Antimicrobial activity of Xylopia pancheri Baill. Leaf extract against susceptible and resistant Staphylococcus aureus.

Antibacterial activity of Xylopia pancheri Baill. (Annonaceae) leaf extract was investigated against susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and extended-spectrum-ß-lactamase (ESBL)-producing Pseudomonas aeruginosa. Results showed that X. pancheri leaf extract displayed antibacterial activity against S. aureus with higher inhibitory effect on MRSA compared to control gentamycin antibiotic, and IC50 value of 36.97 µg/mL [95%CI:29.59-46.18] against MRSA.

Chemical Evaluation, Phytotoxic Potential, and In Silico Study of Essential Oils from Leaves of Guatteria schomburgkiana Mart. and Xylopia frutescens Aubl. (Annonaceae) from the Brazilian Amazon.

The essential oils (EOs) of Guatteria schomburgkiana (Gsch) and Xylopia frutescens (Xfru) (Annonaceae) were obtained by hydrodistillation, and their chemical composition was evaluated by gas chromatography-mass spectrometry (GC/MS). Herbicide activity was measured by analyzing the seed germination percentage and root and hypocotyl elongation of two invasive species: Mimosa pudica and Senna obtusifolia. The highest yield was obtained for the EO of Xfru (1.06%). The chemical composition of Gsch was characterized by the presence of the oxygenated sesquiterpenes spathulenol (22.40%) and caryophyllene oxide (14.70%). Regarding the EO of Xfru, the hydrocarbon monoterpenes α-pinene (35.73%) and ß-pinene (18.90%) were the components identified with the highest concentrations. The germination of seeds of S. obtusifolia (13.33 ± 5.77%) showed higher resistance than that of seeds of M. pudica (86.67 ± 5.77%). S. obtusifolia was also more sensitive to the EO of Xfru in terms of radicle (55.22 ± 2.72%) and hypocotyl (71.12 ± 3.80%) elongation, while M. pudica showed greater sensitivity to the EO of Gsch. To screen the herbicidal activity, the molecular docking study of the major and potent compounds was performed against 4-hydroxyphenylpyruvate dioxygenase (HPPD) protein. Results showed good binding affinities and attributed the strongest inhibitory activity to δ-cadinene for the target protein. This work contributes to the study of the herbicidal properties of the EOs of species of Annonaceae from the Amazon region.

Nutrient digestibility, gut microflora, carcass yield, and meat microbiology of broilers fed diets supplemented Ethiopian pepper (Xylopia aethiopica), cloves (Syzygium aromaticum), and their composite.

The effect of dietary supplementation of Ethiopian pepper (Xylopia aethiopica) and clove (Syzygium aromaticum) and their composite on nutrient digestibility, gut microflora, carcass yield, and meat microbiology were investigated in a 52-day boiler feeding trial. Three hundred and sixty unsexed Ross broilers were used for the study. Four experimental diets were formulated for the starter (0-28 days) and finisher (29-56 days) phases: diet 1 was the control without phytogenic supplementation, diet 2 (supplemented with 1% Ethiopian pepper (EP)), diet 3 (supplemented with 1% clove (CL)), and diet 4 (supplemented with 1% mix of equal quantity (0.5% each) of Ethiopian pepper and clove (EPCL)). Each treatment was replicated 6 times with 15 birds per replicate. Nutrient digestibility was determined on days 28 and 56, gut microflora was determined for the small intestine and caecum on day 56, carcass yield, organ weights, and meat microbiology were also determined on day 56. Data obtained were subjected to a one-way analysis of variance using SAS 2000 and significant means were separated using Tukey's test in the same software. At day 28, broilers fed the diet supplemented EPCL had the highest (P < 0.05) dry matter digestibility (DMD, 86.81%) crude protein digestibility (CPD, 71.28%), and ash digestibility (64.24%). Broilers fed EP supplemented diet had reduced (P < 0.05) DMD (70.50%). Increased (P < 0.05) ether extract digestibility (EED) was observed for broilers fed the diet supplemented CL (75.27%) and EPCL (76.43%). Ash digestibility (AD) was lowest (P < 0.05) for broilers fed control diet (50.30%). At day 56, broilers fed the diet supplemented CL and those fed the EPCL supplemented diet had higher (P < 0.05) CPD (78.07%, 79.35%) and EED (70.20%, 71.42%) than other treatments. Ash digestibility was higher (P < 0.05) for broilers fed diet supplemented EPCL (74.60%) than other treatments. Intestinal clostridium count reduced (P < 0.05) and lactobacillus count increased (P < 0.05) in the intestine and caecum of broilers fed the diet supplemented CL and those fed EPCL supplemented diet. Intestinal coliform and salmonella count reduced (P < 0.05) for broilers fed the diet supplemented EP and those fed the EPCL supplemented diet. Dietary supplementation of EPCL resulted in the highest (P < 0.05) body weight (BW, 2551.38 g), dressing percentage (DP, 81.68%), and percentage of breast muscle (20.01%). Supplementation of EP, CL, and EPCL in the diet of broilers resulted in higher (P < 0.05) spleen weight while dietary supplementation of EP and EPCL resulted in higher (P < 0.05) thymus weight. Clostridium count was reduced (P < 0.05) in the meat of broilers fed the diet supplemented CL and EPCL and the lowest (P < 0.05) salmonella count was observed in the meat of broilers fed the diet supplemented with EPCL. In conclusion, the current study reveals that dietary supplementation with EP and CL composite improves nutrient digestibility, gut microflora, and dressing percentage with reduced meat microbial load of broilers.

A Comprehensive In Silico Exploration of Pharmacological Properties, Bioactivities, Molecular Docking, and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase.

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with -11.8 kcal/mol energy than control vemurafenib -10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme's active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.

Dimeric guaianes from leaves of Xylopia vielana as snail inhibitors identified by high content screening.

The transcriptional repressor Snail trriggers epithelial-mesenchymal transition (EMT), the process allowing cancer cells with invasive and metastasis properties. In this study, we screened medicinal plants for the Snail inhibitory active components by high content screen (HCS) and found that the crude extract of Xylopia vielana leaves showed potential activity. Subsequently, bioassay-guided isolation of the extract of Xylopia vielana was performed to obtain twenty-four dimeric guaianes (1-24), including 16 new analogues (1-5, 8-11, 13-15, 17, 18, 21, and 22). Their structures were elucidated by the comprehensive application of multiple spectroscopic methods. Compounds 1, 11, 12, and 16 were initially identified as the active compounds. Wound healing assay, transwell migration assay and western blot experiments verified that compounds 1 and 12 inhibited the expression of Snail in a concentration-dependent manner, and compound 12 was verified as a potent tumor migration inhibitory agent. This work showed a practical strategy for the discovery of new Snail inhibitors from natural products and provided potential insights for dimeric guaianes as anticancer lead compounds specifically targeting Snail protein.

Alkaloid and phenolic compounds of Xylopia aromatica inhibits tumor growth by down-regulating matrix metalloproteinase-2 (MMP-2) expression.

Annonacea species have been reported to possess antitumor properties. However, the in vitro and in vivo antitumor activities of Xylopia aromatica (Annonacea) have not yet been elucidated. This study aimed to investigate the effects of Xylopia aromatica leaves hexane fraction (XaHF) on Ehrlich ascites carcinoma cells lines (EAC), both in vitro and in vivo. In vitro assays revealed a significant cytotoxic effect with the two lower XaHF concentrations (62.5 and 32.3mg/mL). EAC (2.5x106 cells) were inoculated in the right flank of Swiss mice, and the animals were treated intraperitoneally with 32.3mg kg-1 of XaHF daily, for 20 days. Our findings indicate that XaHF suppressed the growth of EAC in vivo, with a significant decrease (46%) in tumor volume. There was also a decrease in the necrosis area (71%), inflammatory infiltrate, and MMP-2 expression. High-Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) identified secondary metabolites possibly related to phenolic acids, flavonoids, and alkaloids. Thus, the results confirmed the antitumoral activity that may be related to the presence of the identified metabolites in XaHF extract.

MALDI-HRMS imaging and HPLC-HRESI-MSn characterisation of kaurane diterpenes in the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae).

INTRODUCTION: Kaurane diterpenes, notably xylopic acid, have demonstrated important biological activities including analgesia, anti-oxidant, antimicrobial and cytotoxicity. The fruits of Xylopia aethiopica have been reported to be a rich source of kaurane diterpenes. OBJECTIVE: An analytical approach for detailed imaging and characterisation of selected kaurane diterpenes was developed using matrix-assisted laser desorption/ionisation high-resolution mass spectrometry (MALDI-HRMS) imaging techniques and high-performance liquid chromatography-high resolution electrospray ionisation-tandem mass spectrometry (HPLC-HRESI-MSn ) studies, respectively. METHODS: The images of the compounds were constructed based on selected ions from their HRESI-MS spectra. The matrix employed comprised a solution of α-cyano-4-hydroxycinnamic acid (HCCA) in acetonitrile-water with trifluoroacetic acid (TFA). HPLC-HRESI-MSn measurements were conducted on an LTQ-Orbitrap spectrometer equipped with a heated electrospray ionisation (HESI)-II source. RESULTS: The analytical strategy adopted showed the spatial distribution of the compounds in the fruits of X. aethiopica based on the dominant ions at m/z 301.2163 [M + H - HOCOCH3 ]+ and m/z 399.1932 [M + K]+ for xylopic acid, m/z 317.2111 [M + H]+ and m/z 355.1670 [M + K]+ for 15-oxo-ent-kaur-16-en-19-oic acid and m/z 303.2319 [M + H]+ for ent-kaur-16-en-19-oic acid. The fragmentation patterns of the compounds were proposed based on the HRESI-MSn measurements. CONCLUSIONS: The study revealed the spatial variability, differential behaviours and specificity of the selected kaurane diterpenes in the fruit, seed and pericarp. The compounds under study were predominantly restricted to the pericarp of the fruit with trace amounts in the seed.

Vieloplains A-G, seven new guaiane-type sesquiterpenoid dimers from Xylopia vielana.

Seven new guaiane-type sesquiterpene dimers vieloplains A-G, connecting patterns through three different direct CC bonds compounds 1-5 (C-3 to C-3', C-4 to C-1'), compound 6 (C-2 to C-3', C-4 to C-2') and compound 7 (C-2 to C-1', C-4 to C-2') were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOESY analysis, the Cu Kα X-ray crystallographic the experiment circular dichroism (ECD) and the calculated ECD. Among them, only compound 6 showed a considerable cytotoxicity against DU145 cells with IC50 values of 9.5 µM. Flow cytometry analysis confirmed that 6 caused death of DU145 cells via apoptosis induction.

Nanoemulsion containing essential oil from Xylopia ochrantha Mart. produces molluscicidal effects against different species of Biomphalaria (Schistosoma hosts).

BACKGROUND: This work describes a chemical study of the essential oil from leaves of Xylopia ochrantha, an endemic Annonaceae species from Brazil, and its activity against Biomphalaria species. Considering its poor solubility in aqueous medium, the essential oil was nanoemulsified to evaluate its action on controlling some mollusc species of genus Biomphalaria, snail hosts of Schistosoma mansoni that causes schistosomiasis, which mainly affects tropical and subtropical countries. OBJECTIVES: The main aims of this work were to analyse the chemical composition of essential oil from X. ochrantha, and to evaluate the effect of its nanoemulsion on molluscs of genus Biomphalaria and their oviposition. METHODS: Chemical analysis was performed by gas chromatography coupled to mass spectrometry. Nanoemulsions were prepared by a low energy method and characterised by particle size and polydispersity index. Biological assays evaluating the mortality of adult species of B. glabrata, B. straminea and B. tenagophila and their ovipositions upon contact with the most stable nanoemulsion during 24 and 48 h were performed. FINDINGS: Chemical analysis by mass spectrometry revealed the majority presence of bicyclogermacrene and germacrene D in the essential oil. The formulation with a hydrophilic-lipophilic balance (HLB) of 9.26 was the most suitable for the oil delivery system. This nanoemulsion caused the mortality in B. tenagophila, B. straminea and B. glabarata of different sizes at levels ranging from 50 to 100% in 48 h. Additionally, the formulation could inhibit the development of deposited eggs. CONCLUSION: Thus, these results suggest the use of nanoemulsified essential oil from X. ochrantha as a possible alternative in controlling some Biomphalaria species involved in the schistosomiasis cycle.

A Comprehensive View on (-)-7-Oxo-ent-kaur-16-en-19-oic Acid, the Major Constituent of Xylopia sericea Leaves Extract: Complete NMR Assignments, X-Ray Crystallographic Structure, in Vitro Antimalarial Activity and Cytotoxicity.

Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (-)-7-oxo-ent-kaur-16-en-19-oic acid (C20 H28 O3 ) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC-TOCSY, HSQC-NOESY and NOESY) and by X-ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC-NOESY and NOESY) and X-ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine-resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC50 862.6±6.7 µm) by the MTT assay. The unequivocal NMR signals assignments, the X-ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.

Xylopia aethiopica Seeds from Two Countries in West Africa Exhibit Differences in Their Proteomes, Mineral Content and Bioactive Phytochemical Composition.

Aside from its multiple medicinal uses, the fruit of Xylopia aethiopica is widely used in Africa as food. Herein, we characterize the protein profiles, mineral content and bioactive phytochemical composition of the seeds of this plant sourced in Ghana and Nigeria. Using label-free proteomics, a total of 677 proteins were identified, with 260 found in the Ghana-sourced samples while 608 proteins were detected in the samples from Nigeria. However, 114 proteins were common between the samples from the two countries, among which 48 were significantly changed. Bioinformatics and functional analyses revealed that the differential levels of the proteins were mainly linked to pathways involved amino acids metabolism and biosynthesis. The significantly changed proteins related mainly to catalytic activity and carbon metabolism. The samples from Nigeria also exhibited superior qualities in terms of their antioxidant effects, and total phenolic and flavonoid content. Finally, only the content of Na varied to a statistically significant level. This study lends support to its culinary use and hints towards the impact of location of cultivation on the quality of the seeds. There is however need for further mechanistic investigations to unravel the underlying reasons for the observed differences.

Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei.

BACKGROUND: Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relationship that exists in their combined administration determined. METHODS: Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg-1) and xylopic acid (XA) (3, 10, 30 mg kg-1) was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs. CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed. RESULTS: The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected at high doses. CONCLUSION: The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.

Xylopsides A-D, four rare guaiane dimers with two unique bridged pentacyclic skeletons from Xylopia vielana.

Four unprecedented guaiane dimers, xylopsides A-D (1-4), were isolated and identified from the roots of Xylopia vielana. The structures of 1-4 were elucidated by spectroscopic analysis, Cu Kα X-ray crystallography and CD spectra. 1-4 showed two bridged pentacyclic skeletons between two guaiane-type sesquiterpenes, which were characterized as two different bridged ring systems. Among these compounds, 4 exhibited a moderate inhibitory activity against the production of nitric oxide with an IC50 value of 25.7 µM in RAW264.7 cells stimulated by LPS.

New AChE inhibitors from microbial transformation of trachyloban-19-oic acid by Syncephalastrum racemosum.

Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2-3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1-4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimer's disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50 = 0.06 µM, which is about six times higher than activity found for galanthamine (IC50 = 0.38 µM), the positive control used in this assay.

Chemical Variability of Ivoirian Xylopia rubescens Leaf Oil.

Forty-two essential oil samples were isolated from leaves of Xylopia rubescens harvested in three forests of Southern Ivory Coast. All the samples have been submitted to GC-FID and the retention indices (RIs) of individual components have been measured on two capillary columns of different polarity. In addition, 20 oil samples, selected on the basis of their chromatographic profile, were also analyzed by 13 C-NMR and 24 components (78.0 - 92.4% of the whole compositions) have been identified. The content of the main components varied drastically from sample to sample: furanoguaia-1,4-diene (5.7 - 54.1%), furanoguaia-1,3-diene (1.1 - 10.5%), (8Z,11Z,14Z)-heptadeca-8,11,14-trien-2-one (4.3 - 16.0%), and (E)-ß-caryophyllene (1.7 - 17.3%). Hierarchical cluster and principal components analysis of the 42 oil compositions allowed the distinction of two well-differentiated groups of unequal importance within the oil samples. Oil samples of the main group (Group II) contained mainly furanoguaia-1,4-diene (mean [M] = 43.1%; standard deviation [SD] = 3.2%) while furanoguaia-1,3-diene (M = 8.4%; SD = 0.9%) and (8Z,11Z,14Z)-heptadeca-8,11,14-trien-2-one (M = 7.1%; SD = 1.5%) were present at appreciable contents. The composition of Group I was dominated by furanoguaia-1,4-diene (M = 17.0%; SD = 8.5%), (8Z,11Z,14Z)-heptadeca-8,11,14-trien-2-one (M = 10.2%; SD = 2.4%) and (E)-ß-caryophyllene (M = 9.5%; SD = 5.3%).

Cytotoxic Alkaloids from the Stem of Xylopia laevigata.

Xylopia laevigata (Annonaceae), known locally as "meiú" or "pindaíba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (-)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G2/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids.

Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain.

CONTEXT: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. OBJECTIVE: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. MATERIALS AND METHODS: Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. RESULTS: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. CONCLUSION: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.

Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity.

CONTEXT: The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. OBJECTIVE: EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. MATERIALS AND METHODS: EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. RESULTS: The major components of EOX were α-pinene (34.57%) and limonene (31.75%). The HC50 (concentration producing 50% haemolysis) was 293.6 µg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 µg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 µg/ml). The LD50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. CONCLUSION: EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential.

BACKGROUND: Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. METHODS: The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. RESULTS: Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca(2+)]c reduction. CONCLUSION: Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca(2+) influx blockade, which results in [Ca(2+)]c reduction leading to smooth muscle relaxation.

Composition and cytotoxic activity of essential oils from Xylopia aethiopica (Dunal) A. Rich, Xylopia parviflora (A. Rich) Benth.) and Monodora myristica (Gaertn) growing in Chad and Cameroon.

BACKGROUND: Cancer has become a global public health problem and the search for new control measures is urgent. Investigation of plant products such as essential oils from Monodora myristica, Xylopia aethiopica and Xylopia parviflora might lead to new anticancer therapy. In this study, we have investigated the antineoplastic activity of essential oils from fruits of these plants growing in Chad and Cameroon. METHODS: The essential oils obtained by hydrodistillation of fruits of Monodora myristica, Xylopia aethiopica and Xylopia parviflora collected in Chad and Cameroon were analyzed by GC-FID and GC-MS and investigated for their antiproliferative activity against the breast cancer cell line (MCF7). RESULTS: Overall, monoterpenes were mostly found in the six essential oils. Oils from X. aethiopica and X. parviflora from Chad and Cameroon mainly contain ß-pinene at 24.6%, 28.2%, 35.7% and 32.9% respectively. Monodora myristica oils from both origins contain mainly α-phellandrene at 52.7% and 67.1% respectively. The plant origin did not significantly influence the chemical composition of oils. The six essential oils exerted cytotoxic activity against cancer (MCF-7) and normal cell lines (ARPE-19), with more pronounced effect on neoplastic cells in the majority of cases. The highest selectivity was obtained with the essential oils of X. parviflora from Chad and Cameroon (5.87 and 5.54) which were more cytotoxic against MCF-7 than against normal cell line (ARPE-19) with IC50 values of 0.155 µL/mL and 0.166 µL/mL respectively. CONCLUSIONS: Essential oils from fruits of Monodora myristica, Xylopia aethiopica and Xylopia parviflora have shown acceptable antineoplastic potency, and might be investigated further in this regard.