RESUMEN
This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and ß-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 µg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.
Asunto(s)
Antiinflamatorios , Antioxidantes , Aceites Volátiles , Peperomia , Aceites Volátiles/farmacología , Aceites Volátiles/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antioxidantes/farmacología , Antioxidantes/química , Ratones , Animales , Células RAW 264.7 , Peperomia/química , Óxido Nítrico/metabolismo , Hojas de la Planta/química , Cromatografía de Gases y Espectrometría de Masas , Simulación por Computador , Pueblos del Sudeste AsiáticoRESUMEN
A search for anti-trypanosomal natural compounds from plants collected in El Salvador, a country particularly endemic for Chagas disease, resulted in the isolation of five lignan-type compounds (1-5) from Peperomia pseudopereskiifolia. The lignan derivatives 1, 2, and 4 are new. Their absolute configuration was determined by chemical derivatization. Compounds 1, 5, 6, and 8 exhibited anti-trypanosomal activity against the amastigote form of T. cruzi comparable to that of the existing drug benznidazole.
Asunto(s)
Lignanos , Peperomia , Tripanocidas , Trypanosoma cruzi , Lignanos/farmacología , Lignanos/química , Lignanos/aislamiento & purificación , Trypanosoma cruzi/efectos de los fármacos , El Salvador , Tripanocidas/farmacología , Tripanocidas/química , Tripanocidas/aislamiento & purificación , Estructura Molecular , Peperomia/química , Nitroimidazoles/farmacología , Nitroimidazoles/química , Enfermedad de Chagas/tratamiento farmacológicoRESUMEN
Three new secolignans were found in the detailed chemical study of Peperomia blanda (Jacq.) Kunth collected from China. Detailed NMR data analysis, especially 1H NMR, 13C NMR and 2 D NMR, elucidates the structures of the three new secolignans.
Asunto(s)
Peperomia , Peperomia/química , Espectroscopía de Resonancia Magnética , ChinaRESUMEN
Ten previously undescribed metabolites were isolated from Peperomia incana (Haw.) A. Dietr. (Piperaceae), among which four contained a chromene moiety, two were identified as meroterpene lactones, and four were cannabinoid-like compounds. While the chemical structures of the compounds were assigned based on HRESIMS and 1D and 2D-NMR spectra analyses, the relative and absolute configurations were assigned from NOE correlations and a combination of ECD data and X-ray single crystal analyses, respectively. In a cytotoxic assay against a panel of seven human cancer cell lines (A549, MDA-MB-231, HeLa, DU 145, 5637, Hep G2, and MIA PaCa-2, which represent non-small cell lung cancer, as well as breast, cervical, prostate, bladder, liver, and pancreas carcinomas, respectively) most of the isolated compounds showed promising cytotoxic activities. The incanachromenes B, and incanabinoids A and C exhibited the highest cytotoxicity toward all tested cancer cell lines with IC50 values in the range of 5.0-10.0 µM, whereas incanolides A, B, and incanabinoid B showed the lowest cytotoxic activity. In addition, incanachromene C and incanabinoid C produced a significant antibacterial effect toward planktonic cells and biofilms of multidrug-resistant Staphylococcus aureus strains.
Asunto(s)
Antineoplásicos , Cannabinoides , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Staphylococcus aureus Resistente a Meticilina , Peperomia , Humanos , Peperomia/química , Antineoplásicos/farmacología , Estructura MolecularRESUMEN
Much of the new research and investigation in pharmacy sciences are concerned with developing therapeutic agents, and identifying and finding new drugs with their chemical structure to treat different human diseases such as infectious diseases from natural products. Therefore, the present findings relate to isolating five new compounds the dichloromethane extract of Peperomia blanda (Jacq.) Kunth grown on Socotra Island, Yemen. two new secolignans; which have been proposed as peperomin I & J. These compounds were isolated together with the other two polyketides presented as surinone D and dindygulerione F. The chemical structures were elucidated and confirmed with nuclear magnetic resonance (NMR) and liquid chromatography-mass spectroscopy (LCMS) analysis. These compounds were first isolated and reported from this plant. These new compounds' antimicrobial activity has been evaluated, and minimum inhibitory concentration has been recorded in the range of 125-250 µg/mL. The pharmacotherapeutic spectrum of compounds was predicated using PASS software which showed potential activity.
Asunto(s)
Productos Biológicos , Peperomia , Policétidos , Humanos , Peperomia/química , Cloruro de Metileno , Policétidos/farmacología , Policétidos/química , Extractos Vegetales/farmacologíaRESUMEN
Peperomia obtusifolia (L.) A. Dietr., native to Middle America, is an ornamental plant also traditionally used for its mild antimicrobial properties. Chemical investigation on the leaves of P. obtusifolia resulted in the isolation of two previously undescribed compounds, named peperomic ester (1) and peperoside (2), together with five known compounds, viz. N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzamide (3), becatamide (4), peperobtusin A (5), peperomin B (6), and arabinothalictoside (7). The structures of these compounds were elucidated by 1D and 2D NMR techniques and HREIMS analyses. Compounds 1-7 were evaluated for their anthelmintic (against Caenorhabditis elegans), antifungal (against Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (against Bacillus subtilis and Aliivibrio fischeri), and antiproliferative (against PC-3 and HT-29 human cancer cell lines) activities. The known peperobtusin A (5) was the most active compound against the PC-3 cancer cell line with IC50 values of 25.6 µM and 36.0 µM in MTT and CV assays, respectively. This compound also induced 90% inhibition of bacterial growth of the Gram-positive B. subtilis at a concentration of 100 µM. In addition, compound 3 showed anti-oomycotic activity against P. infestans with an inhibition value of 56% by using a concentration of 125 µM. However, no anthelmintic activity was observed.
Asunto(s)
Peperomia , Antibacterianos/farmacología , Antifúngicos/farmacología , Humanos , Peperomia/química , Fenoles/análisis , Extractos Vegetales/química , Hojas de la Planta/químicaRESUMEN
Peperomia pellucida is a species known in the Amazon as "erva-de-jabuti" that has been used in several therapeutic applications based on folk medicine. Herein, we describe the classes, subclasses, and the main compounds of the leaves, stems, and roots from P. pellucida by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry associated with molecular networks, mirror plot on the GNPS library, and machine learning. These data show compounds that were annotated for the first time in the Peperomia genus, such as 2',4',5'-trihydroxybutyrophenonevelutin, dehydroretrofractamide C, and retrofractamide B.
Asunto(s)
Peperomia , Cromatografía Líquida de Alta Presión/métodos , Medicina Tradicional , Peperomia/química , Hojas de la Planta/química , Raíces de Plantas/químicaRESUMEN
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and in Central America, it is considered one of the four most infectious diseases. This study aimed to screen the anti-trypanosomal activity of plant species from Salvadoran flora. Plants were selected through literature search for plants ethnobotanically used for antiparasitic and Chagas disease symptomatology, and reported in Museo de Historia Natural de El Salvador (MUHNES) database. T. cruzi was incubated for 72 h with 2 different concentrations of methanolic extracts of 38 species, among which four species, Piper jacquemontianum, Piper lacunosum, Trichilia havanensis, and Peperomia pseudopereskiifolia, showed the activity (≤ 52.0% viability) at 100 µg/mL. Separation of the methanolic extract of aerial parts from Piper jacquemontianum afforded a new flavanone (4) and four known compounds, 2,2-dimethyl-6-carboxymethoxychroman-4-one (1), 2,2-dimethyl-6-carboxychroman-4-one (2), cardamomin (3), and pinocembrin (5), among which cardamomin exhibited the highest anti-trypanosomal activity (IC50 = 66 µM). Detailed analyses of the spectral data revealed that the new compound 4, named as jaqueflavanone A, was a derivative of pinocembrin having a prenylated benzoate moiety at the 8-position of the A ring.
Asunto(s)
Extractos Vegetales/farmacología , Tripanocidas , Trypanosoma cruzi , Enfermedad de Chagas/tratamiento farmacológico , Humanos , Meliaceae/química , Peperomia/química , Piper/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Peperomia Ruiz and Pav, the second largest genus of the Piperaceae, has over the years shown potential biological activities. In this sense, the present work aimed to carry out a seasonal and circadian study on the chemical composition of Peperomia circinata essential oils and aromas, as well as to evaluate the preliminary toxicity in Artemia salina Leach and carry out an in silico study on the interaction mechanism. The chemical composition was characterized by gas chromatography (GC/MS and GC-FID). In the seasonal study the essential oil yields had a variation of 1.2-7.9%, and in the circadian study the variation was 1.5-5.6%. The major compounds in the seasonal study were ß-phellandrene and elemicin, in the circadian they were ß-phellandrene and myrcene, and the aroma was characterized by the presence of ß-phellandrene. The multivariate analysis showed that the period and time of collection influenced the essential oil and aroma chemical composition. The highest toxicity value was observed for the essential oil obtained from the dry material, collected in July with a value of 14.45 ± 0.25 µg·mL-1, the in silico study showed that the major compounds may be related to potential biological activity demonstrated by the present study.
Asunto(s)
Artemia/efectos de los fármacos , Aceites Volátiles/análisis , Aceites Volátiles/toxicidad , Peperomia/química , Monoterpenos Acíclicos/análisis , Monoterpenos Acíclicos/toxicidad , Alquenos/análisis , Alquenos/toxicidad , Animales , Monoterpenos Ciclohexánicos/análisis , Monoterpenos Ciclohexánicos/toxicidad , Pirogalol/análogos & derivados , Pirogalol/análisis , Pirogalol/toxicidad , Estaciones del AñoRESUMEN
Aerial parts (leaves, flowers, stem) of Peperomia galioides extract administered to mice, was used to confirm its anti-inflammatory and sedative folk uses. The anti-inflammatory activity was assessed by croton oil-induced ear oedema and myeloperoxidase (acute inflammation); cotton pellet-induced granuloma (sub-acute inflammation) and Escherichia coli Lipopolysaccharide (LPS) induced inflammation (cellular mediators). The sedative activity was studied by the pentobarbital-induced sleeping time test. Single doses (300 and 600 mg/kg; i.p.) of the extract reduced croton oil-induced ear oedema and myeloperoxidase activity. Six days administration of the extract (300 mg/kg, i.p.) to mice implanted with cotton pellets diminished granuloma formation. LPS (20 mg/kg, i.p.) enhanced plasma nitrites and TNF-α levels that were inhibited by the extract. The duration but not the onset of sleeping time was enhanced by 300 and 600 mg/kg of the extract. Our results show that P. galioides has anti-inflammatory and sedative activities in mice, which validates its traditional use.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Hipnóticos y Sedantes/farmacología , Peperomia/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Aceite de Crotón/toxicidad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Hipnóticos y Sedantes/química , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ratones , Peroxidasa/metabolismo , Extractos Vegetales/química , Hojas de la Planta/química , Plantas Medicinales/química , Sueño/efectos de los fármacos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Peperomia obtusifolia is a herbaceous perennial plant native to the Americas reported as a traditional medicine to treat snake bites and as a skin cleanser. The bioassay-guided fractionation of crude extracts from aerial parts of P. obtusifolia against a panel of clinically important fungi and bacteria, showed that hexane and dichloromethane extracts demonstrated selective bacterial inhibition, allowing the isolation of the known compounds peperobtusin A (1), and 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3"-methyl-2"-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2H-1-benzopyran-6-carboxylic acid (2) from dichloromethane extract. Compound 2 was active against Gram-positive bacteria including community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates and an Enterococcus faecalis vancomycin-resistant strain, with minimal inhibitory concentration (MIC) values of 4 µg/mL (10.8 µM) and 8 µg/mL (21.6 µM) respectively. The interaction of compound 2 with the bacterial membrane was demonstrated by means of Zeta potential experiments on S. aureus, then confirming the membrane damage by fluorescent microscopy experiments.
Asunto(s)
Antibacterianos/farmacología , Benzopiranos/farmacología , Peperomia/química , Prenilación , Liposomas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Staphylococcus aureus/efectos de los fármacos , Electricidad EstáticaRESUMEN
This study aimed to compare the effect of fermentation and drying on the organoleptic characteristic, total phenolic content, antioxidant and anti-inflammatory activities of Peperomia pellucida (L.) Kunth tea with commercial Camellia sinensis tea. The phenolic content, antioxidant and anti-inflammatory activities in P. pellucida were significantly (p < 0.05) lower than C. sinensis, irrespective of the fermentation and drying methods. Although fermentation decreased the total phenolics, flavonoids and antioxidant activity in both P. pellucida and C. sinensis teas, the anti-inflammatory potential of P. pellucida was significantly (p < 0.05) improved. Principle component analysis revealed that fermentation and drying methods contributed to respective 42.3% and 27.2% of activity variation in P. pellucida. The browning index was positively correlated with fermentation index (r = 0.670, p < 0.05) of leaves samples. Overall, unfermented and fermented P. pellucida leaves were best dried with microwaving and freeze drying, respectively for optimal antioxidant and anti-inflammatory activities with favorable consumer's acceptance.
Asunto(s)
Antiinflamatorios/análisis , Antioxidantes/análisis , Desecación/métodos , Fermentación , Peperomia/química , Tés de Hierbas/análisis , Flavonoides/análisis , Fenoles/análisis , Hojas de la Planta/químicaRESUMEN
Extracts of Peperomia pellucida [L.] Kunth have previously been demonstrated to have in vivo estrogenic-like effects, thereby functioning as an anti-osteoporotic agent. However, the compounds responsible for these effects have not yet been determined. Therefore, the aim of this study is to isolate and elucidate potential compounds with estrogenic activity. The structures of the isolated compounds were identified using 1D 1H and 13C-NMR and confirmed by 2D FT-NMR. The estrogenic activity was evaluated using the E-SCREEN assay, and a molecular docking study was performed to predict the binding affinity of the isolated compounds to estrogen receptors. In this experiment, we successfully isolated three phenylpropanoids and two lignan derivatives, namely, 6-allyl-5-methoxy-1,3-benzodioxol-4-ol (1), pachypostaudin B (2), pellucidin A (3), dillapiole (4), and apiol (5). Among these compounds, the isolation of 1 and 2 from P. pellucida is reported for the first time in this study. Activity assays clearly showed that the ethyl acetate extract and its fractions, subfractions, and isolated compounds exerted estrogenic activity. Methanol fraction of the ethyl acetate extract produced the highest estrogenic activity, while 1 and 2 had partial agonist activity. Some compounds (derivates of dillapiole and pellucidin A) also had, in addition, anti-estrogenic activity. In the docking study, the estrogenic activities of 1-5 appeared to be mediated by a classical ligand-dependent mechanism as suggested by the binding interaction between the compounds and estrogen receptors; binding occurred on Arg 394 and His 524 of the alpha receptor and Arg 346 and His 475 of the beta receptor. In summary, we reveal that P. pellucida is a promising anti-osteoporotic agent due to its estrogenic activity, and the compounds responsible for this activity were found to be lignan and phenylpropanoid derivatives. The presence of other compounds in either the extract or fraction may contribute to a synergistic effect, as suggested by the higher estrogenic activity of the methanol fraction. Hence, we suggest further research on the osteoporotic activity and safety of the identified compounds, especially regarding their effects on estrogen-responsive organs.
Asunto(s)
Lignanos/aislamiento & purificación , Lignanos/farmacología , Peperomia/química , Fitoestrógenos/aislamiento & purificación , Fitoestrógenos/farmacología , Propanoles/aislamiento & purificación , Propanoles/farmacología , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Humanos , Lignanos/metabolismo , Células MCF-7 , Modelos Moleculares , Simulación del Acoplamiento Molecular , Fitoestrógenos/metabolismo , Propanoles/químicaRESUMEN
Bioassay-guided isolation protocol was performed on petroleum ether extract of Peperomia blanda (Jacq.) Kunth using column chromatographic techniques. Five compounds were isolated and their structures were elucidated via one-dimensional (1D) and two-dimensional (2D) NMR, gas chromatography mass sectroscopy (GCMS), liquid chromatography mass spectroscopy (LCMS), and ultraviolet (UV) and infrared (IR) analyses. Dindygulerione E (a new compound), and two compounds isolated from P. blanda for the first time-namely, dindygulerione A and flavokawain A-are reported herein. Antimicrobial activity was screened against selected pathogenic microbes, and minimum inhibitory concentrations (MIC) were recorded within the range of 62-250 µg/mL. Assessment of the pharmacotherapeutic potential has also been done for the isolated compounds, using the Prediction of Activity spectra for Substances (PASS) software, and different activities of compounds were predicted. Molecular docking, molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations have proposed the binding affinity of these compounds toward methylthioadenosine phosphorylase enzyme, which may explain their inhibitory actions.
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Antibacterianos/química , Antibacterianos/farmacología , Peperomia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/aislamiento & purificación , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Petróleo/análisis , Extractos Vegetales/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Peperomia pellucida (L.) Kunth is an annual weed with a preference to humid places with reduced solar radiation. This plant is mainly distributed in the Neotropics, Africa, Southeast Asia, and Australia. It is popularly employed in the treatment of a variety of health conditions such as abscesses, abdominal pain, skin sores, conjunctivitis, measles, and kidney troubles. Several studies have also described its antimicrobial, cytotoxic, antidiabetic and a variety of other bioactivities. THE AIM OF THE REVIEW: The aim of this work is to evaluate, using a critical review, the present ethnomedicinal applications, phytochemistry and pharmacological studies of P. pellucida essential oils (EOs) and extracts from different locations around the world. MATERIALS AND METHODS: This review was performed through an online survey of the ethnomedicinal practices, chemical compositions and pharmacological applications of P. pellucida EOs and extracts. The data were mainly obtained from online journals and books published in English, Portuguese and Spanish. The information was collected from websites such as Google, Google Scholar, PubMed, Science Direct, ResearchGate and other online databases that provided more information about this herb. RESULTS: Peperomia pellucida bioactivities such as antimicrobial, cytotoxic, antioxidant, fracture healing, antidiabetic and anti-hypercholesterolemia have been described in several literature sources. Nonetheless, most reports only provide the phytochemical screening of extracts, which does not allow the identification of the active compounds. From these studies, some reported constituents are not included in the Dictionary of Natural Products (DNP), which raises questions toward their identification. In addition, some biological assays were even performed without standard controls for comparison which also makes these results questionable. CONCLUSION: This review evaluates data regarding the phytopharmaceutical potential of P. pellucida. In general, several important aspects were questionable or missing in these manuscripts, which points out the need of more investigation on the pharmacological properties and phytochemical compositions of this herb.
Asunto(s)
Peperomia , Fitoquímicos/farmacología , Fitoterapia , Animales , Humanos , Medicina Tradicional , Peperomia/química , Fitoquímicos/análisisRESUMEN
In this study, we aimed to evaluate the immunomodulatory effects of crude leaf extracts from Piper gaudichaudianum Kunth, P. arboreum Aub., P. umbellata L., P. fuligineum Kunth, and Peperomia obtusifolia A. Dietr. on an in vitro model of inflammatory response. The crude extracts were previously obtained by maceration of the leaves. The half-maximal inhibitory concentration was determined by the MTT assay using human peripheral blood mononuclear cells. Human monocytes were simultaneously challenged with each crude extract and lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, to induce a strong inflammatory response. After 24 h of incubation, cell-free supernatants were used for evaluating the mediators involved in inflammation: H2O2, TNF-α, IL-8, IL-6, IL-1ß, IL-10, IL-12, FGF-b, and TGF-ß1. We also compared the results with the effects of ketoprofen, a well-known anti-inflammatory drug. The P. gaudichaudianum crude extract downmodulated the production of H2O2, IL-1ß, IL-6, IL-8, and TGF-ß1 by LPS-stimulated monocytes; P. arboreum, IL-1ß, IL-6, IL-8, and TNF-α; P. umbellata and P. fuligineum, H2O2, IL-1ß, IL-6, IL-8, IL-10, and TNF-α; and P. obtusifolia, H2O2, IL-6, IL-8, IL-10, and TNF-α. In general, the crude leaf extracts amplified the anti-inflammatory response when compared with ketoprofen, particularly reducing the production of IL-8, a mediator involved in neutrophil recruitment during tissue damage. Thus, the crude leaf extracts of P. gaudichaudianum, P. arboreum, P. umbellata, P. fuligineum, and Peperomia obtusifolia elicited an anti-inflammatory response against LPS-challenged monocytes. These findings show the anti-inflammatory properties of these crude leaf extracts and offer new perspectives for their use in the treatment of inflammatory diseases.
Asunto(s)
Antiinflamatorios/farmacología , Monocitos/efectos de los fármacos , Peperomia/química , Piper/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Acetatos , Antiinflamatorios/aislamiento & purificación , Brasil , Células Cultivadas , Cloroformo , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Etanol , Hexanos , Humanos , Concentración 50 Inhibidora , Cetoprofeno/farmacología , Lipopolisacáridos/farmacología , Monocitos/inmunología , Monocitos/metabolismo , Extractos Vegetales/aislamiento & purificación , Especificidad de la EspecieRESUMEN
Nineteen secolignans (1-19), including five new ones (1-5), were isolated from the whole plant of Peperomia dindygulensis. Their structures including stereochemistry were determined by spectroscopic methods, in particular NMR and electronic CD (ECD) analysis. All the isolates were evaluated for their inhibitory activities against IFN-γ/STAT1 as well as IL-6/STAT3 signaling pathway by the method of Luciferase assay. Six 2-methene type secolignans (1, 2, 6-9) exhibited significant inhibitory activities against JAK-STAT pathways with the IC50 values both lower than 10µM.
Asunto(s)
Lignanos/farmacología , Peperomia/química , Transducción de Señal/efectos de los fármacos , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Estructura Molecular , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1ß production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.
Asunto(s)
Apigenina/farmacología , Edema/tratamiento farmacológico , Peperomia/química , Extractos Vegetales/farmacología , Enfermedad Aguda , Animales , Apigenina/química , Biomarcadores , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/etiología , Edema/metabolismo , Edema/patología , Mediadores de Inflamación/metabolismo , Estructura Molecular , Fosfolipasas A2 Secretoras/metabolismo , Extractos Vegetales/química , RatasRESUMEN
BACKGROUND: Peperomia pellucida (L.) HBK is consumed as vegetable and used in Cameroonian traditional medicine for the management of diseases and for fracture healing. Therefore the aim of this study was to evaluate the effects of the aqueous whole plant extract of Peperomia pellucida on fracture healing in female Wistar rats. METHODS: A drill hole injury was created by inserting a drill bit inthe diaphysis of the femur. The aqueous extract of the whole plant of Peperomia pellucida was administered orally at the doses of 100, 200 and 400 mg/kg to adult female Wistar rats. The vehicle (distilled water) was given to the control. Besides these rats, one group of rats without fracture received the extract (400 mg/kg). After 14 days of treatment, the rats were sacrificed under anesthesia and the effects of the extract were evaluated on body weight, the relative weights of organs (femurs, uteri and ovaries) and on hematology. Bone (calcium, phosphorus, alkaline phosphatase) and serum biochemical parameters (calcium, phosphorus, alkaline phosphatase) were also evaluated. Radiological and histological tests were carried out on the femurs. The mineral content of the plant extract was also investigated. RESULTS: The extract induced an increase in body weight at high dose and in WBCs count at low doses. Aqueous extract from Peperomia pellucida increased bone calcium at lowest dose but maintained this parameter at normal range at high dose in fractured rat. Alkaline phophatase and phosphorus concentrations reduced significantly (p < 0.01) at the dose of 400 mg/kg as compared to fractured rats. Moreover, radiological tests revealed a dose dependent formation of callus at the level of the fracture gap, confirmed by the formation of a highly dense and compact fibrocartilagenous callus. The mineral content of the plant extract revealed the presence of calcium, phosphorus, magnesium, sodium and potassium. CONCLUSION: The aqueous extract of P. pellucida accelerates bone healing due partly to the mineral content of the extract. These results confirm its traditional use in the treatment of bone fractures.
Asunto(s)
Fracturas del Fémur/tratamiento farmacológico , Curación de Fractura/efectos de los fármacos , Peperomia/química , Extractos Vegetales/administración & dosificación , Animales , Femenino , Fracturas del Fémur/fisiopatología , Fémur/efectos de los fármacos , Fémur/lesiones , Humanos , Extractos Vegetales/química , Ratas , Ratas WistarRESUMEN
Peperomia obtusifolia, an ornamental plant from the Piperaceae family, accumulates a series of secondary metabolites with interesting biological properties. From a biosynthesis standpoint, this species produces several benzopyrans derived from orsellinic acid, which is a polyketide typically found in fungi. Additionally, the chiral benzopyrans were reported as racemic and/or as diastereomeric mixtures, which raises questions about the level of enzymatic control in the cyclization step for the formation of the 3,4-dihydro-2H-pyran moiety. Therefore, this article describes the use of shotgun proteomic and transcriptome studies as well as phytochemical profiling for the characterization of the main biosynthesis pathways active in P. obtusifolia. This combined approach resulted in the identification of a series of proteins involved in its secondary metabolism, including tocopherol cyclase and prenyltransferases. The activity of these enzymes was supported by the phytochemical profiling performed in different organs of P. obtusifolia. However, the polyketide synthases possibly involved in the production of orsellinic acid could not be identified, suggesting that orsellinic acid may be produced by endophytes intimately associated with the plant.