lignans and piperine

A fluorometric imaging plate reader (FLIPR) assay utilizing Chinese hamster ovary (CHO) cells stably transfected with GABA

Topics: Alkaloids; Animals; Benzodioxoles; Biological Assay; Biphenyl Compounds; CHO Cells; Chromatography, High Pressure Liquid; Cricetulus; Fluorometry; Indenes; Lignans; Magnolia; Oocytes; Piper nigrum; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Receptors, GABA-A; Sesquiterpenes; Valerian; Xenopus laevis

The phytochemical profile of Macropiper excelsum (G.Forst.) Miq. subsp. excelsum (Piperaceae), a shrub which is widespread in New Zealand, was investigated by LC-MS-guided isolation and characterization via HR-ESI-TOF-MS and NMR spectroscopy. The isolated compounds were sensorily evaluated to identify their contribution to the overall taste of the crude extract with sweet, bitter, herbal and trigeminal impressions. Besides the known non-volatile Macropiper compounds, the lignans (+)-diayangambin and (+)-excelsin, four further excelsin isomers, (+)-diasesartemin, (+)-sesartemin, (+)-episesartemin A and B were newly characterized. Moreover, piperine and a number of piperine analogues as well as trans-pellitorine and two homologues, kalecide and (2E,4E)-tetradecadienoic acid N-isobutyl amide were identified in M. excelsum, some of them for the first time. Methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate was identified and characterized for the first time in nature. Sensory analysis of the pure amides indicated that they contributed to the known chemesthetic effects of Macropiper leaves and fruits. Since the pungent piperine has been shown to affect glucose and fatty acid metabolism in vivo in previous studies, piperine itself and four of the isolated compounds, piperdardine, chingchengenamide A, dihydropiperlonguminine, and methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate, were investigated regarding their effects on glucose and fatty acid uptake by enterocyte-like Caco-2 cells, in concentrations ranging from 0.1 to 100 μM. Piperdardine showed the most pronounced effect, with glucose uptake increased by 83 ± 18% at 100 μM compared to non-treated control cells. An amide group seems to be advantageous for glucose uptake stimulation, but not necessarily for fatty acid uptake-stimulating effects of piperine-related compounds.

Topics: Alkaloids; Benzodioxoles; Caco-2 Cells; Fatty Acids, Unsaturated; Fruit; Humans; Intestines; Lignans; New Zealand; Piperidines; Polyunsaturated Alkamides

Phyllanthin, a sparingly water-soluble hepatoprotective lignin obtained from Phyllanthus amarus Schum. et Thonn. (Euphorbiaceae) possesses low bioavailability. Phyllanthin along with piperine (a nutraceutical bioenhancer) was formulated as a mixed micellar lipid formulation (MMLF) in the present study and investigated to resolve the low bioavailability and enhance hepatoprotective effects on oral administration. Hepatoprotective, antioxidant and bioavailability studies of MMLF, a complex phosphatidylcholine formulation of phyllanthin (CP-PC), phyllanthin + piperine (CP-P-PC) and its corresponding non-formulated phyllanthin have been carried out. Phyllanthin (30 mg kg(-1) p.o.), CP-PC (30 mg kg(-1) p.o.), CP-P-PC (30 mg kg(-1) p.o.) and the reference drug silymarin (100 mg kg(-1), p.o.) were administered daily to rats for 10 days, followed by liver damage by administering a 1 : 1 (v/v) mixture of CCl4 and olive oil (1 ml kg(-1), i.p.) for 7 days from day 4 to day 10. The degree of protection was evaluated by determining the level of marker enzymes (SGOT and SGPT), bilirubin (TB) and total proteins (TP). Further, the effects of MMLF on lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were estimated in liver homogenates to evaluate the antioxidant activity. Finally the concentration of phyllanthin was evaluated in plasma. EC50 values for the in vitro antioxidant assay with DPPH were found to be 19.99, 15.94 and 13.5 for phyllanthin, CP-PC and CP-P-PC, respectively. CP-P-PC (30 mg kg(-1) p.o.) showed significant (p < 0.05) hepatoprotective effect by reducing the levels of serum marker enzymes (SGOT, SGPT, and TB), whereas, elevated the levels of depleted total protein (TP), lipid peroxidation and antioxidant marker enzyme activities such as, GSH, SOD, CAT, GPX, and GR. The complex MMLF normalized adverse conditions of rat livers more efficiently than the non-formulated phyllanthin. The present findings indicate that the MMLF is helpful in solving the problem of low bioavailability of phyllanthin.

Topics: Administration, Oral; Alkaloids; Animals; Antioxidants; Benzodioxoles; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chemistry, Pharmaceutical; Cytochrome P-450 Enzyme Inhibitors; Glutathione; Glutathione Peroxidase; Lignans; Lipid Peroxidation; Lipids; Liver; Male; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Protective Agents; Rats; Rats, Wistar; Silymarin

It has been reported that piperine (PIP) and deoxyschizandrin (DS) can modulate synchronized Ca²⁺ oscillations in cultured hippocampal neuronal networks. We investigated the modulation effects of four different combinations of piperine and deoxyschizandrin on synchronized Ca²⁺ oscillations in cultured hippocampal neuronal networks. The results showed that all four combinations (PIP:DS 4.9:1.9, 2.45:2.85, 7.35:0.95, and 2.45:0.95 mg/L) inhibit Ca²⁺ oscillation intensity to a similar extent. However, the first three combinations had strong inhibitory effects on the frequency of Ca²⁺ oscillations whereas the last combination (2.45:0.95 mg/L) only slightly enhanced the frequency of Ca²⁺ oscillations. We propose an improved Chay's model to explain the mechanism of the effects of piperine and deoxyschizandrin on synchronized Ca²⁺ oscillations in cultured hippocampal neuronal cells. We concluded that deoxyschizandrin modulated synchronized Ca²⁺ oscillations in cultured hippocampal neuronal networks bidirectionally and the effect depended on concentration. Deoxyschizandrin reduced voltage-gated sodium channel conductance and ATP-sensitive potassium channel conductance, and affected the rate of exchange of intracellular calcium and the pump activity of Ca²⁺-ATPase in the endoplasmic reticulum (ER). Piperine reduced the activity of calcium release in the ER, and reduced the pump activity of calcium in the cytomembrane or enhanced the pump activity of Ca²⁺-ATPase in the ER.

Topics: Alkaloids; Animals; Benzodioxoles; Calcium Channels; Calcium Signaling; Cells, Cultured; Cyclooctanes; Drug Synergism; Hippocampus; Lignans; Models, Biological; Neurons; Piperidines; Polycyclic Compounds; Polyunsaturated Alkamides; Rats

The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step of OTA production and inhibited production of citrinin. Curcumin, a constituent of tumeric, completely inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1% (w/v), showing its effect was on chloroperoxidase and polyketide synthase activity. The potential advantage of these natural products to reduce ochratoxin contamination of agricultural commodities is discussed.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Antioxidants; Aspergillus; Benzodioxoles; Carcinogens; Citrinin; Culture Media; Curcuma; Curcumin; Dioxolanes; Dioxoles; Food Contamination; Lignans; Mycelium; Mycotoxins; Ochratoxins; Piper; Piperidines; Polyunsaturated Alkamides; Sesame Oil