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.

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.

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.

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.

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.

Chemical Composition, Preliminary Toxicity, and Antioxidant Potential of Piper marginatum Sensu Lato Essential Oils and Molecular Modeling Study.

The essential oils (OEs) of the leaves, stems, and spikes of P. marginatum were obtained by hydrodistillation, steam distillation, and simultaneous extraction. The chemical constituents were identified and quantified by GC/MS and GC-FID. The preliminary biological activity was determined by assessing the toxicity of the samples to Artemia salina Leach larvae and calculating the mortality rate and lethal concentration (LC50). The antioxidant activity of the EOs was determined by the DPPH radical scavenging method. Molecular modeling was performed using molecular docking and molecular dynamics, with acetylcholinesterase being the molecular target. The OES yields ranged from 1.49% to 1.83%. The EOs and aromatic constituents of P. marginatum are characterized by the high contents of (E)-isoosmorhizole (19.4-32.9%), 2-methoxy-4,5-methylenedioxypropiophenone (9.0-19.9%), isoosmorhizole (1.6-24.5%), and 2-methoxy-4,5-methylenedioxypropiophenone isomer (1.6-14.3%). The antioxidant potential was significant in the OE of the leaves and stems of P. marginatum extracted by SD in November (84.9 ± 4.0 mg TE·mL-1) and the OEs of the leaves extracted by HD in March (126.8 ± 12.3 mg TE·mL-1). Regarding the preliminary toxicity, the OEs of Pm-SD-L-St-Nov and Pm-HD-L-St-Nov had mortality higher than 80% in concentrations of 25 µg·mL-1. This in silico study on essential oils elucidated the potential mechanism of interaction of the main compounds, which may serve as a basis for advances in this line of research.

Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells.

Piper longum L. is widely cultivated for food, medicine, and other purposes in tropical and subtropical regions. Sixteen compounds including nine new amide alkaloids were isolated from the roots of P. longum. The structures of these compounds were determined by spectroscopic data. All compounds showed better anti-inflammatory activities (IC50 = 1.90 ± 0.68-40.22 ± 0.45 µM) compared to indomethacin (IC50 = 52.88 ± 3.56 µM). Among the isolated compounds, five dimeric amide alkaloids exhibited synergistic effects with three chemotherapeutic drugs (paclitaxel, adriamycin, or vincristine) against cervical cancer cells. Moreover, these dimeric amide alkaloids also enhanced the efficacy of paclitaxel in paclitaxel-resistant cervical cancer cells. The combination treatment of one of these dimeric amide alkaloids and paclitaxel promoted cancer cell apoptosis, which is related to the Src/ERK/STAT3 signaling pathway.

Chemical Constituents and Biological Activities of Piper as Anticancer Agents: A Review.

Cancer has become the primary cause of death worldwide, and anticancer drugs are used to combat this disease. Synthesis of anticancer drugs has limited success due to adverse side effects has made compounds from natural products with minimal toxicity gain much popularity. Piper species are known to have a biological effect on human health. The biological activity is due to Piper species rich with active secondary metabolites that can combat most diseases, including cancer. This review will discuss the phytochemistry of Piper species and their anticancer activity. The identification and characterization of ten active metabolites isolated from Piper species were discussed in detail and their anticancer mechanism. These metabolites were mainly found could inhibit anticancer through caspase and P38/JNK pathways. The findings discussed in this review support the therapeutic potential of Piper species against cancer due to their rich source of active metabolites with demonstrated anticancer activity.

Volatile Metabolites of Piper eriopodon (Miq.) C.DC. from Northern Region of Colombia and Assessment of In Vitro Bioactivities of the Leaf Essential Oil.

Piper eriopodon is one of the Piper species found in the Sierra Nevada de Santa Marta, and the species has been reported with different compositions of their essential oils (EO). In this study, the volatile fractions/essential oil (by HS-SPME/SDE/MWHD-GC-MS/1H-NMR) of different parts from the plant were characterized, and assessments of the in vitro bio-properties of the leaf EO were conducted. The results indicated the following: (i) in the volatile fractions were ß-caryophyllene (~23%)/myrcene (~20%) (inflorescences) and ß-caryophyllene (~43%)/ß-selinene (~20%) (leaves) using HS-SPME; myrcene (~31%)/ß-pinene (~23%) (inflorescences), gibbilimbol B (~60%) (fruits) and gibbilimbol B (~46%)/ß-caryophyllene (~11%) (leaves) through SDE; (ii) leaf EO contained gibbilimbol B (~72%), confirmed with 1H-NMR; (iii) the cytotoxic values (µg/mL) in erythrocytes/lymphocytes/Hep-2 were HC50: 115 ± 3 (eryth.), LC50: 71 ± 4 (lymph.) and LC50: 33 ± 2 (cell-line); (iv) the antibacterial susceptibilities (ϕ inh. zone, mm; 4-16 µg EO) were 22.5 ± 0.4-97 ± 4 (Staphylococcus aureus), 23 ± 2-77 ± 4 (Escherichia coli) and 17 ± 1-48 ± 3 (Listeria monocytogenes); (v) the TAA value was 2249 ± 130 mmol Trolox®/kg; (vi) the IC50 value was 13±1 µg/mL (AChE) with 20 ± 0-37 ± 6% repellency (2-4 h, Sitophilus zeamais). Thus, the EO of P. eriopodon leaves from northern Colombia could be a promising species for sustainable exploitation in the future due to its outstanding bioactivities.

Antifungal activity and metabolomics analysis of Piper sarmentosum extracts against Fusarium graminearum.

AIMS: Fusarium graminearum is a toxic fungus that affects food and feed crops. Piper sarmentosum extract (PSE) is a potential source of anti-mildew natural products for the food and feed industry due to its various pharmacological properties. In this study, we evaluated the antifungal activity and untargeted metabolomics analysis of PSE against F. graminearum. METHODS AND RESULTS: Antifungal activity was evaluated using the mycelium growth rate method. Untargeted metabolomics analysis of PSE was performed using ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that PSE (1 and 2 mg ml-1) possesses inhibitory activity against F. graminearum, and a total of 17 compounds that including 8 alkaloids, 3 phenols, 3 lipids, and 3 organic acids might be the antifungal markers in PSE. Metabolomics analysis further revealed that PSE could significantly increase the levels of guanosine, guanine, adenosine, and L-isoleucine in fungi, which are related to purine and L-isoleucine metabolic pathways. CONCLUSIONS: PSE is a promising anti-mildew agent that inhibits the growth of F. graminearum in food and feed. PSE (1 and 2 mg ml-1) may exert antifungal properties by inhibiting fungal purine nucleotide synthesis and enhancing the level of L-isoleucine compared with the control groups.

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.

Exploring functional and structural features of chemically related natural prenylated hydroquinone and benzoic acid from Piper crassinervium (Piperaceae) on bacterial peroxiredoxin inhibition.

Multiple drug resistance (MDR) bacterial strains are responsible by 1.2 million of human deaths all over the world. The pathogens possess efficient enzymes which are able to mitigate the toxicity of reactive oxygen species (ROS) produced by some antibiotics and the host immune cells. Among them, the bacterial peroxiredoxin alkyl hydroperoxide reductase C (AhpC) is able to decompose efficiently several kinds of hydroperoxides. To decompose their substrates AhpC use a reactive cysteine residue (peroxidatic cysteine-CysP) that together with two other polar residues (Thr/Ser and Arg) comprise the catalytic triad of these enzymes and are involved in the substrate targeting/stabilization to allow a bimolecular nucleophilic substitution (SN2) reaction. Additionally to the high efficiency the AhpC is very abundant in the cells and present virulent properties in some bacterial species. Despite the importance of AhpC in bacteria, few studies aimed at using natural compounds as inhibitors of this class of enzymes. Some natural products were identified as human isoforms, presenting as common characteristics a bulk hydrophobic moiety and an α, ß-unsaturated carbonylic system able to perform a thiol-Michael reaction. In this work, we evaluated two chemically related natural products: 1,4-dihydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzene (C1) and 4-hydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzoic acid (C2), both were isolated from branches Piper crassinervium (Piperaceae), over the peroxidase activity of AhpC from Pseudomonas aeruginosa (PaAhpC) and Staphylococcus epidermidis (SeAhpC). By biochemical assays we show that although both compounds can perform the Michael addition reaction, only compound C2 was able to inhibit the PaAhpC peroxidase activity but not SeAhpC, presenting IC50 = 20.3 µM. SDS-PAGE analysis revealed that the compound was not able to perform a thiol-Michael addition, suggesting another inhibition behavior. Using computer-assisted simulations, we also show that an acidic group present in the structure of compound C2 may be involved in the stabilization by polar interactions with the Thr and Arg residues from the catalytic triad and several apolar interactions with hydrophobic residues. Finally, C2 was not able to interfere in the peroxidase activity of the isoform Prx2 from humans or even the thiol proteins of the Trx reducing system from Escherichia coli (EcTrx and EcTrxR), indicating specificity for P. aeruginosa AhpC.

Characterization and Bioactive Potential of Secondary Metabolites Isolated from Piper sarmentosum Roxb.

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant in South-East Asian countries. The chemical investigation of leaves from this species resulted in the isolation of three previously not described compounds, namely 4″-(3-hydroxy-3-methylglutaroyl)-2″-ß-D-glucopyranosyl vitexin (1), kadukoside (2), and 6-O-trans-p-coumaroyl-D-glucono-1,4-lactone (3), together with 31 known compounds. Of these known compounds, 21 compounds were isolated for the first time from P. sarmentosum. The structures were established by 1D and 2D NMR techniques and HR-ESI-MS analyses. The compounds were evaluated for their anthelmintic (Caenorhabditis elegans), antifungal (Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (Aliivibrio fischeri) and cytotoxic (PC-3 and HT-29 human cancer cells lines) activities. Methyl-3-(4-methoxyphenyl)propionate (8), isoasarone (12), and trans-asarone (15) demonstrated anthelmintic activity with IC50 values between 0.9 and 2.04 mM. Kadukoside (2) was most active against S. tritici with IC50 at 5.0 µM and also induced 94% inhibition of P. infestans growth at 125 µM. Trans-asarone (15), piperolactam A (23), and dehydroformouregine (24) displayed a dose-dependent effect against B. cinerea from 1.5 to 125 µM up to more than 80% inhibition. Paprazine (19), cepharadione A (21) and piperolactam A (23) inhibited bacterial growth by more than 85% at 100 µM. Only mild cytotoxic effects were observed.

Neuroprotective potential of lignan-rich fraction of Piper cubeba L. by improving antioxidant capacity in the rat's brain.

Piper cubeba contains various types of lignans. These compounds have been found to have potential pharmacological activities, one being a neuroprotector through an antioxidant mechanism, especially in the brain. This study examined the antioxidant activity of the lignan-rich fraction of P. cubeba (LF) in rat brains. The rats were given LF (200 and 400 mg/kg), Vitamin C (200 mg/kg), and a carrier as the control group for one-week p.o. The following day, rat brains were collected for antioxidant tests, including examining lipid peroxide inhibition, superoxide dismutase and catalase activity, and determination of nitric oxide (NO) concentration. The phytochemical compounds were analyzed with thin-layer chromatography (TLC), ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS), and gas chromatography-mass spectrometry (GC-MS). Test results show that the LF of both doses of 200 and 400 mg/kg could significantly increase antioxidant activity in the brain by inhibiting lipid peroxidation. LF could also increase catalase, despite the decrease in superoxide dismutase activity. Reduction in NO only occurred in the LF-200 group, while LF-400 showed insignificant results compared to the control group. In conclusion, LF showed potential as an antioxidant in the brain and could be beneficial for treating neurological diseases.

Amino acids L-phenylalanine and L-lysine involvement in trans and cis piperamides biosynthesis in two Piper species.

Several Piper species accumulate piperamides as secondary metabolites, and although they have relevant biological importance, many details of their biosynthetic pathways have not yet been described experimentally. Experiments involving enzymatic reactions and labeled precursor feeding were performed using the species Piper tuberculatum and Piper arboreum. The activities of the phenylalanine ammonia lyase (PAL) enzymes, which are involved in the general phenylpropanoid pathway, were monitored by the conversion of the amino acid L-phenylalanine to cinnamic acid. The activity of the 4-hydroxylase (C4H) enzyme was also observed in P. tuberculatum by converting cinnamic acid to p-coumaric acid. L-[UL-14C]-phenylalanine was fed into the leaves of P. tuberculatum and incorporated into piperine (1), 4,5-dihydropiperine (2), fagaramide (4), trans-piplartine (7), and dihydropiplartine (9). In P. arboreum, it was only incorporated into the piperamide 4,5-dihydropiperiline (3). L-[UL-14C]-lysine was successfully incorporated into the 4,5-dihydropiperine piperidine group (2), dihydropyridinone, and trans- (7) and cis-piplartine (8). These data corroborate the proposal of mixed biosynthetic origin of piperamides with the aromatic moiety originating from cinnamic acid (shikimic acid pathway) and key amide construction with amino acids as precursors.

The potential role of Piper guineense (black pepper) in managing geriatric brain aging: a review.

Brain aging is one of the unavoidable aspects of geriatric life. As one ages, changes such as the shrinking of certain parts (particularly the frontal cortex, which is vital to learning and other complex mental activities) of the brain may occur. Consequently, communications between neurons are less effective, and blood flow to the brain could also decrease. Efforts made at the biological level for repair become inadequate, leading to the accumulation of ß-amyloid peptide in the brain faster than its probable degradation mechanism, resulting in cognitive malfunction. Subsequent clinical usage of drugs in battling related brain-aging ailments has been associated with several undesirable side effects. However, recent research has investigated the potential use of natural compounds from food in combating such occurrences. This review provides information about the use of Piper guineense (black pepper) as a possible agent in managing brain aging because of its implications for practical brain function. P. guineense contains an alkaloid (piperine) reported to be an antioxidant, anti-depressant, and central nervous system stimulant. This alkaloid and other related compounds are neuroprotective agents that reduce lipid oxidation and inhibit tangles in the brain tissues.

Neolignans and polyoxygenated seco-cyclohexenes from the stems and leaves of Piper suipigua Buch.-Ham. ex D. Don.

Five new compounds including, a neolignan, eupomatenoid-19 (1) and four polyoxygenated seco-cyclohexenes, artahongkongenes G-J (2-5), together with fifteen known compounds (6-20) were isolated from the stems and leaves of Piper suipigua Buch.-Ham. ex D. Don. Their structures were determined by spectroscopic evidence (IR, UV, 1H NMR, 13C NMR and 2 D NMR) as well as MS. The absolute configurations of polyoxygenated seco-cyclohexenes 2-8 were identified by NOESY data and by comparison of their experimental and calculated ECD spectral data. Neolignans, eupomatenoid-19 (1) and eupomatenoid-7 (10), displayed cytotoxicity against several cancer cell lines. In addition, eupomatenoid-7 (10) showed antibacterial activity against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus.

Seasonal variation of the composition of essential oils from Piper cernuum Vell and Piper rivinoides Kunth, ADMET study, DFT calculations, molecular docking and dynamics studies of major components as potent inhibitors of the heterodimer methyltransferase complex NSP16-NSP10 SARS COV-2 protein.

Coronavirus disease (COVID-19) has the virus that causes the SARS-CoV-2 severe acute respiratory syndrome, which has reached a pandemic proportion, with thousands of deaths worldwide already registered. It has no standardized effective clinical treatment, arousing the urgent need for the discovery of bioactive compounds for the treatment of symptoms of COVID-19. In this context, the present study aimed to evaluate the influence of seasonality on the yield and chemical composition of the essential oils of Piper cernuum and Piper rivinoides as well as to evaluate the anti-SARS-CoV-2 potential of the major components of each oil by molecular docking and quantum chemical calculation (Density Functional Theory method), being possible indicate that the winter and autumn periods, the seasons of the year where it is possible to obtain the highest percentage of Piper cernuum and Piper rivinoides oils, respectively. Regarding the anti-SARS-Cov-2 potential, the present work showed that the dihydroagarofuran present in Piper cernuum, presented a strong interaction with amino acid residues from Mpro, presenting a potential similar to Remdesivir, a drug for clinical use. Regarding methyltransferase, dihydroagarofuran (Piper cernuum) and myristicin (Piper rivinoids) showed better affinity, with important interactions at the active site of the inhibitor Sinefugin, suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Molecular docking and molecular dynamics studies represent an initial step, being indicative for future in vitro studies of dihydroagarofuran and myristicin, as possible pharmacological tools for COVID-19.Communicated by Ramaswamy H. Sarma.

Antileishmanial Screening, Cytotoxicity, and Chemical Composition of Essential Oils: A Special Focus on Piper callosum Essential Oil.

Leishmania amazonensis is the etiological agent of tegumentary leishmaniasis, a disease characterized by the emergence of cutaneous and mucocutaneous ulcerated lesions that can evolve into severe destruction of skin tissue. Treatment of the disease is often accompanied by high toxicity and variable efficacy. Essential oils stand out for having diverse pharmacological properties. Here, we screened a panel of fourteen essential oils for their anti-L. amazonensis activity, cytotoxicity, and chemical profile. Lippia sidoides (LSEO) and Piper callosum (PCEO) oils displayed the best anti-promastigote and anti-amastigote activities with IC50 of 31 and 21 µg/ml, respectively. PCEO was the safest oil with a desirable selectivity index >10. In addition, PCEO showed no cytotoxicity against the VERO line and erythrocytes. PCEO-treated amastigotes displayed mitochondrial membrane depolarization and high levels of intracellular ROS. Safrole (54.72 %) was the main component of PCEO. The results described here highlight the use of essential oils to combat tegumentary leishmaniasis.