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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.

Polyphenols from agro-food waste represent a valuable source of bioactive molecules that can be recovered to be used for their functional properties. Another option is to use them as starting material to generate molecules with new and better properties through semi-synthesis. A proanthocyanidin-rich (PACs) extract from avocado peels was used to prepare several semi-synthetic derivatives of epicatechin by acid cleavage in the presence of phenol and thiol nucleophiles. The adducts formed by this reaction were successfully purified using one-step centrifugal partition chromatography (CPC) and identified by chromatographic and spectroscopic methods. The nine derivatives showed a concentration-dependent free radical scavenging activity in the DPPH assay. All compounds were also tested against a panel of pathogenic bacterial strains formed by Listeria monocytogenes (ATCC 7644 and 19115), Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 11775 and 25922), and Salmonella enterica (ATCC 13076). In addition, adducts were tested against two no-pathogenic strains, Limosilactobacillus fermentum UCO-979C and Lacticaseibacillus rhamnosus UCO-25A. Overall, thiol-derived adducts displayed antimicrobial properties and, in some specific cases, inhibited biofilm formation, particularly in Listeria monocytogenes (ATCC 7644). Interestingly, phenolic adducts were inactive against all the strains and could not inhibit its biofilm formation. Moreover, depending on the structure, in specific cases, biofilm formation was strongly promoted. These findings contribute to demonstrating that CPC is a powerful tool to isolate new semi-synthetic molecules using avocado peels as starting material for PACc extraction. These compounds represent new lead molecules with antioxidant and antimicrobial activity.

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-β-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 IC 50 17.0 ± 0.016 µM 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 IC 50 value of 0.04 ± 0.007 µM. 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.

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 LD 50 values between 44 to 71 μg/mL., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

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-Aβ complex, constituting a new alternative in the treatment of Alzheimer’s disease (AD).

The objective of the present study was to investigate the impact of phenolic-rich avocado peel extract (APE) as an ingredient in beef and soy-based burgers to increase their antioxidant activity, reduce lipid and protein oxidation during gastric digestion, and inhibit urease and anhydrase carbonic activity, which are considered as key factors in the main steps of Helicobacter pylori adhesion in the stomach. The gastric bioaccessible fraction of soy and beef burgers with added 0.5% APE obtained by in vitro digestion exhibited a higher content of phenolic compounds, including monomeric and oligomeric (epi)catechin forms and quercetin, and reduced levels of thiobarbituric acid-reactive substances (TBARS) and carbonyls (49% to 73% and 57% to 60%, respectively) when compared with control burgers. Moreover, the burgers with APE inhibited urease and carbonic anhydrase activity. Results generally showed that including APE reduces the primary risk factors associated with H. pylori infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Chemical profiling of Buddleja globosa was performed by high-performance liquid chromatography coupled to electrospray ionization (HPLC-DAD-ESI-IT/MS) and quadrupole time-of-flight high-resolution mass spectrometry (HPLC-ESI-QTOF/MS). The identification of 17 main phenolic compounds in B. globosa leaf extracts was achieved. Along with caffeoyl glucoside isomers, caffeoylshikimic acid and several verbascoside derivatives (β-hydroxyverbascoside and β-hydroxyisoverbascoside) were identified. Among flavonoid compounds, the presence of 6-hydroxyluteolin-7- O -glucoside, quercetin-3- O -glucoside, luteolin 7- O -glucoside, apigenin 7- O -glucoside was confirmed. Campneoside I, forsythoside B, lipedoside A and forsythoside A were identified along with verbascoside, isoverbascoside, eukovoside and martynoside. The isolation of two bioactive phenolic compounds verbascoside and forsythoside B from Buddleja globosa (Buddlejaceae) was successfully achieved by centrifugal partition chromatography (CPC). Both compounds were obtained in one-step using optimized CPC methodology with the two-phase solvent system comprising ethyl acetate-n-butanol-ethanol-water (0.25:0.75:0.1:1, v/v ). Additionally, eight Natural Deep Eutectic Solvents (NADESs) were tested for the extraction of polyphenols and compared with 80% methanol. The contents of verbascoside and luteolin 7- O -glucoside after extraction with 80% methanol were 26.165 and 3.206 mg/g, respectively. Among the NADESs tested in this study, proline- citric acid (1:1) and choline chloride-1, 2- propanediol (1:2) were the most promising solvents. With these NADES, extraction yields for verbascoside and luteolin 7- O -glucoside were 51.045 and 4.387 mg/g, respectively. Taken together, the results of this study confirm that CPC enabled the fast isolation of bioactive polyphenols from B. globosa . NADESs displayed higher extraction efficiency of phenolic and therefore could be used as an ecofriendly alternative to classic organic solvents.

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 μg/ml. In the killing curves, fraction one acts faster than control amoxicillin. In the urease assay, F3 exhibited the lowest IC 50 value of 13.5 μg/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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hebel-Gerber, García-Cancino, Urbina, Simirgiotis, Echeverría, Bustamante-Salazar, Sáez-Carrillo, Alarcón and Pastene-Navarrete.)

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 µg/mL), Staphylococcus aureus was only significantly inhibited by APE (≥750 µg/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 µg/mL), and 83.34% on L. monocytogenes (MIC ≥ 125 µg/mL) compared to APE (MIC ≥ 750 µg/mL). Also, HAPE inhibited the biofilm formation at the lowest concentration (125 µg/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.

Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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 µg/mL against D. melanogaster and at 50 µg/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.

Preparative separation of three lycorine type alkaloids from Rhodolirum speciosum (Amaryllidaceae) was successfully carried out using pH-zone-refinement centrifugal partition chromatography (CPC) using the solvent system methyl-tert-butyl ether/acetonitrile/water (4:1:5, v / v / v ) in descending mode. Using this system, Alkaloid 1 (165.7 mg, 88.2%, purity), 2 (60.1 mg, 97.7% purity) and 3 (12.3 mg, 84.4% purity) were obtained in one step. For structure elucidation, the pure alkaloids were subjected to spectroscopy analysis using nuclear magnetic resonance experiments ( 1 H-NMR, 13 C-NMR) and gas chromatography coupled with mass spectrometry (GC-MS). Alkaloids 1, 2, and 3 were identified as 1- O -acetyl-5,6-dehydrolycorine, 1- O -acetyl-lycorine, and 1,2- O -diacetyl-5,6-dehydrolycorine, respectively. The acetylcholinesterase inhibitory activity of these alkaloids was IC 50 151.1 μg/mL, IC 50 203.5 μg/mL, IC 50 470.0 μg/mL, and IC 50 17.1 μg/mL, respectively.

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.

Twenty-five type 2 diabetic volunteer patients (mean age 62 years) were recruited in a quasi-experimental study without a control group to evaluate the effects of Bauhinia forficata Link tea on lipid profiles. Participants drank the tea of 0.4% B. forficata in 200 mL of water twice a day for 3 months. The clinical parameters evaluated were cholesterol and triglycerides (mg/dL), total cholesterol (mg/dL), weight (kg), postprandial glycemia (mg/dL), and glycosylated hemoglobin (HbA 1c ). For the study period, statistically significant decreases in triglycerides and total cholesterol levels of 48 and 17 mg/dL, respectively, were observed. B. forficata tea as a complementary therapy in type 2 diabetic patients may help to reduce the levels of some lipid profile parameters. Further studies are suggested to evaluate the effect of the tea.