Lin Z, et al. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro. Journal of Pharmacy and Pharmacology. 2007;59(4):529-536.

ABSTRACT

Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in‐vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N‐feruloyltyramine (4) and N‐isobutyl‐2E, 4E‐dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1‐(3, 4‐methylenedioxyphenyl)‐decane (10). Compounds 6–10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease. http://onlinelibrary.wiley.com/doi/10.1211/jpp.59.4.0007/abstract

Jung SK, et al. Piper nigrum fruit extract prevents TMA-induced allergic contact dermatitis by regulating Th2 cytokine production. Journal of Agricultural Science. 2015;7(2).

ABSTRACT

Allergic contact dermatitis (ACD) remains a leading skin disease in many countries. In this study, we investigated the preventive effect of Piper nigrum fruit extract (PFE) on trimellitic anhydride (TMA)-induced dermatitis and its potential mechanism of action. Oral administration of PFE and prednisolone (PS) significantly suppressed TMA-induced increases in ear, epidermal thickness, and infiltration of CD4 + cells, while abnormal expression of IgE, mMCP-1, IL-1β and IL-1β mRNA was also significantly counteracted by oral administration of PFE. PFE also significantly suppresses TMA-induced IL-4 and IL-5 production and IL-4 mRNA expression in vivo, as well as OVA-induced IL-4, IL-5, and IL-13 production and GATA3 mRNA expression ex vivo, and IL-4 induced STAT6 phosphorylation in primary cultured splenocytes and HaCaT cells. Interestingly, the PFE component piperine significantly suppressed OVA-induced IL-4, IL-5, and IL-13 secretion ex vivo. Taken together, these results suggest that PFE could be useful in suppressing allergic contact dermatitis.

Piper nigrum Fruit Extract Prevents… (PDF Download Available). Available from: https://www.researchgate.net/publication/276235575_Piper_nigrum_Fruit_Extract_Prevents_TMA-Induced_Allergic_Contact_Dermatitis_by_Regulating_Th2_Cytokine_Production

Choochana P, et al. Development of piperic acid derivatives from Piper nigrum as UV protection agents. Pharm Biol. 2015;53(4):477-82.

ABSTRACT

CONTEXT: There is a need for the discovery of novel natural and semi-synthetic sunscreen that is safe and effective. Piperine has a UV absorption band of 230-400 nm with high molar absorptivity. This compound has a high potential to be developed to sunscreen.

OBJECTIVE: This study develops new UV protection compounds from piperine by using chemical synthesis.

MATERIALS AND METHODS: Piperine was isolated from Piper nigrum L. (Piperaceae) fruits, converted to piperic acid by alkaline hydrolysis, and prepared as ester derivatives by chemical synthesis. The piperate derivatives were prepared as 5% o/w emulsion, and the SPF values were evaluated. The best compound was submitted to cytotoxicity test using MTT assay.

RESULTS: Piperic acid was prepared in 86.96% yield. Next, piperic acid was reacted with alcohols using Steglich reaction to obtain methyl piperate, ethyl piperate, propyl piperate, isopropyl piperate, and isobutyl piperate in 62.39-92.79% yield. All compounds were prepared as 5% oil in water emulsion and measured its SPF and UVA/UVB values using an SPF-290S analyzer. The SPF values (n = 6) of the piperate derivatives were 2.68 ± 0.17, 8.89 ± 0.46, 6.86 ± 0.91, 16.37 ± 1.8, and 9.68 ± 1.71. The UVA/UVB ratios of all compounds ranged from 0.860 to 0.967. Cytotoxicity of isopropyl piperate was evaluated using human skin fibroblast cells and the IC50 was equal to 120.2 μM.

DISCUSSION AND CONCLUSION: From the results, isopropyl piperate is an outstanding compound that can be developed into a UV protection agent. https://www.ncbi.nlm.nih.gov/pubmed/25471519