Piperlonguminine

About: Piperlonguminine is a research topic. Over the lifetime, 106 publications have been published within this topic receiving 3046 citations.

Piperlonguminine from Piper longum with inhibitory effects on alpha-melanocyte-stimulating hormone-induced melanogenesis in melanoma B16 cells.

Abstract: Skin hyperpigmentations such as melasma, freckles and senile lentigines can be subjectively treated by depigmenting agents. In our ongoing study to find melanogenesis inhibitors from natural sources, Piper longum L (fruits, Piperaceae) was discovered to have an inhibitory effect on alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis in melanoma B16 cells. Piperlonguminine has been identified as the melanogenesis inhibitor from P. longum by activity-guided extraction and isolation. The compound showed dose-dependent inhibitory effects with 85.1 +/- 4.9% inhibition at 25 microM, 62.1 +/- 6.1% at 12.5 microM, 36.4 +/- 4.6% at 6.3 microM and 18.4 +/- 5.1% at 3.1 microM on alpha-MSH-induced melanogenesis, showing an IC50 value of 9.6 microM. As a positive control, kojic acid exhibited an IC50 value of 44.6 microM on the melanogenesis. As to the mode of action, piperlonguminine showed an inhibitory effect on alpha-MSH-induced tyrosinase synthesis, documented by Western immunoblot analysis. However, piperlonguminine did not show an inhibitory effect on tyrosinase activity or a direct depigmenting effect of melanin.

Identification and characterization of stress degradation products of piperine and profiling of a black pepper (Piper nigrum L.) extract using LC/Q-TOF-dual ESI-MS

Abstract: A rapid, specific and reliable high-performance liquid chromatography combined with quadrupole time-of-flight dual electrospray ionization mass spectrometry (LC/Q-TOF-dual ESI-MS) method has been developed and validated for the identification and characterization of stressed degradation products of piperine. Piperine, an anti-hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH-specified conditions. The drug showed extensive degradation under oxidation and hydrolysis (acid and base) stress conditions. However, it was more stable under thermal stress than under acidic, alkaline, neutral and photolysis stress conditions. A total of four degradation products were observed and the chromatographic separation of the drug and its degradation products was achieved on a C18 column (4.6 × 50 mm, 5 μm). To characterize the degradation products, fragmentation patterns and accurate masses of the degradation products were established by subjecting them to LC-MS/Q-TOF analysis. Structure elucidation of the degradation products was achieved by comparing their fragmentation patterns with that of the drug, and confirmation was achieved through profiling a black pepper extract (Piper nigrum L.). The method identified dihydropiperine, piperylin, piperlonguminine, trans-piperine, cis-piperine, dihydropiperlonguminine, trans-piperettine and cis-piperettine. The liquid chromatography-mass spectroscopy method was validated with respect to its specificity, linearity, accuracy and precision.

Piperlongumine attenuates collagen-induced arthritis via expansion of myeloid-derived suppressor cells and inhibition of the activation of fibroblast-like synoviocytes

Abstract: Piperlonguminine (PL), a key compound from the Piper longum fruit, is known to exhibit anti‑tumor and anti‑inflammatory activities. However, little is known about its effects on collagen‑induced arthritis (CIA). Fibroblast‑like synoviocytes (FLS) have a pivotal role in the development of rheumatoid arthritis (RA). Myeloid‑derived suppressor cells (MDSCs) are able to suppress T cell responses and have important roles in the regulation of autoimmune arthritis. The current study investigated whether PL alters the progression of RA. It was determined that PL reduces the arthritis score and histopathologic lesions in a mouse model of CIA. PL also reduces the expression levels of serum anti‑collagen II antibodies (anti‑CⅡ), tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑23 and IL‑17 in CIA mice. In draining lymph nodes (DLNs), MDSCs were significantly expanded, however, the number of Th17 cells was markedly decreased by PL treatment. Additionally, PL reduced secretion of IL‑1β, IL‑23 and IL‑17 by TNF‑α‑stimulated human RA FLS. PL significantly inhibited the migration and invasion of TNF‑α‑stimulated human RA FLS. These results indicate that PL may be a candidate therapeutic agent for the treatment of RA, via the expansion of MDSCs and the inhibition of the Th17 response and activation of FLS.

In vitro acaricidal activity of Piper nigrum and Piper longum fruit extracts and their active components against Rhipicephalus (Boophilus) microplus ticks

Abstract: In vitro acaricidal activity of Piper nigrum and P longum fruit extracts and their active components (piperine for P nigrum and piperine and piperlonguminine for P longum) was evaluated against adults engorged females of Rhipicephalus (Boophilus) microplus using adult immersion test Three concentrations of each extract with four replications were used in the bioassay Extracts significantly affected mortality rates of ticks in dose-dependent manner ranged 125–958% for P nigrum and 292–875% for P longum, with an additional effect on the reproductive physiology of ticks by inhibiting oviposition (281–969% by P nigrum and 361–893% by P longum) However, the acaricidal and oviposition limiting properties were decreased significantly when the active component(s) of each extract was tested separately However, the combination of piperine and piperlonguminine (obtained from P longum extract) caused 792% mortality of ticks which is equivalent to the corresponding concentration (~ 5%) of the extract It can be concluded that the fruit extracts of P nigrum and P longum had both acaricidal and oviposition limiting actions against the adults of R (B) microplus which could make it a valuable component of developing sustainable strategy for integrated tick management

Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling.

Abstract: The natural products piperlongumine and piperine have been shown to inhibit cancer cell proliferation through elevation of reactive oxidative species (ROS) and eventually cell death, but only have modest cytotoxic potencies. A series of 14 novel phenylallylidenecyclohexenone analogues based on piperlongumine and piperine therefore were designed and synthesized, and their pharmacological properties were evaluated. Most of the compounds produced antiproliferative activities against five human cancer cells with IC50 values lower than those of piperlongumine and piperine. Among these, compound 9m exerted the most potent antiproliferative activity against drug-resistant Bel-7402/5-FU human liver cancer 5-FU resistant cells (IC50 = 0.8 μM), which was approximately 10-fold lower than piperlongumine (IC50 = 8.4 μM). Further, 9m showed considerably lower cytotoxicity against LO2 human normal liver epithelial cells compared to Bel-7402/5-FU. Mechanistically, compound 9m inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, reduced mitochondrial transmembrane potential (MTP), and induced autophagy in Bel-7402/5-FU cells via regulation of autophagy-related proteins LC3, p62, and beclin-1. Finally, 9m activated significantly the p38 signaling pathways and suppressed the Akt/mTOR signaling pathways. In conclusion, 9m could be a promising candidate for the treatment of drug-resistant cancer cells and, as such, warrants further investigation.