Piperlonguminine

Pigment Cell Res. 2006 Feb;19(1):90-8.

Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression.[Pubmed: 16420250 ]

Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be improved by treatment with depigmenting agents.
METHODS AND RESULTS:
In the present study, Piperlonguminine from Piper longum was discovered to inhibit melanin production in melanoma B16 cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH), 3-isobutyl-1-methylxanthine or protoporphyrin IX, where the compound exhibited stronger depigmenting efficacy than kojic acid. However, Piperlonguminine did not affect 1-oleoyl-2-acetyl-sn-glycerol-induced melanogenesis and did not affect protein kinase C-mediated melanin production. Surprisingly, Piperlonguminine did not inhibit the catalytic activity of cell-free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA expression. This effect was attributed to the inhibitory action of Piperlonguminine on alpha-MSH-induced signaling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia-associated transcription factor, a key activator of the tyrosinase promoter.
CONCLUSIONS:
This study demonstrates that Piperlonguminine is an efficient depigmenting agent with a novel mechanism of action.

Acta Trop. 2013 Mar;125(3):349-56.

The natural compounds piperovatine and piperlonguminine induce autophagic cell death on Trypanosoma cruzi.[Pubmed: 23228524 ]

The currently available treatments for Chagas disease show limited therapeutic potential and are associated with serious side effects. Our group has been attempting to find alternative drugs isolated from natural products as a potential source of pharmacological agents against Trypanosoma cruzi.
METHODS AND RESULTS:
Here, we demonstrate the antitrypanosomal activity of the amides piperovatine and Piperlonguminine isolated from Piper ovatum against epimastigotes and intracellular amastigotes. We also investigated the mechanisms of action of these compounds on extracellular amastigote and epimastigote forms of T. cruzi. These amides showed low toxicity to LLCMK(2) mammalian cells. By using transmission and scanning electron microscopy, we observed that the compounds caused severe alterations in T. cruzi. These alterations were mainly located in plasma membrane and mitochondria. Furthermore, the study of treated parasites labeled with Rh123, PI and MDC corroborate with our TEM data. These mitochondrial dysfunctions induced by the amides might trigger biochemical alterations that lead to cell death.
CONCLUSIONS:
Altogether, our data evidence a possible autophagic process.

Journal of Applied Toxicology, 2008, 28(5):599-607.

In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species.[Pubmed: 17975786]

Many authors have already emphasized that phytochemicals from spices have biological applications. Piperlonguminine is a known alkaloid amide from peppers, including Piper divaricatum. The aim of this study was to investigate the in vitro and in vivo antitumor effects of Piperlonguminine in experimental models. In order to evaluate the toxicological aspects related to Piperlonguminine treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed.
METHODS AND RESULTS:
Piperlonguminine did not show any significant in vitro cytotoxic effect at experimental exposure levels, but showed an in vivo antitumor effect. After 7 days of treatment, the inhibition rates were 38.71% and 40.68% at doses of 25 mg kg(-1) and 50 mg kg(-1), respectively. The histopathological analysis suggests that the liver and kidney were only weakly affected by Piperlonguminine treatment. Neither the enzymatic activity of transaminases (AST and ALT) nor the urea levels were significantly altered. In the hematological analysis, all parameters analysed remained constant after Piperlonguminine treatment.
CONCLUSIONS:
In conclusion, these data reinforce the anticancer potential of spice components.

Food Science, 2014.

Preventive Effects of Piperlonguminine on Alcoholic Fatty Liver Disease in Mice.[Reference: WebLink]

This study aimed to investigate the preventive and therapeutic effects of Piperlonguminine(GBN) on alcoholic fatty liver disease(AFLD) in mice.
METHODS AND RESULTS:
Adult male Kunming mice were randomly divided into four groups: normal control, model, GBN low dose and high dose groups. The mice in normal control group were fed with a normal diet, and those in the other groups were fed with high-fat diet, and, at the same time, administered with alcohol daily at a level of 0.8 mL/30 g bw. The mice in GBN low and high dose groups were intragastrically administered with 0.8 mL/30 g bw of GBN at doses of 10 and 40 mg/(kg·d), respectively, and the normal control and model groups were given equal volume of distilled water, continuously for 6 weeks. After 12 h of fasting following the last administration, all the mice were sacrificed for the measurement of liver index, aspartate transaminase(AST), alanine transaminase(ALT), total cholesterol(TC) and triglyceride(TG) levels in serum and the pathological histological observation of liver tissue. Compared with the model group, the low and high dose groups significantly decreased liver index to(4.42 ± 0.50)% and(4.53 ± 0.44)%, respectively. Also, the levels of AST, ALT, TC and TG in serum were significantly decreased(P 0.01). And pathological histology showed that GBN obviously improved hepatocyte fatty degeneration of alcoholic fatty liver in mice.
CONCLUSIONS:
In conclusion, GBN can effectively prevent the occurrence and development of alcoholic fatty liver.