Dehydropipernonaline

Amide alkaloids characterization and neuroprotective properties of Piper nigrum L.: A comparative study with fruits, pericarp, stalks and leaves.[Pubmed:34474242]

Food Chem. 2022 Jan 30;368:130832.

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, Dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.

Chemical profile, traditional uses, and biological activities of Piper chaba Hunter: A review.[Pubmed:32283191]

J Ethnopharmacol. 2020 Jul 15;257:112853.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper chaba Hunter, called Chui Jhal or Choi Jhal, is commonly used as a culinary (spice) herb in India and Bangladesh. It exhibits numerous important biological activities and has been widely used in traditional medicine. AIM OF THE STUDY: This review focuses on the chemical and pharmacological activities of a culinary ingredient P. chaba based on information extracted from the literature to highlight its use in traditional medicine. METHODS: A literature search in known databases was conducted (till September 2019) for published articles using the relevant keywords. RESULTS: Findings suggest that, to date, a number of important phytoconstituents such as dimeric alkaloids, and alkamides have been isolated from various parts of P. chaba. Extracts from P. chaba or derived compounds exhibit diverse biological activities, such as anti-microbial, anti-leishmanial, anti-malarial, anti-parasitic, cytotoxic/anticancer, adipogenic, hepato- and gastro-protective, anti-diabetic, analgesic, anti-diarrheal, depressive, anti-inflammatory, diuretic, anti-hypertensive, antipyretic, anti-ulcer, and immunomodulatory effect. Among the isolated compounds, chabamides, piperine, piplartine, retrofractamides A/B, methylenedioxyphenyl)-nona-2E,4E,8E-trienoic acid, n-butyl or n-pentyl amine, piperlonguminine, pipernonaline, Dehydropipernonaline, N-isobutyl-(2E,4E)-octadecadienamide, and N-isobutyl-(2E,4E,14Z)-eicosatrienamide have documented important biological effects in various test systems. CONCLUSIONS: Taken together, P. chaba may be a potential source of plant-based therapeutic lead compounds, which justify its uses in traditional medicine.

Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.[Pubmed:28185326]

Phytother Res. 2017 Apr;31(4):663-670.

In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), Dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC(50) values of 6.8, 14.5, 30.2, 23.7, and 38.5 muM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC(50) value of 9.5 muM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and gamma-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright (c) 2017 John Wiley & Sons, Ltd.

Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase.[Pubmed:21741367]

Biochem Biophys Res Commun. 2011 Jul 22;411(1):219-25.

The fruits of Piper retrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and Dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor delta (PPARdelta) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARdelta protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300mg/kg/day for 8weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPARdelta, and regulate lipid metabolism, suggesting their potential anti-obesity effects.

[Alkaloids and lignans from stems of Piper betle].[Pubmed:21137339]

Zhongguo Zhong Yao Za Zhi. 2010 Sep;35(17):2285-8.

Alkaloids and lignans from the stems of Piper betle were studied. Compounds were isolated and purified by repeated silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography and preparative thin layer chromatography. The structures were elucidated on the basis of spectral analysis. From the ethyl acetate soluble fractions of the 70% acetone extract, ten compounds were isolated and identified as piperine (1), pellitorine (2), N-isobutyl-2E,4E-dodecadienamide (3), Dehydropipernonaline (4), piperdardine (5), piperolein-B (6), guineensine (7), (2E,4E)-N-isobutyl-7-(3',4'-methylenedioxyphenyl)-2,4-heptadienamide (8), syringaresinol-O-beta-D-glucopyranoside (9),pinoresinol (10). All Compounds were isolated from the plant for the first time, and compounds 9 and 10 were isolated firstly from the genus.

Activation of TRPV1 and TRPA1 by black pepper components.[Pubmed:20460725]

Biosci Biotechnol Biochem. 2010;74(5):1068-72.

We searched in this study for novel agonists of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in pepper, focusing attention on 19 compounds contained in black pepper. Almost all the compounds in HEK cells heterogeneously expressed TRPV1 or TRPA1, increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a concentration-dependent manner. Among these, piperine, isopiperine, isochavicine, piperanine, pipernonaline, Dehydropipernonaline, retrofractamide C, piperolein A, and piperolein B relatively strongly activated TRPV1. The EC(50) values of these compounds for TRPV1 were 0.6-128 microM. Piperine, isopiperine, isochavicine, piperanine, piperolein A, piperolein B, and N-isobutyl-(2E,4E)-tetradeca-2,4-diamide also relatively strongly activated TRPA1, the EC(50) values of these compounds for TRPA1 were 7.8-148 microM. The Ca(2+) responses of these compounds for TRPV1 and TRPA1 were significantly suppressed by co-applying each antagonist. We identified in this study new transient receptor potential (TRP) agonists present in black pepper and found that piperine, isopiperine, isochavicine, piperanine, piperolein A, and piperolein B activated both TRPV1 and TRPA1.

Alkamides from the fruits of Piper longum and Piper nigrum displaying potent cell adhesion inhibition.[Pubmed:18672369]

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4544-6.

Eight alkamides 1-8 were isolated by bioassay-guided isolation of EtOH extracts of the fruits of Piper longum and Piper nigum (Piperaceae). Their structures were elucidated by spectroscopic analysis ((1)H, (13)C NMR, and ESI-MS) as follows: guineensine (1), retrofracamide C (2), (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (3), pipernonaline (4), piperrolein B (5), piperchabamide D (6), pellitorin (7), and Dehydropipernonaline (8). Their compounds 3-5, 7, and 8 inhibited potently the direct binding between sICAM-1 and LFA-1 of THP-1 cells in a dose-dependent manner, with IC(50) values of 10.7, 8.8, 13.4, 13.5, and 6.0 microg/mL, respectively.

Inhibition of diacylglycerol acyltransferase by alkamides isolated from the fruits of Piper longum and Piper nigrum.[Pubmed:17177498]

J Agric Food Chem. 2006 Dec 27;54(26):9759-63.

Pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) has emerged as a potential therapy for the treatment of obesity and type 2 diabetes. Bioassay-guided isolation of CHCl3 extracts of the fruits of Piper longum and Piper nigum (Piperaceae), using an in vitro DGAT inhibitory assay, lead to isolation of a new alkamide named (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (2), together with four known alkamides: retrofractamide C (1), pipernonaline (3), piperrolein B (4), and Dehydropipernonaline (5). Compounds 2-5 inhibited DGAT with IC50 values of 29.8 (2), 37.2 (3), 20.1 (4), and 21.2 (5) microM, respectively, but the IC50 value for 1 was more than 900 microM. This finding indicates that compounds possessing piperidine groups (2-5) can be potential DGAT inhibitors.

New amides and gastroprotective constituents from the fruit of Piper chaba.[Pubmed:14994194]

Planta Med. 2004 Feb;70(2):152-9.

The 80 % aqueous acetone extract from the fruit of Piper chaba was found to show protective effects on ethanol- and indomethacin-induced gastric lesions in rats. From the aqueous acetone extract, four new amides named piperchabamides A ( 1), B ( 2), C ( 3), and D ( 4) were isolated, and their structures were determined on the basis of chemical and physicochemical evidence. In addition, the gastroprotective effects of the principal constituents, piperine ( 5), piperanine ( 6), pipernonaline ( 7), Dehydropipernonaline ( 8), piperlonguminine ( 9), retrofractamide B ( 10), guineensine ( 11), N-isobutyl-(2 E,4 E)-octadecadienamide ( 12), N-isobutyl-(2 E,4 E,14 Z)-eicosatrienamide ( 13), and methyl piperate ( 14), were examined. As a result, compounds 5 - 10 and 12 - 14 significantly inhibited ethanol-induced gastric lesions at a dose of 25 mg/kg, p. o., while 5, 7, 8, 10, 12, and 13 also significantly inhibited indomethacin-induced gastric lesions at the same dose.

Dehydropipernonaline, an amide possessing coronary vasodilating activity, isolated from Piper longum L.[Pubmed:3559927]

J Pharm Sci. 1986 Dec;75(12):1188-9.

An amide (Dehydropipernonaline) that has coronary vasorelaxant activity was isolated from the fruit of Piper longum L. This substance was characterized on the basis of spectroscopic data.