UV Irradiation Affects Melanocyte Stimulatory Activity and Protein Binding of Piperine

Abstract

Piperine, the major alkaloid of black pepper (Piper nigrum L.; Piperaceae), stimulates melanocyte proliferation and dendrite formation in vitro. This property renders it a potential treatment for the skin depigmentation disorder vitiligo. However, piperine does not stimulate melanin synthesis in vitro, and treatments based on this compound may therefore be more effective with concomitant exposure of the skin to ultraviolet (UV) radiation or sunlight. The present study investigated the effect of UVA and simulated solar radiation (SSR) on the chemical stability of piperine, its melanocyte stimulatory effects and its ability to bind protein and DNA. Chromatographic and spectroscopic analysis confirmed the anticipated photoisomerization of irradiated piperine and showed the absence of any hydrolysis to piperinic acid. Isomerization resulted in the loss of ability to stimulate proliferation of a mouse melanocyte cell line, and to bind to human serum albumin. There was no evidence of DNA binding by piperine either before or after irradiation, showing the absence of photoadduct formation by either piperine or its geometric isomers. This is unlike the situation with psoralens, which form DNA adducts when administered with UVA in treating skin diseases. The present study suggests that exposure to bright sunlight should be avoided both during active application of piperine to the skin and in the storage of piperine products. If UVA radiation is used with piperine in the treatment of vitiligo, application of the compound and irradiation should be staggered to minimize photoisomerization. This approach is shown to effectively induce pigmentation in a sparsely pigmented mouse strain.

Amides fromPiper nigrumL. with dissimilar effects on melanocyte proliferation in-vitro

“…Compound 10 was also inactive. Novel results reported here on compounds 2-5 and 7, and those from earlier studies on other compounds (Lin et al 1999b;Venkatasamy et al 2004, Soumyanath et al 2006 allow some structure-activity relationships to be proposed. The main features of the piperine molecule are a methylenedioxyphenyl group, a piperidine amide function and a linking chain consisting of a trans-conjugated diene moiety.…”

“…Piperine appears to work in-vitro by stimulation of protein kinase C (Lin et al 1999b). The ability of piperine to stimulate pigmentation in-vivo has recently been reported (Soumyanath et al 2006), validating the in-vitro melanocyte proliferation screen (Lin et al 1999a, b).…”

“…After initial positive results in this line (Lin et al 1999b), we found that piperine also stimulates the replication of human melanoblasts (Lin et al 1998). Our initial studies (Lin et al 1999b) demonstrated the ability of a hot-water extract of P. nigrum fruit and piperine to stimulate melanocyte proliferation in-vitro, and of piperine to stimulate pigmentation in-vivo (Soumyanath et al 2006). Sequential Soxhlet extraction of P. nigrum fruit with solvents of increasing polarity (hexane, chloroform, methanol and water) yielded extracts containing 25.3, 36.8, 32.5 and 0.6% w/w piperine, respectively, as determined by HPLC.…”

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

“…Test agents were dissolved in vehicle (either OA ⁄PEG or in DMSO) to a final concentration of 175 mmol L )1 and 100 lL (17AE5 lmoles) applied with a micropipette on the central area of mouse dorsal skin (2-3 cm 2 ), twice a day (weekdays only) with an interval of 5-6 h between applications. In protocols with UVR exposure, the irradiations were carried out every Monday, Wednesday and Friday immediately prior to the first daily application, to avoid a possible photosensitizing effect and ⁄or photodamage 17 to the test compound.…”

Monitoring human melanocytic cell responses to piperine using multispectral imaging

“…3 Piperine, the main component of the spice black pepper, has been shown to stimulate the proliferation of mouse melanocytes in vitro, [4][5][6] and in a sparsely pigmented mouse model in vivo. 7,8 In this study we assessed the ability of piperine to stimulate human melanocyte proliferation in vitro to establish the potential of piperine to serve as a repigmentary agent for the treatment of GV in humans. …”