Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

Oxidative stress induction by essential oil from Piper alatipetiolatum (Piperaceae) triggers lethality in the larvae of Culex quinquefasciatus (Diptera: Culicidae).

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.

Employing Piper longum extract for eco-friendly fabrication of PtPd alloy nanoclusters: advancing electrolytic performance of formic acid and methanol oxidation.

Advancement in bioinspired alloy nanomaterials has a crucial impact on fuel cell applications. Here, we report the synthesis of PtPd alloy nanoclusters via the hydrothermal method using Piper longum extract, representing a novel and environmentally friendly approach. Physicochemical characteristics of the synthesized nanoclusters were investigated using various instrumentation techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, and High-Resolution Transmission electron microscopy. The electrocatalytic activity of the biogenic PtPd nanoclusters towards the oxidation of formic acid and methanol was evaluated chronoamperometry and cyclic voltammetry studies. The surface area of the electrocatalyst was determined to be 36.6 m2g-1 by Electrochemical Surface Area (ECSA) analysis. The biologically inspired PtPd alloy nanoclusters exhibited significantly higher electrocatalytic activity compared to commercial Pt/C, with specific current responses of 0.24 mA cm - 2 and 0.17 mA cm - 2 at synthesis temperatures of 180 °C and 200 °C, respectively, representing approximately four times higher oxidation current after 120 min. This innovative synthesis approach offers a promising pathway for the development of PtPd alloy nanoclusters with enhanced electrocatalytic activity, thereby advancing fuel cell technology towards a sustainable energy solution.

Metabolite profiling of Piper longum L. fruit volatiles by two-dimensional gas chromatography and time-of-flight mass spectrometry: Insights into the chemical complexity.

Piper longum L. (long pepper) is an economically and industrially important medicinal plant. However, the characterization of its volatiles has only been analyzed by gas chromatography-mass spectrometry (GC-MS). In the present study, precise characterization of P. longum fruit volatiles has been performed for the first time through advanced two-dimensional gas chromatography-time-of-flight spectrometry (GC×GC-TOFMS). A total of 146 constituents accounting for 93.79% were identified, of which 30 were reported for the first time. All these constituents were classified into alcohols (4.5%), alkanes (8.9%), alkenes (6.71%), esters (6.15%), ketones (0.58%), monoterpene hydrocarbons (1.64%), oxygenated monoterpenes (2.24%), sesquiterpene hydrocarbons (49.61%), oxygenated sesquiterpenes (13.03%), phenylpropanoid (0.23%), and diterpenes (0.2%). Among all the classes, sesquiterpene hydrocarbons were abundant, with germacrene-D (2.87% ± 0.01%) as the major one, followed by 8-heptadecene (2.69% ± 0.03%), ß-caryophyllene (2.43% ± 0.03%), n-heptadecane (2.4% ± 0.04%), n-pentadecane (2.11% ± 0.05%), and so forth. Further, 20 constituents were observed to be coeluted and separated precisely in the two-dimensional column. The investigation provides an extensive metabolite profiling of P. longum fruit volatiles, which could be helpful to improve its therapeutic potential.

Chemical Composition of Piper nigrum L. Cultivar Guajarina Essential Oils and Their Biological Activity.

The essential oils and aroma derived from the leaves (L), stems (St), and spikes (s) of Piper nigrum L. cv. Guajarina were extracted; the essential oils were extracted using hydrodistillation (HD), and steam distillation (SD), and the aroma was obtained by simultaneous distillation and extraction (SDE). Chemical constituents were identified and quantified using GC/MS and GC-FID. Preliminary biological activity was assessed by determining the toxicity against Artemia salina Leach larvae, calculating mortality rates, and determining lethal concentration values (LC50). The predominant compounds in essential oil samples included α-pinene (0-5.6%), ß-pinene (0-22.7%), limonene (0-19.3%), 35 linalool (0-5.3%), δ-elemene (0-10.1%), ß-caryophyllene (0.5-21.9%), γ-elemene (7.5-33.9%), and curzerene (6.9-31.7%). Multivariate analysis, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), revealed three groups among the identified classes and two groups among individual compounds. The highest antioxidant activity was found for essential oils derived from the leaves (167.9 41 mg TE mL-1). Larvicidal potential against A. salina was observed in essential oils obtained from the leaves (LC50 6.40 µg mL-1) and spikes (LC50 6.44 µg mL-1). The in silico studies demonstrated that the main compounds can interact with acetylcholinesterase, thus showing the potential molecular interaction responsible for the toxicity of the essential oil in A. salina.

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases.

Nature is an important source of bioactive compounds and has continuously made a large contribution to the discovery of new drug leads. Particularly, plant-derived compounds have long been identified as highly interesting in the field of aging research and senescence. Many plants contain bioactive compounds that have the potential to influence cellular processes and provide health benefits. Among them, Piper alkaloids have emerged as interesting candidates in the context of age-related diseases and particularly senescence. These compounds have been shown to display a variety of features, including antioxidant, anti-inflammatory, neuroprotective, and other bioactive properties that may help counteracting the effects of cellular aging processes. In the review, we will put the emphasis on piperlongumine and other related derivatives, which belong to the Piper alkaloids, and whose senomodulating potential has emerged during the last several years. We will also provide a survey on their potential in therapeutic perspectives of age-related diseases.

N-Cinnamoylpyrrole-derived alkaloids from the genus Piper as promising agents for ischemic stroke by targeting eEF1A1.

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PURPOSE: The present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. METHODS: N-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. RESULTS: The results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. CONCLUSION: Our research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.

Undescribed (2-7')-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production.

A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.

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.

Tissue-specific variations of piperine in ten populations of Piper longum L.: bioactivities and toxicological profile.

P. longum L., one of the most significant species of the genus Piperaceae, is most frequently employed in Indian-Ayurvedic and other traditional medicinal-systems for treating a variety of illnesses. The alkaloid piperine, is the key phytoconstituent of the plant, primarily responsible for its' pharmacological-impacts. The aim of the study is to analyse the intra-specific variation in piperine content among different chemotypes (PL1 to PL 30) and identify high piperine yielding chemotype (elite-chemotype) collected from 10 different geographical regions of West Bengal by validated HPTLC chromatography method. The study also focused on the pharmacological-screening to better understand the antioxidant activity of the methanol extracts of P. longum by DPPH and ABTS radical-scavenging activity and genotoxic activity by Allium cepa root tip assay. It was found that the P. longum fruit chemotypes contain high amount piperine (highest 16.362 mg/g in chemotype PL9) than the stem and leaf chemotypes. Both DPPH and ABTS antioxidant assays revealed that P. longum showed moderate radical-scavenging activity and the highest activity was found in PL9 (fruit) chemotype with IC50 values of 124.2 ± 0.97 and 104 ± 0.78 µg/ml respectively. The A. cepa root tip assay showed no such significant genotoxic-effect and change in mitotic-index. The quick, reproducible, and validated HPTLC approach offers a useful tool for determining quantitative variations of piperine among P. longum chemotypes from different geographical-regions and also according to the different tissues and choose elite genotypes with high piperine production for continued propagation and commercialization for the pharmaceutical sector. Additionally, the plant's in-vitro antioxidant property and lack of genotoxicity directly supports its' widespread and long history of use as a medicinal and culinary plant.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Essential Oils from the Genus Piper Promote Antinociception by Modulating TRP Channels and Anti-Inflammatory Effects in Adult Zebrafish.

The Piper genus, known for its pharmacological potential, comprises 2,263 species primarily found in tropical regions. Despite recent advancements in pain therapies, the demand for more effective and well-tolerated analgesics and anti-inflammatories, particularly for chronic pain, remains. This study assessed the effects of essential oils from Piper caldense, Piper mosenii, and Piper mikanianum on nociceptive behavior induced by formalin and capsaicin, as well as their anti-inflammatory impact induced by carrageenan, using adult zebrafish models. Results indicated non-toxic essential oils with antinociceptive properties in both neurogenic and inflammatory phases of formalin-induced nociception through interaction with the TRPA1 receptor. Additionally, P. mosenii essential oil also blocked the nociceptive effect of capsaicin, a TRPV1 receptor agonist. Furthermore, essential oils from P. caldense and P. mikanianum exhibited significant anti-inflammatory effects by reducing carrageenan-induced abdominal edema. These findings highlight the pharmacological potential of Piper's essential oils as antinociceptive and anti-inflammatory agents.

Chemical Profile and Biological Activities Of Piper mikanianum (Kunth) Steud Essential Oil for Development and Improvement of Oral Rinse.

INTRODUCTION: Studies prove that the use of medicinal plants is a custom carried out by man since ancient times, the evolution of the pharmaceutical industry makes more people consume more natural products. Currently, we can observe that mouthwashes containing natural compounds have shown a growth in demand in the markets and in the professional community. OBJECTIVE: The present study aims to carry out the chemical characterization and microbiological potential of Piper mikanianum (Kunth) Steud essential oil (EOPm), providing data that allows the development of a low-cost mouthwash formulation aimed at vulnerable communities. METHODS: The evaluation of the antibacterial activity and modulator of bacterial resistance was performed by the microdilution method to determine the minimum inhibitory concentration (MIC). The chemical components were characterized by gas chromatography coupled to mass spectrometry, identified 28 constituents, in which Safrole Phenylpropanoid is the major compound, representing 72.6 % of the total composition, followed by α-pinene (10.7 %), Limonene (2 %), ß-caryophyllene (2 %), E-nerolidol (1.9 %), spathulenol (1.3 %) and camphene (1.1 %). RESULTS: The EOPm showed a MIC minimum inhibitory concentration≥1024 µg/mL for all bacterial strains used in the tests. When the EOPm modulating activity combined with chlorhexidine, mouthwash, ampicillin, gentamicin and penicillin G was evaluated against bacterial resistance, the oil showed significant synergistic activity, reducing the MIC of the products tested in combination, in percentage between 20.6 % to 98 .4 %. CONCLUSIONS: We recommend the expansion of tests with greater variation of EOPm concentration combinations and the products used in this study, as well as toxicity evaluation and in vivo tests, seeking the development of a possible low-cost mouthwash formulation accessible to the most vulnerable population.

Antifungal Constituents of Piper crocatum and Their Activities as Ergosterol Biosynthesis Inhibitors Discovered via In Silico Study Using ADMET and Drug-Likeness Analysis.

Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with -11.14, -12.78, -12.00, and -6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10-3, 4 × 10-4, 1.6 × 10-3, and 8.88 µM. On the other hand, an ADMET analysis of 1-3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans.

Network pharmacology-based anti-colorectal cancer activity of piperlonguminine in the ethanolic root extract of Piper longum L.

Colorectal cancer (CRC) has the second highest incidence and fatality rates of any malignancy, at 10.2 and 9.2%, respectively. Plants and plants-based products for thousands of years have been utilized to treat cancer along with other associated health issues. Alkaloids are a valuable class of chemical compounds with great potential as new medicine possibilities. Piper longum Linn contains various types of alkaloids. In this research, the ethanolic root extract of P. longum (EREPL) is the subject of study based on network pharmacology. Two alkaloids were chosen from the gas chromatography mass spectrometry (GC-MS) analysis. However, only piperlonguminine received preference because it adhered to Lipinski's rule and depicted no toxicity. Web tools which are available online, like, Swiss ADME, pkCSMand ProTox-II were used to evaluate the pharmacokinetics and physiochemical properties of piperlonguminine. The database that SwissTargetPrediction and TCMSP maintain contains the targets for piperlonguminine. Using DisGeNET, GeneCards and Open Targets Platform databases, we were able to identify targets of CRC. The top four hub genes identified by Cytoscape are SRC, MTOR, EZH2, and MAPK3. The participation of hub genes in colorectal cancer-related pathways was examined using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The colorectal cancer pathway, the ErbB signaling pathway and the mTOR signaling pathway emerged to be important. Our findings show that the hub genes are involved in the aforementioned pathways for tumor growth, which calls for their downregulation. Additionally, piperlonguminine has the potential to become a successful medicine in the future for the treatment of CRC.

Promotion of ABCG2 gene expression by neolignans from Piper longum L.

We focused on Piper longum L., a herbal drug produced in Myanmar, which has a renoprotective effect. Thus, we attempted to isolate and identify compounds that enhance the expression of the ABCG2 gene from the aerial parts of the plant except for the fruit. Among the various P. longum extracts, we isolated and identified the components. Using Caco-2 cells, the hABCG2 mRNA expression-enhancing effects of the isolated compounds were compared with the positive reference compound (3-methylcholanthrene [3MC]) using real-time polymerase chain reaction. Six compounds were isolated and identified from the methanol extract of P. longum. Among the isolated compounds, licarin A and neopomatene had lower toxicity and higher hABCG2 mRNA expression-enhancing effects in Caco-2 cells. Suppression of hAhR expression by siRNA reduced the activity of licarin A and neopomatene, as well as the hAhR agonist 3MC, suggesting that these 2 compounds may act as hAhR agonists to promote hABCG2 expression.

Piper chaba, an Indian spice plant extract, inhibits cell cycle G1/S phase transition and induces intrinsic apoptotic pathway in luminal breast cancer cells.

Piper chaba (Piperaceae) is a medicinal spice plant that possesses several pharmacological activities. In the present study, we for the first time studied the effect of P. chaba extract on breast cancer cells. P. chaba stem methanolic (PCSM) extract produced time and dose dependent cytotoxicity in luminal breast cancer cells (MCF-7 and T47D) with a minimal toxicity in breast normal cells (MCF-10A) at 10-100 µg/mL concentration. PCSM extract exerts 16.79 and 31.21 µg/mL IC50 for T47D and MCF-7 cells, respectively, in 48 h treatment. PCSM significantly arrests the T47D cells at the G0/G1 phase by reducing the CCND1 and CDK4 expression at mRNA and protein levels. PCSM extract treatment significantly altered nuclear morphology, mitochondria membrane potential, and production of reactive oxygen species in T47D cells at IC50 concentration. Extract treatment significantly altered the Bax/Bcl-2 ratio and altered caspase 8 and 3 mRNA/protein levels in T47D cells. Confocal microscopy showed an increase in late apoptosis in PCSM extract-treated breast cancer cells at IC50 . Further, an increased caspase 9 and caspase 3/7 enzymatic activity was observed in test cells compared with nontreated cells. In conclusion, P. chaba phytocompound possesses the potential to induce cell cycle arrest and induce apoptosis in luminal breast cancer cells.

Quality Control and Authentication of Black Betel Leaf Extract (Piper acre Blume) from East Kalimantan as an Antimicrobial Agent Using a Combination of High-Performance Liquid Chromatography and Chemometric Fourier Transform Infrared.

Black betel leaf from East Kalimantan contains various secondary metabolites such as alkaloid saponins, flavonoids, and tannins. A compound, piperenamide A, which has antimicrobial activity, is also found in black betel leaf. This study aims to identify and authenticate the compound piperenamide A found in black betel leaf extract in other types of betel plant using HPLC and FTIR-chemometrics. The extraction method used was maceration with 70% ethanol solvent. Determination of piperenamide A content in black betel leaf extract was via HPLC column C18, with a maximum wavelength of 259 nm and a mobile phase of water:acetonitrile at a flow rate of 1 mL/minute. From the results, piperenamide A was only found in black betel (Piper acre) and not in Piper betel and Piper crocatum. Piperenamide A levels obtained were 4.03, 6.84, 5.35, 13.85, and 2.15%, respectively, in the samples studied. The combination of FTIR spectra with chemometric methods such as PCA and PLS-DA was used to distinguish the three types of betel. Discriminant analysis can classify black betel (Piper acre), Piper betel, and Piper crocatum according to its type. These methods can be used for identification and authentication of black betel.

Water-soluble polysaccharides from Piper regnellii (Pariparoba) leaves: Structural characterization and antinociceptive and anti-inflammatory activities.

Piper regnellii is a plant popularly known as "Pariparoba" and it is widely used in folk medicine to treat pain, inflammation, among others. This work presents the extraction, purification and characterization of polysaccharides present in the plant leaves and evaluation of their anti-inflammatory and antinociceptive activities. From the crude aqueous extract of P. regnellii leaves, a polysaccharide fraction named PR30R, predominantly constituted of arabinose, galactose and galacturonic acid monosaccharide units, was obtained. Methylation and NMR analysis showed that the main polysaccharides of PR30R are a type II arabinogalactan, formed by a ß-D-Galp-(1 â†’ 3) main chain, substituted at O-6 by side chains of ß-D-Galp-(1 â†’ 6), which are substituted at O-3 by non-reducing α-L-Araf ends, and a homogalacturonan, formed by →4)-α-D-GalpA-(1→ units. Intraperitoneal administration of the crude polysaccharide fraction PRSF reduced significantly nociception induced by acetic acid in mice at the doses tested, and the PR30R fraction, derived from PRSF, presented antinociceptive and anti-inflammatory effects at a dose of 0.1096 mg/kg (PRSF ED50). These data support the use of the plant leaves in folk medicine as an herbal tea to treat pain and inflammation.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Melanoma is a deadly form of skin cancer that originates from melanocytes in the skin. Skin is a major barrier to drug delivery. Transferosome is a liquid nanoformulation that has the capacity for deeper skin penetration. The transferosome was prepared from standardized Piper longum fruit ethanolic extract (PLFEE) and loaded into gel to form a transgelosome for improved skin application and patient compliance. Compared with extract-loaded plain gel, the transgelosome showed good pharmaceutical properties with better activity in melanoma (B16F10)-bearing female C57BL/6 mice. The therapeutic activity of the standard anticancer drug dacarbazine was improved with the prepared PLFEE transgelosome.