydropiperine [THP, 5-(3,4-methylenedioxyphenyl)-pentanoylpiperidine], a cyclohexyl analogue of piperine [CHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylcyclohexylamine], and reduced CHP [rCHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentanoylcyclohexylamine]. Sparsely pigmented, HRA/Skh-II mice were randomized to receive topical treatment with test compounds or vehicle twice a day for five days a week, with or without ultraviolet (UV) irradiation on 3 days a week. Treatment was either continuous or interrupted to evaluate fading and repigmentation. Skin inflammation and pigmentation were evaluated regularly during treatment. DOPA+ melanocytes were determined histologically at the termination of treatment. Results Four weeks of treatment with one of the compounds PIP, THP or rCHP, but not CHP, induced greater pigmentation than vehicle with low levels of inflammation. Additional exposure to UVR led to darker pigmentation than did the compound or UVR alone, and greater numbers of DOPA+ melanocytes were found. The combination produced an even pigmentation pattern, contrasting with the speckled, perifollicular pattern produced by UVR alone. Treatment interruption led to a decrease in pigmentation but not its loss. Repigmentation was achieved by administering one of the compounds, UVR or both, and occurred faster than in naive mice. Conclusions Treatment with PIP, THP or rCHP and UVR induced a marked pigmentation response in HRA/Skh-II mice, with clinically better results than UVR alone. This result supports the potential use of these compounds in treating vitiligo