Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro

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.

Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats

“…Previous studies have revealed that compounds isolated from plants of the genus Piper had potent anticancer properties (13,(21)(22)(23)(24). The results of the present study illustrated that the PFPE had anticancer and cancer preventive effects on mammary tumorigenesis in rats.…”

“…The pepper alkaloids are also present in the dried fruits of P. nigrum, piperine, and piplartine and have exhibited cytotoxic effects on HL-60, CEM, HCT-8, and B-16 cell lines (23). In addition, P. nigrum and its derivative extracts have been reported to inhibit tumor growth in vitro and in vivo (13,16,24). While screening for cytotoxic effects of plants of the genus Piper in our previous study, we found that the recrystallized extract of P. nigrum that was piperine free had a potent cytotoxic activity on breast cancer cell lines.…”

Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxygen Species and Has Therapeutic Potential for Rheumatoid Arthritis

“…Extracts of P. longum have been demonstrated to exert various properties, such as immunomodulatory effects, as well as hepatoprotective and antiasthmatic activity (20). It has been reported that PLM inhibits platelet aggregation (21), atherosclerosis plaque formation (22), and tumor cell growth (23,24). Interestingly, a recent report indicates that PLM can selectively kill tumor cells through increasing ROS levels (25).…”

Rapid validated HPTLC method for estimation of piperine and piperlongumine in root of Piper longum extract and its commercial formulation

“…It also possesses radioprotective effects (Aggarwal & Kaul, 1992). Piperlongumine (2) is reported for killing of cancer cells by a small molecule targeting the stress response to ROS (Raj et al, 2011), antiplatelet (Lee et al, 2010), melanocyte stimulatory activity (Lin et al, 2007). It also acts as an antiaflatoxin agent (Lee et al, 2002).…”