Antioxidant, antimicrobial and healing properties of an extract from coffee pulp for the development of a phytocosmetic.

Consumer demand for natural, chemical-free products has grown. Food industry residues, like coffee pulp, rich in caffeine, chlorogenic acid and phenolic compounds, offer potential for pharmaceutical and cosmetic applications due to their antioxidant, anti-inflammatory, and antibacterial properties. Therefore, the objective of this work was to develop a phytocosmetic only with natural products containing coffee pulp extract as active pharmaceutical ingredient with antioxidant, antimicrobial and healing activity. Eight samples from Coffea arabica and Coffea canephora Pierre were analyzed for caffeine, chlorogenic acid, phenolic compounds, tannins, flavonoids, cytotoxicity, antibacterial activity, and healing potential. The Robusta IAC-extract had the greatest prominence with 192.92 µg/mL of chlorogenic acid, 58.98 ± 2.88 mg GAE/g sample in the FRAP test, 79.53 ± 5.61 mg GAE/g sample in the test of total phenolics, was not cytotoxic, and MIC 3 mg/mL against Staphylococcus aureus. This extract was incorporated into a stable formulation and preferred by 88% of volunteers. At last, a scratch assay exhibited the formulation promoted cell migration after 24 h, therefore, increased scratch retraction. In this way, it was possible to develop a phytocosmetic with the coffee pulp that showed desirable antioxidant, antimicrobial and healing properties.

Genome mining reveals secondary metabolites of Antarctic bacterium Streptomyces albidoflavus related to antimicrobial and antiproliferative activities.

The urgent need for new antimicrobials arises from antimicrobial resistance. Actinobacteria, especially Streptomyces genus, are responsible for production of numerous clinical antibiotics and anticancer agents. Genome mining reveals the biosynthetic gene clusters (BGCs) related to secondary metabolites and the genetic potential of a strain to produce natural products. However, this potential may not be expressed under laboratory conditions. In the present study, the Antarctic bacterium was taxonomically affiliated as Streptomyces albidoflavus ANT_B131 (CBMAI 1855). The crude extracts showed antimicrobial activity against both fungi, Gram-positive and Gram-negative bacteria and antiproliferative activity against five human tumor cell lines. Whole-genome sequencing reveals a genome size of 6.96 Mb, and the genome mining identified 24 BGCs, representing 13.3% of the genome. The use of three culture media and three extraction methods reveals the expression and recovery of 20.8% of the BGCs. The natural products identified included compounds, such as surugamide A, surugamide D, desferrioxamine B + Al, desferrioxamine E, and ectoine. This study reveals the potential of S. albidoflavus ANT_B131 as a natural product producer. Yet, the diversity of culture media and extraction methods could enhance the BGCs expression and recovery of natural products, and could be a strategy to intensify the BGC expression of natural products.

Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae.

BACKGROUND: Carboxymethylated Lasiodiplodan (LaEPS-C), Lasiodiplodia theobromae ß-glucan exopolysaccharide derivative, has a well-known range of biological activities. Compared to LaEPS-C, its fractions, Linear (LLaEPS-C) and Branched (BLaEPS-C), have biological potentialities scarcely described in the literature. So, in this study, we investigate the immunomodulatory, antiviral, antiproliferative, and anticoagulant activities of LLaEPS-C and BLaEPS-C and compare them to the LaEPS-C. METHODS: LaEPS was obtained from L. theobromae MMBJ. After carboxymethylation, LaEPS-C structural characteristics were confirmed by Elementary Composition Analysis by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (NMR). The immunomodulatory activity on cytokine secretion was evaluated in human monocyte-derived macrophage cultures. The antiviral activity was evaluated by Hep-2 cell viability in the presence or absence of hRSV (human respiratory syncytial virus). In vitro antiproliferative activity was tested by sulforhodamine B assay. The anticoagulant activity was determined by APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time). RESULTS: LaEPS-C showed low macrophage cell viability only at 100 µg/mL (52.84 ± 24.06, 48 h), and LLaEPS-C presented no effect. Conversely, BLaEPS-C showed cytotoxicity from 25 to 100 µg/mL (44.36 ± 20.16, 40.64 ± 25.55, 33.87 ± 25.16; 48 h). LaEPS-C and LLaEPS-C showed anti-inflammatory activity. LaEPS-C presented this at 100 µg/mL (36.75 ± 5.53, 48 h) for IL-10, and LLaEPS-C reduces TNF-α cytokine productions at 100 µg/mL (18.27 ± 5.80, 48 h). LLaEPS-C showed an anti-hRSV activity (0.7 µg/ml) plus a low cytotoxic activity for Hep-2 cells (1.4 µg/ml). LaEPS-C presented an antiproliferative activity for NCI-ADR/RES (GI50 65.3 µg/mL). A better PT was achieved for LLaEPS-C at 5.0 µg/mL (11.85 ± 0.87s). CONCLUSIONS: These findings demonstrated that carboxymethylation effectively improves the biological potential of the LaEPS-C and their fractions. From those polysaccharides tested, LLaEPS provided the best results with low toxicity for anti-inflammatory, antiviral, and anticoagulant activities.

Evaluation of a Standardized Extract Obtained from Cashew Apple (Anacardium occidentale L.) Bagasse in DSS-Induced Mouse Colitis.

Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. Several studies relate eating habits to different aspects of IBD, such as progression and worsening of the clinical condition. Therefore, many natural products (NPs) such as polyphenols and carotenoids have been identified as promising agents in supporting IBD. An interesting source for obtaining bioactive NPs is the by-products of the food industry. The present study evaluated the potential beneficial effect of a standardized extract (CAE) obtained from cashew apple bagasse in the dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice. This was the first time that CAE had been evaluated in this experimental model. Chemical evaluation of CAE identified carotenoids (96.28 ± 0.15 mg/100 g), phenolic compounds (37.49 ± 0.64 mg/100 g), and a mixture of anacardic acids (C15:3 = 94.2 ± 0.6 mg/100 g; C15:2 = 108.4 ± 0.1 mg/100 g; C15:1 = 214.8 ± 0.2 mg/100 g). Administration of CAE (500 mg/kg, 4 days, p.o.) after DSS challenge was more effective in delaying disease progression compared with prior treatment (500 mg/kg, 30 days, p.o.), according to the disease activity index. However, no treatment strategy with CAE was able to prevent or inhibit disease progression, since all parameters evaluated (macroscopic, biochemical, and histopathological) in CAE-treated animals were similar to those observed in DSS-challenged animals. Despite the high dose (500 mg/kg), the standardized extract (CAE) did not result in an effective concentration of carotenoids. Furthermore, as some anacardic acids have been reported as histone acetyltransferases inhibitors, there could be a possible antagonistic relationship between carotenoids and anacardic acids. Complementary research will be necessary to test the hypothesis of antagonism. Thus, an optimized extract, with an even higher concentration of carotenoids, obtained from cashew apple bagasse, can be developed as a possible adjuvant food supplement for inflammatory bowel diseases.

Chemical composition and anti-proliferative activity of essential oils from some medicinal plants from Cachicadán, Región La Libertad, Perú.

This study evaluated the chemical composition and anti-proliferative activity of essential oils (EOs) obtained by hydrodistillation from seven medicinal plants from Cachicadán, La Libertad Región, Perú. Limonene (0.64 to 44.43%) and linalool (0.36 to 2.12%) were identified in all EOs by gas chromatography coupled to mass spectrometry analysis. The major components (relative intensity ≥ 10%) were cis-dihydro carvone, carvone, and cis-piperitone epoxide for Minthostachys mollis leaves; ß-pinene, limonene, and ledol for Lepechinia heteromorpha leaves; limonene, neral, and geranial for Aloysia citriodora, both leaves and flowers; α-pinene, and limonene for Myrcianthes myrsinoides leaves; and α-pinene, ß-myrcene, and (E)-ß-Ocimene for Dalea carthagenensis leaves. Constituted by (Z)-ß-ocimene, dihydrotagetone, (Z)-tagetone, and car-3-en-2-one, EO of Tagetes minuta leaves induced an irreversible cytostatic effect against MCF-7 human breast tumor cells. Further in vivo studies must be carried out to establish the safe and efficient dose of T. minuta EO as adjuvant treatment in oncological therapies.

Investigating the antiproliferative activities of new CuII complexes with pyridine hydrazone derivatives of nalidixic acid.

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)]4BF4∙H2O (1), and [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)3]4BF4∙3H2O (%) (2) were synthesized using h2py and h3py with Cu(BF4)2∙nH2O as precursor, whereas the [Cu(C18H17N5O2)Cl2]∙0.5H2O complex (3) was synthesized with h2py and CuCl2∙2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type κ3(O,N,N') as well as bidentate modes of type κ2(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.

Gastrointestinal effects of Mentha aquatica L. essential oil.

Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect (> 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD.

Structural properties and evaluation of the antiproliferative activity of limonene-1,2-diol obtained by the fungal biotransformation of R-(+)- and S-(-)-limonene.

Limonene-1,2-diol is a limonene oxygenated metabolite that possesses eight different stereoisomers, which could result in different biological properties. Nonetheless, the relation between its spatial configuration and biological function is still little explored. The present study aimed to perform the stereoisomers identification using nuclear magnetic resonance (NMR) investigation of the limonene-1,2-diol produced via R-(+)- and S-(-)-limonene biotransformation by Colletotrichum nymphaeae and S-(-)-limonene biotransformation by Fusarium oxysporum 152B. Besides, in vitro antiproliferative activity was evaluated against human tumor and nontumor cell lines. The NMR analysis showed that R-(+)-limonene biotransformation afforded exclusively (+)-(1S,2S,4R-limonene-1,2-diol), whereas S-(-)-limonene biotransformation afforded exclusively (-)-(1R,2R,4S-limonene-1,2-diol) independent on the fungi used. Despite no significant cytostatic effects, a possible influence of stereogenic center on the antiproliferative activity of these limonene biotransformation products was evidenced. Moreover, the lack of in vitro antiproliferative effect of limonene-1,2-diol against nontumor cells suggested a safe dose range for further in vivo evaluations, including food applications.

Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma.

Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-o-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.

In vitro antiproliferative activity of alkaloids isolated from Tabernaemontana catharinensis A.DC (Apocynaceae).

In this work, four alkaloids from the stem bark of T. catharinensis were isolated, namely: voacangine (1); ethyl apovincaminate (2); affinisine (3) and voachalotine (4). The alkaloids were tested in vitro for antiproliferative capacity in eight tumor cell lines: U251 (glioma), MCF-7 (breast), NCI-ADR/RES (drug resistant ovary), 786-0 (kidney), NCI-H460 (lung), HT-29 (colon), K562 (leukemia) and PC-3 (prostate) and a non-tumor keratinocyte cell line (HaCat). Antiproliferative activity was observed after 48 hours and results expressed as the concentration needed to induce 50% growth inhibition (GI50) in µM. The chemotherapy drug Doxorubicin was used as a standard. The alkaloid affinisine (3) was the most promising, showing moderate inhibition rates in addition to the cytotoxic and cytocidal effect against all strains tested. It also proved to be a very promising compound, showing high selectivity rates when compared to the non-tumor keratinocyte cell line (HaCat).

Mentha aquatica L. aerial parts: in vitro anti-proliferative evaluation on human tumour and non-tumour cell lines.

Bearing in mind the several medicinal properties of Mentha genus, this work aimed to evaluate the anti-proliferative potential of the ethanolic extract (EE) and fractions from M. aquatica L aerial parts. Using the anti-proliferative protocol developed by the NCI/USA, four fractions (F2 - F4 and F6) obtained from EE showed promising anti-proliferative profile against a panel of human tumor and non-tumor cell lines. After 24-h exposure, F2 (0.25 µg/mL) showed potent and irreversible anti-proliferative effect without inducing cell cycle arrest in both NCI-H460 and MCF-7 cells, without (anti) estrogenic activity. These effects were lost after storage of F2 diluted in dimethyl sulfoxide at -80 °C during 2 weeks. Analysis by gas chromatography coupled to mass detection evidenced some chemical changes induced by F2 storage in solution. The present study demonstrated the anti-proliferative effect of M. aquatica. Further studies are necessary to determine better storage conditions to enhance F2 stability.

Biological properties of Schinus terebinthifolia Raddi essential oil

Abstract Schinus terebinthifolia Raddi green fruits essential oil (EO) was evaluated regarding its phytochemical profile, antimicrobial and cytotoxic activities, and toxicity. Gas chromatography with mass spectrometry was applied to identify its constituents, thereafter the minimum inhibitory concentration, minimum bactericidal and fungicidal concentrations, and its antibiofilm activity were evaluated. The EO cytotoxicity was assessed in tumor and non-tumor human cells, and in vivo toxicity was evaluated in a Galleria mellonella model. The major constituents of S. terebinthifolia EO were alpha-phellandrene and beta-phellandrene. The EO had a weak activity against all strains of Candida albicans (MIC 1000µg/mL) and had no activity against non-albicans strains, bacteria, and C. albicans biofilm. Cytostatic activity against all tumor cell lines was shown. Additionally, cell viability remained at EO concentrations up to 62.5 µg/mL. At 16 mg/mL, 50% hemolysis was observed, and it had low toxicity in vivo. Overall, the S. terebinthifolia EO was characterized by low antimicrobial and antibiofilm activities, with no evidence of toxicity to human tumor and non-tumor cells

Chemical Composition and Antiproliferative Activity of the Ethanolic Extract of Cyperus articulatus L. (Cyperaceae).

Cyperus articulatus L. (Priprioca) is a plant of the Cyperaceae family traditionally used in traditional medicine in the Amazon region. Studies of the essential oil of this species have identified many terpene compounds. However, little is known about the possible uses of solid waste generated by the extraction of essential oils. This study aimed to investigate the chemical composition of volatile compounds and to evaluate the antiproliferative activity of the ethanolic extract of solid residues generated by the extraction of the essential oil of C. articulatus L. rizhomes in experimental models in vitro using peritoneal macrophages of mice and human tumor cell lines. The analysis of the chemical composition of volatile compounds indicated the presence of sesquiterpenes and particularly sequiterpenic ketones as main constituents. The results showed that the treatment with ethanolic extract of C. articulatus L. reduced the activity of the enzyme arginase and proliferation of cancer cells (p < 0.0001). The extract also showed no cytotoxicity in macrophages in concentrations between 12.5; 25 and 50 mg/mL (p < 0.0001). The results indicated that the extract of C. articulatus L. exerts antiproliferative activity (p < 0.0001) with low toxicity on healthy cells in experimental models in vitro.

Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line.

Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.

A study of the bioactive potential of seven neglected and underutilized leaves consumed in Brazil.

This study investigated the vitamin C content, total phenolic compounds (TPC), and the potential bioactivities (antioxidant, antiproliferative, antibacterial activities, and inhibition capacity against N-nitrosation) of seven neglected and underutilized species (NUS): culantro (Eryngium foetidum), false roselle (Hibiscus acetosella), roselle (Hibiscus sabdariffa), tree basil (Ocimum gratissimum), Barbados Gooseberry (Pereskia aculeata), purslane (Portulaca oleracea), and tannia (Xanthosoma sagittifolium). Phenolic-rich extracts were obtained by a sequential optimization strategy (Plackett-Burman and Central Composite Design). O. gratissimum presented the highest TPC and X. sagittifolium the greater total vitamin C content. Overall, the plant extracts presented promising bioactive capacities, as scavenging capacity against HOCl, H2O2 and ROO• induced oxidation. P. oleracea demonstrated the highest cytostatic effect against ovarian and kidney tumor cells. O. gratissimum effectively inhibited S. Choleraesuis growth. Maximum inhibition on n-nitrosation was showed by O. gratissimum and E. foetidum. These results highlight the studied NUS as sources of potential health-promoting compounds.

Antiglycation and antitumoral activity of Tribulus terrestris dry extract.

OBJECTIVE: Investigation of the antiglycation and antitumoral potential of standardized and saponins-enriched extracts of Tribulus terrestris herbal medicine. MATERIALS AND METHODS: The procedures for the evaluation of the antiglycation activity of the standardized (TtSE) and saponins-enriched (TtEE) extracts of T. terrestris were: determination of relative mobility in electrophoresis (RME), free amino groups using OPA method and advanced glycation end-products (AGEs) fluorescence. Antioxidant activity was determined by DPPH radical scavenging test. In vitro antitumor activity of TtSE and TtEE was evaluated in human tumor cell lines. RESULTS: The results were obtained by antiglycation tests (RME, OPA method and AGEs fluorescence determination), using BSA as protein and ribose as glycation agent, and antioxidant assay (DPPH test); it was verified that both extracts of T. terrestris have antiglycation and antioxidant activity. In addition, the extracts were able to induce death of more than 50% of human tumor cell lines. CONCLUSION: The present study showed that standardized and saponins-enriched extracts of T. terrestris herbal medicine present antiglycation and antioxidant and antiproliferative action in human tumor cells lines. The saponins-enriched extract proved a greater antiglycation and antioxidant activity in comparison to the standardized type.

In vitro performance of free and encapsulated bromelain.

For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.

New cadinene-sesquiterpene from Chromolaena laevigata (lam.) R. M. King & H. Rob (Asteraceae) aerial parts and biological activities.

Phytochemical investigation of Chromolaena laevigata led to the isolation of a new cadinene-sesquiterpene, chromolaevigone glucoside (1), along with nine known compounds: daucosterol (2), stigmasterol glycoside (3), stigmasterol (4), ß-sitosterol (5), pilloin (6), gonzalitosin I (7), quercetin-3-O-α-rhamnopyranoside (8), 7,7-dihydroxy-calamen-12-oic acid lactone (9) and trachelanthic acid (10). Others 11 known compounds were identified by UHPLC-HRMS/MS. These compounds are being described for the first time in this species, with the exception of cadinene 9. Furthermore, due to the limitation of pharmacological studies, antiproliferative, antiviral, and antimicrobial activities of C. laevigata were evaluated. The best results in the cytotoxicity, antimicrobial and antiproliferative tests, presenting GI50 values on ovarian tumour cells (OVCAR-03) of 1.9 µg mL-1 and kidney (786-0) of 2.5 µg mL-1 were observed for the hexanic fraction.[Figure: see text].

Antiproliferative, antileishmanial and antimicrobial studies on Cnidoscolus quercifolius Pohl (Euphorbiaceae).

Cnidoscolus quercifolius is an Euphorbiaceae endemic to the northeast region of Brazil, which is used in folk medicine as anti-inflammatory, analgesic and antibiotic. An ethanolic extract was prepared with the leaves from C. quercifolius, and also partitioned and chromatographed leading to the isolation of cyanoglucoside linamarin (1), cinnamic acid (2), as well as a mixture of steroids and terpenoids (3-6). Structural elucidation of the compounds was done by IR, MS and NMR analysis. For the cyanoglucoside (1) were also evaluated its antimicrobial and antileishmanial viabilities by plaque microdilution and MTT test, respectively. Both tests showed from moderate to zero activity against the organisms evaluated. In addition, the antiproliferative activity of compounds 1 and 5-6 were tested against tumor cells, which did not show statistically significant growth inhibition 50% (GI50). The obtained results suggested that further pharmacological studies should prove the folk medicinal uses.

Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies.

Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound's relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents.