Viphyllin™, a standardized extract from black pepper seeds, mitigates intestinal inflammation, oxidative stress, and anxiety-like behavior in DSS-induced colitis mice.

Inflammatory bowel diseases (IBD) are the common health concern in populations across the world. Clinical evidence suggests that IBD, characterized by intestinal inflammation, is associated with neuronal manifestations to a greater extent. In this study, we have investigated the protective effects of Viphyllin™, a standardized black pepper (Piper nigrum) seed extract containing 30% ß-caryophyllene against dextran sodium sulfate (DSS)-induced colitis in mice. Oral pretreatment of Viphyllin at the 50 mg and 100 mg/kg doses significantly reversed the clinical symptoms of colitis in mice. Viphyllin markedly inhibited NLRP3 inflammasome activation and improved barrier function in colon tissue. Viphyllin further mitigated the DSS-induced anxiety-like behavior in mice. Interestingly, Viphyllin improved brain antioxidant status and promoted neuronal cell survival in colitis model mice. In conclusion, our findings strongly support the health claims of Viphyllin as a functional ingredient to deal with IBD and related neuronal symptoms. PRACTICAL APPLICATIONS: Prevalence of inflammatory bowel diseases is not uncommon in the modern lifestyle. Gut health is associated with neurological disorders that contribute substantially to the deterioration of quality of life and socioeconomic development. In this research work, the protective action of a black pepper seed extract standardized to 30% ß-caryophyllene (Viphyllin) is evaluated against Dextran sodium sulfate-induced experimental colitis model. Here we have demonstrated the beneficial role of Viphyllin in mitigating intestinal inflammation as a function of NLRP3 inflammasome inhibition. Further, the extract improves intestinal barrier function. In an important aspect of the study, we have provided the data on the effect of Viphyllin on neurological symptoms and brain health in colitis model mice.

The Effect of a Traditional Preparation Containing Piper nigrum L. and Bunium persicum (Boiss.) B.Fedtsch. on Immobility Stress-Induced Memory Loss in Mice.

OBJECTIVE: Alzheimer's disease is a progressive, age-related, and neurodegenerative disease characterized by mental decline. The exact cause of Alzheimer's disease is unclear, but cholinergic dysfunction, protein accumulation, and oxidative stress are among the most important hypotheses. The main purpose of our study was to investigate the effects of aqueous and hydroalcoholic extract combination of these two medicinal plants, black pepper and cumin (as a related formulation in traditional Persian medicine), on memory and learning of an immobilized stress animal model. METHODS: In this study, hydroalcoholic and aqueous extracts of cumin and black pepper fruits were prepared. Six groups of mice were treated orally for 2 weeks: control group, immobility stress, and stress-induced immobility mice received different doses of the hydroalcoholic extract (100 and 200 mg/kg) and aqueous extract (100 and 200 mg/kg). The shuttle box, novel object detection, and rotarod test were used to evaluate memory and learning. The activities of acetylcholinesterase, catalase (CAT), and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the brain tissue. RESULTS: Immobility stress significantly reduced learning and motor coordination. Furthermore, MDA levels and acetylcholinesterase activity were significantly increased, while CAT and SOD activities were significantly reduced in the brain of immobility-induced stress mice. Other findings indicated that hydroalcoholic and aqueous extracts (100 and 200 mg/kg) of cumin and black pepper fruits have an improving effect on animal motor coordination and learning ability, GSH content, and CAT, SOD, and acetylcholinesterase enzyme function in comparison with stress groups (p < 0.05). CONCLUSION: The hydroalcoholic and aqueous extracts of cumin and black pepper fruits have protective effects against stress-induced memory deficit and oxidative stress and may have beneficial therapeutic effect in the treatment of neurodegenerative diseases.

Antioxidant, hepatoprotective and antifungal activities of black pepper (Piper nigrum L.) essential oil.

The essential oil extracted from the black Piper nigrum L. (BPEO) was analyzed for antioxidant, hepatoprotective and antifungal activities. BPEO is rich in total phenolics, total flavonoids and proanthocyanidins, and showed good free radicals and lipid peroxidation scavenging capacities. In a CCl4-induced liver injury mice model, the BPEO treated groups showed increases in the catalase (CAT), glutathione (GSH) and total superoxide dismutase (T-SOD) activities present in the liver and kidney, and reverses the CCl4-elevated total bilirubin (TBIL), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and malondialdehyde (MDA) level, which were confirmed in further analyses of kidney tissue sections. BPEO can effectively inhibit the growth of Aspergillus flavus spoilage fungus in maize. Further analyses indicated that BPEO disrupt the permeability barrier of the cell membrane and lead to mitochondrial dysfunction in A. flavus. Therefore, the current study proved BPEO's potential as hepatoprotective products and natural food preservatives.

Secondary Metabolic Profile as a Tool for Distinction and Characterization of Cultivars of Black Pepper (Piper nigrum L.) Cultivated in Pará State, Brazil.

This study evaluated the chemical compositions of the leaves and fruits of eight black pepper cultivars cultivated in Pará State (Amazon, Brazil). Hydrodistillation and gas chromatography-mass spectrometry were employed to extract and analyze the volatile compounds, respectively. Sesquiterpene hydrocarbons were predominant (58.5-90.9%) in the cultivars "Cingapura", "Equador", "Guajarina", "Iaçará", and "Kottanadan", and "Bragantina", "Clonada", and "Uthirankota" displayed oxygenated sesquiterpenoids (50.6-75.0%). The multivariate statistical analysis applied using volatile composition grouped the samples into four groups: γ-Elemene, curzerene, and δ-elemene ("Equador"/"Guajarina", I); δ-elemene ("Iaçará"/"Kottanadan"/"Cingapura", II); elemol ("Clonada"/"Uthirankota", III) and α-muurolol, bicyclogermacrene, and cubebol ("Bragantina", IV). The major compounds in all fruit samples were monoterpene hydrocarbons such as α-pinene, ß-pinene, and limonene. Among the cultivar leaves, phenolics content (44.75-140.53 mg GAE·g-1 FW), the enzymatic activity of phenylalanine-ammonia lyase (20.19-57.22 µU·mL-1), and carotenoids (0.21-2.31 µg·mL-1) displayed significant variations. Due to black pepper's susceptibility to Fusarium infection, a molecular docking analysis was carried out on Fusarium protein targets using each cultivar's volatile components. F. oxysporum endoglucanase was identified as the preferential protein target of the compounds. These results can be used to identify chemical markers related to the susceptibility degree of black pepper cultivars to plant diseases prevalent in Pará State.

Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper (Piper nigrum L.) Products Based on LC-MS/MS Analysis.

In the present study, nontargeted metabolomics was used to screen the phenolic and polyhydroxy compounds in pepper products. A total of 186 phenolic and polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl quinic acid O-hexoside, quinic acid (polyhydroxy compounds), etc. For the selected 50 types of phenolic compound, except malvidin 3,5-diglucoside (malvin), l-epicatechin and 4'-hydroxy-5,7-dimethoxyflavanone, other compound contents were present in high contents in freeze-dried pepper berries, and pinocembrin was relatively abundant in two kinds of pepper products. The score plots of principal component analysis indicated that the pepper samples can be classified into four groups on the basis of the type pepper processing. This study provided a comprehensive profile of the phenolic and polyhydroxy compounds of different pepper products and partly clarified the factors responsible for different metabolite profiles in ongoing studies and the changes of phenolic compounds for the browning mechanism of black pepper.

Black pepper-based beverage induced appetite-suppressing effects without altering postprandial glycaemia, gut and thyroid hormones or gastrointestinal well-being: a randomized crossover study in healthy subjects.

Pleiotropic effects of spices on health, particularly on glucose metabolism and energy regulation, deserve further clinical investigation into their efficacy. The aim of the current study was to evaluate whether consumption of a black pepper-based beverage (BPB) preload containing 20 mg gallic acid equivalent (GAE) would exert any effect on postprandial glycaemia, appetite sensations, gut hormones, thyroid function, and gastrointestinal well-being after a white wheat bread (WWB) challenge meal containing 50 g available carbohydrates (CHO) compared to a control beverage. Sixteen healthy subjects (10 men; 6 women; 26 ± 0.9 years; BMI 22.93 ± 0.53 kg m-2) completed a randomized, crossover intervention study. The BPB's bioactive compounds were characterized using ultra high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer with an electrospray ionization source (UHPLC-DAD-ESI-QTOF-MS). Nine compounds tentatively identified in BPB include: dihydroxybenzoic acid hexoside-pentoside, decaffeoyl-acteoside, cynaroside A, apigenin 6,8-di-C-hexoside, luteolin 6-C-hexoside-8-C-rhamnoside, apigenin 8-C-hexoside-C-deoxyhexoside, kaempferol 3-rhamnoside-4'-xyloside, apigenin 7-neohesperidoside, and apigenin-8-C-arabinopyranoside-2''-rhamnoside. Blood glucose and serum insulin responses, insulin sensitivity and ß-cell function were not affected during the acute intervention with BPB. Neither were effects on gastrointestinal well-being observed after BPB. However, BPB modulated overall acute appetite by lowering 'hunger', 'desire to eat', and 'prospective consumption', and increasing 'satiety' and 'fullness'. In contrast, there were no changes in gut (peptide tyrosine-tyrosine [PYY] and glucagon-like peptide-1 [GLP-1]) and thyroid (triiodothyronine [T3] and thyroxine [T4]) hormones after BPB compared to the control beverage. In conclusion, inclusion of BPB prior to the WWB challenge meal might be beneficial for appetite modulation, but we did not find supporting evidence in glycaemia, gut and thyroid hormones. Further studies are needed to elucidate the mechanisms of appetite-reducing pungent spices, such as black pepper.

Contribution of Polyphenol Oxidation, Chlorophyll and Vitamin C Degradation to the Blackening of Piper nigrum L.

Black pepper (Piper nigrum L.) is the most widely used spice in the world. Blackening is considered to be beneficial and important in the processing of black pepper because it contributes to its color and flavor. The purpose of this paper is to investigate polyphenol oxidation as well as the chlorophyll and vitamin C (VC) degradation in the blackening of Piper nigrum L. Black pepper was produced by four methods, and changes in polyphenols, chlorophyll and VC were studied by high performance liquid chromatography (HPLC) and ultraviolet-visible and visible (UV-Vis) spectrophotometry. The results show that polyphenol oxidase activity significantly decreased during the preparation of black pepper, and the concentrations of phenolic compounds, VC, and chlorophyll a and b also significantly decreased. Polyphenol oxidation and chlorophyll and VC degradation contribute to the blackening. A crude extract of phenolic compounds from black pepper was prepared by the system solvent method. The greater the polarity of the extraction solvent, the higher the extraction rates of the phenolic compounds and the total phenol content. Pepper phenolic compounds were analyzed by HPLC analysis.

Pharmacokinetic based study on "lagged stimulation" of Curcumae Longae Rhizoma - Piper nigrum couplet in their main active components' metabolism using UPLC-MS-MS.

BACKGROUND: Curcumae Longae Rhizoma is one of the commonly used traditional Chinese medicines, which has multiple biological activities such as relieving stagnation and stasis, pain alleviation, curing amenorrhea and wounds. However, its main active component-curcumin has poor absorption and very fast metabolism in body. To solve this problem, Piper nigrum was introduced for its ability to strengthen bioavailability of other compounds. PURPOSE: In most cases of TCM couplets, all ingredients were prepared and taken simultaneously, which in our opinion did not take full advantage of their interactions. Therefore, order of administration should be adjusted according to pharmacokinetic parameters of the ingredients, which the ones act as supplement can first be taken, and main therapeutic components followed when the former reached its peak. METHOD: the extract of Piper nigrum (containing at least 95% piperine) was taken by rats 6h before taking Curcumae Longae Rhizoma extract (containing at least 95% curcumin). Then, a UPLC-MS-MS method was developed to determine their content in plasma simultaneously. Determination was carried out by on a C18 column within 5min by isocratic elution using 0.2% formic acid and acetonitrile (50:50, v/v). Tandem mass detection was conducted by selective reaction monitoring (SRM) via electrospray ionization (ESI) source in positive mode. Samples were pre-treated by liquid-liquid extraction (LLE), and verapamil was used as internal standard (IS). RESULTS: For both curcumin and piperine, the proposed method had good linearity (r2=0.999) within the concentration range of 1-1000ng/ml, with good recovery, precision and stability. The lower limit of quantification (LLOQ) was 1ng/ml. As pharmacokinetic data indicated, Maximum concentration (Cmax) of curcumin increased significantly to 394.06; the time reach maximum concentration (Tmax) and elimination half-life (T1/2) were 0.5 and 0.67h, respectively; CONCLUSION: The results provide a good strategy for the investigation of TCM formula especially the couplets, as well as a fast, selective and sensitive UPLC-MS-MS method determining active components in-vivo. Furthermore, the finding of "lagged stimulation" suggested that the use of complex formula should take pharmacokinetics into much more careful consideration.

Integrated plant nutrient system - with special emphasis on mineral nutriton and biofertilizers for Black pepper and cardamom - A review.

Integrated Plant Nutrition System (IPNS) as a concept and farm management strategy embraces and transcends from single season crop fertilization efforts to planning and management of plant nutrients in crop rotations and farming systems on a long-term basis for enhanced productivity, profitability and sustainability. It is estimated that about two-thirds of the required increase in crop production in developing countries will have to come from yield increases from lands already under cultivation. IPNS enhances soil productivity through a balanced use of soil nutrients, chemical fertilizers, combined with organic sources of plant nutrients, including bio-inoculants and nutrient transfer through agro-forestry systems and has adaptation to farming systems in both irrigated and rainfed agriculture. Horticultural crops, mainly plantation crops, management practices include application of fertilizers and pesticides which become inevitable due to the depletion of soil organic matter and incidence of pests and diseases. The extensive use of chemical fertilizers in these crops deteriorated soil health that in turn affected the productivity. To revitalize soil health and to enhance productivity, it is inexorable to enrich the soil using microorganisms. The lacunae observed here is the lack of exploitation of indigenous microbes having the potential to fix atmospheric nitrogen (N) and to solubilize Phosphorus (P) and Potassium (K). The concept of biofertilizer application appears to be technically simple and financially feasible, but the task of developing biofertilizers with efficient strains in appropriate combinations in a consortia mode is not easier. More than developing consortia, a suitable delivery system to discharge the microbial inoculants warranted much effort. This review focuses on the integrated plant nutrition system incorporating biofertilizer with special emphasis on developing and formulating biofertilizer consortium.

Increasing Carotenoid Bioaccessibility from Yellow Peppers Using Excipient Emulsions: Impact of Lipid Type and Thermal Processing.

Many phytochemicals from fruits and vegetables exert biological activities that may be beneficial to human health, but these benefits are not fully realized because of their poor oral bioavailability. The objective of this research was to establish the potential of excipient emulsions to increase carotenoid bioaccessibility from raw and cooked yellow peppers using a gastrointestinal model that included oral, gastric, and intestine phases. The influence of oil type (medium chain triglycerides, MCT; long chain triglycerides, LCT; and, indigestible orange oil, OO) on microstructural changes, particle properties, lipid digestibility, and carotenoid bioaccessibility was investigated. Oil type had a major impact, with carotenoid bioaccessibility decreasing in the following order: LCT > MCT > OO > control (no oil). Conversely, thermal treatment (raw versus boiled) had little influence on carotenoid bioaccessibility. These results will facilitate the rational design of excipient emulsions that boost the bioavailability of phytochemicals in fruits and vegetables.

Piper nigrum: micropropagation, antioxidative enzyme activities, and chromatographic fingerprint analysis for quality control.

A reliable in vitro regeneration system for the economical and medicinally important Piper nigrum L. has been established. Callus and shoot regeneration was encouraged from leaf portions on Murashige and Skoog (MS) medium augmented with varied concentrations of plant growth regulators. A higher callus production (90 %) was observed in explants incubated on MS medium incorporated with 1.0 mg L(-1) 6-benzyladenine (BA) along with 0.5 mg L(-1) gibberellic acid after 4 weeks of culture. Moreover, a callogenic response of 85 % was also recorded for 1.0 mg L(-1) BA in combination with 0.25 mg L(-1) α-naphthalene acetic acid (NAA) and 0.25 mg L(-1) 2,4-dichlorophenoxyacetic acid or 0.5 mg L(-1) indole butyric acid (IBA) along with 0.25 mg L(-1) NAA and indole acetic acid. Subsequent sub-culturing of callus after 4 weeks of culture onto MS medium supplemented with 1.5 mg L(-1) thiodiazoran or 1.5 mg L(-1) IBA induced 100 % shoot response. Rooted plantlets were achieved on medium containing varied concentrations of auxins. The antioxidative enzyme activities [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)] revealed that significantly higher SOD was observed in regenerated plantlets than in other tissues. However, POD, CAT, and APX were higher in callus than in other tissues. A high-performance liquid chromatography (HPLC) fingerprint analysis protocol was established for quality control in different in vitro-regenerated tissues of P. nigrum L. During analysis, most of the common peaks represent the active principle "piperine." The chemical contents, especially piperine, showed variation from callus culture to whole plantlet regeneration. Based on the deviation in chromatographic peaks, the in vitro-regenerated plantlets exhibit a nearly similar piperine profile to acclimated plantlets. The in vitro regeneration system and HPLC fingerprint analysis established here brought a novel approach to the quality control of in vitro plantlets, producing metabolites of interest with substantial applications for the conservation of germplasm.

Pepper leaf matrix as a promising analyte protectant prior to the analysis of thermolabile terbufos and its metabolites in pepper using GC-FPD.

During gas chromatography (GC), the matrix can deactivate the active site during the transport of the compound from the injector to the detector. This deactivation capacity varies among matrices, as it is dependant on the concentrations of the different constituent compounds of each matrix. During the analysis of terbufos and its metabolites, two of its metabolites were highly thermolabile, and were readily decomposed inside the GC system. As the matrix can mask the active site, we carried out a matrix-matched calibration in an effort to protect the analyte against decomposition. As a component of our analysis, the pepper matrix was the first to be matched; however, it failed to completely protect the metabolites. Subsequently, a variety of different compounds, including 3-ethoxy-1,2-propanediol, gulonolactone, and sorbitol at 10, 1, and 1mg/mL were tested; however, none of these generated the desired effect. We surmised that some of the compounds may have decomposed inside the injection port, so we introduced a carbofrit inlet liner, which is highly inert. But, this step did not improve the protective qualities of the matrices. Finally, pepper leaf matrix was added to the pepper matrix, and we observed a profound protective effect for almost all of the analytes tested. A selective detector (flame photometric detector with phosphorus filter) was used to facilitate a high matrix concentration without interaction with the analyte. After resolving the problem of these two metabolites, terbufos and its five toxic metabolites were analyzed in pepper and pepper leaf samples. The recovery rates for terbufos and its metabolites were 73-114.5% with a relative standard deviation of <12%. This method was successfully applied to field samples, and terbufos sulfone, terbufos sulfoxide, and terbufoxon sulfoxide were found as residues in the suspected pepper and pepper leaf samples.

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation.

Alkamides from the fruits of Piper longum and Piper nigrum displaying potent cell adhesion inhibition.

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.