Showing papers on "Piperlonguminine published in 2020"

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.

Evaluation of anti-nociceptive and anti-inflammatory activities of Piper sylvaticum (Roxb.) stem by experimental and computational approaches

Abstract: Piper sylvaticum Roxb., (Family: Piperaceae), commonly known as pahaari peepal, is used in traditional medicine for the treatment of rheumatic pain, headache, asthma, chronic cough, diarrhea, and wounds. To provide scientific proof for its traditional use, the present study was designed to investigate the antinociceptive and anti-inflammatory properties of methanol extract of P. sylvaticum stem (MEPSS) in pain models. Additionally, computational studies viz. molecular docking, ADME and toxicological property predictions were performed to identify the potent phytochemicals of this plant for antinociceptive and anti-inflammatory activities with good oral bioavailability and safety features. Quantitative phytochemical analysis of MEPSS was performed using established protocols. The antinociceptive activity was determined using acetic acid and formalin test in mice at the doses of 200 and 400 mg/kg while paw edema induced by carrageenan used for anti-inflammatory activity. Molecular docking study was performed by Schrodinger Maestro 10.1 whereas the SwissADME and admetSAR were used for ADME and toxicity prediction respectively. The total phenolic and flavonoid contents of MEPSS were 93.39 and 53.74 mg gallic acid and quercetin equivalent/g of extract respectively. The methanol extract exhibited significant and dose-dependent antinociceptive and anti-inflammatory effects in experimental pain models. Also, our docking study showed that piperine, piperlonguminine, and sylvamide have the best binding affinities to cyclooxygenase enzymes with good ADME/T properties. This study confirmed that MEPSS possess significant antinociceptive and anti-inflammatory activities which could be due to the presence of phytochemicals and three bioactive compounds (piperine, piperlonguminine, and sylvamide) were found to be most effective in computational studies.

A bioinformatics-based investigation to screen and analyze the bioactivity of Piper longum Linn. compounds as a ground-breaking hostile to antidiabetic activity

Abstract: As of today, the utilization of herbal medicines has taken up the pace in treating diseases. This is due to the fact that they have lower risk of adverse reactions. Numerous plants are being used traditionally to treat various dreadful diseases including diabetes. Piper longum is one of the major and important medicinal plants in various systems of medicine, including the Ayurvedic system of medicine. Among the major bioactive compounds found in this plant, few compounds, viz., piperine, piperlongumine, piperlonguminine, and retrofractamide A, have been selected for studying the effectiveness on antidiabetic activity. An in silico approach was utilized to observe the major phytochemical properties and interaction studies of the constituents of P. longum, and finally, a pharmacophore investigation was carried out. In this study, we have observed the interaction of the four bioactive compounds taken from P. longum with the receptors via molecular docking technique. The binding of the ligands firmly with the receptors confirmed the fact that piperine, piperlongumine, piperlonguminine, and retrofractamide A act as inhibitors for dipeptidyl peptidase-4, GKRP, 11β-hydroxysteroid dehydrogenase type 1, glutamine-fructose-6-phosphate transaminase 1, and protein tyrosine phosphatase 1B, which encourage the glucose digestion and increment insulin affectability. The information acquired from this investigation might be taken further for in vitro examinations, which may, in the long run, be useful in recognizable proof of novel and successful particles. The outcomes acquired from this examination might provide strong understanding in the utility of phytochemicals against diabetes.