QUERCETIN OXIDATION LEADS TO THE FORMATION OF A METABOLITE, 2-(3,4-DIHYDROXYBENZOYL)-2,4,6-TRIHYDROXY-3(2H)-BENZOFURANONE, WHOSE ANTIOXIDANT POTENCY WAS RECENTLY REPORTED TO BE A 1000-FOLD HIGHER THAN THAT OF ITS PRECURSOR. THE FORMATION OF SIMILAR METABOLITES (BZF) IS LIMITED TO CERTAIN FLAVONOLS (FL), AMONG WHICH ARE MYRICETIN, FISETIN, AND MORIN. HERE WE ADDRESSED THE CONSEQUENCES OF INDUCING THE AUTO-OXIDATION OF THESE FLAVONOLS IN TERMS OF THEIR ANTIOXIDANT PROPERTIES (ASSESSED IN ROS-EXPOSED CACO-2 CELLS). THE MIXTURES THAT RESULT FROM THEIR OXIDATION (FLOX) EXHIBITED ANTIOXIDANT ACTIVITIES 10-TO-50-FOLD HIGHER THAN THOSE OF THEIR PRECURSORS. SUCH AMPLIFICATION WAS FULLY ATTRIBUTABLE TO THE PRESENCE OF BZF IN EACH FLOX (ESTABLISHED BY HPLC-ESI-MS/MS AND CHEMICAL SUBTRACTION TECHNIQUES). AN IDENTICAL AMPLIFICATION WAS ALSO FOUND WHEN THE ANTIOXIDANT ACTIVITIES OF BZF, ISOLATED FROM EACH FLOX, AND FL WERE COMPARED. THESE FINDINGS WARRANT THE SEARCH OF THESE BZF IN EDIBLE PLANTS AND THEIR SUBSEQUENT EVALUATION AS A NEW TYPE OF FUNCTIONAL FOOD INGREDIENTS.

TYPE 2 DIABETES AND OBESITY ARE MAJOR PROBLEMS WORLDWIDE AND DIETARY POLYPHENOLS HAVE SHOWN EFFICACY TO AMELIORATE SIGNS OF THESE DISEASES. ANTHOCYANINS FROM BERRIES DISPLAY POTENT ANTIOXIDANTS AND PROTECT AGAINST WEIGHT GAIN AND INSULIN RESISTANCE IN DIFFERENT MODELS OF DIET-INDUCED METABOLIC SYNDROME. OLANZAPINE IS KNOWN TO INDUCE AN ACCELERATED FORM OF METABOLIC SYNDROME. DUE TO THE AFOREMENTIONED, WE EVALUATED WHETHER DELPHINIDIN-3,5-O-DIGLUCOSIDE (DG) AND DELPHINIDIN-3-O-SAMBUBIOSIDE-5-O-GLUCOSIDE (DS), TWO POTENT ANTIDIABETIC ANTHOCYANINS ISOLATED FROM ARISTOTELIA CHILENSIS FRUIT, COULD PREVENT OLANZAPINE-INDUCED STEATOSIS AND INSULIN RESISTANCE IN LIVER AND SKELETAL MUSCLE CELLS, RESPECTIVELY. HEPG2 LIVER CELLS AND L6 SKELETAL MUSCLE CELLS WERE CO-INCUBATED WITH DG 50 ?G/ML OR DS 50 ?G/ML PLUS OLANZAPINE 50 ?G/ML. LIPID ACCUMULATION WAS DETERMINED IN HEPG2 CELLS WHILE THE EXPRESSION OF P-AKT AS A KEY REGULATOR OF THE INSULIN-ACTIVATED SIGNALING PATHWAYS, MITOCHONDRIAL FUNCTION, AND GLUCOSE UPTAKE WAS ASSESSED IN L6 CELLS. DS AND DG PREVENTED OLANZAPINE-INDUCED LIPID ACCUMULATION IN LIVER CELLS. HOWEVER, INSULIN SIGNALING IMPAIRMENT INDUCED BY OLANZAPINE IN L6 CELLS WAS NOT RESCUED BY DS AND DG. THUS, ANTHOCYANINS MODULATE LIPID METABOLISM, WHICH IS A RELEVANT FACTOR IN HEPATIC TISSUE, BUT DO NOT SIGNIFICANTLY INFLUENCE SKELETAL MUSCLE, WHERE A POTENT ANTIOXIDANT EFFECT OF OLANZAPINE WAS FOUND.

THE CHILEAN PLANTS DISCARIA CHACAYE, TALGUENEA QUINQUENERVIA (RHAMNACEAE), PEUMUS BOLDUS (MONIMIACEAE), AND CRYPTOCARYA ALBA (LAURACEAE) WERE EVALUATED AGAINST CODLING MOTH: CYDIA POMONELLA L. (LEPIDOPTERA: TORTRICIDAE) AND FRUIT FLY DROSOPHILA MELANOGASTER (DIPTERA: DROSOPHILIDAE), WHICH IS ONE OF THE MOST WIDESPREAD AND DESTRUCTIVE PRIMARY PESTS OF PRUNUS (PLUMS, CHERRIES, PEACHES, NECTARINES, APRICOTS, ALMONDS), PEAR, WALNUTS, AND CHESTNUTS, AMONG OTHER. FOUR BENZYLISOQUINOLINE ALKALOIDS (COCLAURINE, LAUROLITSINE, BOLDINE, AND PUKATEINE) WERE ISOLATED FROM THE ABOVE MENTIONED PLANT SPECIES AND EVALUATED REGARDING THEIR INSECTICIDAL ACTIVITY AGAINST THE CODLING MOTH AND FRUIT FLY. THE RESULTS SHOWED THAT THESE ALKALOIDS POSSESS ACUTE AND CHRONIC INSECTICIDAL EFFECTS. THE MOST RELEVANT EFFECT WAS OBSERVED AT 10 ?G/ML AGAINST D. MELANOGASTER AND AT 50 ?G/ML AGAINST C. POMONELLA, BEING THE ALTERATION OF THE FEEDING, DEFORMATIONS, FAILURE IN THE DISPLACEMENT OF THE LARVAE IN THE FEEDING MEDIUM OF D. MELANOGASTER, AND MORTALITY VISIBLE EFFECTS. IN ADDITION, THE DOCKING RESULTS SHOW THAT THESE TYPE OF ALKALOIDS PRESENT A GOOD INTERACTION WITH OCTOPAMINE AND ECDYSONE RECEPTOR SHOWING A POSSIBLE ACTION MECHANISM.

THE PURPOSE OF THIS STUDY WAS TO DETERMINE THE INHIBITORY CAPACITY OF CEANOTHANES TRITERPENES ISOLATE FROM CHILEAN RHAMNACEAE ON ACETYLCHOLINESTERASE (ACHE) AND BUTYRYLCHOLINESTERASE (BCHE) ENZYMES. SEVEN CEANOTHANES TRITERPENES WERE ISOLATED FROM AERIAL PARTS OF PLANT MATERIAL BY CLASSICAL PHYTOCHEMICAL METHODS OR PREPARED BY THE HEMISYNTHETIC METHOD. STRUCTURES WERE DETERMINED BY THE SPECTROSCOPIC METHOD (1H-NMR AND 13C NMR) AND MASS SPECTROMETRY (MS). ACHE AND BCHE ACTIVITY WERE DETERMINED BY THE ELLMANN METHOD FOR ALL COMPOUNDS. ALL TESTED COMPOUNDS EXERTED A GREATER AFFINITY TO ACHE THAN TO BCHE, WHERE COMPOUND 3 HAS AN IC50 OF 0.126 UM FOR ACHE AND OF >500 UM TO BCHE. KINETIC STUDIES INDICATED THAT ITS INHIBITION WAS COMPETITIVE AND REVERSIBLE. ACCORDING TO THE MOLECULAR COUPLING AND DISPLACEMENT STUDIES OF THE PROPIDIUM IODIDE TEST, THE INHIBITORY EFFECT OF COMPOUND 3 WOULD BE PRODUCED BY INTERACTION WITH THE PERIPHERAL ANIONIC SITE (PAS) OF ACHE. THE COMPOUNDS TESTED (1?7) SHOWED AN IMPORTANT INHIBITORY ACTIVITY OF ACHE, BINDING TO PAS. THEREFORE, INHIBITORS THAT BIND TO PAS WOULD PREVENT THE FORMATION OF THE ACHE-A? COMPLEX, CONSTITUTING A NEW ALTERNATIVE IN THE TREATMENT OF ALZHEIMER?S DISEASE (AD).

VITIS VINIFERA VAR. L. PAÍS LEAF EXTRACT, PREVIOUSLY CHARACTERIZED, WAS MICROENCAPSULATED BY EMULSION-SOLVENT EVAPORATION METHOD USING TWO DIFFERENT PROCEDURES: THE CONVENTIONAL DROPWISE AND MICROMIXER DEVICE. THE POLY-3-HYDROXYBUTYRATE-CO-3-HYDROXYVALERATE (PHBV) WAS USED AS ENCAPSULATING POLYMER. IN ADDITION, THE EFFECT OF EXTRACTION TIME AND ETHANOL:WATER RATIO ON THE YIELD AND THE CONTENT OF BIOACTIVE COMPOUNDS OF GRAPE LEAF EXTRACT OBTAINED BY SOXHLET METHOD WAS DETERMINED USING THE FACE-CENTERED CENTRAL COMPOSITE DESIGN. THE HIGHEST BIOACTIVE COMPOUND WERE OBTAINED USING A 70:30 ETHANOL:WATER SOLVENT RATIO DURING 4 CYCLES. THIS EXTRACT IS MAINLY COMPOSED OF CINNAMIC ACID, QUERCETIN-3-GLUCOSIDE AND QUERCETIN-3-GLUCORINIDE, CONTAINING 3.56, 2.08 AND 1.19 MG G?1 EXTRACT, RESPECTIVELY. THE TOTAL POLYPHENOL CONTENT DETERMINED BY FOLIN CIOCALTEU METHOD WAS 164 ± 14 MG GAE G?1 EXTRACT. THE MICROPARTICLES (2?3 ?M) HAD SPHERICAL SHAPE WITH ROUGH AND POROUS SURFACE. THE ENCAPSULATION EFFICIENCY WAS 15.1% AND 60.6% FOR THE PHBV MICROPARTICLES PREPARED USING CONVENTIONAL DROPWISE AND MICROMIXER DEVICE, RESPECTIVELY. THE ANTIOXIDANT ACTIVITY PRESENT IN THE ORIGINAL EXTRACT WAS PRESERVED AROUND 50%?80% AND 20%?70% IN THE LOADED MICROPARTICLES. THE BEST RESULTS WERE ACHIEVED WHEN GRAPE LEAF EXTRACT WAS ENCAPSULATED USING MICROMIXER DEVICE. THE CELL VIABILITY ASSAY IN 3T3-L1 FIBROBLASTS, SHOWED THAT LOADED MICROPARTICLES ARE NOT CYTOTOXIC. IN CONCLUSION MICROMIXER DEVICE SHOWED TO BE EFFECTIVE FOR THE MICROENCAPSULATION OF GRAPE LEAF EXTRACT USING PHBV AS ENCAPSULING POLYMER.

BUDDLEJA GLOBOSA HOPE (BUDDLEJACEAE) IS A NATIVE SPECIES CULTIVATED IN CHILE, PERU AND ARGENTINA. IN FOLK MEDICINE, THIS PLANT IS FREQUENTLY USED FOR THE TREATMENT OF DIFFERENT WOUNDS (INTERNAL AND EXTERNAL), AS WELL AS INTESTINAL AND LIVER DISEASES. THERE IS GROWING SCIENTIFIC EVIDENCE ON THE GROWING CONDITIONS FOR BUDDLEJA GLOBOSA AND HOW ITS CULTIVATION COULD BE OPTIMIZED. METHODS FOR ITS VEGETATIVE PROPAGATION HAVE ALSO BEEN SUCCESSFULLY ELABORATED. THE LEAVES CONTAIN PHENYLPROPANOIDS, IRIDOIDS, TERPENES AND FLAVONOIDS. ETHNOPHARMACOLOGICAL VALIDATION STUDIES SUGGEST THAT PHENYLPROPANOIDS AND FLAVONOIDS ARE THE MAIN AND MOST IMPORTANT COMPOUNDS IN DEFINING THE THERAPEUTIC ACTIVITY OF BUDDLEJA GLOBOSA. THIS CHEMICAL COMPOSITION EXPLAINS ITS PHARMACOLOGICAL ACTIVITY AS ANTIOXIDANT, ANTI-INFLAMMATORY, ANTIMICROBIAL AND, IN PARTICULAR, ITS WOUND HEALING EFFECTS. DUE TO ITS UNDENIABLE POTENTIAL AS A DOMESTICATED, CULTIVATED MEDICINAL PLANT AND ITS REMARKABLE CHEMICAL COMPOSITION, IT IS STILL NECESSARY TO DEVELOP ITS PROPERLY STANDARDIZED, CLINICALLY VALIDATED PHYTOPHARMACEUTICAL PRODUCTS.

ALZHEIMER?S DISEASE (AD) IS A MULTIFACTORIAL AND FATAL NEURODEGENERATIVE DISORDER. ACETYLCHOLINESTERASE (ACHE) PLAYS A KEY ROLE IN THE REGULATION OF THE CHOLINERGIC SYSTEM AND PARTICULARLY IN THE FORMATION OF AMYLOID PLAQUES; THEREFORE, THE INHIBITION OF ACHE HAS BECOME ONE OF THE MOST PROMISING STRATEGIES FOR THE TREATMENT OF AD, PARTICULARLY CONCERNING ACHE INHIBITORS THAT INTERACT WITH THE PERIPHERAL ANIONIC SITE (PAS). CEANOTHIC ACID ISOLATED FROM THE CHILEAN RHAMNACEAE PLANTS IS AN INHIBITOR OF ACHE THROUGH ITS INTERACTION WITH PAS. IN THIS STUDY, SIX CEANOTHIC ACID DERIVATIVES WERE PREPARED, AND ALL SHOWED INHIBITORY ACTIVITY AGAINST ACHE. THE STRUCTURAL MODIFICATIONS WERE PERFORMED STARTING FROM CEANOTHIC ACID BY APPLICATION OF SIMPLE SYNTHETIC ROUTES: ESTERIFICATION, REDUCTION, AND OXIDATION. ACHE ACTIVITY WAS DETERMINED BY THE ELLMANN METHOD FOR ALL COMPOUNDS. KINETIC STUDIES INDICATED THAT ITS INHIBITION WAS COMPETITIVE AND REVERSIBLE. ACCORDING TO THE MOLECULAR COUPLING AND DISPLACEMENT STUDIES OF THE PROPIDIUM IODIDE TEST, THE INHIBITORY EFFECT OF COMPOUNDS WOULD BE PRODUCED BY INTERACTION WITH THE PAS OF ACHE. IN SILICO PREDICTIONS OF PHYSICOCHEMICAL PROPERTIES, PHARMACOKINETICS, DRUG-LIKENESS, AND MEDICINAL CHEMISTRY FRIENDLINESS OF THE CEANOTHANE DERIVATIVES WERE PERFORMED USING THE SWISS ADME TOOL.

BIOFILM-PRODUCING BACTERIA ARE ASSOCIATED WITH INFECTIOUS PATHOLOGIES THAT CAUSE GREAT HEALTH CONCERNS. MANY OF THESE MICROORGANISM INCREASE THEIR VIRULENCE AND SURVIVAL THANKS TO THE FORMATION OF THIS MECHANICAL BARRIER. ON THE OTHER HAND, BENEFICIAL PROBIOTICS SUCH AS LACTOBACILLI STRAINS USED IN THE FOOD INDUSTRY MAY ALSO GENERATE BIOFILMS OF HIGH STABILITY. THEREFORE, A MAJOR CHALLENGE IS TO LOOK FOR AGENTS (OR COMBINATIONS THEREOF) THAT SELECTIVELY REGULATE THE BIOFILM-FORMING PHENOTYPE IN PATHOGENIC AND NON-PATHOGENIC BACTERIA. IN THIS WORK WE FIRST PREPARED FLAVAN-3-OL-ADDUCTS FROM NATURAL PROANTHOCYANIDINS AS BUILDING BLOCKS, WHICH WERE PURIFIED USING CENTRIFUGAL PARTITION CHROMATOGRAPHY (CPC). AFTERWARDS, THESE COMPOUNDS WERE OXIDIZED IN PRESENCE OF ISOLATED GREEN TEA GALLOCATECHINS (EGCG) UNDER DIFFERENT EXPERIMENTAL CONDITIONS USING CHEMICAL AND ENZYMATIC STRATEGIES. TO ACHIEVE THIS GOAL, WE USED A SECOND CPC SYSTEM EQUIPPED WITH TWO COLUMNS (V T = 500 ML). THE OXIDATION PROCESS WAS PERFORMED IN THE FIRST CPC COLUMN AND THE FRACTIONATION WAS CARRIED OUT USING AND ADDITIONAL CPC COLUMN. BIO-GUIDED SEPARATION ALLOWED TO DETECT FRACTIONS ABLE TO MODULATE BIOFILM-FORMING PROPERTIES IN LISTERIA MONOCYTOGENES, PSEUDOMONAS AERUGINOSA, HELICOBACTER PYLORI AND STAPHYLOCCOCUS AUREUS. FINALLY, OXIDATION PRODUCTS WERE INVESTIGATED BY HPLC-ESI-MS/MS, AND EPR METHODS. E. COLI K-12 (NON-PATHOGENIC) SEEM TO BE UNAFFECTED BY THESE COMPOUNDS. INTERESTINGLY, BIOFILM-FORMATION IN LACTOBACILLUS FERMENTUM WAS PROMOTED BY THEM. THESE NEW MOLECULES WERE TENTATIVELY IDENTIFIED AS THEAFLAVIN-LIKE DERIVATIVES. OVERALL, THEAFLAVIN-LIKE PRODUCTS OBTAINED UNDER CONTROLLED OXIDATION COULD BE CONSIDERED AS STARTING POINT TO SYNTHESIZE NEW MOLECULES THAT REGULATE BIOFILMS PRODUCTION WITH POTENTIAL FOOD AND PHARMACEUTICAL APPLICATION. AKNOWLEDGEMENTS: FONDECYT 1150498; FONDEQUIP 150025.

THE FULL UHPLC-MS METABOLOME FINGERPRINTING AND ANTI-HELICOBACTER PYLORI EFFECT OF GUNNERA TINCTORIA (MOLINA) MIRB. (NALCA) TOTAL EXTRACT (GTE) AND FRACTIONS PREPARED FROM ITS EDIBLE FRESH PETIOLES WERE EVALUATED. THE ACTIVITY OF G. TINCTORIA AGAINST H. PYLORI STRAINS ATCC 45504 AND J99 WAS ASSESSED IN VITRO BY MEANS OF AGAR DIFFUSION ASSAY, MINIMUM INHIBITION CONCENTRATION (MIC), AND MINIMUM BACTERICIDAL CONCENTRATION (MBC), WHILE KILLING CURVE AND TRANSMISSION ELECTRONIC MICROSCOPY (TEM) WERE CONDUCTED IN ORDER TO DETERMINE THE EFFECT OF THE PLANT EXTRACT ON BACTERIAL GROWTH AND ULTRASTRUCTURE. ADDITIONALLY, THE INHIBITORY EFFECT UPON UREASE WAS EVALUATED USING BOTH THE JACK BEAN AND H. PYLORI ENZYMES. TO DETERMINE WHICH MOLECULES COULD BE RESPONSIBLE FOR THE ANTIBACTERIAL EFFECTS, TENTATIVE IDENTIFICATION WAS DONE BY ULTRA-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED WITH HIGH-RESOLUTION MASS SPECTROMETRY (UHPLC-Q-ORBITRAP®-HR-MS). FURTHERMORE, THE TOTAL G. TINCTORIA EXTRACT WAS FRACTIONATED USING CENTRIFUGAL PARTITION CHROMATOGRAPHY (CPC), GIVING FOUR ACTIVE FRACTIONS (1-4). IT WAS DETERMINED THAT THE CRUDE EXTRACT AND CENTRIFUGAL PARTITION CHROMATOGRAPHY FRACTIONS OF G. TINCTORIA HAVE A BACTERICIDAL EFFECT BEING THE LOWEST MIC AND MBC = 32 ?G/ML. IN THE KILLING CURVES, FRACTION ONE ACTS FASTER THAN CONTROL AMOXICILLIN. IN THE UREASE ASSAY, F3 EXHIBITED THE LOWEST IC50 VALUE OF 13.5 ?G/ML. TRANSMISSION ELECTRONIC MICROSCOPY SHOWED THAT CRUDE G. TINCTORIA EXTRACT PROMOTES DISRUPTION AND SEPARATION OF THE CELLULAR WALL AND OUTER MEMBRANE DETACHMENT ON H. PYLORI CAUSING BACTERIAL CELL DEATH.

CYCLOPEPTIDE ALKALOIDS WITH DIFFERENT BIOLOGICAL ACTIVITIES ARE PRESENT IN PLANTS OF THE FAMILY RHAMNACEAE. PLANTS OF THIS FAMILY GROW IN A SYMBIOTIC RELATIONSHIP WITH AEROBIC GRAM-POSITIVE ACTINOMYCETES BELONGING TO THE GENUS FRANKIA. THIS GOAL OF THIS RESEARCH WAS A STUDY OF THE COMPARATIVE PROFILE OF ALKALOIDS PRESENT IN DISCARIA CHACAYE AND TO ESTABLISH A CONNECTION BETWEEN THE PRESENCE OR ABSENCE OF FRANKIA SP. AND THE ALKALOIDS. IN ADDITION, INSECTICIDAL ACTIVITIES OF THE ALKALOIDAL EXTRACT WERE EXAMINED. A TOTAL OF 24 ALKALOIDS WERE IDENTIFIED, OF WHICH 12 HAVE A BENZYLISOQUINOLINE SKELETON, 9 WERE CYCLOPEPTIDES, 2 ISOQUINOLINES, AND 1 APORPHINE. THE PRESENCE OF CYCLOPEPTIDE ALKALOIDS IS ASSOCIATED WITH FRANKIA NODULES IN THE PLANT ROOT. THE ALKALOID EXTRACTS SHOWED INSECTICIDAL ACTIVITY WITH MORTALITY DOSE-DEPENDENCE AND LD50 VALUES BETWEEN 44 TO 71 ?G/ML.

OBTENER UN FITOFÁRMACO A BASE DE EXTRACTO SECO DE LIMÓN CON ESTÁNDARES DE CALIDAD, PROCESAMIENTO AMIGABLE CON EL MEDIO AMBIENTE Y CON ANTECEDENTES DE EFECTIVIDAD Y SEGURIDAD, EVALUANDO SUS EFECTOS EN PACIENTES HIPERTENSOS CON FRECUENTES CRISIS HIPERTENSIVAS. MÉTODOS Y RESULTADOS: SE SELECCIONÓ LA POBLACIÓN DE LIMÓNES DE LAS REGIONES METROPOLITANA Y COQUIMBO CON LAS CONCENTRACIONES MÁS ALTAS DE ÁCIDO ASCÓRBICO Y FLAVONOIDES TOTALES, RESPECTIVAMENTE. SE UTILIZÓ LIOFILIZACIÓN PARA OBTENER JUGO DE LIMÓN EN POLVO. SÓLO DURANTE EL PERÍODO DE ESTUDIO, SE INFORMÓ UN CASO DE AUMENTO/ CRISIS HIPERTENSIVA. LA FORMULACIÓN CON LA CONCENTRACIÓN MÁS ALTA DE ÁCIDO ASCÓRBICO DISMINUYÓ LA PRESIÓN ARTERIAL SISTÓLICA Y DIASTÓLICA EN 16 MMHG DESDE 10 MINUTOS HASTA 60 MINUTOS. POR OTRO LADO, LA FORMULACIÓN CON MAYOR CONCENTRACIÓN DE FLAVONOIDES DISMINUYÓ LA PRESIÓN ARTERIAL EN 12 A 30 MMHG DESDE 5 A 60 MINUTOS. CONCLUSIÓN: SE OBTUVO UN PRODUCTO INNOVADOR COMO COMPLEMENTO AL MANEJO DE LOS AUMENTOS DE PRESIÓN ARTERIAL. LOS PRINCIPIOS ACTIVOS CON MAYOR CONTRIBUCIÓN AL MECANISMO ANTIHIPERTENSIVO DEL JUGO DE LIMÓN CORRESPONDEN A COMPUESTOS FENÓLICOS, ESPECÍFICAMENTE, FLAVONOIDES.

IN ORDER TO FIND MOLECULES OF NATURAL ORIGIN WITH POTENTIAL BIOLOGICAL ACTIVITIES, WE ISOLATE AND SYNTHESISE COMPOUNDS WITH AGAROFURAN SKELETONS (EPOXYEUDESMANES). FROM THE SEEDS OF MAYTENUS DISTICHA AND MAYTENUS MAGELLANICA WE OBTAINED SIX DIHYDRO-?-AGAROFURANS, AND BY MEANS OF THE ROBINSON ANNULATION REACTION WE SYNTHESISED FIVE COMPOUNDS WITH THE SAME SKELETON. THE STRUCTURES WERE ESTABLISHED ON THE BASIS OF NMR, IR, AND MS. THE EVALUATED COMPOUNDS SHOWED INHIBITORY ACTIVITY ON THE ACETYLCHOLINESTERASE ENZYME AND ON THE COX ENZYMES. COMPOUND 4 EMERGED AS THE MOST POTENT IN THE ACETYLCHOLINESTERASE INHIBITION ASSAY WITH IC50 17.0 ± 0.016 ?M ON ACETYLCHOLINESTERASE (ACHE). THE COMPOUNDS EVALUATED WERE SHOWN TO BE SELECTIVE FOR ACHE. THE MOLECULAR DOCKING, AND THE PROPIDIUM DISPLACEMENT ASSAY SUGGESTED THAT THE COMPOUNDS DO NOT BIND TO THE ACTIVE SITE OF THE ENZYME ACHE, BUT RATHER BIND TO THE PERIPHERAL ANIONIC SITE (PAS) OF THE ENZYME, ON THE OTHER HAND, THE NATURAL COMPOUND 8, SHOWED THE BEST INHIBITORY ACTIVITY ON THE COX-2 ENZYME WITH AN IC50 VALUE OF 0.04 ± 0.007 ?M. THE PHARMACOKINETIC PROFILE CALCULATED IN SILICO USING THE SWISSADME PLATFORM SHOWS THAT THESE MOLECULES COULD BE CONSIDERED AS POTENTIAL DRUGS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES SUCH AS AD.

THIS WORK IS AIMED TO THE STUDY THE EFFECT OF AQUEOUS EXTRACTS OBTAINED FROM LEAVES OF UGNI MOLINAE AND THEIR RESPECTIVE PRODUCTS OF IN VITRO GASTROINTESTINAL DIGESTION ON THE VIABILITY OF COLON CANCER CELLS. METHODS: UGNI MOLINAE LEAVES WERE USED TO PREPARE A 1%, AQUEOUS EXTRACT AND WITH THIS, AN IN VITRO GASTROINTESTINAL DIGESTION WAS PERFORMED, OBTAINING, FRACTION PRODUCTS OF DIGESTION GASTROINTESTINAL (DGI) AND FRACTION RESIDUE. THIS FRACTION WAS IDENTIFIED THROUGH LIQUID CHROMATOGRAPHY (HPLC-UV) AND LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY (HPLC-MS), AND THEN THESE SAMPLES WERE EVALUATED IN DIFFERENT VIABILITY TESTS, SUCH AS TRYPAN BLUE EXCLUSION, METABOLIC ACTIVITY 3-(4,5-DIMETHYLTHIAZOL-2-YL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE (MTT) AND CYTOTOXICITY BY LACTATE DEHYDROGENASE (LDH), ON COLORECTAL CANCER CELLS (CACO-2) AND HUMAN EMBRYONIC KIDNEY 293 CELLS (HEK) FOR A PERIOD OF 24 AND 48 HOURS. RESULTS AND DISCUSSION: THE AQUEOUS EXTRACTS OF LEAVES OF UGNI MOLINAE AND THEIR DIGESTION FRACTIONS CAUSED INHIBITION OF THE VIABILITY OF CACO-2 CELLS. IN MOST CASES, THE EFFECT WAS CONCENTRATION-DEPENDENT AND IN PARTICULAR, THE ONLY COMPOUND THAT GENERATED INHIBITION OF THE VIABILITY IN ALL TRIALS CORRESPONDED TO THE DGI FRACTION. CONCLUSION: THE RESULTS ARE FAVORABLE, SINCE IT IS FINALLY IS THIS PRODUCT THAT WOULD ACT IN THE GASTROINTESTINAL TRACT, INTERACTING WITH THE TARGET CELLS. THESE RESULTS ARE IMPORTANT SINCE IN MOST CASES, THESE COMPOUNDS HAD EFFECTS ON CANCER CELLS CACO-2 AND NOT ON HEK CELLS AT THE SAME CONCENTRATIONS USED IN EACH TRIAL.

AMARYLLIDACEAE PLANTS ARE WELL KNOWN FOR PRODUCING ISOQUINOLINE-TYPE ALKALOIDS WHICH HAVE IMPORTANT BIOLOGICAL ACTIVITIES, HOWEVER THE PRODUCTION OF THESE SECONDARY METABOLITES IN PLANTS IS VERY LOW, IT?S NECESSARY TO STUDY MECHANISMS TO INCREASE THE PRODUCTIVITY OF THEM. OUR STUDY SHOWS THE ALKALOIDS COMPOSITION ON THE WILD BULBS AND IN VITRO BULBS OF FOUR SPECIES CHILEAN AMARYLLIDACEAE. QUALITATIVE AND SEMI-QUANTITATIVE ANALYSIS OF ALKALOID EXTRACTS CARRIED OUT BY GC/MS?MS WE FOUND A TOTAL OF 48 DIFFERENT ALKALOIDS PRODUCED IN WILD PLANTS AND IN VITRO CULTURE; 38 ALKALOIDS WERE IDENTIFIED. THESE RESULTS SUGGEST THAT DIFFERENT COMBINATIONS OF AUXINS AND CYTOKININS CAN MODULATE PLANT BIOCHEMICAL PATHWAYS THAT REGULATE ALKALOID BIOGENESIS AND SHOW THE HIGH POTENTIAL THAT PLANTS OF THE AMARYLLIDACEAE FAMILY HAVE TO PRODUCE LYCORINE TYPE ALKALOIDS. THIS STUDY ALLOWED KNOWING THE CONTENT OF ALKALOIDS IN WILD AND IN VITRO BULBS OF THE STUDIED SPECIES. THESE RESULTS ENABLE TO ESTABLISH THE CULTURE MEDIA WITH 4.44 ?M BAP AND 2.70 ?M NAA AND 2.20 ?M BAP AND 5.40 ?M NAA INCREASED THE PRODUCTION OF LYCORINE-TYPE ALKALOIDS FOR R. ADVENA AND R. PRATENSIS RESPECTIVELY, THEREFORE IT IS ABLE TO PROMOTE OXIDATIVE PHENOL COUPLING VIA ORTHO-PARA' AND DEMONSTRATES HOW IT IS POSSIBLE TO DIRECT THE PRODUCTION OF THESE MOLECULES THROUGH THE USE OF PHYTOHORMONES IN IN VITRO CULTURE. FINALLY, WE CAN SAY THAT THE RESULTS CONFIRM THAT MICROPROPAGATION IS A GOOD TOOL TO PRODUCE THIS TYPE OF ALKALOIDS.

BURNS ARE A MAJOR THREAT TO PUBLIC HEALTH AND THE ECONOMY DUE TO THEIR COSTLY AND LABORIOUS TREATMENT AND HIGH SUSCEPTIBILITY TO INFECTION. EFFORTS HAVE BEEN MADE RECENTLY TO INVESTIGATE NATURAL BIOACTIVE COMPOUNDS WITH POTENTIAL USE IN WOUND HEALING. THE IMPORTANCE LIES IN THE CAPACITIES THAT THESE COMPOUNDS COULD POSSESS BOTH IN INFECTION CONTROL BY COMMON AND RESISTANT MICROORGANISMS, AS WELL AS IN THE REGENERATION OF THE AFFECTED TISSUES, HAVING IN BOTH CASES LOW ADVERSE EFFECTS. HOWEVER, SOME BIOACTIVE MOLECULES ARE CHEMICALLY UNSTABLE, POORLY SOLUBLE, AND SUSCEPTIBLE TO OXIDATIVE DEGRADATION OR HAVE LOW BIOAVAILABILITY. THEREFORE, DEVELOPING NEW TECHNOLOGIES FOR AN EFFICIENT TREATMENT OF WOUND HEALING POSES A REAL CHALLENGE. IN THIS CONTEXT, ELECTROSPUN NANOFIBERS HAVE GAINED INCREASING RESEARCH INTEREST BECAUSE BIOACTIVE MOLECULES CAN BE EASILY LOADED WITHIN THE NANOFIBER, RESULTING IN OPTIMAL BURST CONTROL AND ENHANCED DRUG STABILITY. ADDITIONALLY, THE NANOFIBERS CAN MIMIC THE EXTRACELLULAR COLLAGEN MATRIX, PROVIDING A SUITABLE HIGHLY POROUS STRUCTURAL SUPPORT FOR GROWING CELLS THAT FACILITATE AND ACCELERATE SKIN BURNS HEALING. THIS REVIEW GIVES AN OVERVIEW OF THE CURRENT STATE OF ELECTROSPUN FIBERS LOADED WITH NATURAL BIOACTIVE COMPOUNDS AS A BIOMEDICAL SYSTEM FOR SKIN BURN TREATMENT.

THE LOSS OF AGRICULTURAL PRODUCTS BY PESTS AND MICROORGANISMS IS INTENSELY FOUGHT WITH SYNTHETIC PRODUCTS THAT CAN POSE A SERIOUS THREAT TO THE ENVIRONMENT, HEALTH, AND FOODS. THE USE OF PLANT-DERIVED PRODUCTS IN THE MANAGEMENT OF THESE ORGANISMS IS A SUSTAINABLE AND SAFE ALTERNATIVE. IN THIS STUDY, WE INVESTIGATED FABIANA IMBRICATA, A VERY WELL-KNOWN SPECIES OF SOLANACEAE FOUND IN THE PATAGONIAN REGION. THE TOXICOLOGICAL EFFECTS OF ITS FRACTIONS WERE TESTED AGAINST DROSOPHILA MELANOGASTER AND TENEBRIO MOLITOR. THESE FRACTIONS WERE ALSO SCREENED FOR REPELLENCY ON ACANTHOSCELIDES OBTECTUS AND ANTIMICROBIAL ACTIVITY. ADDITIONALLY, THE MORTALITY ASSAY OF D. MELANOGASTER LARVAE REVEALED HIGHER ACTIVITY FOR THE STEM (LC50 VALUE OF 7.5 ?G/ML) AND LEAF (LC50 VALUE OF 19.8 ?G/ML) PETROLEUM BENZINE FRACTIONS. TENEBRIO MOLITOR LARVAE NEEDED TO BE EXPOSED TO A HIGH CONCENTRATION OF STEM FRACTIONS (200 AND 300 ?G/ML) TO OBSERVE ABOUT 50 AND 90% MORTALITY, RESPECTIVELY. MOREOVER, REPELLENCY AFTER 4 H OF EXPOSURE WAS MAINLY OBSERVED WITH THE STEM DICHLOROMETHANE FRACTION (CONC. 100 ?G/ML). THE ACETATE FRACTION OF THE STEM (FE-C) WAS RESPONSIBLE FOR THE GREATEST GROWTH INHIBITION OF THE TESTED BACTERIA (ESCHERICHIA COLI, LISTERIA MONOCYTOGENES, L. INNOCUA, SALMONELLA SP., AND S. AUREUS). BASED ON THE FINDINGS, STEM FRACTIONS WERE SELECTED FOR STUDIES OF TOXICITY IN NON-TARGET ORGANISMS AND SYSTEMIC EFFECTS ON PROTEINS AND DETOXIFICATION ENZYMES FROM T. MOLITOR LARVAE. THE FRACTIONS TESTED AGAINST ADULT BEES WERE SAFE UP TO 500 ?G/ML FOR 4 H OF EXPOSURE AND 48 H OF OBSERVATION. TOTAL PROTEINS AND ENZYMES ACHE, GST/GSH, AND CARBOXYLASE WERE SIGNIFICANTLY REDUCED, MAINLY WITH FE-C. IN CONTRAST, ACP AND ALP WERE UP-REGULATED, WITH THE SAME FRACTION AS THE MAJOR INDUCER. THE CHEMICAL PROFILES OF THE FRACTIONS ANALYZED BY GC-MS AND NMR SHOWED THAT FE-C HAD SCOPOLETIN AS THE MAIN COMPONENT. THEREFORE, WE SELECTED THIS COMPOUND FOR IN SILICO ANALYSIS OF ACHE DOCKING, QUALITATIVE AND QUANT

AVOCADO HASS (PERSEA AMERICANA MILL) PEEL EXTRACT (APE) HAS THE POTENTIAL AS A NATURAL INGREDIENT TO SUBSTITUTE FOR CHEMICAL PRESERVATIVES. THE OBJECTIVES OF THIS STUDY WERE TO ASSESS THE PHYTOCHEMICAL COMPOSITION BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY?QUADRUPOLE TIME-OF-FLIGHT MASS/MASS SPECTROMETRY (HPLC-QTOF-MS/MS), TOTAL PHENOLIC CONTENT (TPC), PROANTHOCYANIDIN (PAC) CONTENT, AND ANTIOXIDANT ACTIVITY OF THE APE, THE ORGANIC FRACTION (OF), THE AQUEOUS FRACTION (AF), AND THE ACID-MICROWAVE HYDROLYZED APE (HAPE), ON THE ANTIBACTERIAL ACTIVITY (ABA). THE RESULTS INDICATED THAT APE AND OF CONTAINED (P ? 0.05) A HIGHER PHENOLIC COMPOSITION AND ANTIOXIDANT ACTIVITY THAN AF AND HAPE. THE ABA SPECIFIED THAT PSEUDOMONAS AERUGINOSA AND BACILLUS CEREUS WERE INHIBITED BY ALL THE EXTRACTS (MINIMAL INHIBITORY CONCENTRATION?MIC ? 500 ?G/ML), STAPHYLOCOCCUS AUREUS WAS ONLY SIGNIFICANTLY INHIBITED BY APE (?750 ?G/ML), THE SAME MIC WAS OBSERVED FOR THE OF ON SALMONELLA SPP. AND LISTERIA MONOCYTOGENES. THE HAPE INCREASED THE INHIBITORY EFFICIENCY UP TO 25% ON ESCHERICHIA COLI AND SALMONELLA SPP. (MIC ? 750 ?G/ML), AND 83.34% ON L. MONOCYTOGENES (MIC ? 125 ?G/ML) COMPARED TO APE (MIC ? 750 ?G/ML). ALSO, HAPE INHIBITED THE BIOFILM FORMATION AT THE LOWEST CONCENTRATION (125 ?G/ML); MEANWHILE, THE BIOFILM DISRUPTION SHOWED TO BE CONCENTRATION-TIME-DEPENDENT (P ? 0.05) COMPARED TO AMOXICILLIN. IN CONCLUSION, THE FRACTIONATION AND HYDROLYZATION OF APE IMPROVED THE ABA; THUS, THOSE STRATEGIES ARE USEFUL TO DESIGN NEW ANTIMICROBIAL COMPOUNDS.

PEUMUS BOLDUS MOL., IS A CHILEAN MEDICINAL TREE USED FOR GASTROINTESTINAL AND LIVER DISEASES. SUCH MEDICINAL PROPERTIES ARE ASSOCIATED WITH THE PRESENCE OF BIOACTIVE FLAVONOIDS AND APORPHINE ALKALOIDS. IN THIS STUDY, A NEW GREEN AND EFFICIENT EXTRACTION METHOD USED SEVEN NATURAL DEEP EUTECTIC SOLVENTS (NADES) AS EXTRACTION MEDIA. THE EXTRACTION EFFICIENCY OF THESE NADES WAS ASSESSED, DETERMINING THE CONTENTS OF BOLDINE AND TOTAL PHENOLIC COMPOUNDS (TPC). CHEMICAL PROFILING OF P. BOLDUS WAS DONE BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED TO PHOTO DIODE ARRAY DETECTOR AND ELECTROSPRAY ION-TRAP MASS SPECTROMETRY (HPLC-PDA-ESI-IT/MS) AND ELECTROSPRAY IONIZATION QUADRUPOLE TIME-OF-FLIGHT HIGH-RESOLUTION MASS SPECTROMETRY (HPLC-ESI-QTOF-MS). AMONG THE NADES TESTED, NADES4 (CHOLINE CHLORIDE-LACTIC ACID) AND NADES6 (PROLINE-OXALIC ACID) ENABLE BETTER EXTRACTION OF BOLDINE WITH 0.427 ± 0.018 AND 2.362 ± 0.055 MG OF BOLDINE G-1 OF PLANT, RESPECTIVELY. EXTRACTION OF BOLDINE WITH NADES4 AND NADES6 WAS MORE EFFICIENT THAN EXTRACTIONS PERFORMED WITH METHANOL AND WATER. ON THE OTHER HAND, THE HIGHEST TPC WERE OBTAINED USING NADES6, 179.442 ± 3.79 MG OF GALLIC ACID EQUIVALENTS (GAE G-1). MOREOVER, TPC IN EXTRACTS OBTAINED WITH METHANOL DOES NOT SHOW SIGNIFICANT DIFFERENCES WITH NADES6. THE HPLC-PAD-MS/MS ANALYSIS ENABLE THE TENTATIVE IDENTIFICATION OF 9 ALKALOIDS AND 22 PHENOLIC COMPOUNDS. THE RESULTS OF THIS STUDY DEMONSTRATE THAT NADES ARE A PROMISING GREEN EXTRACTION MEDIA TO EXTRACT P. BOLDUS BIOACTIVE COMPOUNDS AND COULD BE A VALUABLE ALTERNATIVE TO CLASSIC ORGANIC SOLVENTS.

HAPLOPAPPUS BAYLAHUEN J. RÉMY (ASTERACEAE) IS A MEDICINAL PLANT GROWING IN CHILE AND ARGENTINA. THIS IS ONE OF SEVENTEEN NATIVE HAPLOPAPPUS SPP. SPECIES COMMERCIALIZED IN CHILE UNDER THE NAME ?BAILAHUÉN?. IN FOLK MEDICINE, THESE PLANTS ARE MAINLY USED FOR THE TREATMENT OF INTESTINAL AND LIVER DISEASES. LEAVES, FLOWERS AND STEMS CONTAIN FLAVONOIDS, COUMARINS, PHENOLIC ACIDS AND DITERPENES. ALTHOUGH SEVERAL CHEMICAL PROFILING STUDIES HAVE PROVIDED IMPORTANT BACKGROUND THAT ALLOWS DEDUCING SOME BIOLOGICAL EFFECTS OF SPECIFIC ?BAILAHUÉN? SPECIES, IT IS CLEAR THAT IT IS NECESSARY TO RE-STUDY SOME CHEMICAL-BIOLOGICAL ASPECTS USING ADVANCED BIOANALYTICAL TECHNIQUES. HITHERTO, ONLY PART OF THE ISOLATED COMPOUNDS EXPLAINS THE ANTIOXIDANT, DIURETIC, ANTI-INFLAMMATORY AND ANTIMICROBIAL ACTIVITIES. ADDITIONALLY, JUST A FEW IN VIVO STUDIES HAVE BEEN CARRIED OUT, EXCLUSIVELY IN MURINE MODELS. TO DATE, NO CLINICAL STUDIES HAVE BEEN CONDUCTED IN CHILE WITH ANY OF THE SPECIES REPRESENTING THIS GENUS.