N-Alkylamides from Piper longum L. and their stimulative effects on the melanin content and tyrosinase activity in B16 melanoma cells

Abstract

Piper longum L., known as long pepper, is an edible and medicinal plant used as spice and for the treatment of stomach disease and analgesia in traditional Chinese medicine. N-Alkylamides are the major secondary metabolites in this plant. Sixteen known N-alkylamides were isolated from P. longum. Their structures were established on the basis of spectroscopic data and comparison to reported literatures. Among them, five compounds were isolated from this plant for the first time. Ethanol extract, compounds 1, 2, 3, 7 and 11 exhibited potent ability to increase the melanin content and weak stimulative effect on the tyrosinase activity in a concentration-dependent manner. Moreover, compound 2 also presented strong capacity to increase the tyrosinase activity in a concentration-dependent manner. These results indicated that P. longum might be a good natural source of lead compound for skin disorder diseases.     

Aedes aegypti larvicide from the ethanolic extract of Piper nigrum black peppercorns

Due to unavailability of a vaccine and a specific cure to dengue, the focus nowadays is to develop an effective vector control method against the female Aedes aegypti mosquito. This study aims to determine the larvicidal fractions from Piper nigrum ethanolic extracts (PnPcmE) and to elucidate the identity of the bioactive compounds that comprise these larvicidal fractions. Larvicidal assay was performed by subjecting 3rd to 4th A. aegypti instar larvae to PnPcmE of P. nigrum. The PnPcmE exhibited potential larvicidal activity having an LC₅₀ of 7.1246 ± 0.1304 ppm (mean ± Std error). Normal phase vacuum liquid chromatography of the PnPcmE was employed which resulted in five fractions, two of which showed larvicidal activity. The most active of the PnPcmE fractions is PnPcmE-1A, with an LC₅₀ and LC₉₀ of 1.7101 ± 0.0491 ppm and 3.7078 ppm, respectively. Subsequent purification of PnPcmE-1A allowed the identification of the larvicidal compound as oleic acid.     

Green synthesis of silver nanoparticles using Piper longum catkin extract irradiated by sunlight: antibacterial and catalytic activity

Research on Chemical Intermediates - In this study, rapid and cost-effective biosynthesis of silver nanoparticles (AgNPs) was synthesized by using Piper longum (P. longum) catkin extract. The...     

Antifertility activity of Piper longum Linn. in female rats

The crude extract, its different fractions and the major pure compound from the active fraction of the powdered fruits of Piper longum were studied for the antifertility effect in female rats. The crude extract and its hexane fraction exhibited 100 and 86% efficacy respectively (days 1-7 post-coitum (p.c.) schedule). On the other hand, 1-butanol soluble, 1-butanol insoluble and chloroform fractions were inactive.     

Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity

A bioassay-guided isolation of the ethanol extract from the fruits of Piper longum yielded a known piperidine alkaloid, piperine, as a monoamine oxidase (MAO) inhibitor. Piperine showed an inhibitory effect against MAO-A (IC50 value: 20.9 microM) and MAO-B (IC50 value: 7.0 microM). Kinetic analyses by a Lineweaver-Burk plot clearly indicated that piperine competitively inhibited MAO-A and MAO-B with Ki values of 19.0+/-0.9 microM and 3.19+/-0.5 microM, respectively. The inhibition by piperine was found to be reversible by dialysis of the incubation mixture. In addition, the immobility times in the tail suspension test were significantly reduced by piperine, similar to that of the reference antidepressant fluoxetine, without accompanying changes in ambulation when assessed in an open-field. These results suggest that piperine possesses potent antidepressant-like properties that are mediated in part through the inhibition of MAO activity, and therefore represent a promising pharmacotherapeutic candidate as an antidepressant agent.     

Epigenetic Modifiers Affect the Bioactive Compounds Secreted by an Endophyte of the Tropical Plant Piper longum

Seven endophytic fungi were isolated from the tropical medicinal plant Piper longum L. After preliminary screening, Phomopsis heveicola was selected for the epigenetic activation treatments. The antibacterial, antifungal, and antioxidant potentials of crude extracts obtained from the treatments (with and without epigenetic modifiers) were analyzed in vitro. The extracts inhibited growth of the human pathogens Pseudomonas aeruginosa, Shigella sonnei, Streptococcus pyogenes, and Salmonella typhi, as well as the phytopathogens Puccinia recondita, Rhizoctonia solani, Phytophthora infestans, and Botrytis cinerea. Furthermore, DPPH-scavenging activity was higher in valproic acid treated extracts. Volatile chemicals with known biological activities (measured with GC-MS/MS), were released in the valproic acid treatment. The antimicrobial potentials of the extracts were confirmed using MRM/MS analysis. The experiments revealed a new promising endophytic fungus, P. heveicola, to be utilized in biological plant protection and in biomedical applications.     

Two New Bis‐alkaloids from the Aerial Part of Piper flaviflorum

Two new bis‐alkaloids, flavifloramides A ( 1 ) and B ( 2 ), as well as two known alkaloids, N‐trans‐feruloyltyramine ( 3 ) and paprazine ( 4 ), were isolated from the aerial part of Piper flaviflorum. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D‐NMR techniques.     

Improving the knowledge on Piper betle: Targeted metabolite analysis and effect on acetylcholinesterase

Piper betle is a species growing in South East Asia, where its leaves are economically and medicinally important. To screen the highest possible number of volatile and semivolatile components, the leaves were subjected to headspace solid‐phase microextraction, hydrodistillation and Soxhlet extraction, prior to analysis by GC/MS. Fifty compounds (identified by comparison with standard compounds or tentatively by National Institute of Standards and Technology database) were determined, 23 being described for the first time in this matrix. An aqueous extract was also analysed, in which only seven compounds were characterized. The organic acids' composition of this extract was determined by HPLC/UV and eight compounds are reported for the first time in P. betle. This extract also displayed acetylcholinesterase inhibitory capacity.     

Comparative Quantification of the Phenolic Compounds,Piperine Content,and Total Polyphenols along with the Antioxidant Activities in the Piper trichostachyon and P. nigrum

India is the largest producer in the world of black pepper and it is the center of origin for Piper. The present study gives a comparative account of the chemical composition of the Piper nigrum and its wild putative parent the P. trichostachyon. Microextractions were performed and the quantification of six phenolic compounds (namely epicatechin, gallic acid, catechol, chlorogenic acid, caffeic acid, and catechin), piperine from leaves, petioles, and the fruits of both the species, were accomplished using the RP-UFLC system. The polyphenols (phenolic, flavonoid) and their antioxidant activities were also estimated. Among the six phenolic compounds studied, only three were detected and quantified. The polyphenol content correlating to the antioxidant activities was higher in the P. trichostachyon, whereas the piperine content was 108 times greater in the P. nigrum fruits. The Piper trichostachyon comparatively showed a higher content of polyphenols. The microextractions reduced the solvent consumption, the quantity of the plant material, and the amount of time used for the extraction. The first report on the TPC, TF, and the antioxidant activity of the P. trichostachyon has been described, and it also forms a scientific basis for its use in traditional medicine. The petioles of both species are good sources of phenolic compounds. A quantitative chemical analysis is a useful index in the identification and comparison of the species.     

Biodereplication of Antiplasmodial Extracts: Application of the Amazonian Medicinal Plant Piper coruscans Kunth

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay. Molecular networking and automated annotation of targeted mass through data mining were followed by mass-guided compound isolation by taking advantage of the versatility and finely tunable selectivity offered by centrifugal partition chromatography. This biodereplication workflow was applied to an ethanolic extract of the Amazonian medicinal plant Piper coruscans Kunth (Piperaceae) showing an IC₅₀ of 1.36 µg/mL on the 3D7 Plasmodium falciparum strain. It resulted in the isolation of twelve compounds designated as potential antiplasmodial compounds by the biodereplication workflow. Two chalcones, aurentiacin (1) and cardamonin (3), with IC₅₀ values of 2.25 and 5.5 µM, respectively, can be considered to bear the antiplasmodial activity of the extract, with the latter not relying on a heme-binding mechanism. This biodereplication method constitutes a rapid, efficient, and robust technique to identify potential antimalarial compounds in complex extracts such as plant extracts.     

1H and 13C NMR data,occurrence, biosynthesis,and biological activity of Piper amides

Alkamides are the major and characteristic chemical compounds of the plants belonging to the Piper genus. These compounds are responsible for the flavor of pepper spices and for its broad use in cuisine across many regions of the world. Humans are in contact every day with these substances, which additionally show a broad variety of pharmacological activities, making them an important research target. A large amount of NMR data for these natural products is dispersed throughout literature. Its organization will help those research groups interested in their identification and structural elucidation. This review summarizes the ¹H and ¹³C NMR data of 268 Piper amides in a systematic and orderly way, with a discussion on their biological activities, biosynthetic aspects, and NMR analysis of typical and relevant aspects of this information.     

Methanolic Extract of Piper sarmentosum Attenuates Obesity and Hyperlipidemia in Fructose-Induced Metabolic Syndrome Rats

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG—Untreated group; CTRL—control; FDW—olive oil + 20% fructose; FDW-PS—PS (125 mg/kg) + 20% fructose; FDW-NGN—naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia.     

Piper betle (L): Recent Review of Antibacterial and Antifungal Properties,Safety Profiles,and Commercial Applications

Piper betle (L) is a popular medicinal plant in Asia. Plant leaves have been used as a traditional medicine to treat various health conditions. It is highly abundant and inexpensive, therefore promoting further research and industrialization development, including in the food and pharmaceutical industries. Articles published from 2010 to 2020 were reviewed in detail to show recent updates on the antibacterial and antifungal properties of betel leaves. This current review showed that betel leaves extract, essential oil, preparations, and isolates could inhibit microbial growth and kill various Gram-negative and Gram-positive bacteria as well as fungal species, including those that are multidrug-resistant and cause serious infectious diseases. P. betle leaves displayed high efficiency on Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram-positive bacteria such as Staphylococcus aureus, and Candida albicans. The ratio of MBC/MIC indicated bactericidal and bacteriostatic effects of P. betle leaves, while MFC/MIC values showed fungicidal and fungistatic effects. This review also provides a list of phytochemical compounds in betel leaves extracts and essential oils, safety profiles, and value-added products of betel leaves. Some studies also showed that the combination of betel leaves extract and essential oil with antibiotics (streptomycin, chloramphenicol and gentamicin) could provide potentiating antibacterial properties. Moreover, this review delivers a scientific resume for researchers in respected areas and manufacturers who want to develop betel leaves-based products.     

Purification and identification of 4-allylbenzene-1,2-diol: an antilisterial and biofilm preventing compound from the leaves of Piper betle L. var Pachaikodi

Antibiotic-resistant food-borne Listeriosis has been rising with up to 30% mortality threat in humans since several decades. Hence, discovering antilisterial from the extracts of ethnomedicinal plants may be of value as a novel antidote. In our preceding study, we reported that ethanolic extract of Piper betle L. var Pachaikodi leaves exhibited antibacterial activity towards Listeria monocytogenes MTCC 657. Consequently in the present study, the bioactive molecule responsible for anti-Listeria activity was purified and identified as 4-allylbenzene-1,2-diol. This identified bioactive compound may have significance while used as antimicrobials and/or food additives in food processing sector as evidenced by dual action: biofilm inhibition and pore formation on cell membrane.     

Piper longum catkin extract mediated synthesis of Ag,Cu, and Ni nanoparticles and their applications as biological and environmental remediation agents

Piper longum (long pepper) in dried form is used in several traditional medicines and as a spice. The present study highlights nutritional and toxic elements content, synthesis, and characterization of silver, copper oxide, and nickel nanoparticles using P. longum catkin extract. The study also determined anticancer, antioxidant, antimicrobial, and redox catalytic activities of the synthesized NPs. The P. longum extract mediated nanoparticles (PLNPs) synthesized at different pH and ratios were characterized by UV–Vis (ultra-violet-visible), FT-IR (Fourier-Transform infrared), and scanning electron and atomic force microscopic (SEM, AFM) techniques. Elemental content of P. longum catkin determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and ICP-mass spectrometry (ICP-MS) indicated appreciable concentrations of nutritional elements, and well below permissible ranges of toxic elements. Well-defined and stable silver nanoparticles (PLAgNPs) were formed in 1:4 to 1:6 ratios, while copper oxide and nickel NPs (PLCuONPs and PLNiNPs) were found prominent in 1:6 ratio. In determining the effect of pH on synthesized PLNPs, sharp intense absorption peaks were obtained under slightly neutral to highly basic conditions (pH 6 to 13) for PLAgNPs, whereas for PLCuONPs and PLNiNPs, pH 7–8 was optimum. In biological activities, PLNPs exhibited significant anticancer efficacy against DU-145 (prostate cancer) cell line in the range from 92.7% (PLCuONPs) to 100% (PLAgNPs, PLNiNPs). Fuurthermore, the sythesized NPs exhibited significant antioxidant, antimicrobial, and redox catalytic properties. This study concluded the promising nutritional, biological and environmental remediation applications, and hence, further exploration of the synthesized NPs in biological and clinical applications is currently under investigation.     

Profiling of Piper betle Linn. cultivars by direct analysis in real time mass spectrometric technique

Piper betle Linn. is a traditional plant associated with the Asian and southeast Asian cultures. Its use is also recorded in folk medicines in these regions. Several of its medicinal properties have recently been proven. Phytochemical analysis showed the presence of mainly terpenes and phenols in betel leaves. These constituents vary in the different cultivars of Piper betle. In this paper we have attempted to profile eight locally available betel cultivars using the recently developed mass spectral ionization technique of direct analysis in real time (DART). Principal component analysis has also been employed to analyze the DART MS data of these betel cultivars. The results show that the cultivars of Piper betle could be differentiated using DART MS data.     

The new ether derivative of phenylpropanoid and bioactivity was investigated from the leaves of Piper betle L.

Abstract

A new ether derivative of phenylpropanoid compound, γ-(γ′-isohydroxychavicol)-chavicol octanyl ether (K1) along with one known phenylpropanoid named allyl-pyrocatechol or hydroxychavicol (2) were isolated from Piper betle var. kali collected from Tumluk district, West Bengal India. We first report the presence of compound K1 in the genus Piper. Their structures were established on the basis of various spectroscopic analyses. Compounds K1 and 2 showed excellent antioxidant DPPH free radical scavenging activity with IC₅₀ values of 4.61 and 4.12?µg/mL compared to ascorbic acid as a standard antioxidant drug with IC₅₀ value of 3.42?µg/mL, respectively. Evaluation of in vitro cytotoxic activities of compounds K1 and 2 showed significant effects against human oral cancer cell lines (AW13516 and AW8507), human hepatoma cell lines (HEPG2 and PLC-PRF-5) and a human pancreatic cell line (MIA-PA-CA-2), compared to Doxorubicin^® as a standard cytotoxic drug with GI₅₀ values of <10 and 18.18?µg/mL.     

应用立式逆流色谱和反相液相色谱制备性分离荜菝中的酰胺类化合物

A versatile countercurrent chromatography with upright type-J multilayer coil planet centrifuge,named upright countercurrent chromatography (UCCC),was applied to the isolation and purification of amides from Piper Longum L., which is widely used as an anodyne and a treatment for stomach disease in China. After saponification by KOH of the ethanol extracts solution of crud drug "Piper Longi Fructus", the fruits of Piper Longum L., the remaining solution was extracted with petroleum ether and red crude oil was obtained. Using 2.5 g red crude oil as sample, the preparative UCCC with a two-phase system composed of petroleum ether (b. p. 60 ～ 90 ℃)-ethyl acetate-tetrachloromethanemethanol-water ( 1: 1: 8: 6: 1, v/v) was successfully performed, yielding ten fractions. Then these fractions were further purified by use of reversed-phase liquid chromatography with a glass column of 500 × 10 mm I. D.packed with reversed - phase silica gel. As a result,nine amides with more than 98% purity, i.e., (2E,4E)-N-isobutyl-eicosa-2,4-dienamide, (2E, 4E, 8Z)-N-isobutyl-eicosa-2,4,8-trienamide, (2E, 4E, 8Z)-N-isobutyl-ocatadeca-2,4,8-trienamide, guineensine, pipemonaline, ( 2E, 4E )-N-isobutyl-2, 4-didecadienamide, piperine, piperanine, and piperlonguminine were isolated preparatively.     

Biological and Cytoprotective Effect of Piper kadsura Ohwi against Hydrogen-Peroxide-Induced Oxidative Stress in Human SW1353 Cells

Oxidative stress plays a role in regulating a variety of physiological functions in living organisms and in the pathogenesis of articular cartilage diseases. Piper kadsura Ohwi is a traditional Chinese medicine that is used as a treatment for rheumatic pain, and the extracts have anti-inflammatory and antioxidant effects. However, there is still no study related to cell protection by P. kadsura. The P. kadsura extracts (PKE) were obtained by microwave-assisted extraction, liquid-liquid extraction, and column chromatography separation. The extracts could effectively scavenge free radicals in the antioxidant test, the EC₅₀ of extracts is approximately the same as vitamin C. PKE decreased the apoptosis of SW1353 cells treated with H₂O₂ and could upregulate the gene expression of antioxidant enzymes (SOD-2, GPx, and CAT) and the Bcl-2/Bax ratio, as well as regulate PARP, thus conferring resistance to H₂O₂ attack. PKE protects cells against apoptosis caused by free radicals through the three pathways of JNK, MEK/ERK, and p38 by treatment with MAPK inhibitor. The identified components of PKE were bicyclo [2.2.1] heptan-2-ol-1,7,7-trimethyl-,(1S-endo)-, alpha-humulene, and hydroxychavicol by gas chromatography–mass spectrometry.     

GC-EIMS analysis,antifungal and anti-aflatoxigenic activity of Capsicum chinense and Piper nigrum fruits and their bioactive compounds capsaicin and piperine upon Aspergillus parasiticus

Abstract

GC-EIMS analysis, antifungal- and anti-aflatoxigenic activities of the ethanolic extract of Capsicum chinense and Piper nigrum fruits and their main bioactive compounds were evaluated upon Aspergillus parasiticus. The GC-EIMS analysis showed capsaicin (50.49%) and piperine (95.94%) as the major constituents in C. chinense and P. nigrum, respectively. MIC₅₀ values revealed that capsaicin (39?μg/mL) and piperine (67?μg/mL) were lower than those from fruit extracts of C. chinense (381?μg/mL) and P. nigrum (68?μg/mL). Extracts and bioactive compounds showed anti-aflatoxigenic activity. Maximum aflatoxin inhibition occurred at 150?µg/mL of extracts and compounds. The present study showed satisfactory results concerning the effects of ethanolic extract of C. chinense and P. nigrum fruits upon A. parasiticus, showing the capabilities of inhibiting fungal growth development and altering aflatoxins production.