RESUMEN
Larrea divaricata Cav. is an autochthonous South American plant popularly used in inflammatory and infectious diseases with reported anti - inflammatory, immunomodulatory, antimicrobial and antioxidant activities. Covid - 19 is an infection ca used by the severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). This virus can cause pneumonia and even death in about 5% of the cases. The objective of the article was to demonstrate, through a literature review, that L. divaricata has sufficie nt attributes to be assayed against SARS - CoV - 2. For this, the chemical composition, reported activities and docking studies were taken into account. This review demonstrated that the plant extracts are capable of inhibiting the proliferation of fungi, bact eria and viruses and that they exert anti - inflammatory and immunomodulatory actions in different " in vitro " and " in vivo " models. These results suggest that the plant is a good candidate to be studied for the prevention and/or treatment of SARS - CoV - 2.
Larrea divaricata Cav. es una planta autóctona Sudamericana, utilizada popularmente en enfermedades inflamatorias e infecciosas, con activida d anti - inflamatoria, inmunomoduladora, antimicrobiana y antioxidante reportada. El Covid - 19 es una infección causada por una cepa de coronavirus, SARS - CoV - 2 (coronavirus tipo 2 causante del síndrome respiratorio agudo severo). Este virus puede originar neu monía e incluso la muerte en alrededor del 5% de los casos. Nuestro objetivo fue demostrar, a través de una revisión bibliográfica, que esta planta tiene atributos suficientes para ser ensayada en estudios contra SARS - CoV - 2. Se tuvo en cuenta la composici ón química, los antecedentes científicos y los estudios de acoplamiento molecular. Esta revisión permitió demostrar que extractos de la planta son capaces de inhibir la proliferación de hongos, bacterias y virus y que presentan acción anti - inflamatoria en diferentes modelos " in vitro " e " in vivo ", lo que los hace candidatos a ser estudiados en la prevención y/o tratamiento de la infección contra SARS - CoV - 2.
Asunto(s)
Larrea/química , COVID-19/prevención & control , COVID-19/terapia , Antivirales/uso terapéutico , Plantas Medicinales/química , Extractos Vegetales/farmacologíaRESUMEN
For centuries, traditional medicine from plants (phytotherapy) was the only treatment for infectious and non-infectious diseases. Although it is still practiced in several countries with excellent therapeutic results, it is frequently underestimated because, unlike Western medicine, it is not based on an empirical scientific foundation. However, interest in the search for plant-based therapeutic resources has been stimulated by disciplines such as phytochemistry and the side effects of conventional pharmacological therapies. For example, Larrea tridentata is a perennial shrub used in traditional medicine in northern Mexico and the southern United States to treat infertility, rheumatism, arthritis, colds, diarrhea, skin problems, pain, inflammation and excess body weight. Scientific research has revealed its beneficial effects-antioxidant, antitumor, neuroprotective, regenerative, antibacterial, antiviral, antifungal, anthelmintic, antiprotozoal and insecticidal-although reports indicate that some compounds in Larrea tridentata may be hepatotoxic and nephrotoxic. Therefore, the aim of this review was to highlight the updates regarding phytochemical compounds and the pharmacological properties of Larrea tridentata.
Asunto(s)
Larrea , Antioxidantes/farmacología , Larrea/química , Medicina Tradicional , Fitoquímicos/farmacología , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , PlantasRESUMEN
Bovine mastitis is one of the most common diseases in dairy cows, and it causes significant economic losses in dairy industries worldwide. Gram-positive and Gram-negative bacteria can cause bovine mastitis, and many of them have developed antimicrobial resistance. There is an urgent need for novel therapeutic options to treat the disease. Larrea tridentata-derived compounds represent an important potential alternative treatment. The aim of the present study was to isolate and characterize antibacterial compounds from Larrea tridentata against multidrug-resistant bacteria associated with bovine mastitis. The L. tridentata hydroalcoholic extract (LTHE) exhibited antibacterial activity. The extract was subjected to a bipartition, giving an aqueous fraction (moderate antibacterial activity) and an organic fraction (higher antibacterial activity). Chromatographic separation of the organic fraction enabled us to obtain four active sub-fractions. Chemical analyses through HPLC techniques were conducted for the LTHE, fractions, and sub-fraction Ltc1-F3, from which we isolated two compounds, characterized by 1H and 13C NMR analyses. Compound nor-3 demethoxyisoguaiacin exhibited the best antibacterial activity against the evaluated bacteria (MIC: 0.01-3.12 mg/mL; MBC: 0.02-3.12 mg/mL). The results indicated that nor-3 demethoxyisoguaiacin can be used as an alternative treatment for multidrug-resistant bacteria associated with mastitis.
Asunto(s)
Larrea , Mastitis Bovina , Animales , Antibacterianos/química , Bacterias , Bovinos , Femenino , Bacterias Gramnegativas , Bacterias Grampositivas , Larrea/química , Mastitis Bovina/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Naftoles , Extractos Vegetales/químicaRESUMEN
BACKGROUND: The oxidized low density lipoprotein (ox-LDL) contributes to inflammation and oxidative stress through the activation of macrophages under hyperglycemia contributing to the development of diabetes mellitus and to atherosclerosis. Plants are a source of effective and innocuous antioxidants. Larrea divaricata Cav. (Zygophyllaceae) is used in Argentina folk medicine for its anti-inflammatory properties. METHODS: The aim of this work was to study the antioxidant and anti-inflammatory effects of the aqueous extract (AE) of L. divaricata on macrophages under glucose stimulation and on human LDL and HDL particles under free radical generators. RESULTS: AE reduced the lipid peroxidation (17%), nitric oxide (NO) (47-50%), tumor necrosis factor-α (TNF-α) (32%) and free radicals (50%) induced by glucose on macrophages. Also prevented HDL nitration (28%), thus preserving its function and structure and inhibited LDL oxidation. The effect on the nitrosative stress was mainly driven by nordihydroguaiaretic acid (NDGA). CONCLUSIONS: These results suggest a potential usefulness of AE as an adjuvant phytotherapy in patients with diabetes mellitus and atherosclerosis.
Asunto(s)
Antiinflamatorios no Esteroideos , Antioxidantes , Larrea , Lipoproteínas LDL , Macrófagos , Extractos Vegetales , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Humanos , Larrea/química , Lipoproteínas LDL/metabolismo , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacologíaRESUMEN
Most of the deaths from skin cancer are caused by melanoma, a malignancy in which STAT3 plays a crucial role. The inhibition of STAT3 is considered a potential target to induce cell death, tumor regression and metastasis inhibition. The objective of this work was to evaluate the activity of the aqueous extract of Larrea divaricata (Aq), a fraction rich in polyphenols (EA),and the isolated compound quercetin-3-methyl ether (Q3ME) on B16F10 melanoma cells. The effects of Aq, EA and Q3ME were assessed on B16F10 cells by determining the proliferation, viability, apoptosis induction and the expression and phosphorylation of STAT3. The phytochemical composition of the extracts was determined by High Performance Liquid Chromatography. Aq, EA and Q3ME presented antiproliferative activity on B6F10 cells through p-STAT3 inhibition and early and late apoptosis induction (EC50 EA= ≤0.1 µg/ml; Aq= 316 ± 30 µg/ml; Q3ME= <0.1 µg/ml). L. divaricata could be considered for the development of adjuvant phytotherapies in melanoma treatment.
Asunto(s)
Larrea , Melanoma , Línea Celular , Línea Celular Tumoral , Humanos , Larrea/química , Melanoma/tratamiento farmacológico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , AguaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jarilla is the common name of an appreciated group of native plants from the semi-arid region in Argentina (Larrea cuneifolia Cav., Larrea divaricata Cav. and Zuccagnia punctata Cav.) that have been historically consumed to heal respiratory, musculoskeletal and skin ailments, as well as recommended for weakness/tiredness, hypertension, diabetes and cancer treatment. It was previously reported that some biological properties could be improved when these plants are used jointly. Infusions of a defined mixture, composed by three Jarilla species, L. cuneifolia: L. divaricata: Z. punctata (0.5:0.25:0.25) (HM2) showed synergistic and additive effect on antioxidant activity even after passing through the gastro-duodenal tract. AIM OF THE STUDY: The main purpose of this work was to evaluate antigenotoxic, antitumor, and anti-metastatic properties of the Jarilla species that grow in the Northwest of Argentina and a herbal combination of them. MATERIAL AND METHODS: Infusions of Jarilla mixture (HM2), and of each single plant species were prepared. Phenolic profiles of infusions were analyzed by HPLC-ESI-MS/MS and two relevant chemical markers were quantified. The antigenotoxic activity was evaluated by using the Ames test and the Cytokinesis-Block Micronucleus (CBMN) assay against direct mutagens. Evaluations of both cytotoxicity and antiproliferative effects were conducted on tumor and non-tumor cell lines. Both in vivo tumoral growth and metastasis inhibition were evaluated by using a carcinoma model on Balb/c mice. RESULTS: HM2 mix could suppress genetic and chromosome mutations induced by 4-nitro-o-phenylendiamine (4-NPD) and doxorubicin. Herbal mixture and single plant infusions showed cytotoxic effect against mammary, uterus, and brain tumoral cells without a selective action vs normal human cell line. HM2 mix was able to reduce mammary tumor mass on the Balb/c mice model and showed a significant reduction in the number of metastatic nodules in the lungs. CONCLUSIONS: Our results suggest that the combinations of three Jarilla species from northwest Argentina would be a promising alternative to treat or slow down the development of chronic diseases, such as cancer.
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Antimutagênicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Fabaceae , Larrea , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antimutagênicos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Argentina , Células CHO , Cricetulus , Fabaceae/química , Células HeLa , Humanos , Larrea/química , Células MCF-7 , Masculino , Medicina Tradicional , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Neoplasias/patología , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas MedicinalesRESUMEN
INTRODUCTION: Tissue engineering is an elementary necessity for several applications in the biomedical field through the use of several biopolymers derived from plants. Larrea tridentata (LT) is a very used plant for various medicinal applications with interesting properties; however, its use into cellulose hydrogels for possible regenerative therapeutics is still limited. Cellulose films could be applied in medical field as wound healing, scaffold for connective tissue for periodontal applications, and so on. The aim of this study was to evaluate the mechanical properties and in vivo and in vitro biocompatibility of cellulose hydrogels that have been enriched with LT in a rat model. METHODS: By in vivo and in vitro assays, the concentration of LT was varied from 1 to 5 wt%, respectively. Hydrogel films were implanted intramuscularly into female Wistar rats, 250 g in weight and aged 2 months, to analyze their cytocompatibility and biocompatibility. RESULTS: No case showed any evidence of inflammation or toxicity. Regarding cell morphology and adhesion, the prepared LT cellulose films had better cytocompatibility values than when polystyrene (PS) dishes were used as the control. In all cases, the results suggest that the addition of LT to the hydrogel films did not affect their cytocompatibility or biocompatibility properties and increases their clinical application due to the reported uses of LT. CONCLUSIONS: Cellulose hydrogel films enriched with LT have the potential to be used in the biomedical field acting as regenerative scaffolds.
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Celulosa , Hidrogeles , Larrea/química , Ensayo de Materiales , Membranas Artificiales , Animales , Celulosa/química , Celulosa/farmacología , Evaluación Preclínica de Medicamentos , Femenino , Hidrogeles/síntesis química , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Células 3T3 NIH , Ratas , Ratas WistarRESUMEN
Currently, the world health sector faces a big problem due to the increase of bacterial strains resistant to antibiotics. In 2017, the World Health Organization reported a list of resistant bacteria, among which Pseudomonas aeruginosa was present. This opportunistic pathogen is associated to nosocomial infections, and no effective vaccines against this bacterium have been found. Larrea divaricata Cav. (jarilla) is a shrub highly distributed in America and widely used in folk medicine. In our laboratory, cross-reactivity of antibodies obtained from the recognition of jarilla proteins against proteins from gram-negative bacteria has been demonstrated. The objective of this study was to study the cross-reactivity of anti-L. divaricata antibodies with P. aeruginosa extracellular proteins in order to find an innocuous prophylactic therapy against this nosocomial pathogen. We observed that antibodies generated by proteins from jarilla crude extract recognized antigenic determinants present in extracellular proteins of P. aeruginosa. However, further studies are needed to investigate the neutralizing capacity of these antibodies on the specific enzymatic proteins involved in the pathogenicity of this bacterium.
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Reacciones Cruzadas/inmunología , Larrea/química , Larrea/inmunología , Imitación Molecular , Extractos Vegetales/inmunología , Proteínas de Plantas/inmunología , Pseudomonas aeruginosa/inmunología , Animales , Anticuerpos/inmunología , Ensayo de Inmunoadsorción Enzimática , Inmunidad Humoral , Inmunoglobulina G/inmunología , Larrea/metabolismo , Ratones , Extractos Vegetales/química , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificaciónRESUMEN
BACKGROUND: Oxidative stress is an imbalance between the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS) and endogenous antioxidants. The aetiology and pathogenesis of several oral diseases are attributed to this process. The antioxidant enzymes secreted in the saliva by submandibular glands maintain oral health through the scavenging of ROS. The objective of this work was to study the capacity of an aqueous extract of L. divaricata (AE), and its majority compound, nordihydroguariaretic acid (NDGA), to modulate the pro-oxidant/antioxidant status in submandibular glands in a model of oxidative stress induced by streptozotocin (STZ) in rats. METHODS: To induce oxidative stress with STZ, a group of animals was treated i.p. with 1 X PBS (control group) and other group was injected i.p. once with STZ (60 mg/kg). Ten days after the treatment, blood samples were taken from the tail vain to determine the glucose levels. Animals with glucose values ≥300 mg/ml were selected. The submandibular glands of control and STZ treated animals were incubated with either the AE (500 µg/ml) or with NDGA (1.5 µg/ml), and the content of malondialdehyde (MDA), protein carbonyl groups, ROS and RNS, and the activity and expression of peroxidase (Px), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) were assayed. RESULTS: AE decreased the levels of MDA (##P < 0.01) and protein carbonyl groups (#P < 0.05), and modulated the levels of ROS such as hydrogen peroxide (H2O2)(##P < 0.01), superoxide anion (O2.-) (#P < 0.05) and nitric oxide (NO) (#P < 0.05) in relation to the modulation of Px and iNOS expression. NDGA was found to be involved in these effects. CONCLUSIONS: The antioxidant activity of the AE in the submandibular glands would allow the maintenance of the antioxidant pool to prevent oral oxidative diseases.
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Diabetes Mellitus Experimental/metabolismo , Larrea/química , Masoprocol/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Glándula Submandibular/efectos de los fármacos , Animales , Antioxidantes/farmacología , Femenino , Malondialdehído/análisis , Oxidorreductasas/análisis , Ratas , Ratas Wistar , Glándula Submandibular/química , Glándula Submandibular/enzimologíaRESUMEN
In this work, the antioxidant properties of methanolic extract of Larrea tridentata were assessed through the free radical scavenging method, ferric reducing antioxidant power and oxygen radical absorbance capacity. The phenolic acids content in the extract was quantified by high-performance liquid chromatography (HPLC) and the total phenol content by the Folin-Ciocalteu method. The extract was used as an antioxidant in biodiesel from canola oil composed mostly by fatty acid methyl esters identified and quantified by gas chromatography-mass spectrophotometry (GC-MS). The performance of the extract as an antioxidant was assessed by the oxidative stability index (OSI) with a Rancimat equipment at 100, 110, 120 and 130 °C. Additionally, the change of the peroxide value (PV) and the higher heating value under conditions of oxidative stress at 100 °C and air injection were measured. The antioxidant capacity of the extract reached 50,000 TAEC (micromole of Trolox antioxidant equivalent capacity per gram). The biodiesel was constituted by more than 70% of unsaturated fatty acid methyl esters (FAME), mainly methyl oleate. The time needed to reach a PV of 100 meqO2/kg was almost four times longer with an antioxidant concentration of 250 mg/L than the blank. The biodiesel showed an OSI time of 1.25 h at 110 °C, while it increased to 8.8, 15.89 and 32.27 h with the antioxidant at concentrations of 250, 500 and 1000 mg/L, respectively. The methanolic Larrea tridentata extract proved to have an antioxidant capacity and it is a green antioxidant in biodiesel to increase its oxidative stability. According to the results obtained, the L. tridentata methanolic extract is an alternative to the commercial synthetic antioxidants used in biodiesel nowadays.
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Antioxidantes/análisis , Biocombustibles/análisis , Larrea/química , Extractos Vegetales/análisis , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Metanol/química , Oxidación-Reducción , Oxígeno/química , Fenoles/química , TemperaturaRESUMEN
Candida albicans is an opportunistic pathogenic yeast commonly found in mouth, gastrointestinal tract and vagina. Under certain conditions, it causes skin, mucosal and systemic infections. With growing concern over the emergence of resistant strains to conventional antifungals, the development of novel antifungal agents for the management of this pathogen is an urgent need. In the present work, novel bioextracts from folk medicinal plants were directly used as active ingredient in a topical formulation for dermal candidiasis. With the aim to replace hazardous traditional reagents, a natural solvent composed by lactic acid: glucose: water (LGH) was used as vehicle for bioactive compound extraction. Furthermore, phenolic and alkaloid composition were determined by HPLC and their individual antifungal effect was evaluated. LGH extracts of Larrea spices demonstrate a significant antimicrobial activity against C. albicans being higher than their individual bioactive constituents. Notably, the mixture of Larrea cuneifolia and L divaricata extracts in topical formulations reveal a synergistic antifungal effect highlighting their potential for candidiasis treatment.
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Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Larrea/química , Extractos Vegetales/farmacología , Solventes/química , Antifúngicos/aislamiento & purificación , Composición de Medicamentos , Glucosa/química , Ácido Láctico/química , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/aislamiento & purificación , Agua/químicaRESUMEN
BACKGROUND: In our previous study the synergism of four combinations of Zuccagnia punctata (ZpE) and Larrea nitida (LnE) exudates with the reliable statistical-based MixLow method was assessed, and the markers of the most anti-C. albicans synergistic ZpE-LnE bi-herbal combination were quantified according to European Medicines Agency (EMA). PURPOSE: To study the mechanisms of action as well as the cytotoxic properties of the ZpE-LnE most synergistic combination found in the previous work. MATERIALS AND METHODS: Minimum Fungicidal Concentration (MFC) and rate of killing of ZpE-LnE were assessed with the microbroth dilution and the time-kill assays respectively. Morphological alterations were observed with both confocal and fluorescence microscopy on the yeast Schizosaccharomyces pombe. The ergosterol exogenous assay, the quantification of ergosterol, the sorbitol as well as glucan synthase (GS) and chitin synthase (ChS) assays were used to detect the effects on the fungal membrane and cell wall respectively. The capacity of ZpE-LnE of inhibiting Candida virulence factors was assessed with previously reported methods. The effect of ZpE-LnE and of ZpE or LnE alone on cell viability was determined on human hepatoma cells line Huh7. RESULTS: ZpE-Ln E was fungicidal killing C. albicans in a shorter time than amphotericin B and produced malformations in S. pombe cells. ZpE-LnE showed to bind to ergosterol but not to inhibit any step of the ergosterol biosynthesis. ZpE-LnE showed a low or moderate capacity of inhibiting GS and ChS. Regarding inhibition of virulence factors, ZpE-LnE significantly decreased the capacity of adhesion to eukaryotic buccal epithelial cells (BECs), did not inhibit the germ tube formation and inhibited the secretion of phospholipases and proteinases but not of haemolysins. ZpE-LnE demonstrated very low toxicity on Huh7 cells, much lower than that each extract alone. CONCLUSION: The fungicidal properties of ZpE-LnE against C. albicans, its dual mechanism of action targeting the fungal membrane's ergosterol as well as the cell wall, its capacity of inhibiting several important virulence factors added to its low toxicity, make ZpE-LnE a good candidate for the development of a new antifungal bi-Herbal Medicinal Product.
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Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Fabaceae/química , Larrea/química , Extractos Vegetales/farmacología , Anfotericina B/farmacología , Ergosterol/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Plantas MedicinalesRESUMEN
Staphylococcus aureus is an opportunistic pathogen. Over- and improper-use of pharmaceuticals against S. aureus has led to the development of antibiotic resistance, including methicillin-resistant S. aureus (MRSA). This study examined the efficacy of botanical extracts as an alternative form of treatment to S. aureus and MRSA, including penicillin/methicillin-resistant S. aureus (PenR ), and multidrug resistant S. aureus (MDR). Initial screening of botanicals was done via a minimum inhibitory concentration procedure. In addition, a temporal growth curve was performed in order to quantify the growth of the bacteria in the presence of the extracts. Results demonstrated 13 botanicals that had varying activities against S. aureus, PenR , and MDR. These botanicals were separated into mild, moderate, and highly efficacious based on the concentration needed to inhibit bacterial growth. These results propose a comparison of botanical-derived antimicrobial extracts that may be utilized against S. aureus and different antibiotic resistant strains of MRSA.
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Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Extractos Vegetales/farmacología , Antibacterianos/aislamiento & purificación , Arctostaphylos/química , Eucalyptus/química , Humanos , Hypericum/química , Larrea/química , Meticilina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Oxidative stress has been linked to neurodegenerative diseases such as Huntington's, Parkinson's, Alzheimer's and amyotrophic lateral sclerosis diseases. Larrea tridentata (LT) also known as Creosote Bush is an evergreen shrub found in the Chihuahuan desert which has been used medicinally by Native American tribes in southwestern North America and the Amerindians of South America. However, studies of the antioxidant capacity of the crude extract of LT towards the discovery of novel molecular therapies bearing antioxidants and drug-like properties are lacking. In this study, we assessed the antioxidant properties of Larrea tridentata, collected specifically from the Chihuahuan desert in the region of El Paso del Norte, TX, USA. LT phytochemicals were obtained from three different extracts (ethanol; ethanol: water (60:40) and water). Then the extracts were evaluated in eight different assays (DPPH, ABTS, superoxide; FRAP activity, nitric oxide, phenolic content, UV visible absorption and cytotoxicity in non-cancerous HS27 cells). The three extracts were not affecting the HS27 cells at concentrations up to 120 µg/mL. Among the three extracts, we found that the mixture of ethanol: water (60:40) LT extract has the most efficient antioxidant properties (IC50 (DPPH at 30 min) = 111.7 ± 3.8 µg/mL; IC50 (ABTS) = 8.49 ± 2.28 µg/mL; IC50 (superoxide) = 0.43 ± 0.17 µg/mL; IC50 (NO) = 230.4 ± 130.4 µg/mL; and the highest phenolic content was estimated to 212.46 ± 7.05 mg GAE/L). In addition, there was a strong correlation between phenolic content and the free-radical scavenging activity assays. HPLC-MS study identified nine compounds from the LT-ethanol: water extract including Justicidin B and Beta peltain have been previously reported as secondary metabolites of Larrea tridentata.
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Antioxidantes/farmacología , Larrea/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Antioxidantes/química , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Flavonoides/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Humanos , Espectrometría de Masas , Estructura Molecular , Óxido Nítrico/metabolismo , Fenoles/química , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Hojas de la PlantaRESUMEN
A detailed study of biomaterials is mandatory to comprehend their feasible biomedical applications in terms of drug delivery and tissue regeneration. Particularly, mucoadhesive biopolymers such as chitosan (chi) and carboxymethylcellulose (CMC) have become interesting biomaterials regards to their biocompatibility and non-toxicity for oral mucosal drug delivery. In this work, pH-responsive biopolymer-silica composites (Chi-SiO2, Chi-CMC-SiO2) were developed. These two types of composites presented a different swelling behavior due to the environmental pH. Moreover, the nanocomposites were loaded with aqueous Larrea divaricata Cav. extract (Ld), a South American plant which presents antioxidant properties suitable for the treatment of gingivoperiodontal diseases. Chi-CMC-SiO2 composites showed the highest incorporation and reached the 100% of extract release in almost 4â¯days while they preserved their antioxidant properties. In this study, thermal and swelling behavior were pointed out to show the distinct water-composite interaction and therefore to evaluate their mucoadhesivity. Furthermore, a cytotoxicity test with 3T3 fibroblasts was assessed, showing that in both composites the addition of Larrea divaricata Cav. extract increased fibroblast proliferation. Lastly, preliminary in vitro studies were performed with simulated body fluids. Indeed, SEM-EDS analysis indicated that only chi-SiO2 composite may provide an environment for possible biomineralization while the addition of CMC to the composites discouraged calcium accumulation. In conclusion, the development of bioactive composites could promote the regeneration of periodontal tissue damaged throughout periodontal disease and the presence of silica nanoparticles could provide an environment for biomineralization.
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Antioxidantes/farmacología , Biopolímeros/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Larrea/química , Picratos/antagonistas & inhibidores , Extractos Vegetales/farmacología , Dióxido de Silicio/farmacología , Células 3T3 , Animales , Antioxidantes/química , Biopolímeros/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Concentración de Iones de Hidrógeno , Ratones , Nanopartículas/química , Tamaño de la Partícula , Extractos Vegetales/química , Dióxido de Silicio/química , Propiedades de SuperficieRESUMEN
Pseudomonas aeruginosa is an opportunistic pathogen implicated in nosocomial infections for which no vaccines have been approved. Larrea divaricata Cav. (Jarilla) is a widely spread plant in America and it is used in folk medicine to treat several pathologies. It has also been shown that antibodies elicited against Jarilla proteins of crude extract (JPCE) cross-react with proteins from gram-negative bacteria. In this study we aim to assess the contribution of anti-JPCE antibodies in the opsonophagocytosis of P. aeruginosa by murine macrophages. Levels of reactivity of anti-JPCE IgG and IgA antibodies against cell and membrane proteins suggest that these proteins induce a response that could favor opsonic bacterial recognition, which is important for the elimination of bacteria on mucous membranes, useful in the early stages of infection. Opsonophagocytosis assays also show that these antibodies could favor bacteria intake. These results together with previous observations that indicate that anti-JPCE antibodies are able to neutralize P. aeruginosa enzymes point L. divaricata proteins as candidates for vaccine development.
Asunto(s)
Inmunización , Larrea/química , Macrófagos/efectos de los fármacos , Fagocitos/efectos de los fármacos , Extractos Vegetales/inmunología , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Anticuerpos , Anticuerpos Antibacterianos , Supervivencia Celular/efectos de los fármacos , Reacciones Cruzadas , Bacterias Gramnegativas/efectos de los fármacos , Inmunoglobulina A , Inmunoglobulina G , Macrófagos/inmunología , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Fagocitos/inmunología , Extractos Vegetales/farmacología , Proteínas de Plantas/inmunología , Tracheophyta/química , VacunaciónRESUMEN
To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content. Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver triglycerides. NDGA treatment also improved insulin sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator-activated receptor α (PPARα; the master regulator of fatty acid oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP homologous protein, compared with chow or the ALIOS diet, and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise, NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS-fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating the PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.
Asunto(s)
Dieta Occidental/efectos adversos , Larrea/química , Estilo de Vida , Masoprocol/farmacología , Obesidad/metabolismo , Obesidad/prevención & control , Adipogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ácidos Grasos/metabolismo , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/inducido químicamente , Obesidad/patología , Oxidación-Reducción/efectos de los fármacos , PPAR alfa/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
An in vitro study was conducted to determine the anthelminthic activity of hydro-methanolic extracts of Larrea tridentata on sheathed and exsheathed larvae of Haemonchus contortus. Larvae of the parasite were incubated at 20-25 °C in hydro-methanolic extracts at concentrations of 12.5, 25, 50, 100, and 200 mg/mL for 24, 48, or 72 h. Ivermectin and water were the positive and negative controls, respectively. Total phenolic compounds of leaves of L. tridentata were 97.88 ± 10.45 mg/g of dry matter. Other compounds detected in this shrub by HPLC-mass spectrometry were sesamin, galocatechin, peonidin 3-O rutinoside, methyl galangin, epigallocatechin 7-O-glucuronide, and epigalocatechin. Mortality rate of sheathed and exsheathed H. contortus was low (16-34%) with doses ≤ 100 mg/mL of the extracts. At 200 mg/ml, the hydro-methanolic extracts of L. tridentata killed 32.1 and 68.4% of sheathed and exsheathed larvae, respectively, regardless of incubation time. The effective concentration of the L. tridentata extract for 50% larvae mortality (EC50) after 24 h of incubation was 36 mg/mL (CI = 6-94). Microscopic observations revealed damage to the cuticle of this parasite exposed to extracts of L. tridentata. These in vitro results provided evidence that L. tridentata extracts possess anti-Haemonchus contortus properties, particularly during the exsheathed stage of this nematode. It would be necessary to assess the safety of this shrub in vivo and also to carry out in vivo efficacy studies.
Asunto(s)
Antihelmínticos/análisis , Larrea/química , Extractos Vegetales/química , Animales , Haemonchus , Ivermectina , Larva , Metanol , NematodosRESUMEN
Larrea divaricata Cav. (Zygophyllaceae) is a South American plant widely distributed in Argentina that is used in folk medicine to treat inflammatory diseases. The aqueous extract is known to have well-documented biological activities such as antitumour, immunomodulatory, antimicrobial, antiinflammatory and antioxidant. However, its stability in gastrointestinal fluids is unknown. The latter is an important factor to assure the bioavailability of plant extracts intended to be administered via the oral route. The aim of this work was to study the stability of a lyophilized aqueous extract of L. divaricata compressed as a pill. To this end, the main polyphenol compound found in the extract, that is, the nordihydroguaiaretic acid, the total polyphenols and flavonoids content and the antioxidant activity such as diphenylpicrylhydrazyl scavenger activity and reducing power were assayed after subjecting the extract to different incubation times in simulated digestive fluids. The HPLC and spectroscopic methods were employed. Although the levels of polyphenols and flavonoids decreased upon incubation in gastric and intestinal fluids, the extract maintained its antioxidant activity related to the presence of nordihydroguaiaretic acid. These results are promising and encourage the potential use of the extract by the oral route as a supplement or phytomedicine with antioxidant activity. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Digestión , Larrea/química , Extractos Vegetales/química , Antioxidantes/análisis , Argentina , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Flavonoides/análisis , Jugo Gástrico , Masoprocol/análisis , Medicina Tradicional , Hojas de la Planta/química , Polifenoles/análisis , AguaRESUMEN
Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.