Medicinal plant Miconia albicans synergizes with ampicillin and ciprofloxacin against multi-drug resistant Acinetobacter baumannii and Staphylococcus aureus.

BACKGROUND: Given the rising occurrence of antibiotic resistance due to the existence and ongoing development of resistant bacteria and phenotypes, the identification of new treatments and sources of antimicrobial agents is of utmost urgency. An important strategy for tackling bacterial resistance involves the utilization of drug combinations, and natural products derived from plants hold significant potential as a rich source of bioactive compounds that can act as effective adjuvants. This study, therefore, aimed to assess the antibacterial potential and the chemical composition of Miconia albicans, a Brazilian medicinal plant used to treat various diseases. METHODS: Ethanolic extracts from leaves and stems of M. albicans were obtained and subsequently partitioned to give the corresponding hexane, chloroform, ethyl acetate, and hydromethanolic phases. All extracts and phases had their chemical constitution investigated by HPLC-DAD-MS/MS and GC-MS and were assessed for their antibiofilm and antimicrobial efficacy against Staphylococcus aureus. Furthermore, their individual effects and synergistic potential in combination with antibiotics were examined against clinical strains of both S. aureus and Acinetobacter baumannii. In addition, 10 isolated compounds were obtained from the leaves phases and used for confirmation of the chemical profiles and for antibacterial assays. RESULTS: Based on the chemical profile analysis, 32 compounds were successfully or tentatively identified, including gallic and ellagic acid derivatives, flavonol glycosides, triterpenes and pheophorbides. Extracts and phases obtained from the medicinal plant M. albicans demonstrated synergistic effects when combined with the commercial antibiotics ampicillin and ciprofloxacin, against multi-drug resistant bacteria S. aureus and A. baumannii, restoring their antibacterial efficacy. Extracts and phases also exhibited antibiofilm property against S. aureus. Three key compounds commonly found in the samples, namely gallic acid, quercitrin, and corosolic acid, did not exhibit significant antibacterial activity when assessed individually or in combination with antibiotics against clinical bacterial strains. CONCLUSIONS: Our findings reveal that M. albicans exhibits remarkable adjuvant potential for enhancing the effectiveness of antimicrobial drugs against resistant bacteria.

Myricitrin from Combretum lanceolatum Exhibits Inhibitory Effect on DNA-Topoisomerase Type IIα and Protective Effect Against In Vivo Doxorubicin-Induced Mutagenicity.

Flavonoids-compounds abundant in balanced daily diets-have been extensively investigated for biological activity. The pronounced antiproliferative effects of flavonoids have prompted studies to elucidate their mode of action against tumor cells. The anticancer properties of myricetin, a 3',4',5'-tri-hydroxylated flavonol, have been confirmed for a number of neoplasms, but myricitrin, its 3-O-rhamnoside derivative found in fruits and other parts of edible plants, has been scarcely investigated as a chemopreventive agent. This study evaluated the antiproliferative potential of myricitrin obtained from Combretum lanceolatum (Combretaceae) against MCF7 (breast), PC-3 (prostate), HT-29 (colon), 786-0 (kidney), and HL-60 (acute promyelocytic leukemia) cancer cell lines, using the sulforhodamine B and tetrazolium salt assays. Myricitrin proved most effective in inhibiting growth of HL-60 cells (GI50 = 53.4 µmol·L-1), yet showed weak antiproliferative activity against other cell lines. Possible cytotoxic mechanisms involving inhibition of topoisomerases I and IIα by myricitrin were also evaluated, revealing inhibitory activity only against topoisomerase IIα. The results suggested that topoisomerase IIα inhibition is the probable mechanism responsible for the antiproliferative activity of myricitrin. In vivo mutagenicity by myricitrin and its possible antimutagenic effect on doxorubicin-induced DNA damage were also investigated by performing the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Myricitrin proved nonmutagenic to the offspring of standard (ST) and high-bioactivation (HB) crosses, while cotreatments with doxorubicin revealed the antimutagenic properties of myricitrin, even under conditions of high metabolic activation.

Therapeutic Effects of Morinda citrifolia Linn. (Noni) Aqueous Fruit Extract on the Glucose and Lipid Metabolism in High-Fat/High-Fructose-Fed Swiss Mice.

The aim of this study was to evaluate the therapeutic effects of two different doses (250 and 500 mg/kg) of Morinda citrifolia fruit aqueous extract (AE) in high-fat/high-fructose-fed Swiss mice. The food intake, body weight, serum biochemical, oral glucose tolerance test (OGTT), and enzyme-linked immunosorbent assay (ELISA), as well as histological analyses of the liver, pancreatic, and epididymal adipose tissue, were used to determine the biochemical and histological parameters. The chemical profile of the extract was determined by ultra-fast liquid chromatography-diode array detector-tandem mass spectrometry (UFLC-DAD-MS), and quantitative real-time PCR (qRT-PCR) was used to evaluate the gene expressions involved in the lipid and glucose metabolism, such as peroxisome proliferative-activated receptors-γ (PPAR-γ), -α (PPAR-α), fatty acid synthase (FAS), glucose-6-phosphatase (G6P), sterol regulatory binding protein-1c (SREBP-1c), carbohydrate-responsive element-binding protein (ChREBP), and fetuin-A. Seventeen compounds were tentatively identified, including iridoids, noniosides, and the flavonoid rutin. The higher dose of AE (AE 500 mg/kg) was demonstrated to improve the glucose tolerance; however, both doses did not have effects on the other metabolic and histological parameters. AE at 500 mg/kg downregulated the PPAR-γ, SREBP-1c, and fetuin-A mRNA in the liver and upregulated the PPAR-α mRNA in white adipose tissue, suggesting that the hypoglycemic effects could be associated with the expression of genes involved in de novo lipogenesis.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots.

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC-MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2ß-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Antimicrobial Potential of Essential Oils from Cerrado Plants against Multidrug-Resistant Foodborne Microorganisms.

Foodborne pathogens are a real public health concern in an escalating antimicrobial resistance scenario. Natural products represent a promising source of bioactive molecules, and essential oils have attracted much attention due to their myriad of biological properties, including antibacterial activities. In this context, essential oils obtained from the leaves of Chromolaena squalida, Campomanesia sessiliflora, Myrsine guianensis, Matayba guianensis, Siparuna guianensis, Ocotea minarum and Endlicheria paniculata-species from the Cerrado biome of Midwest Brazil-were extracted and evaluated for their antibacterial activity against a panel of four standard and three clinical multidrug-resistant bacterial strains. All tested oils showed moderate to good activity against at least four bacterial strains, including Salmonella Typhi and oxacillin-resistant Staphylococcus. The essential oils from C. squalida, C. sessiliflora, My. guianensis and Ma. guianensis showed strong inhibition of clinical Staphylococcus strains, which cause bovine mastitis and are related to milk-borne diseases. Their chemical profiles were investigated by gas chromatography coupled to mass spectrometry (GC/MS), which revealed a predominance of mono- and sesquiterpene hydrocarbons, some of which with well-known antimicrobial properties. The essential oil from Cerrado plants proved active against resistant Gram-positive and Gram-negative bacteria, revealing their potentialities for the development of new alternative agents to prevent the spreading of resistant bacterial contamination.

Cytotoxic Phenanthrene, Dihydrophenanthrene, and Dihydrostilbene Derivatives and Other Aromatic Compounds from Combretum laxum.

The chemical investigation of the roots and stems of Combretum laxum yielded a new dihydrostilbene derivative, 4'-hydroxy-3,3',4-trimethoxy-5-(3,4,5-trimethoxyphenoxy)-bibenzyl (1), two phenanthrenes (2-3), and three dihydrophenanthrenes (4-6), along with one lignan, three triterpenoids, one aurone, one flavone, one naphthoquinone, and two benzoic acid derivatives. Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic techniques and/or mass spectrometry data. The occurrence of dihydrostilbenoid, phenanthrene and dihydrophenanthrene derivatives is unprecedented in a Combretum species native to the American continent. 2,7-Dihydroxy-4,6-dimethoxyphenanthrene, 2,6-dihydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene and 5-O-methyl apigenin are novel findings in the Combretaceae, as is the isolation of compounds belonging to the chemical classes of aurones and naphthoquinones, while (+)-syringaresinol is reported for the first time in the genus Combretum. Compounds 1-6 were also evaluated for their in vitro cytotoxicity against five human cancer cell lines, and radical-scavenging ability against 1,1-diphenyl-2-picryl-hydrazyl (DPPH). 6-Methoxycoelonin (4) was the most cytotoxic against melanoma cells (IC50 2.59 ± 0.11 µM), with a high selectivity index compared with its toxicity against nontumor mammalian cells (SI 25.1). Callosin (6), despite exhibiting the strongest DPPH-scavenging activity (IC50 17.7 ± 0.3 µM), proved marginally inhibitory to the five cancer cell lines tested, indicating that, at least for these cells, antioxidant potential is unrelated to antiproliferative activity.

Larvicidal efficacies of plants from Midwestern Brazil: melianodiol from Guarea kunthiana as a potential biopesticide against Aedes aegypti

A total of 36 ethanol extracts from different anatomical parts of 27 plant species (18 families), native to the Pantanal and Cerrado biomes in Midwest Brazil, was assessed for their effect against Aedes aegypti larvae, the vector of dengue, hemorrhagic dengue, Zika and chikungunya fevers. Only the extract obtained from seeds of Guarea kunthiana (Meliaceae) proved active (LC50 = 169.93 μg/mL). A bioassay-guided investigation of this extract led to the isolation and identification of melianodiol, a protolimonoid, as the active constituent (LC50 = 14.44 mg/mL). Meliantriol, which was also obtained from the bioactive fraction, was nevertheless devoid of any larval toxicity, even at the highest concentration tested (LC50 > 100.0 mg/mL). These results indicate that the larvicidal activity of melianodiol stems from the presence of the carbonyl moiety at C-3 in the 21,23-epoxy-21,24,25-trihydroxy-tirucall-7-ene-type skeleton. The structures of both protolimonoids were established on the basis of spectral methods (1H and 13C NMR and MS). This is the first report on the toxicity of melianodiol against Ae. aegypti larvae. Based on the results, melianodiol can be regarded as a potential candidate for use as an ecologically sound biocontrol agent for reducing the larval population of this vector.

Larvicidal efficacies of plants from Midwestern Brazil: melianodiol from Guarea kunthiana as a potential biopesticide against Aedes aegypti.

A total of 36 ethanol extracts from different anatomical parts of 27 plant species (18 families), native to the Pantanal and Cerrado biomes in Midwest Brazil, was assessed for their effect against Aedes aegypti larvae, the vector of dengue, hemorrhagic dengue, Zika and chikungunya fevers. Only the extract obtained from seeds of Guarea kunthiana (Meliaceae) proved active (LC50 = 169.93 µg/mL). A bioassay-guided investigation of this extract led to the isolation and identification of melianodiol, a protolimonoid, as the active constituent (LC50 = 14.44 mg/mL). Meliantriol, which was also obtained from the bioactive fraction, was nevertheless devoid of any larval toxicity, even at the highest concentration tested (LC50 > 100.0 mg/mL). These results indicate that the larvicidal activity of melianodiol stems from the presence of the carbonyl moiety at C-3 in the 21,23-epoxy-21,24,25-trihydroxy-tirucall-7-ene-type skeleton. The structures of both protolimonoids were established on the basis of spectral methods (1H and 13C NMR and MS). This is the first report on the toxicity of melianodiol against Ae. aegypti larvae. Based on the results, melianodiol can be regarded as a potential candidate for use as an ecologically sound biocontrol agent for reducing the larval population of this vector.

Anti-inflammatory and antinociceptive activities of Croton urucurana Baillon bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana (Euphorbiaceae) is popularly used in Brazil to treat inflammatory processes, pain, and gastric ulcers. AIM OF STUDY: To evaluate the anti-inflammatory and antinociceptive properties of the methanol extract from the bark of C. urucurana (MECu) in mice and identify its chemical constituents. MATERIALS AND METHODS: The extract was characterized by UHPLC-DAD-ESI-Q-TOF-MS/MS. Extract doses of 25, 100, and 400mg/kg were employed in the biological assays. Evaluation of anti-inflammatory activity was based on paw edema and leukocyte recruitment into the peritoneal cavity of mice, both induced by carrageenan. Abdominal writhing caused by acetic acid and duration of formalin-induced paw-licking were the models employed to evaluate antinociceptive activity. RESULTS: Ten compounds were identified in the extract: (+)-gallocatechin (1), procyanidin B3 (2), (+)-catechin (3), (-)-epicatechin (4), tembetarine (5), magnoflorine (6), taspine (7), methyl-3-oxo-12-epi-barbascoate (8), methyl-12-epi-barbascoate (9), and hardwickiic acid (10). This is the first report of compounds 2, 4, 6, 7, and 10 in C. urucurana and compound 5 in the genus Croton. In addition to inhibiting paw edema and leukocyte recruitment (particularly of polymorphonuclear cells) into the peritoneal cavity of mice, MECu reduced the number of abdominal writhings induced by acetic acid and the duration of formalin-induced paw licking. CONCLUSIONS: The methanol extract of C. urucurana bark exhibited anti-inflammatory and antinociceptive properties, corroborating its use in folk medicine. These effects may be related to the presence of diterpenes, alkaloids, and flavonoids.

In vitro activities of plant extracts from the Brazilian Cerrado and Pantanal against Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

A total of 73 ethanol extracts from different anatomical parts of 44 plant species belonging to 24 families, native to the Mid-Western region of Brazil, were assessed in vitro for their effect on the reproductive cycle of engorged females of the cattle tick Rhipicephalus (Boophilus) microplus, using the adult immersion test. All extracts were evaluated at the concentration of 0.2 % and, among the extracts tested, the one obtained from the fruits of Guarea kunthiana (Meliaceae) proved to be highly efficacious, showing 99.1 % of product effectiveness. Extracts from other three species were shown to be moderately active, namely Nymphaea amazonum trunk (Nymphaeaceae) [51.7 %], Strychnos pseudoquina trunk (Loganiaceae) [48 %] [corrected] and Ocotea lancifolia leaves (Lauraceae) [34.5 %], while the remaining extracts were shown to be weakly active or inactive. This is the first report on the bioactivity of these species on egg production by engorged females of R. microplus.

Antimicrobial activity of some medicinal plants from the cerrado of the central-western region of Brazil

Ethanol extracts from six selected species from the Cerrado of the Central-Western region of Brazil, which are used in traditional medicine for the treatment of infectious diseases and other medical conditions, namely Erythroxylum suberosum St. Hil. (Erythroxylaceae), Hyptis crenata Pohl. ex Benth. (Lamiaceae), Roupala brasiliensis Klotz. (Proteaceae), Simarouba versicolor St. Hil. (Simaroubaceae), Guazuma ulmifolia Lam. (Sterculiaceae) and Protium heptaphyllum (Aubl.) March. (Burseraceae), as well as fractions resulting from partition of these crude extracts, were screened in vitro for their antifungal and antibacterial properties. The antimicrobial activities were assessed by the broth microdilution assay against six control fungal strains, Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans, and five control Gram-positive and negative bacterial strains, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Toxicity of the extracts and fractions against Artemia salina was also evaluated in this work. All plants investigated showed antimicrobial properties against at least one microorganism and two species were also significantly toxic to brine shrimp larvae. The results tend to support the traditional use of these plants for the treatment of respiratory and gastrointestinal disorders and/or skin diseases, opening the possibility of finding new antimicrobial agents from these natural sources.Among the species investigated, Hyptis crenata, Erythroxylum suberosum and Roupala brasiliensis were considered the most promising candidates for developing of future bioactivity-guided phytochemical investigations.

Chemical composition and biological activities of essential oil from Hyptis crenata growing in the Brazilian cerrado.

Essential oils from species of the genus Hyptis are well-known for their significant biological properties, including antimicrobial and acaricidal activities. The essential oil from the aerial parts of H. crenata was obtained by hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were characterized by GC-MS as its major constituents. The essential oil was evaluated in vitro for its antimicrobial activities against six fungal and five bacterial strains, by measuring the respective MICs, MFCs and MBCs, using broth microdilution methods. The strongest bactericidal activities were shown against Staphylococcus aureus and Enterococcus faecalis, while the strongest fungicidal activities were against Cryptococcus neoformans, Candida glabrata and Candida tropicalis. The oil was also assessed for its anti-tick properties and, at a concentration of 2.5%, it significantly inhibited in vivo oviposition of engorged females of the cattle tick Rhipicephalus (Boophilus) microplus, using the adult immersion test., with an effectiveness of 94.4%.

Antimicrobial activity of some medicinal plants from the cerrado of the centralwestern region of Brazil.

Ethanol extracts from six selected species from the Cerrado of the Central-Western region of Brazil, which are used in traditional medicine for the treatment of infectious diseases and other medical conditions, namely Erythroxylum suberosum St. Hil. (Erythroxylaceae), Hyptis crenata Pohl. ex Benth. (Lamiaceae), Roupala brasiliensis Klotz. (Proteaceae), Simarouba versicolor St. Hil. (Simaroubaceae), Guazuma ulmifolia Lam. (Sterculiaceae) and Protium heptaphyllum (Aubl.) March. (Burseraceae), as well as fractions resulting from partition of these crude extracts, were screened in vitro for their antifungal and antibacterial properties. The antimicrobial activities were assessed by the broth microdilution assay against six control fungal strains, Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans, and five control Gram-positive and negative bacterial strains, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Toxicity of the extracts and fractions against Artemia salina was also evaluated in this work. All plants investigated showed antimicrobial properties against at least one microorganism and two species were also significantly toxic to brine shrimp larvae. The results tend to support the traditional use of these plants for the treatment of respiratory and gastrointestinal disorders and/or skin diseases, opening the possibility of finding new antimicrobial agents from these natural sources. Among the species investigated, Hyptis crenata, Erythroxylum suberosum and Roupala brasiliensis were considered the most promising candidates for developing of future bioactivity-guided phytochemical investigations.

Bioactive pentacyclic triterpenes from the stems of Combretum laxum.

Two new triterpene glucosides, beta-D-glucopyranosyl 2alpha,3beta,24-trihydroxyolean- 12-en-28-oate and beta-D-glucopyranosyl 2alpha,3beta,23,24-tetrahydroxyurs-12-en-28-oate, in addition to nine known compounds belonging to three different triterpene classes (oleanane-, ursane- and lupane-type) have been isolated from the stems of a specimen of Combretum laxum growing in the "Pantanal" of the central-western region of Brazil. Among the known triterpenes, beta-D-glucopyranosyl 2alpha,3beta,6beta-trihydroxyolean-12-en-28-oate is reported for the first time in the Combretaceae, while bellericoside and asiatic acid are described for the first time in the genus Combretum. The structures of the isolated compounds have been established on the basis of spectral techniques (1D-, 2D-NMR and MS). Their in vitro antifungal activities against standard strains of Candida albicans, C. krusei and Cryptococcus neoformans were also evaluated in this work.