Cubeb (Piper cubeba L.): nutritional value, phytochemical profiling and dermacosmeceutical properties.

Introduction: Cubeb, Piper cubeba L., has been used for centuries in traditional medicine and culinary practices, with a wide range of biological and pharmacological activities. Objective: Herein, we determined the phytochemical profile, mineral, fatty acids, and amino acid contents of P. cubeba berries and assessed the dermacosmeceutical properties of their water extract and essential oil (EO). These included assessing their antioxidant and antibacterial activities as well as their in vitro inhibitory activities against tyrosinase and elastase enzymes. In addition, molecular docking and molecular dynamics studies were performed on the major identified compounds of the EO. Results and discussion: A total of forty-three compounds belonging to organic acids, phenolic acids and flavonoids were found in the water extract, while 36 volatile compounds were identified in the EO with Z-isoeugenol, dihydroeugenol, ß-pinene, E-caryophyllene, and 1,8-cineole as major constituents. The berries were found to be rich in sodium and iron, have moderate zinc content along with low contents of total nitrogen, phosphorus, and potassium. Amino acid analysis revealed a considerable concentration of isoleucine and phenylalanine, whereas 11,14,17-eicosatrienoic acid and linoleic acid were identified as the major fatty acids. In the DPPH and FRAP assays, the water extract elicited considerable antioxidant activity compared to the reference compounds. Enzyme inhibitory assays revealed that the EO had a potential to inhibit tyrosinase and elastase enzymes with IC50 values of 340.56 and 86.04 µg/mL, respectively. The water extract and EO completely inhibited the bacterial growth at MIC of 50 mg/mL and 20%, respectively. At sub-MIC concentrations, the extract and the EO substantially reduced the biofilm formation by up to 26.63 and 77.77%, respectively, as well as the swimming and swarming motilities in a dose-dependent manner. Molecular docking and molecular dynamics showed that the five main components of P. cubeba EO could be the major contributors to the elastase and tyrosinase inhibitory effect. Conclusion: This study emphasizes the promising potential of P. cubeba as a valuable source of natural compounds that can be utilized for the development of innovative pharmaceuticals, dietary supplements, and dermacosmeceutical agents.

Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae).

The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30µg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.

Green synthesis and characterization of silver nanoparticles through the Piper cubeba ethanolic extract and their enzyme inhibitory activities.

Introduction: The area of "Green Synthesis of Nano-medicine," as compared to its synthetic counterparts, is a relatively safer research technology for various biomedical applications, including identification, therapeutic application, and prevention of pathological conditions, pain control, safety, and development of human wellness. The present study explored the synthesis and characterization of AgNPs using the ethanolic extract of Piper cubeba fruit as a reducing and stabilizing agent and its potential as an enzyme inhibitory agent. Urease inhibitors are helpful against many severe diseases, including gastric ulcers induced by Helicobacter pylori. Method: The fruits of the Piper cubeba plant were taken and ground to a fine powder. Plant material was added to 500 ml ethanol, and the mixture was filtered. The solvent of the filtrate was evaporated, and a thick, gummy extract was obtained and stored at 4°C in the refrigerator. AgNPs were green synthesized from solutions of AgNO3 using the P. cubeba extract, which was indicated by a change in the color from light brown to deep brown. The synthesized AgNPs were characterized via Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Results and Discussion: Analysis showed the reduction of Ag+ to Ag0 at room temperature (25°C), and the average particle size of AgNPs was in the range of 40-80 nm. Consequently, the synthesized AgNPs were evaluated for their anti-urease activity. The maximum urease inhibition of the Piper cubeba ethanolic extract was 88.5% at 5 mg conc., and of derived nanoparticles was 78.6% at 0.05 mg conc. The results were nearly similar to the control drug, i.e., thiourea (0.5 and 0.6 mM conc., respectively). Conclusion: The study concluded that the P. cubeba extract, as well as its green-derived AgNPs, might prove to be a better and safer substitute for their enzyme inhibitory potential in emerging medicine and novel drug delivery techniques to improve and maintain human health.

A review on multi-therapeutic potential of (-)-cubebin: experimental evidences.

Lignans are a large category of polyphenolic compounds that have low molecular weight and are widely distributed in the plant kingdom. They have been recognized for their potential antioxidizing and antiproliferative action. One of the most important lignans is cubebin which is abundantly isolated from the leaves and seeds of Piper cubeba and Piper nigrum. Cubebin possesses numerous biological actions such as antileukemic, trypanocidal, antimycobacterial, analgesic, anti-inflammatory, histamine antagonist, antifungal, and antispasmodic. This review discusses the in vitro and in vivo pharmacological studies on cubebin related to biochemistry and pharmacological applications and it ensures that it widely shows therapeutic potential. We expect that these therapeutic actions will set a new track in the formation of novel biological agents by the derivatization of cubebin. This review will assuredly fascinate countless researchers to begin further experimentation that might lead to novel agents for the treatment and prevention of diseases.

Cubeb (Piper cubeba L.f.): A comprehensive review of its botany, phytochemistry, traditional uses, and pharmacological properties.

Piper cubeba L.f. (Piperaceae), known as cubeb, is a popular traditional herbal medicine used for the treatment of many diseases, especially digestive and respiratory disorders. The plant is rich in essential oil, found mainly in fruits, and this makes it economically important. Many traditional utilizations have been also validated from the plant and its isolated compounds owing to their antioxidant, antibacterial, anti-inflammatory and anticancer effects. These biological activities are attributed to the phytochemicals (phenolic compounds, lignans and alkaloids) and the essential oil of the plant. The present work aims to provide an up-to-date review on the traditional uses, phytochemistry and pharmacology of the plant and discusses the future perspectives to promote its valorization for nutritional- and health-promoting effects.

In vitro and in silico cytotoxicity of hinokinin-loaded PLGA microparticle systems against tumoral SiHa cells.

This work aimed to synthesize poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles containing hinokinin (HNK) and to evaluate their cytotoxic activity against tumoral SiHa cells and non-tumoral HaCaT cells. Hinokinin was incorporated into PLGA (PLGA-HNK) with an encapsulation efficiency of 84.18 ± 2.32%. PLGA and PLGA-HNK were characterized by SEM microscopy and showed spherical morphology with an average size of ∼3.33. Encapsulation efficiency was determined by a calibration curve using UV-vis spectroscopy. PLGA-HNK more active inhibiting proliferation of SiHa cells (IC50 = 14.68 µM) than free HNK (IC50 = 225.5 µM). In relation to HaCaT cells, PLGA-HNK showed no significant difference compared to the negative control. These results led to an increase in HNK bioavailability and thereby, biological activity. In silico prediction analysis suggests that HNK is cytotoxic against SiHa cells with E6 and MDM2 inhibition as possible main mechanism of action.

Antimicrobial and Wound Healing Potential of a New Chemotype from Piper cubeba L. Essential Oil and In Silico Study on S. aureus tyrosyl-tRNA Synthetase Protein.

Piper cubeba is an important plant commonly known as cubeb or Java pepper, and it is cultivated for its fruit and essential oils, largely used to treat various diseases. Up to today, there was no scientific report on wound healing activity. Thus, this study was initiated to evaluate for the first time the antimicrobial activity and wound healing potential of a new chemotype from Piper cubeba essential oil (PCEO) from fruits. Thirteen microbial strains have been selected to investigate the antimicrobial potential of PCEO. For the evaluation of the wound healing potential, sixteen rats were excised on the dorsal back and divided into four groups. The effect of PCEO on the malondialdehyde (MDA) and superoxide dismutase (SOD) activities in the healed wound area of rats and the biochemical parameters and skin histological analysis were also assessed. Results: Data showed that PCEO exhibited a powerful antimicrobial potential especially against Listeria monocytogenes and Staphylococcus aureus. In addition, the topical application of PCEO cream appears to increase the SOD level, wound healing and contraction but reduced the MDA amount suggesting an impressive and a rapid cutaneous healing power. Additionally, histopathological analysis of the granulation tissue revealed that the derma is properly restored and arranged after treatment with PCEO. The docking analysis of PCEO constituents against S. aureus tyrosyl-tRNA synthetase enzyme showed binding energies values in the range of -7.2 to -4.8 kcal/mol. In conclusion, the topic use of PCEO healing cream showed significant effect in accelerating the healing process, which may be attributed to the synergetic effect of antioxidant and antimicrobial properties of PCEO volatile constituents, making it a relevant therapeutic agent for the management of wounds and therefore confirming the popular traditional uses of this plant.

Antioxidant Activities of a New Chemotype of Piper cubeba L. Fruit Essential Oil (Methyleugenol/Eugenol): In Silico Molecular Docking and ADMET Studies.

Piper cubeba L. fruit is an important species used in folk medicine for different types of pains such as rheumatism, chills, flu, colds, muscular aches, and fever. This study examines the chemical constituents, antioxidant activity, and potential inhibitory effect against human peroxiredoxin 5, a key enzyme of P. cubeba essential oil from fruits. Using gas chromatography coupled with mass spectrometry (GC-MS), the principal components were methyleugenol (41.31%) and eugenol (33.95%), followed by (E)-caryophyllene (5.65%), p-cymene-8-ol (3.50%), 1,8-cineole (2.94%), and α-terpinolene (1.41%). Results showed similar scavenging activity via 2,2-diphenyl-1-picrylhydrazyl DPPH radical scavenging activity (IC50 = 110.00 ± 0.08 µg/mL), as well as very potent antioxidant activity against both ferric reducing/antioxidant power (FRAP) (106.00 ± 0.11 µg/mL) and ß-carotene bleaching (IC50 = 315.00 ± 2.08 µg/mL) assays when compared to positive butylated hydroxytoluene and ascorbic acid. The molecular docking approach has also been performed to screen the antioxidant activities of the major and potent compounds against human protein target peroxiredoxin 5. Results showed good binding profiles and attributed the strongest inhibitory activity to ß-caryophyllene oxide (-5.8 kcal/mol), followed respectively by isocembrol and α-selinene (-5.4 kcal/mol), and viridiflorol (-5.1 kcal/mol). Furthermore, ADME (absorption, distribution, metabolism and excretion)-related physicochemical and pharmacokinetic properties have been assessed and support our in vitro findings. This work demonstrates the powerful antioxidant potency of cubeba pepper and paves the way for the discovery and development of antioxidant agent with high potency.

MsrA Efflux Pump Inhibitory Activity of Piper cubeba L.f. and its Phytoconstituents against Staphylococcus aureus RN4220.

MsrA, an efflux pump belonging to ATP-binding cassette (ABC) transporter family that conferred resistance to macrolides, was detected in Staphylococcus aureus strains. Herein, we report the isolation of phytoconstituents from Piper cubeba fruit methanol extract and investigated their efflux pump inhibitory potential against S. aureus MsrA pump. Four isolated compounds, viz. pellitorine, sesamin, piperic acid and tetrahydropiperine studied in combination with erythromycin in S. aureus RN4220, exhibited 2-8-fold reduction in minimum inhibitory concentration (MIC) of erythromycin. Pellitorine and sesamin decreased MIC of erythromycin by 8-fold. The real-time fluorometry-based efflux and accumulation studies of ethidium bromide (EtBr) on S. aureus RN4220 in the presence of these compounds showed reduced efflux and enhanced uptake, thus indicating inhibition of the efflux pump. Pellitorine showed significant post-antibiotic effect of erythromycin. The results revealed that the primary mechanism of action of these compounds involves steady ATP production impairment.

Biological Activities and Chemical Constituents of Essential Oils from Piper cubeba Bojer and Piper nigrum L.

In this study, we evaluated antioxidant, antihyperuricemic, and herbicidal activities of essential oils (EOs) from Piper cubeba Bojer and Piper nigrum L.; two pepper species widely distributed in tropics, and examined their chemical compositions. Dried berries of P. cubeba and P. nigrum were hydro-distilled to yield essential oil (EO) of 1.23 and 1.11% dry weight, respectively. In the antioxidant assay, the radical scavenging capacities of P. cubeba EO against DPPH and ABTS free radicals were 28.69 and 24.13% greater than P. nigrum, respectively. In the antihyperuricemic activity, P. cubeba EO also exhibited stronger inhibitory effects on xanthine oxidase (IC50 = 54.87 µg/mL) than P. nigrum EO (IC50 = 77.11 µg/mL). In the herbicidal activity, P. cubeba EO showed greater inhibition on germination and growth of Bidens pilosa and Echinochloa crus-galli than P. nigrum EO. Besides, P. cubeba EO decreased 15.98-73.00% of photosynthesis pigments of B. pilosa and E. crus-galli, while electrolyte leakages, lipid peroxidations, prolines, phenolics, and flavonoids contents were increased 10.82-80.82% at 1.93 mg/mL dose. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analyses revealed that P. nigrum and P. cubeba EOs principally possessed complex mixtures of monoterpenes and sesquiterpenes. Terpinen-4-ol (42.41%), α-copaene (20.04%), and γ-elemene (17.68%) were the major components of P. cubeba EO, whereas ß-caryophyllene (51.12%) and ß-thujene (20.58%) were the dominant components of P. nigrum EO. Findings of this study suggest both P. cubeba and P. nigrum EOs were potential to treat antioxidative stress and antihyperuricemic related diseases. In addition, the EOs of the two plants may be useful to control B. pilosa and E. crus-galli, the two invasive and problematic weeds in agriculture practice.

Wound healing evaluation of self-nanoemulsifying drug delivery system containing Piper cubeba essential oil.

The objective of this work was to characterize and evaluate wound healing potential of Piper cubeba oil (PO) via self-nanoemulsifying drug delivery system (SNEDDS) in comparison with standard gentamycin. PO loaded SNEDDS was prepared by low energy emulsification technique and characterized for thermodynamic stability, self-emulsification power and various physico-chemical parameters. An optimal formula of PO SNEDDS was subjected to wound healing evaluation, collagen determination and histomorphological examination in female Wistar rats as compared with pure PO and standard antibiotic/gentamycin. An optimal formula of PO SNEDDS showed significant wound healing effects in Wistar female rats in comparison with pure PO. However, wound healing effects of optimized SNEDDS were comparable with standard gentamycin. An optimized formulation also indicated significant enhancement in collagen content (0.82 mg/g) in comparison with pure PO (0.53 mg/g) and negative control (0.33 mg/g). While, the collagen content of SNEDDS (0.82 mg/g) treated rats were comparable with standard gentamycin treated animals (0.98 mg/g). Histopathological examinations of optimized SNEDDS treated animals showed no signs of inflammatory cells which indicated that prepared SNEDDS was safe and nontoxic to rats. The results obtained in this work showed the potential application of SNEDDS in enhancement of the wound healing activity of PO upon oral administration.

Development of a Validated High-Performance Liquid Chromatography Method and Optimization of the Extraction of Lignans from Piper cubeba.

Piper cubeba L. f. is a food seasoning, which contains secondary metabolites displaying several biological properties, such as cytotoxic, anti-inflammatory, and antiparasitic activities. The lignans (+)-dihydroclusin, (-)-clusin, (-)-cubebin, (-)-yatein, and (-)-haplomyrfolin were isolated, with (-)-haplomyrfolin reported for the first time in P. cubeba seeds. Chromatographic standards were used to develop a reliable reverse-phase high-performance liquid chromatography analytical method according to the Agência Nacional de Vigilância Sanitária and International Conference on Harmonization guidelines to quantitate these lignans in both P. cubeba seeds and their extracts. The extraction of the lignans was also optimized, with the best conditions being ultrasound-assisted extraction, with 84% aqueous ethanol for 38 min in a single extraction. This procedure allows for the extraction of more than 80% of the total lignans, which is better in comparison to other techniques, such as maceration and Soxhlet extraction.

Evaluation of Lignans from Piper cubeba against Schistosoma mansoni Adult Worms: A Combined Experimental and Theoretical Study.

Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value.

Effect of Piper cubeba L. fruit on ethylene glycol and ammonium chloride induced urolithiasis in male Sprague Dawley rats.

BACKGROUND: To investigate the antilithiatic effect of hydroalcoholic extract of Kabab Chini (Piper cubeba L.) fruit in male Sprague Dawley rats. METHODS: Rats were divided into six groups of six each. Group I received regular rat food and drinking water ad libitum. Groups II to VI were administered with ethylene glycol (EG) 0.75% (V/V) and ammonium chloride (AC) 1% (W/V) in drinking water for 7 days to induce urolithiasis. From 8th day Group I received 1 mL of 5% gum acacia. Group IV was treated with Cystone; V and VI groups with the hydro-alcoholic extract of Piper cubeba L. Treatment was continued for further 14 days, thereafter animals sacrificed. While Group II animals were sacrificed just after 7 days treatment with EG and AC. Group III was left untreated until 14 days and sacrificed on 22nd day. Crystalluria was analyzed on 8th and 22nd day while, urinary calcium, phosphorus, creatinine, sodium and magnesium on 22nd day. Biochemistry and histopathological studies of kidney were also carried out. RESULTS: Test groups showed significant reduction (p < 0.001) of crystals in urine. Serum creatinine and urea (p < 0.01) were also decreased significantly. Urine analysis showed significant increase in magnesium while calcium, sodium, chloride and phosphorus significantly decreased along with histopathological improvement in kidney tissue in treated groups. CONCLUSION: From the above results it can be concluded that hydroalcoholic extract of P. cubeba L. fruit has significant inhibitory effect in calcium oxalate urolithiasis.

Antioxidant properties and anti-mutagenic potential of Piper Cubeba fruit extract and molecular docking of certain bioactive compounds.

Spices and herbs are recognized as sources of natural antioxidants and thus play an important role in the chemoprevention of diseases and aging. Piper cubeba is one among them and known for its medicinal properties for decades. Various biological activities are associated with its extract and phytocompounds. However, the anti-mutagenic activity of antioxidant rich extract is less explored. In this study, we performed the fraction-based antioxidant activity of P. cubeba using four different assays and evaluated the anti-mutagenic activity of most potent antioxidant fraction using Salmonella typhimurium tester strains against four mutagens (methyl methanesulfonate [MMS], sodium azide [SA], benzo(a)pyrene, and 2-aminoflourene) respectively. Among all tested fractions at 25-200 µg/ml, ethanolic extract revealed highest antioxidant activity and significant anti-mutagenicity against both direct and indirect acting mutagens at least one tester strain. Phytochemical analysis by gas chromatography-mass spectrometry (GC/MS) revealed the presence of various phytocompounds including copaene, isocaryophyllene, α-cubebene, etc. Molecular docking studies on DNA binding interactions of GC/MS detected phytocompounds highlight the possible mode of binding. In summary, these in vitro studies have provided the scientific basis for validation of using this plant in the traditional system of medicine and highlighted the need for exploring the role of various compounds for therapeutic efficacy. On the other hand, synergistic interaction among phytocompounds is to be explored to optimize or standardize the extracts for the exploitation in modern phytomedicine.

Development and Evaluation of Naproxen Sodium Gel Using Piper cubeba for Enhanced Transdermal Drug Delivery and Therapeutic Facilitation.

BACKGROUND: The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents. OBJECTIVE: The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients. METHOD: Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP). RESULT: The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61µg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer. CONCLUSION: It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed.

Effects of Piper cubeba L. essential oil on methicillin-resistant Staphylococcus aureus: an AFM and TEM study.

The increasing prevalence of antibiotic-resistant bacteria is creating a real challenge for health care systems worldwide, making the development of novel antibiotics a necessity. In addition to the development of new antibiotics, there is an urgent need for in-depth characterization of the mechanisms of bacterial resistance toward new drugs. Here, we used essential oils extracted in our laboratory from Piper cubeba against methicillin-resistant Staphylococcus aureus ATCC 43300, one of the most prominent antibiotic-resistant bacteria. Effects of the essential oils extracted from P cubeba on bacteria were mainly evaluated using 2 powerful microscopy techniques: atomic force microscopy and transmission electron microscopy. High-resolution atomic force microscopy images of the cells were obtained close to their native environment by immobilizing the cells on porous Polyether sulfone membranes, which were prepared in our laboratory with a wide range and distribution of pore sizes and depth. Inhibition zones (mm) and minimum inhibitory concentrations were determined. Two different concentrations of the oil were used to treat the cells: 50 µg/mL minimum inhibitory concentration and 25 µg/mL. The 50 µg/mL oil solution caused severe damage to the bacterial cells at microscopic levels while the 25 µg/mL solution showed no effects compared to the control. However, at nanoscopic levels, the 25 µg/mL oil solution caused significant changes in the cell wall, which could potentially impair bacterial activities. These results were also confirmed by transmission electron microscopy micrographs. Our results indicate that the extract has a good biological activity against methicillin- and oxacillin-resistant S aureus and that it acts on the cell wall and plasma (cytoplasmic) membrane.

In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.

Parâmetros sanguíneos de frangos de corte alimentados com dietas suplementadas com sementes secas de Piper cubeba como aditivo fitogênico / Blood parameters of broiler chickens fed diets supplemented with dried seeds of Piper cubeba as an phytogenic additive

Dois experimentos foram realizados com o objetivo de avaliar o uso das sementes secas de Piper cubeba nas dietas de frangos de corte de 1 a 21 dias de idades e seus efeitos sobre o perfil bioquímicos do sangue e na biometria dos órgãos das aves. Em cada experimento 240 pintos de corte machos, com um dia de idade da linhagem Cobb foram distribuídos em um delineamento inteiramente casualizado, com cinco tratamentos e quatro repetições de 12 aves por parcela experimental. No primeiro experimento foi avaliado o uso da Piper cubeba em dietas consideradas de alta digestibilidade, a base de milho e farelo de soja, e no segundo avaliou-se o uso da pimenta em dietas de baixa digestibilidade, as quais foram obtidas com a inclusão de farinha de carne e ossos. Com relação aos dados de perfil bioquímico sanguíneo do experimento I, com exceção da gama glutamil transferase, todos os demais níveis séricos se apresentaram dentro dos limites recomendados para aves, e apenas os níveis de triglicerídeos diferiram entre os tratamentos (P<0,05). No experimento II houve diferença significativa para os níveis de albumina, colesterol e ácido úrico, porém isso não foi resultado de desordens metabólicas, visto que com exceção da gama glutamil transferase, todos os níveis encontraram-se dentro dos limites recomendados. Em ambos os experimentos não foram observadas diferenças (P>0,05) para a biometria dos órgãos. Nas condições em que os experimentos foram realizados a inclusão das sementes de Piper cubeba na ração para frangos de corte não proporcionou alterações bioquímicas e biométricas que possam limitar seu uso como material vegetal para os estudos fitogênicos.(AU)

Two experiments were conducted to evaluate the use of dried seeds of Piper cubeba in the diets of 1 to 21-day-old broilers and its effect on biochemical blood profile and biometry of the organs. In each experiment, 240 one-day-old male broiler chicks Cobb were distributed in a completely randomized design with five treatments and four replicates of 12 birds per experimental plot. The first experiment evaluated the use of Piper cubeba in considered highly digestible diets based on corn and soybean meal, and the second evaluated the use of pepper in low digestibility diets, which were obtained with the inclusion of meat and bone meal. Regarding the blood chemistry profile data of the experiment I, with the exception of gamma glutamyl transferase, all other serum levels were within recommended limits for poultry, and only triglyceride levels differed between treatments (P <0.05). In the second experiment there was significant difference in albumin levels, cholesterol and uric acid, but this was not the result of metabolic disorders, because except for the gama glutamyl transferase levels, all variables were within recommended levels. In both experiments, there were no differences (P> 0.05) for the biometry of organs. The conditions under which the experiments were performed at inclusion of Piper cubeba seeds in feed for broilers has not provided any toxicity to poultry.(AU)

Antibacterial activity of (-)-cubebin isolated from Piper cubeba and its semisynthetic derivatives against microorganisms that cause endodontic infections

Abstract Recent publications have highlighted the numerous biological activities attributed to the lignan (-)-cubebin (1), Piper cubeba L. f., Piperaceae, and ongoing studies have focused on its structural optimization, in order to obtain derivatives with greater pharmacological potential. The aim of this study was the obtainment of (1), its semisynthetic derivatives and evaluation of antibacterial activity. The extract of the seeds of P. cubeba was chromatographed, subjected to recrystallization and was analyzed by HPLC and spectrometric techniques. It was used for the synthesis of: (-)-O-methylcubebin (2), (-)-O-benzylcubebin (3), (-)-O-acetylcubebin (4), (-)-O-(N, N-dimethylamino-ethyl)-cubebin (5), (-)-hinokinin (6) and (-)-6.6'-dinitrohinokinin (7). The evaluation of the antibacterial activity has been done by broth microdilution technique for determination of the minimum inhibitory concentration and the minimum bactericidal concentration against Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces naeslundii, Bacteroides fragilis and Fusobacterium nucleatum. It was possible to make an analysis regarding the relationship between structure and antimicrobial activity of derivatives against microorganisms that cause endodontic infections. The most promising were minimum inhibitory concentration =50 µg/ml against P. gingivalis by (2) and (3), and minimum inhibitory concentration =100 µg/ml against B. fragilis by (6). Cytotoxicity assays demonstrated that (1) and its derivatives do not display toxicity.