Human Metabolism and Excretion of Kawakawa (Piper excelsum) Leaf Chemicals.

SCOPE: Piper excelsum (kawakawa) has a history of therapeutic use by Maori in Aotearoa New Zealand. It is currently widely consumed as a beverage and included as an ingredient in "functional" food product. Leaves contain compounds that are also found in a wide range of other spices, foods, and medicinal plants. This study investigates the human metabolism and excretion of kawakawa leaf chemicals. METHODS AND RESULTS: Six healthy male volunteers in one study (Bioavailability of Kawakawa Tea metabolites in human volunteers [BOKA-T]) and 30 volunteers (15 male and 15 female) in a second study (Impact of acute Kawakawa Tea ingestion on postprandial glucose metabolism in healthy human volunteers [TOAST]) consume a hot water infusion of dried kawakawa leaves (kawakawa tea [KT]). Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analyses of urine samples from BOKA-T identified 26 urinary metabolites that are significantly associated with KT consumption, confirmed by the analysis of samples from the independent TOAST study. Seven of the 26 metabolites are also detected in plasma. Thirteen of the 26 urinary compounds are provisionally identified as metabolites of specific compounds in KT, eight metabolites are identified as being derived from specific compounds in KT but without resolution of chemical structure, and five are of unknown origin. CONCLUSIONS: Several kawakawa compounds that are also widely found in other plants are bioavailable and are modified by phase 1 and 2 metabolism.

Ethanol extract of Piper wallichii ameliorates DSS-induced ulcerative colitis in mice: Involvement of TLR4/NF-κB/COX-2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper wallichii (family: Piperaceae), a folk herbal medicine with anti-inflammatory and anti-thrombotic properties, has been traditionally used to treat rheumatic arthralgia, lumbocrural pain, gastrointestinal flatulence, and other intestinal diseases in China, Thailand, and India. However, there is no scientific report on the efficacy and potential mechanisms of Piper wallichii for ulcerative colitis (UC). AIM OF THE STUDY: The study aims to investigate the therapeutic effect and possible molecular mechanisms of the ethanol extract of Piper wallichii (EEPW) on DSS-induced UC in BALB/c mice. MATERIALS AND METHODS: The main components in EEPW were characterized by UPLC-QE-Orbitrap-MS. Subsequently, the anti-inflammatory effect of EEPW in vitro was preliminarily evaluated in RAW264.7 cells stimulated with LPS. UC model mice were triggered by free access to 4% DSS aqueous solution for 12 consecutive days, and simultaneously, EEPW (25, 50, and 100 mg/kg) and tofacitinib (positive control, 30 mg/kg) were orally administrated, respectively. The therapeutic efficacy of EEPW on UC was assessed by body weight, DAI, colon length, and pathological morphology. Besides, we investigated the effects of EEPW on intestinal barrier function, inflammatory factors, and immune systems of UC mice through immunohistochemistry (IHC), flow cytometry, and other techniques. Moreover, the expression of related proteins in the TLR4/NF-κB/COX-2 pathway was analyzed by Western blot. RESULTS: A total of 14 components were identified in the positive and negative modes, including isofutoquinol A (11), hancinone C (12), and futoquinol (14) which characterized by references. In the RAW264.7 cells experiments, the extract significantly suppressed the levels of TNF-α and IL-6. More importantly, EEPW distinctly improved the symptoms of DSS-induced UC mice as reflected by a significant recovery from body weight, colon length, pathological injuries of the colon, and so on. Further research found that EEPW remarkably restored the levels of occludin, promoted proliferation, and inhibited apoptosis in colon to maintain the integrity of intestinal barrier. In addition, the down-regulation of TNF-α and IL-1ß in colon, Th1 and Th17 cells in spleen, as well as the up-regulation of IL-10 in colon and Th2 cells in spleen were distinctly observed in EEPW-treated groups. Furthermore, the protein expression of TLR4, p-IκB-α, p-p65, and COX-2 were significantly inhibited by EEPW. CONCLUSIONS: This study confirmed for the first time that EEPW effectively ameliorated DSS-induced UC in mice, which might be related to improving intestinal barrier function, maintaining the levels of inflammatory factors, and regulating the immune system. In addition, we found that the anti-inflammatory effect of EEPW on UC mice was involved in the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, Piper wallichii can be used as a candidate for the treatment of UC.

Green Tea Extract Containing Piper retrofractum Fruit Ameliorates DSS-Induced Colitis via Modulating MicroRNA-21 Expression and NF-κB Activity.

The aim of the present study was to examine the effect of green tea extract containing Piper retrofractum fruit (GTP) on dextran-sulfate-sodium (DSS)-induced colitis, the regulatory mechanisms of microRNA (miR)-21, and the nuclear factor-κB (NF-κB) pathway. Different doses of GTP (50, 100, and 200 mg/kg) were administered orally once daily for 14 days, followed by GTP with 3% DSS for 7 days. Compared with the DSS-treated control, GTP administration alleviated clinical symptoms, including the disease activity index (DAI), colon shortening, and the degree of histological damage. Moreover, GTP suppressed miR-21 expression and NF-κB activity in colon tissue of DSS-induced colitis mice. The mRNA levels of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were downregulated by GTP. Colonic nitric oxide (NO) and prostaglandin E2 (PGE2) production, and myeloperoxidase (MPO) activity were also lowered by GTP. Taken together, our results revealed that GTP inhibits DSS-induced colonic inflammation by suppressing miR-21 expression and NF-κB activity, suggesting that it may be used as a potential functional material for improving colitis.

Acute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population.

Background: Piper excelsum (kawakawa) is an endemic shrub of Aotearoa, New Zealand, of cultural and medicinal importance to Maori. Its fruits and leaves are often consumed. These tissues contain several compounds that have been shown to be biologically active and which may underpin its putative health-promoting effects. The current study investigates whether kawakawa tea can modulate postprandial glucose metabolism. Methods: We report a pilot three-arm randomized crossover study to assess the bioavailability of kawakawa tea (BOKA-T) in six male participants with each arm having an acute intervention of kawakawa tea (4 g/250 mL water; 1 g/250 mL water; water) and a follow-up two-arm randomized crossover study to assess the impact of acute kawakawa tea ingestion on postprandial glucose metabolism in healthy human volunteers (TOAST) (4 g/250 mL water; and water; n = 30 (15 male and 15 female)). Participants consumed 250 mL of kawakawa tea or water control within each study prior to consuming a high-glycemic breakfast. Pre- and postprandial plasma glucose and insulin concentrations were measured, and the Matsuda index was calculated to measure insulin sensitivity. Results: In the BOKA-T study, lower plasma glucose (p < 0.01) and insulin (p < 0.01) concentrations at 60 min were observed after consumption of a high-dose kawakawa tea in comparison to low-dose or water. In the TOAST study, only plasma insulin (p = 0.01) was lower at 60 min in the high-dose kawakawa group compared to the control group. Both studies showed a trend towards higher insulin sensitivity in the high-dose kawakawa group compared to water only. Conclusions: Consuming kawakawa tea may modulate postprandial glucose metabolism. Further investigations with a longer-term intervention study are warranted.

Piper tectoniifolium Kunth: A New Natural Source of the Bioactive Neolignan (-)-Grandisin.

The Piper species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Piper tectoniifolium Kunth is presented as a promising natural source of the bioactive (-)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (-)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (-)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC50 of 9.8 ± 1.22 µM and around 80% relaxation at 30 µM. These results suggest that P. tectoniifolium has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.

Phytochemical profiling of Piper crocatum and its antifungal mechanism action as Lanosterol 14 alpha demethylase CYP51 inhibitor: a review.

Mycoses or fungal infections are a general health problem that often occurs in healthy and immunocompromised people in the community. The development of resistant strains in Fungi and the incidence of azole antibiotic resistance in the Asia Pacific which reached 83% become a critical problem nowadays. To control fungal infections, substances and extracts isolated from natural resources, especially in the form of plants as the main sources of drug molecules today, are needed. Especially from Piperaceae, which have long been used in India, China, and Korea to treat human ailments in traditional medicine. The purpose of this review is to describe the antifungal mechanism action from Piper crocatum and its phytochemical profiling against lanosterol 14a demethylase CYP51. The methods used to search databases from Google Scholar to find the appropriate databases using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Flow Diagram as a clinical information retrieval method. From 1.150.000 results searched by database, there is 73 final results article to review. The review shows that P. crocatum contains flavonoids, tannins, terpenes, saponins, polyphenols, eugenol, alkaloids, quinones, chavibetol acetate, glycosides, triterpenoids or steroids, hydroxychavikol, phenolics, glucosides, isoprenoids, and non-protein amino acids. Its antifungal mechanisms in fungal cells occur due to ergosterol, especially lanosterol 14a demethylase (CYP51) inhibition, which is one of the main target sites for antifungal activity because it functions to maintain the integrity and function of cell membranes in Candida. P. crocatum has an antifungal activity through its phytochemical profiling against fungal by inhibiting the lanosterol 14a demethylase, make damaging cell membranes, fungal growth inhibition, and fungal cell lysis.

Anti-Leishmania activity of extracts from Piper cabralanum C.DC. (Piperaceae).

Species of Piperaceae are known by biological properties, including antiparasitic such as leishmanicidal, antimalarial and in the treatment of schistosomiasis. The aim of this work was to evaluate the antileishmania activity, cytotoxic effect, and macrophage activation patterns of the methanol (MeOH), hexane (HEX), dichloromethane (DCM) and ethyl acetate (EtOAc) extract fractions from the leaves of Piper cabralanum C.DC. The MeOH, HEX and DCM fractions inhibited Leishmanina amazonensis promastigote-like forms growth with a half maximal inhibitory concentration (IC50) of 144.54, 59.92, and 64.87 µg/mL, respectively. The EtOAc fraction did not show any relevant activity. The half maximal cytotoxic concentration (CC50) for macrophages were determined as 370.70, 83.99, 113.68 and 607 µg/mL for the MeOH, HEX and DCM fractions, respectively. The macrophage infectivity was concentration-dependent, especially for HEX and DCM. MeOH, HEX and DCM fractions showed activity against L. amazonensis with low cytotoxicity to murine macrophages and lowering infectivity by the parasite. Our results provide support for in vivo studies related to a potential application of P. cabralanum extract and fractions as a promising natural resource in the treatment of leishmaniasis.

Metabolomic approach of the antiprotozoal activity of medicinal Piper species used in Peruvian Amazon.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Peruvian Amazon as in the tropical countries of South America, the use of medicinal Piper species (cordoncillos) is common practice, particularly against symptoms of infection by protozoal parasites. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point of this work was a set of interviews of people living in six rural communities from the Peruvian Amazon (Alto Amazonas Province) about their uses of plants from Piper genus: one community of Amerindian native people (Shawi community) and five communities of mestizos. Infections caused by parasitic protozoa take a huge toll on public health in the Amazonian communities, who partly fight it using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help to identify new antiprotozoal compounds. AIMS OF STUDY: To record and validate the use of medicinal Piper species by rural people of Alto Amazonas Province (Peru) and annotate active compounds using a correlation study and a data mining approach. MATERIALS AND METHODS: Rural communities were interviewed about traditional medication against parasite infections with medicinal Piper species. Ethnopharmacological surveys were undertaken in five mestizo villages, namely: Nueva Arica, Shucushuyacu, Parinari, Lagunas and Esperanza, and one Shawi community (Balsapuerto village). All communities belong to the Alto Amazonas Province (Loreto region, Peru). Seventeen Piper species were collected according to their traditional use for the treatment of parasitic diseases, 35 extracts (leaves or leaves and stems) were tested in vitro on P. falciparum (3D7 chloroquine-sensitive strain and W2 chloroquine-resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Assessments were performed on HUVEC cells and RAW 264.7 macrophages. The annotation of active compounds was realized by metabolomic analysis and molecular networking approach. RESULTS: Nine extracts were active (IC50 ≤ 10 µg/mL) on 3D7 P. falciparum and only one on W2 P. falciparum, six on L. donovani (axenic and intramacrophagic amastigotes) and seven on Trypanosoma brucei gambiense. Only one extract was active on all three parasites (P. lineatum). After metabolomic analyses and annotation of compounds active on Leishmania, P. strigosum and P. pseudoarboreum were considered as potential sources of leishmanicidal compounds. CONCLUSIONS: This ethnopharmacological study and the associated in vitro bioassays corroborated the relevance of use of Piper species in the Amazonian traditional medicine, especially in Peru. A series of Piper species with few previously available phytochemical data have good antiprotozoal activity and could be a starting point for subsequent promising work. Metabolomic approach appears to be a smart, quick but still limited methodology to identify compounds with high probability of biological activity.

Morphological and immunohistochemical study of the midgut and fat body of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: noctuidae) treated with essential oils of the genus Piper.

Essential oils are a promising alternative to insecticides. We investigated the LD50 of oils extracted from Piper corcovadensis, P. marginatum, and P. arboreum after 48 h topical contact with Spodoptera frugiperda larvae using morphometry, histochemistry and immunohistochemistry of the midgut and fat body. Chromatography revealed that E-caryophyllene was the principal compound common to the Piper species. The essential oils of P. corcovadensis, P. marginatum and P. arboreum caused deleterious changes in the midgut of S. frugiperda larvae. P. corcovadensis oil produced the lowest LD50 and significant histopathological alterations including elongation of the columnar cells, formation of cytoplasmic protrusions, reduction in carbohydrate, increased apoptotic index and decreased cell proliferation. P. arboreum oil caused histopathological alterations similar to P. corcovadensis, but caused the highest rate of cell proliferation and increased regenerative cells, which indicated rapid regeneration of the epithelium. Our findings demonstrated the insecticidal potential of P. corcovadensis for control of S. frugiperda owing to the significant damage it inflicted on S. frugiperda midgut.

Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies.

Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect via several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine.

Growth, photosynthetic pigments and production of essential oil of long-pepper under different light conditions

ABSTRACT Piper hispidinervum C. DC. is popularly known as long-pepper and it owns a commercial value due to the essential oil it produces. Long-pepper oil is rich in safrole and eugenoln components that have insecticidal, fungicidal and bactericidal activity. It has been establish that to medicinal plants light influences not only growth but also essential oil production. The growth, the content of photosynthetic pigments and the essential oil production of Piper hispidinervum at greenhouses with different light conditions was evaluated. The treatments were characterized by cultivation of plants for 180 days under different light conditions, produced by shading greenhouses with 50% and 30% of natural incident irradiance, two colored shading nets red (RN) and blue (BN) both blocking 50% of the incident radiation and one treatment at full-sun (0% of shade). The results showed that the treatments of 50% shade and RN and BN were the ones which stimulated the greater growth. Blue and red light also had the best production of photosynthetic pigments. Essential oil yielded more under full sun therefore this is the most indicated condition to produce seedlings for the chemical and pharmaceutical industry.

Growth, photosynthetic pigments and production of essential oil of long-pepper under different light conditions.

Piper hispidinervum C. DC. is popularly known as long-pepper and it owns a commercial value due to the essential oil it produces. Long-pepper oil is rich in safrole and eugenoln components that have insecticidal, fungicidal and bactericidal activity. It has been establish that to medicinal plants light influences not only growth but also essential oil production. The growth, the content of photosynthetic pigments and the essential oil production of Piper hispidinervum at greenhouses with different light conditions was evaluated. The treatments were characterized by cultivation of plants for 180 days under different light conditions, produced by shading greenhouses with 50% and 30% of natural incident irradiance, two colored shading nets red (RN) and blue (BN) both blocking 50% of the incident radiation and one treatment at full-sun (0% of shade). The results showed that the treatments of 50% shade and RN and BN were the ones which stimulated the greater growth. Blue and red light also had the best production of photosynthetic pigments. Essential oil yielded more under full sun therefore this is the most indicated condition to produce seedlings for the chemical and pharmaceutical industry.

[Concentrations of alkaloids, cyanogenic glycosides, polyphenols and saponins in selected medicinal plants from Ecuador and their relationship with acute toxicity against Artemia salina]. / Concentraciones de alcaloides, glucósidos cianogénicos, polifenoles y saponinas en plantas medicinales seleccionadas en Ecuador y su relación con la toxicidad aguda contra Artemia salina.

Alkaloids, polyphenols, cyanogenic glycosides and saponins are among the main chemical compounds synthesized by plants but not considered essential for their basic metabolism. These compounds have different functions in plants, and have been recognized with medicinal and pharmacological properties. In this research, concentrations of the mentioned secondary metabolites were determined in the medicinal plants Artemisia absinthium, Cnidoscolus aconitifolius, Parthenium hysterophorus, Piper carpunya and Taraxacum officinale, from Ecuador, and related with cytotoxic effects against Artemia salina. Alcoholic and aqueous extracts from leaves of these selected plants were prepared at different concentrations. To assess cytotoxicity of these extracts, different bioassays with A. salina were undertaken, and the mortality rates and LC50 were obtained. Besides, concentrations of alkaloids, cyanogenic glycosides, phenols, tannins and saponins were determined by spectrophotometric methods; this constituted the first report of quantification of secondary metabolites in the selected plants from Ecuador. T. officinale had the highest concentration of total phenols (22.30 ± 0.23 mg/g) and tannins (11.70 ± 0.10 mg/g), C. aconitifolius of cyanogenic glycosides (5.02 ± 0.37 µg/g) and P. hysterophorus of saponins (6.12 ± 0.02 mg/g). Tannins values obtained were not adverse to their consumption. Alcoholic and aqueous extracts of selected plants had hemolytic activity depending on the concentration of saponins. Although the values of cyanogenic glycosides were permissible, it was necessary to monitor the presence of this metabolite in plants to minimize health problems. LC50 values ranged from extremely toxic (3.37 µg/mL) to highly toxic (274.34 µg/mL), in P. carpunya and T. officinale, respectively. From correlation analysis, it was observed that increase values of alkaloids concentrations had highly significant (p<0.001) acute toxicity against A. salina, while at a higher polyphenol concentration the level of plants cytotoxicity decreased significantly (p<0.001). The results of principal component analysis showed that saponins apparently were in synergy with polyphenols to decrease cytotoxicity, but antagonize with alkaloids and cyanogenic glycosides, indicating that these secondary metabolites present variability in the mechanisms of action against A. salina, as cytotoxic compounds. These results also demonstrate that polyphenols and saponins can be lethal at low concentrations, demonstrating the potential of brine shrimp bioassay as a model to evaluate plant extracts containing low concentrations of chemical compounds with high polarities. The significant positive correlation between cytotoxicity and concentration of alkaloids confirmed by the bioassay of brine shrimp can be useful to identify promising sources of antitumor compounds, and to evaluate tolerable limits not affecting other benign cells. Contents of secondary metabolites found in the selected plants confer them great pharmacologic values.

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products.

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

Screening of polyphenolic compounds in Piper trioicum (Roxb. ) extracts / Cribado de compuestos polifenólicos en extractos de Piper trioicum (Roxb. )

Aims: Present study aims to reveal the polyphenol content in Piper trioicum (Roxb.) extracts. Materials and methods: In the present study, the phenolic content of the ethanol and water extracts of Piper trioicum (Roxb.) plants was determined by chromatography techniques like Thin layer chromatography, high performance thin layer Chromatography, high performance liquid chromatography and Gas chromatography with Mass spectrometric detection. Total phenol was determined by UV method. Results: All the results of analytical methods were compared with standard phenolic compounds. The ethanol extract contained maximum total phenolic content (2.323mg GAE/g) than the water extract. 13 compounds identified by chromatography techniques. The results suggested Arbutin, quercetin, caffeic acid, Ferulic acid, chlorogenic acid, Gallic acid and its derivatives may be present in ethanolic and water extracts of Piper trioicum. Conclusions: The water and ethanol could extract the highest concentration of polyphenols from the Piper trioicum (Roxb) plant; these extracts may have a good pharmacological potency due to the presence of polyphenols compounds

Objetivo: El presente estudio tiene como objetivo revelar el contenido de polifenoles en extractos de Piper trioicum ( Roxb. ). Materiales y métodos: El contenido de fenoles totales en los extractos etanólicos y acuosos de Piper trioicum ( Roxb. ) se determinó mediante técnicas cromatografías, como la cromatografía en capa fina, cromatografía en capa fina de alto rendimiento, cromatografía líquida de alta resolución y cromatografía de gases con espectrometría de masas detección. El contenido de fenoles totales se determinó por el método UV. Resultados: Los resultados de los métodos de análisis se compararon con compuestos fenólicos estándar . Los extractos de etanol tienen un contenido mayor de fenoles totales ( 2.323mg GAE / g ) que los extracto acuosos. Se han identificado 13 compuestos por técnicas de cromatografía . Los resultados sugirieron que arbutina, quercetina, ácido caféico, ácido ferúlico, ácido clorogénico, ácido gálico y sus derivados puede estar presente en los extractos etanólicos y acuoso de Piper trioicum. Conclusiones: El agua y el etanol podrían extraer la mayor concentración de polifenoles de la planta Piper trioicum (Roxb); estos extractos pueden tener un buen potencial farmacológico debido a la presencia de compuestos fenolicos

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

BACKGROUND: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. MATERIALS AND METHODS: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. RESULTS: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. CONCLUSIONS: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Histochemical visualization of ROS and antioxidant response to viral infections of vegetable crops grown in Azerbaijan.

Extremes of environmental conditions, such as biotic stresses, strongly affect plant growth and development and may adversely affect photosynthetic process. Virus infection is especially problematic in crops, because unlike other diseases, its impact cannot be reduced by phytosanitary treatments. The vegetable crops (Solanum lycopеrsicum L, Cucurbita melo L., Cucumis sativus L., Piper longum L., Solánum melongéna L., Vicia faba L.) showing virus-like symptoms were collected from fields located in the main crop production provinces of Azerbaijan. Infection of the plants were confirmed by Enzyme-linked immunosorbent assay using commercial kits for the following viruses: Tomato yellow leaf curl virus, Tomato mosaic virus, Tomato chlorosis virus, Melon necrotic spot virus and Cucumber mosaic virus, Bean common mosaic virus and Bean yellow mosaic virus. Generation sites of superoxide and hydrogen peroxide radicals and activities of enzymes involved in the detoxification of reactive oxygen species (catalase, glutathione reductase, ascorbate peroxidase, guaiacol peroxidase and superoxide dismutase) were examined in uninfected leaves and in leaves infected with viruses. High accumulation of superoxide and hydrogen peroxide radicals was visualized in infected leaves as a purple discoloration of nitro blue tetrazolium and 3,3'-diaminobenzidine tetrahydrochloride. It was found that the activities of APX and CAT significantly increased in all infected samples compared with non-infected ones. Dynamics of GR and Cu/Zn-SOD activities differed from those of CAT and APX, and slightly increased in stressed samples. Electrophoretic mobility profiling of APX, GPX and CAT isoenzymes was also studied.

Secondary metabolites from polar fractions of Piper umbellatum.

Seven known secondary metabolites were isolated from the methanol extract of the branches of Piper umbellatum. The identification of these compounds was mainly achieved by 2D NMR spectroscopic techniques and FAB-MS. Among them, the known cepharadiones A and B can be considered aschemotaxonomic markers of the genus Piper.

Piper peltatum: biomass and 4-nerolidylcatechol production.

Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerolidylcatechol (4-NC) is a valuable natural product that has important anti-inflammatory, antimalarial, and antioxidant properties. 4-NC is a component of P. peltatum and P. umbellatum extracts, which are used in cosmetics. The aim of this work was to evaluate the production of plant biomass and the production of 4-NC in roots of cultivated P. peltatum over a full life cycle. Seedlings were produced in a greenhouse and then transplanted. The weight of dry plant parts (leaves, stems, roots, and inflorescences); numbers of stems, leaves, and inflorescences; and the leaf-to-stem ratio were evaluated at intervals of 60 days after transplanting (DAT). Extracts were prepared using 1:1 ethanol-chloroform and an ultrasound bath. Roots, leaves, and inflorescences contained 4-NC according to TLC photodensitometry analysis. Quantification of 4-NC in root extracts was performed using HPLC-DAD analysis. Per-hectare production of 4-NC by roots was estimated based on quantitative HPLC analysis and biomass data. Optimal per-hectare yields of 4-NC were obtained by harvesting roots between 350 and 400 DAT. In this period, the average yield was 27 kg 4-NC per hectare. Importantly, at the time of maximal overall production of root biomass (470 DAT), there was a decrease in the production of 4-NC (23.8 kg/ha), probably due to the onset of senescence.

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.