Plant Piper Research Articles

Identification of pancreatin inhibitors from Thai medicinal Piper plants for antidiabetic and anti-obesity activities using high-performance thin-layer chromatography-bioautographic assay

Exploring the potential of natural products against diabetes and obesity is in demand nowadays. Pancreatic α-amylase and pancreatic lipase are the drug targets to minimize the absorption of glucose from starch and fatty acids from lipids, respectively. In this study, five Piper species, namely P. sarmentosum (Ps), P. wallichii (Pw), P. retrofractum (Pr), P. nigrum (Pn), and P. betle (Pb), which are commonly used as food ingredients and traditional medicines, were evaluated for their inhibitory activities against pancreatin using the microtiter plate method. Additionally, pancreatin inhibitors were identified through a cost-effective high-performance thin-layer chromatography (HPTLC)-bioautography developed using red starch and p-nitrophenyl palmitate, corresponding to anti-amylase and -lipase activities, respectively. Of the 15 samples tested, leaf samples from Pb, which had the highest total phenolic and total flavonoid contents, exhibited remarkable inhibitory activity against pancreatin, with a relative amylase inhibitory capacity (RAIC) ranging between 4.260 × 10−5 and 4.861 × 10−5 and a reciprocal half-maximal inhibitory concentration (1/IC50, PTL) of 0.390–0.510 (mg/mL)−1. Additionally, Ps samples demonstrated the second-ranked anti-pancreatin activity. Principal component analysis indicated that total phenolic content contributed to the anti-pancreatin activities of Pb samples. The anti-pancreatin bands were isolated and identified as caffeic acid, myricetin, genistein, piperine, and eugenol. Myricetin, in the roots of Ps samples, showed notable anti-pancreatin activity, which was consistent with results from the in silico prediction toward pancreatic α-amylase and pancreatic lipase. Caffeic acid and eugenol were present in Pb samples. In conclusion, the developed cost-effective pancreatin HPTLC-bioautography efficiently identified amylase and lipase inhibitors from Piper herbs, which supported the use of these plants for antidiabetes and anti-obesity.

Antioxidant profile, and fatty acids analysis of leaves of medicinal plant Piper chaba H. (Chuijhal): a promising source of antioxidant and fatty acids

Antioxidant profile, and fatty acids analysis of leaves of medicinal plant Piper chaba H. (Chuijhal): a promising source of antioxidant and fatty acids

Leaf-feeding species of the genus Liothrips from China (Thysanoptera, Phlaeothripinae).

The 250 species of the second largest genus of Thysanoptera, Liothrips, are known as feeding mainly on green leaves, with many inducing galls or associated with galls. In China, 33 species are recognized including L. brevis sp. n., L. elongatus sp. n., L. longistylus sp. n., L. motuoensis sp. n., L. piceae sp. n., L. populi sp. n. and L. tibetanus sp. n., also seven species are recorded from this country for the first time. Four Hans Liothrips species are considered as new synonymies of L. vaneeckei that might be widespread in the Holarctic region. Three species are newly combined as Liothrips aporosae comb.n., Teuchothrips fuscus comb.n. and T. turkestanicus comb.n. The illustrated identification key to Chinese Liothrips species excludes L. hsuae but includes L. mirabilis due to its potential as a pest of Piper plants are growing throughout Southern China. Biology, structural variation, and generic relationships are also discussed.

Effect of Piper Cubeba Extract on Biofim Producing Pseudomonas Aeruginosa Isolated from Clinical Samples

Background: The species of Pseudomonas aeruginosa is a nosocomial bacterium that increases the risk of multidrug-resistant infections, especially in vulnerable patients. The plant Piper cubeba, commonly referred to as cubeb or tailed pepper, it is specifically cultivated for its fruit and essential oil. The plant belongs to the genus Piper. The study aims at assessing the effectiveness of Piper cubeba extract against different P. aeruginosa strains that could produce biofilm and carry blaIMP gene. Method: Isolates from 85 samples (17 sputum, 40 urine and 28 diarrhea samples). Collected from Al Nasiriyah Teaching Hospital during the period of December 2021 to March 2022. Samples were cultivated using routine cultivation methods, catalase test, oxidase reaction, and the Api20E system were performed to identify P. aeruginosa. Results: Out of a total of 17 isolated samples of Pseudomonas aeruginosa, 3 (17.64%) were from sputum, 6(35.29%) from urine, and 8 (47.05%) diarrhea samples. Out of 17 isolates 6 were sensitive in stool isolates 4 isolates were moderate sensitive and 7 isolates were resistance. Conclusion at concentrations of 25, 50, 75, and 100 mg/mL for Piper cubeba, respectively, the greatest MBC of plant extracts was noted. Also, all the isolates were capable of producing a biofilm by using presterilized 96-well polystyrene microtiter plates. Out of 17 isolates, 9 had a potent biofilm ability and the remaining 7 were moderate biofilm producers. Additionally, 7 of the isolates (41.17%) carried the blaIMP gene. Conclusion: Piper cubeba extract has potential as an antimicrobial agent against both sensitive and moderately resistant strains of Pseudomonas aeruginosa. This antimicrobial effect becomes more pronounced with an increase in the concentration of the extract. Additionally, Pseudomonas aeruginosa that produce biofilms tend to consistently produce more Metallo-beta-lactamase (MBL), which can further contribute to antibiotic resistance.

UNVEILING THE PHARMACOLOGICAL SPECTRUM AND APPROVED THERAPEUTIC ACTIVITIES OF PIPER METHYSTICUM: AN IN-DEPTH REVIEW

In the plant Piper methysticum G. (Forst), Piperaceae, kava has active constituent storage in its roots and rhizomes. Kava root has been conventionally employed by individuals for alleviating anxiety, stress, managing drug withdrawal symptoms, addressing sleep-related concerns, and various other purposes; however, it is noteworthy that there is a lack of robust scientific evidence substantiating these purported therapeutic uses. The examination of existing literature reveals that kava lactones exert biological activity encompassing local anesthesia, antispasmodic effects, muscular relaxation, antimitotic properties, sedative attributes, anticonvulsive actions, analgesic properties, anxiolytic effects, and neuroprotective characteristics, thereby affirming their pharmacological potency. However, the plant’s medicinal value as an anti-depressant, anti-anxiety, or antioxidant has yet to be verified. Synthetic medications, on the other hand, are routinely recommended to alleviate stress and stress-related symptoms, but their tendency to induce drowsiness or sleep, the risk of dependence, and withdrawal effects limit their long-term usage. Clinical studies reveal that kava has 1-week efficacy at a modest dose. Evidently, herbal formulations assert enhancement of physical endurance, cognitive capacities, and non-specific resilience to stress without altering physiological functions; hence, imperative investigation into their safety and efficacy for therapeutic applications is warranted.

Effects of Habitat and Fruit Scent on the Interactions between Short-tailed Fruit Bats and Piper Plants.

Piper is a mega-diverse genus of pioneer plants that contributes to the maintenance and regeneration of tropical forests. In the Neotropics, Carollia bats use olfaction to forage for Piper fruit and are a main disperser of Piper seeds via consumption and subsequent defecation during flight. In return, Piper fruits provide essential nutrients for Carollia year-round. There is evidence that the types and diversity of Piper frugivores are influenced by the primary habitat type of different Piper species (forest and gap), with forest Piper depending more on bats for seed dispersal; however, this pattern has not been tested broadly. We aimed to characterize and compare the interactions between Carollia and Piper across forested and gap habitats, and further investigate whether differences in fruit traits relevant to bat foraging (i.e., scent) could underlie differences in Carollia-Piper interactions. We collected nightly acoustic ultrasonic recordings and 24 h camera trap data in La Selva, Costa Rica across 12 species of Piper (six forest, six gap) and integrated this information with data on Carollia diet and Piper fruit scent. Merging biomonitoring modalities allowed us to characterize ecological interactions in a hierarchical manner: from general activity and presence of bats, to visitations and inspections of plants, to acquisition and consumption of fruits. We found significant differences in Carollia-Piper interactions between forested and gap habitats; however, the type of biomonitoring modality (camera trap, acoustics, diet) influenced our ability to detect these differences. Forest Piper were exclusively visited by bats, whereas gap Piper had a more diverse suite of frugivores; the annual diet of Carollia, however, is dominated by gap Piper since these plants produce fruit year-round. We found evidence that fruit scent composition significantly differs between forest and gap Piper, which highlights the possibility that bats could be using chemical cues to differentially forage for gap vs. forest Piper. By integrating studies of Piper fruit scent, plant visitation patterns, and Carollia diet composition, we paint a clearer picture of the ecological interactions between Piper and Carollia, and plant-animal mutualisms more generally.

Antibacterial and Cytotoxicity Effect of Flavokawain B Loaded Silver Nanoparticles

: Silver nanoparticles (Ag NPs) are used in sterilizing nanomaterials, medical products, textiles, food storage bags, and personal care products. Ag NPs exhibited significant antibacterial activity due to the sustained release of free Ag. Flavokawain B (FKB) is a natural chalcone extracted from the roots of the kava-kava plant Piper methysticum. In this study, Ag NPs were synthesized by the chemical method using hydrazine hydrate and poly (vinyl alcohol) as reducing and stabilizing agents, respectively. FKB-loaded Ag NPs showed a red shift and were positioned at 421 nm, indicating Ag NPs presence. The FTIR spectrum confirmed the presence of the aromatic compoundand#39;s functional groups (at different absorption bands). The XRD pattern indicated the crystalline nature of the loaded Ag NPs with face-centered cubic (fcc) Ag crystals. SEM image revealed the crystalline nature of FKB-loaded Ag NPs. FESEM image revealed the loading of Ag NPs on the clear and flat surface of FKB, and a spherical shape of Ag NPs with an average size of 60 nm was obtained. The minimum inhibitory concentration (MIC) of AgFKB against Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa was found to be 100 μg/mL. However, 100 μg/mL of FKB discs did not show any inhibition zone in the activity. These findings indicated the improved antibacterial activity of FKB-loaded Ag NPs (Ag-FKB).

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate–methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate–methanol–water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1′S)-1′-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1–6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Assessment of Contact Toxicity and Repellent Effects of Essential Oils from Piper Plants Piper yunnanense and Piper boehmeriifolium against Three Stored-Product Insects.

Storage is a crucial part during grain production for the massive spoilage caused by stored product insects. Essential oils (EOs) of plant origin have been highly recommended to combating insects which are biodegradable and safe mode of action. Hence, to make the fullest use of natural resources, essential oils of different parts from Piper yunnanense (the whole part, PYW; fruits, PYF; leaves, PYL) and Piper boehmeriifolium (leaves, PBL) were extracted by steam distillation method in the present study. Gas chromatography-mass spectrometry (GC-MS) characterization revealed bicyclogermacrene (PYW), γ-muurolene (PYF), δ-cadinene (PYL) and methyl 4,7,10,13,16,19-docosahexaenoate (PBL) as the principal compound of each essential oil. Sesquiterpene hydrocarbons were also recognized as the richest class accounting for 56.3 %-94.9 % of the total oil. Three storage pests, Tribolium castaneum, Lasioderma serricorne and Liposceis bostrychophila, were exposed to different concentrations of EOs to determine their insecticidal effects. All tested samples performed modest contact toxicity in contrast to a bioactive ingredient pyrethrin, among which the most substantial effects were observed in PYF EOs against T. castaneum (35.84 μg/adult), PBL EOs against L. serricorne (15.76 μg/adult) and PYW EOs against L. bostrychophila (57.70 μg/cm2 ). In terms of repellency tests, essential oils of PYF at 78.63 nL/cm2 demonstrated to have a remarkable repellence against T. castaneum at 2h and 4h post-exposure. The investigations indicate diverse variations in the chemical profiles and insecticidal efficacies of P. yunnanense and P. boehmeriifolium EOs, providing more experimental evidence for the use of the Piper plants.

Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer.

Piperlongumine (PL), an alkaloid found primarily in the fruits and roots of the plant Piper longum L. (Piperaceae), is a natural compound that exhibits potent activity against various cancer cell proliferation. The most frequently caused malignancy in women globally, breast cancer (BC), has been demonstrated to be significantly inhibited by PL. Apoptosis, cell cycle arrest, increased ROS generation, and changes in the signalling protein's expression are all caused by the numerous signalling pathways that PL impacts. Since BC cells resist conventional chemotherapeutic drugs (doxorubicin, docetaxel etc.), researchers have shown that the drugs in combination with PL can exhibit a synergistic effect, greater than the effects of the drug or PL alone. Recently, techniques for drug packaging based on nanotechnology have been employed to improve PL release. The review has presented an outline of the chemistry of PL, its molecular basis in BC, its bioavailability, toxicity, and nanotechnological applications. An attempt to understand the future prospects and direction of research about the compound has also been discussed.

Potent multi-target natural inhibitors against SARS-CoV-2 from medicinal plants of the Himalaya: a discovery from hybrid machine learning, chemoinformatics, and simulation assisted screening

The emergence and immune evasion ability of SARS-CoV-2 Omicron strains, mainly BA.5.2 and BF.7 and other variants of concern have raised global apprehensions. With this context, the discovery of multitarget inhibitors may be proven more comprehensive paradigm than its one-drug-to-one target counterpart. In the current study, a library of 271 phytochemicals from 25 medicinal plants from the Indian Himalayan Region has been virtually screened against SARS-CoV-2 by targeting nine virus proteins, viz., papain-like protease, main protease, nsp12, helicase, nsp14, nsp15, nsp16, envelope, and nucleocapsid for screening of a multi-target inhibitor against the viral replication. Initially, 94 phytochemicals were screened by a hybrid machine learning model constructed by combining 6 confirmatory bioassays against SARS-CoV-2 replication using an instance-based learner lazy k-nearest neighbour classifier. Further, 25 screened compounds with excellent drug-like properties were subjected to molecular docking. The phytochemical Cepharadione A from the plant Piper longum showed binding potential against four proteins with the highest binding energy of −10.90 kcal/mol. The compound has acceptable absorption, distribution, metabolism, excretion, and toxicity properties and exhibits stable binding behaviour in terms of root mean square deviation (0.068 ± 0.05 nm), root-mean-square fluctuation, hydrogen bonds, solvent accessible surface area (83.88–161.89 nm2), and molecular mechanics Poisson-Boltzmann surface area during molecular dynamics simulation of 200 ns with selected target proteins. Concerning the utility of natural compounds in the therapeutics formulation, Cepharadione A could be further investigated as a remarkable lead candidate for the development of therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Usos tradicionales y prácticas de manejo de <em>Piper auritum</em> en comunidades maya rurales de Yucatán

Background: Plant domestication is a continuous, multidirectional process that is directed via plant selection and management. In the current study we use Piper auritum, an aromatic plant frequently used in Mexican cuisine and for medicinal purpose, to characterize the domestication level using information about its cultural relevance, management practices and leaf traits differentiation in managed and ruderal populations.
 Questions: What is the level of domestication of the aromatic plant Piper auritum? Are there any morphological or phytochemical differences between home garden and ruderal populations?
 Studied species: Piper auritum, Kunth
 Study site and dates: Ten communities in eastern Yucatan, México, from 2019 to 2021.
 Methods: Fifty-three Semi-structured interviews were applied (72 % women and 28 % men). Morphological and phytochemical leaf traits were measured to test management effects using home garden and ruderal populations.
 Results: People interviewed knew P. auritum and its uses. Five culinary and 12 medicinal uses were registered. P. auritum is grown in homegardens and the main management activity is irrigation. The selection occurs at the leaf level according to their size and resistance. Home garden plants registered greater foliar area and hardness and decreased safrole, compared to ruderal.
 Conclusions: Piper auritum is widely known in the communities and has a variety of culinary and medicinal uses. Management is vital for its survival in home gardens, but the species germinates spontaneously and is not usually planted. We found differences in leaf traits in managed and unmanaged populations. With this evidence we propose that P. auritumis under incipient domestication.

Formulation of Brevibacillus agri and compost to improve growth and phytochemicals compound of Piper caninum herbal plant

Most herbal plant farming operations still rely on conventional methods, negatively impacting human health and the environment. However, by using rhizobacteria to boost the yield and quality of herbal plants, farmers can make a more environmentally responsible and safe choice for consumers. Therefore, the present study aimed to determine the dosage of Brevibacillus agri added to the medicinal plant Piper caninum to boost its growth and phytochemical content. Piper caninum is a popularly used medicinal plant with antifungal and antibacterial properties and the ability to improve the quality of mouse sperm. The investigation was carried out in a greenhouse using a randomized group approach. The results indicated that the most effective formula for promoting growth and enhancing phytochemical composition was F1 (100 g of compost and 3 kg of soil plus 1% Brevibacillus agri), which contained 1% B. agri. Treating the Piper caninum plant with 1%, 2%, or 3% B. agri yielded positive results, likely due to the bacteria's nitrogen-fixing ability and favorable outcomes for the IAA test and protease enzyme. Brevibacillus agri was also found to colonize the roots of Piper caninum and produce the phytochemicals butanoic acid, propanediol, and cyclopropane. In conclusion, using rhizobacteria in sustainable agriculture was highly effective, providing an ecologically responsible and safe alternative to conventional farming methods.

Identification of Piper species that are resistant to Phytophthora capsici, Meloidogyne incognita, and waterlogging in Vietnam

AbstractBlack pepper (Piper nigrum) is a spice commonly used in kitchens throughout the world. Black pepper production is devastated by a range of pathogenic agents, including Phytophthora capsici and Meloidogyne incognita. Many efforts have been directed towards finding black pepper cultivars that are resistant to these pathogens. In this work, a 39‐accession germplasm panel of species in the Piper family collected throughout Vietnam was described. Preliminary tests using P. capsici inoculation onto leaves were carried out to identify potentially resistant accessions. Next, candidate plants were inoculated with P. capsici mycelial suspension and survival rates were assessed 15, 30 and 45 days postinoculation. In addition, Piper plants were challenged with M. incognita by adding larvae/juveniles to growing pots. Resistance to M. incognita was determined by the number of root galls and the percentage of plants with yellow leaves 1, 2 and 4 months after treatment. Piper accessions were also subjected to a 4‐day waterlogged treatment. Two accessions (HUIB_PH30 and HUIB_PD36) demonstrated high levels of resistance to all biological and water stresses. Micromorphological characterizations revealed that the amount of intercellular spaces in the root cortex correlated with the resistance to P. capsici and waterlogging tolerance. Hence, the abundance of intercellular spaces can serve as a guide for further selection of black pepper accessions that are resistant to common diseases and tolerant to waterlogged conditions.

Isolation, Characterization and Antibacterial Activity of 4-Allylbenzene-1,2-diol from Piper austrosinense.

Isolation for antibacterial compounds from natural plants is a promising approach to develop new pesticides. In this study, two compounds were obtained from the Chinese endemic plant Piper austrosinense using bioassay-guided fractionation. Based on analyses of 1H-NMR, 13C-NMR, and mass spectral data, the isolated compounds were identified as 4-allylbenzene-1,2-diol and (S)-4-allyl-5-(1-(3,4-dihydroxyphenyl)allyl)benzene-1,2-diol. 4-Allylbenzene-1,2-diol was shown to have strong antibacterial activity against four plant pathogens, including Xanthomonas oryzae pathovar oryzae (Xoo), X. axonopodis pv. citri (Xac), X. oryzae pv. oryzicola (Xoc) and X. campestris pv. mangiferaeindicae (Xcm). Further bioassay results exhibited that 4-allylbenzene-1,2-diol had a broad antibacterial spectrum, including Xoo, Xac, Xoc, Xcm, X. fragariae (Xf), X. campestris pv. campestris (Xcc), Pectobacterium carotovorum subspecies brasiliense (Pcb) and P. carotovorum subsp. carotovorum (Pcc), with minimum inhibitory concentration (MIC) values ranging from 333.75 to 1335 μmol/L. The pot experiment showed that 4-allylbenzene-1,2-diol exerted an excellent protective effect against Xoo, with a controlled efficacy reaching 72.73% at 4 MIC, which was superior to the positive control kasugamycin (53.03%) at 4 MIC. Further results demonstrated that the 4-allylbenzene-1,2-diol damaged the integrity of the cell membrane and increased cell membrane permeability. In addition, 4-allylbenzene-1,2-diol also prevented the pathogenicity-related biofilm formation in Xoo, thus limiting the movement of Xoo and reducing the production of extracellular polysaccharides (EPS) in Xoo. These findings suggest the value of 4-allylbenzene-1,2-diol and P. austrosinense could be as promising resources for developing novel antibacterial agents.

Essential Oils of Piper pendulispicum C. DC. and Piper hymenophyllum Miq.: Chemical Composition and Anti-microbial activity

From hydro-distillation and GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analysis, chemical compositions in essential oils of two Vietnamese Piper plants Piper pendulispicum C. DC. and P. hymenophyllum Miq. were identified. Essential oils of P. pendulispicum leaf and stem are highlighted with the predominant amount of sesquiterpene hydrocarbons (73.21-78.06%), in which bicyclogermacrene (12.17-12.54%) and β-caryophyllene (12.10-14.51%) were the principal compounds. Monoterpene hydrocarbons (87.44%) are the main chemical class of P. hymenophyllum leaf oil, in which α-pinene (52.92%) and β-pinene (26.65%) are the principal compounds. These obtained essential oils with the MIC (minimum inhibitory concentration) values of 16-128 μg/mL are better than the positive control streptomycin ((MIC 128-256 μg/mL) in antimicrobial assay against three Gram-positive bacteria Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, and Bacillus cereus ATCC 14579. P. pendulispicum essential oils (MIC 16-32 μg/mL) are also comparable to the other standard cycloheximide (MIC 32 μg/mL) against the yeast Candida albicans ATCC 10231. In general, P. pendulispicum essential oil is better than P. hymenophyllum leaf oil for antimicrobial treatment.

Essential Oil Extraction of Piper betle, Piper ramipilum, and Piper aduncum and their Antibacterial Activity against Food borne Pathogens

Traditional uses of piper plants to cure diseases are associated with their constituents. In this research, we extracted the essential oils from Piper betle, Piper ramipilum, and Piper aduncum by steam distillation yielding extracts of 1.44%, 1.11%, and 1.93% (v/w), respectively. GC-MS analysis showed low-oxygenated terpenes in these Piper species. The identified components of P. betle, P. ramipilum, and P. aduncum consisted of 46, 42, and 43 compounds, respectively. P. betle had β-phellandrene (8.67%), 4-terpineol (7.05%), trans-β-caryophyllene (5.44%), α-humulene (6.30%), and caryophyllene oxide (5.53%) as its main constituents. The compounds of β-phellandrene, trans-β-caryophyllene, and caryophyllene oxide were also identified as predominant constituents in P. ramipilum along with α-pinene, linalool, and β-selinene compounds with percentages of 7.79, 14.76, 5.36, 6.02, 9.41, and 6.68%, respectively. In addition, P. aduncum was dominated by apiole (33.49%) and trans-β-caryophyllene (6.67%). Antibacterial activity against foodborne pathogens was evaluated by a disk diffusion method against Staphylococcus aureus and Escherichia coli. The diluted essential oils of P. betle showed the highest sensitivity to E. coli with the inhibition zone and activity percentage of 15.38±0.22 mm and 47.11±1.03%, respectively. Meanwhile, the highest antibacterial activity against S. aureus was obtained from P. ramipilum with an inhibition zone of 11.25 ± 0.22 mm and an activity percentage of 31.48±0.93%. Generally, these Piper species had higher activity against E. coli than S. aureus. Our results demonstrate that P. betle and P. ramipilum have good potential to be developed as complementary or alternative treatments for foodborne diseases.

Synthetic Analogues of Gibbilimbol B Induce Bioenergetic Damage and Calcium Imbalance in Trypanosoma cruzi

Chagas disease is an endemic tropical disease caused by the protozoan Trypanosoma cruzi, which affects around 7 million people worldwide, mostly in development countries. The treatment relies on only two available drugs, with severe adverse effects and a limited efficacy. Therefore, the search for new therapies is a legitimate need. Within this context, our group reported the anti-Trypanosoma cruzi activity of gibbilimbol B, a natural alkylphenol isolated from the plant Piper malacophyllum. Two synthetic derivatives, LINS03018 (1) and LINS03024 (2), demonstrated a higher antiparasitic potency and were selected for mechanism of action investigations. Our studies revealed no alterations in the plasma membrane potential, but a rapid alkalinization of the acidocalcisomes. Nevertheless, compound 1 exhibit a pronounced effect in the bioenergetics metabolism, with a mitochondrial impairment and consequent decrease in ATP and reactive oxygen species (ROS) levels. Compound 2 only depolarized the mitochondrial membrane potential, with no interferences in the respiratory chain. Additionally, no macrophages response of nitric oxide (NO) was observed in both compounds. Noteworthy, simple structure modifications in these derivatives induced significant differences in their lethal effects. Thus, this work reinforces the importance of the mechanism of action investigations at the early phases of drug discovery and support further developments of the series.

Structure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design

Gibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these compounds against T. cruzi trypomastigotes and explore structure–activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups – ester and amide – and variating the substituent at the p-position in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 μM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 μM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results suggested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.

Biodereplication of Antiplasmodial Extracts: Application of the Amazonian Medicinal Plant Piper coruscans Kunth.

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay. Molecular networking and automated annotation of targeted mass through data mining were followed by mass-guided compound isolation by taking advantage of the versatility and finely tunable selectivity offered by centrifugal partition chromatography. This biodereplication workflow was applied to an ethanolic extract of the Amazonian medicinal plant Piper coruscans Kunth (Piperaceae) showing an IC50 of 1.36 µg/mL on the 3D7 Plasmodium falciparum strain. It resulted in the isolation of twelve compounds designated as potential antiplasmodial compounds by the biodereplication workflow. Two chalcones, aurentiacin (1) and cardamonin (3), with IC50 values of 2.25 and 5.5 µM, respectively, can be considered to bear the antiplasmodial activity of the extract, with the latter not relying on a heme-binding mechanism. This biodereplication method constitutes a rapid, efficient, and robust technique to identify potential antimalarial compounds in complex extracts such as plant extracts.