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In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82–2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food.

The analysis of root extracts from Lonchocarpus montanus A.M.G. Azevedo resulted in the isolation of twenty three compounds chiefly flavonoids of which five (four flavonoids and one benzophenone) are described for the first time. The molecular structures of the new compounds (1-5) were determined through spectral analysis (UV, IR, MS and NMR) as being: 2'-hydroxy-8-(a,a-dimethylallyl)-2", 2"-dimethylpyrano-(5",6":3',4')-dibenzoylmethane (1), 2'-methoxy-8-(a, a-dimethylallyl)-2", 2"-dimethylpyrano-(5",6":3',4')-dibenzoylmethane (2), 4'-methoxy-2",2"-dimethylpyrano-(5",6":8,7)-flavone (3), 2"-(1-hydroxy-1-methylethyl)-furano-(4",5":8,7)-flavone (4) and [2'-methoxy-furano-(4",5":3',4')-phenyl]-phenylmethanone (5). Additionally, fifteen fatty acids were detected through GC-MS analysis of the corresponding methyl esters [(CH3)2CH(CH2)8COOH and CH3(CH2)nCOOH (n = 6, 12-24)]. Quantitative RP-HPLC showed that the most abundant flavonoids in the petroleum ether and dichloromethane extracts were pongamol (19%) and lanceolatine B (8.0%), respectively. In the bioautography assay, the extracts, pongamol (9), lanceolatine B (10), isolonchocarpin (14), derriobtusone A (17) and medicarpine (18) were active against Staphilococus aureus whereas 9 also against Bacillus subtilis and Cladosporium cladosporioides. Compound 1, 2",2"-dimethylpyrano-(5",6":8,7)-flavone (11) and furano-(1200,1300:7,8)- 4'-methoxy flavone (12) were active against Fusarium oxysporium whereas 11 also against Rhizopus orizae. The extracts, compounds 9, 10, 17 and (E)-7-O-methoxypongamol (23) displayed high toxicity in the brine shrimp lethality assay.A análise dos extratos das raízes de L. montanus A.M.G. Azevedo resultou no isolamento de vinte e três compostos principalmente flavonóides dos quais cinco são descritos pela primeira vez. As estruturas moleculares dos novos compostos (1-5) foram propostas através da análise dos espectros de UV, IV, EM e RMN como sendo: 2'-hidroxi-8-(a, a-dimetilalil)-2", 2"-dimetilpirano-(5", 6":3',4')-dibenzoilmetano (1), 2'-metoxi-8-(a,a-dimetilalil)-2", 2"-dimetilpirano-(5", 6":3',4')-dibenzoilmetano (2), 4'-metoxi-2", 2"-dimetilpirano-(5", 6":8,7)-flavona (3), 2"-(1-hidroxi-1-metiletil)-furano-(4", 5":8,7)-flavona (4) e [2'-metoxi-furano(4", 5":3',4')-fenil]-fenilmetanona (5). Adicionalmente quinze ácidos graxos foram detectados através da análise de CG-EM dos ésteres metílicos correspondentes [(CH3)2CH(CH2)8COOH e CH3(CH2)nCOOH (n = 6, 12-24)]. A análise quantitativa por CLAE mostrou que os flavonóides mais abundantes nos extratos éter de petróleo e diclorometânico foram pongamol (19%) e lanceolatina B (8.0%), respectivamente. Nos ensaios de bioautografia, os extratos, pongamol (9), laceolatina B (10), isolonchocarpina (14), derriobtusona A (17) e medicarpina (18) foram ativos contra Staphilococcus aureus enquanto 9, também contra Bacillus subtilis e Cladosporium cladosporióides. O composto 1, 2", 2"-dimetilpirano-(5", 6":8,7)-flavona (11) e furano-(2", 3":7,8)-4'-metoxiflavona (12) foram ativos contra Fusarium oxysporium, enquanto 11, também contra Rhizopus oryzae. Os extratos assim como os compostos 9, 10, 17 e (E)-7-O-metoxipongamol (23) apresentaram alta toxicidade no ensaio de letalidade com Artemia salina.

The light petroleum extract from the roots of Lonchocarpus muehlbergianus Hassl contained nine flavonoids, including six new ones. These are 2,4-cis-2,4,5,8-tetramethoxy-(2,3:6,7)-furanoflavan; 2,4-cis-4-hydroxy-2,5,8-trimethoxy-(2,3:6,7)-furanoflavan; 2,4-cis-2-prenyloxy-4,5,8-trimethoxy-(2,3:6,7)-fu-ranoflavan; 2,4-cis-2-prenyloxy-4-hydroxy-5,8-dimethoxy-(2,3:6,7)-furanoflavan; 2',5',6'-trimethoxy-9-(1,1-dimethylallyoxy)-[2,3:3,4]-furanochalcone; 5,6-dimethoxy-(2,3:7,8)-furanoflavone, identi-fied by analysis of their spectral data (UV, IR, ¹H and 13C NMR, 2D-NMR, NOE and MS). The natural occurrence of 2,4-dioxygenated flavan derivatives is being reported for the first time. Quantitative analysis of the petrol extract, by using reversed-phase HPLC, showed that the most abundant flavonoid in the extract is 2,4-cis-2,4,5,8- tetramethoxy-(2,3:6,7)-furanoflavan.

Our taxonomic interest in the Neoraputia stimulated an investigation of N. paraensis searching for alkaloids. Fractions were monitored by ¹H NMR and ESI-MS/MS and only those which showed features of anthranilate alkaloids and flavonoids absent in the previous investigations were examined. Stems afforded the alkaloids flindersine, skimmianine, 8-methoxyflindersine and dictamnine; leaves yielded 3',4',7,8-tetramethoxy-5,6-(2",2"-dimethylpyrano)-flavone, 3',4',5,7,8-pentamethoxyflavone, 5-hydroxy-3',4',6,7-tetramethoxyflavone, 3',4'-methylenedioxy-5,6,7-trimethoxyflavone and 5-hydroxy-3',4'-methylenedioxy-6,7-dimethoxyflavone. The alkaloids have remained undiscovered for 10 years. A number of flavonoids isolated from N. paraensis, N. magnifica, Murraya paniculata, Citrus sinensis graft (Rutaceae), Lonchocarpus montanus (Leguminosae) were evaluated for their ability to inhibit the enzymatic activity of the protein glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi. Highly oxygenated flavones and isoflavone were the most actives.

The native tree Geoffroea decorticans (chañar) grows in the arid lands of northern Chile. It has been used as a food plant since prehistoric times. Phenolic-enriched extracts (PEEs) of Chilean chañar fruits were assessed for their chemical composition, antioxidant properties and inhibition of pro-inflammatory and metabolic syndrome-associated enzymes. Phenolic profiles were determined by HPLC-DAD-MS/MS. The PEEs of G. decorticans showed a strong effect towards the enzymes COX-1/COX-2, with inhibition percentages ranging from inactive to 92.1% and inactive to 76.0% at 50 µg PEE/mL, respectively. The IC50 values of the PEEs towards lipoxygenase and phospholipase A2 inhibitory activity were between 43.6–96.8 and 98.9–156.0 μg PEE/mL, respectively. Samples inhibited α-glucosidase (IC50 0.8–7.3 μg PEE/mL) and lipase (9.9 to >100 μg PEE/mL). However, samples did not inhibit α-amylase. The HPLC-DAD-MS analysis of the PEEs allowed the tentative identification of 53 compounds, mainly flavonol glycosides and procyanidins. The procyanidin content of the Chilean G. decorticans pulp was positively correlated with the antioxidant activity and the inhibition of the enzyme α-glucosidase. These results indicate that the Chilean chañar fruit contains bioactive polyphenols with functional properties.

The native tree Geoffroea decorticans (chañar) grows in the arid lands of northern Chile. It has been used as a food plant since prehistoric times. Phenolic-enriched extracts (PEEs) of Chilean chañar fruits were assessed for their chemical composition, antioxidant properties and inhibition of pro-inflammatory and metabolic syndrome-associated enzymes. Phenolic profiles were determined by HPLC-DAD-MS/MS. The PEEs of G. decorticans showed a strong effect towards the enzymes COX-1/COX-2, with inhibition percentages ranging from inactive to 92.1% and inactive to 76.0% at 50 µg PEE/mL, respectively. The IC50 values of the PEEs towards lipoxygenase and phospholipase A2 inhibitory activity were between 43.6-96.8 and 98.9-156.0 μg PEE/mL, respectively. Samples inhibited α-glucosidase (IC50 0.8-7.3 μg PEE/mL) and lipase (9.9 to >100 μg PEE/mL). However, samples did not inhibit α-amylase. The HPLC-DAD-MS analysis of the PEEs allowed the tentative identification of 53 compounds, mainly flavonol glycosides and procyanidins. The procyanidin content of the Chilean G. decorticans pulp was positively correlated with the antioxidant activity and the inhibition of the enzyme α-glucosidase. These results indicate that the Chilean chañar fruit contains bioactive polyphenols with functional properties [ABSTRACT FROM AUTHOR]

In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82-2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food. [ABSTRACT FROM AUTHOR]

Copao (Eulychnia acida Phil., Cactaceae) is an endemic species occurring in arid areas of northern Chile. The fruits are commercialized by peasants within the Elqui and Limari valleys and are appreciated for its acidic and refreshing taste. We now report the total phenolic (TP) and total flavonoid (TF) content, antioxidant activity, phenolic composition and main phenolic distribution in pulp and epicarp of copao fruits from different harvesting places from both valleys. The ascorbic acid content was determined in fresh fruit pulp, epicarp and juice. The phenolic-enriched extract was analyzed for antioxidant effect and composition. Ferulic acid, 9,10-dihydroxy-4,7-megastigmadien-3-one hexoside, isorhamnetin and quercetin glycosides were identified by HPLC-DAD-MS/MS analysis. The main compounds were isolated and fully characterized by NMR techniques. The main phenolic in the samples was isorhamnetin-3-O-[ॅ-rhamnopyranosyl-(1→6)-β-glucopyranoside]. The HPLC pattern of the phenolic-enriched extracts of the fruits allows a differentiation of samples from the Elqui and Limari valleys. All fruit extracts and Amberlite-retained fraction from the methanolic extract were devoid of toxicity against human gastric AGS cells and human lung fibroblasts, with IC50 values >400μg/mL for AGS and 344 to >400μg/mL for fibroblasts, respectively. The compound identification, associated with the antioxidant activity and insignificant cell toxicity, adds relevant information for the possible development of this native fruit into a new crop. [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries., Methods: IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student's T test., Results: IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns., Conclusions: Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery., (© 2024. The Author(s).)

The progression of neurodegenerative diseases is reciprocally associated with impairments in peripheral immune responses. We investigated different contexts of selective neurodegeneration to identify specific alterations of peripheral immune cells and, at the same time, discover potential biomarkers associated to this pathological condition. Consequently, a model of human cerebellar degeneration and ataxia -the Purkinje Cell Degeneration (PCD) mouse- has been employed, as it allows the study of different processes of selective neuronal death in the same animal, i.e., Purkinje cells in the cerebellum and mitral cells in the olfactory bulb. Infiltrated leukocytes were studied in both brain areas and compared with those from other standardized neuroinflammatory models obtained by administering either gamma radiation or lipopolysaccharide. Moreover, both myeloid and lymphoid splenic populations were analyzed by flow cytometry, focusing on markers of functional maturity and antigen presentation. The severity and type of neural damage and inflammation affected immune cell infiltration. Leukocytes were more numerous in the cerebellum of PCD mice, being located predominantly within those cerebellar layers mostly affected by neurodegeneration, in a completely different manner than the typical models of induced neuroinflammation. Furthermore, the milder degeneration of the olfactory bulb did not foster leukocyte attraction. Concerning the splenic analysis, in PCD mice we found: (1) a decreased percentage of several myeloid cell subsets, and (2) a reduced mean fluorescence intensity in those myeloid markers related to both antigen presentation and functional maturity. In conclusion, the selective degeneration of Purkinje cells triggers a specific effect on peripheral immune cells, fostering both attraction and functional changes. This fact endorses the employment of peripheral immune cell populations as concrete biomarkers for monitoring different neuronal death processes., 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 del Pilar, Lebrón-Galán, Pérez-Martín, Pérez-Revuelta, Ávila-Zarza, Alonso, Clemente, Weruaga and Díaz.)

Oleoylethanolamide (OEA) is an endocannabinoid that has been proposed to prevent neuronal damage and neuroinflammation. In this study, we evaluated the effects of OEA on the disruption of both cerebellar structure and physiology and on the behavior of Purkinje cell degeneration (PCD) mutant mice. These mice exhibit cerebellar degeneration, displaying microtubule alterations that trigger the selective loss of Purkinje cells and consequent behavioral impairments. The effects of different doses (1, 5, and 10 mg/kg, i.p.) and administration schedules (chronic and acute) of OEA were assessed at the behavioral, histological, cellular, and molecular levels to determine the most effective OEA treatment regimen. Our in vivo results demonstrated that OEA treatment prior to the onset of the preneurodegenerative phase prevented morphological alterations in Purkinje neurons (the somata and dendritic arbors) and decreased Purkinje cell death. This effect followed an inverted U-shaped time-response curve, with acute administration on postnatal day 12 (10 mg/kg, i.p.) being the most effective treatment regimen tested. Indeed, PCD mice that received this specific OEA treatment regimen showed improvements in motor, cognitive and social functions, which were impaired in these mice. Moreover, these in vivo neuroprotective effects of OEA were mediated by the PPARα receptor, as pretreatment with the PPARα antagonist GW6471 (2.5 mg/kg, i.p.) abolished them. Finally, our in vitro results suggested that the molecular effect of OEA was related to microtubule stability and structure since OEA administration normalized some alterations in microtubule features in PCD-like cells. These findings provide strong evidence supporting the use of OEA as a pharmacological agent to limit severe cerebellar neurodegenerative processes., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)

Cell therapy has been proven to be a promising treatment for fighting neurodegenerative diseases. As neuronal replacement presents undeniable complications, the neuroprotection of live neurons arises as the most suitable therapeutic approach. Accordingly, the earlier the diagnosis and treatment, the better the prognosis. However, these diseases are commonly diagnosed when symptoms have already progressed towards an irreversible degenerative stage. This problem is especially dramatic when neurodegeneration is aggressive and rapidly progresses. One of the most interesting approaches for neuroprotection is the fusion between healthy bone marrow-derived cells and neurons, as the former can provide the latter with regular/protective genes without harming brain parenchyma. So far, this phenomenon has only been identified in Purkinje cells, whose death is the cause of different diseases like cerebellar ataxias. Here we have employed a model of aggressive cerebellar neurodegeneration, the Purkinje Cell Degeneration mouse, to optimize a cell therapy based on bone marrow-derived cell and cell fusion. Our findings show that the substitution of bone marrow in diseased animals by healthy bone marrow, even prior to the onset of neurodegeneration, is not fast enough to stop neuronal loss in time. Conversely, avoiding bone marrow replacement and ensuring a regular supply of healthy cells through continuous, daily transplants, the neurodegenerative milieu of PCD is enough to attract those transplanted elements. Furthermore, in the most affected cerebellar regions, more than a half of surviving neurons undergo a process of cell fusion. Therefore, this method deserves consideration as a means to impede neuronal cell death., (© 2019 John Wiley & Sons, Ltd.)

Ankle arthroscopy provides a minimally invasive approach to the diagnosis and treatment of certain ankle disorders. Neurological complications resulting from ankle arthroscopy have been well documented in orthopaedic and podiatric literature. Owing to the superficial location of the ankle joint and the abundance of overlying periarticular neurovascular structures, complications reported in ankle arthroscopy are greater than those reported for other joints. In particular, all reported neurovascular injuries following ankle arthroscopy have been the direct result of distractor pin or portal placement. The standard posteromedial portal has recognized risks because of the proximity of the posterior neurovascular structures. There can be considerable variability in the course of these portals and their proximity to the neurovascular structures. We found one report of intra-articular damage to the posterior tibial nerve as a result of ankle arthroscopy in the English-language literature and we report this paper as a second case described in the literature.