Mass Spectrometric Identification of Licania rigida Benth Leaf Extracts and Evaluation of Their Therapeutic Effects on Lipopolysaccharide-Induced Inflammatory Response.

Licania rigida Benth has been evaluated as an alternative drug to treat diseases associated with inflammatory processes. This study evaluated the anti-inflammatory effects of aqueous and hydroalcoholic leaf extracts of L. rigida with inflammation induced by lipopolysaccharides in in vitro and in vivo inflammation models. The phytochemical profile of the extracts, analyzed by ultra-fast liquid chromatography coupled with tandem mass spectrometry, revealed the presence of gallic and ellagic acids in both extracts, whereas isovitexin, ferulate, bulky amino acids (e.g., phenylalanine), pheophorbide, lactic acid, and pyridoxine were detected in the hydroalcoholic extract. The extracts displayed the ability to modulate in vitro and in vivo inflammatory responses, reducing approximately 50% of pro-inflammatory cytokine secretion (TNF-α, IL-1ß, and IL-6), and inhibiting both NO production and leukocyte migration by approximately 30 and 40% at 100 and 500 µg/mL, respectively. Overall, the results highlight and identify, for the first time, the ability of L. rigida leaf extract to modulate inflammatory processes. These data suggest that the leaf extracts of this plant have potential in the development of herbal formulations for the treatment of inflammation.

HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn characterization of polyphenols in the leaves of Neocarya macrophylla (Sabine) Prance ex F. White and cytotoxicity to gastric carcinoma cells.

Among several extracts from species from Guinea-Bissauan flora, the hydroethanol extract obtained from the leaves of gingerbread plum (Neocarya macrophylla (Sabine) Prance ex F. White.) revealed to be one of the most cytotoxic towards human gastric AGS carcinoma cells. Considering the increasing use of N. macrophylla in the food industry and the abundant biomass of agricultural wastes being generated, the identification of phenolic bioactives has been attained by HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn. Twenty-seven phenolic constituents were identified for the first time in the monotypic genus Neosartorya, 5-O-caffeoylquinic acid being detected as the major constituent (4.90 ± 0.20 mg g-1 dry extract). While 15 flavan-3-ols derivatives were determined, the extract is predominantly characterized by the occurrence of quercetin, kaempferol, apigenin and chrysoeriol glycosides. Typical apoptotic changes in gastric adenocarcinoma AGS cells upon exposure to N. macrophylla leaf extract were observed. The apoptotic cell death is mediated by the activation of the mitochondrial pathway, as loss of mitochondrial membrane potential was detected, as well as increased caspase-9 and -3 activities. The industrial relevance of this plant material, along with the data presented here on the potential anticancer effects of N. macrophylla and the efficient extraction of phenolic bioactives using water and ethanol (GRAS substance), calls for further research on the leaves as a potential functional food and/or ingredient.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Licania rigida leaf extract: Protective effect on oxidative stress, associated with cytotoxic, mutagenic and preclinical aspects.

Brazilian plant biodiversity is a rich alternative source of bioactive compounds since plant-derived extracts and/or their secondary metabolites exhibit potential properties to treat several diseases. In this context, Licania rigida Benth (Chrysobalanaceae Family), a large evergreen tree distributed in Brazilian semi-arid regions, deserves attention for its widespread use in popular medicine, although its biological properties are still poorly studied. The aim of this study was to examine (1) acute and sub-chronic oral toxicity at 2000 mg/kg dose; (2) in vitro cytotoxicity at 0.1; 1; 10; 100 or 1000 µg/ml; (3) in vivo mutagenicity at 5, 10 or 20 mg/ml, and (4) potential antioxidant protective effect of L. rigida aqueous leaf extract of (AELr). No marked apparent toxic and genotoxic effects were observed using in vitro and in vivo assays after in vitro treatment of Chinese hamster ovary cell line (CHO-K1) with AELr or in vivo exposure of Wistar rats and Drosophila melanogaster to different extract concentrations. Concerning the antioxidant effect, the extract exhibited a protective effect by decreasing lipid peroxidation as determined by malondialdehyde levels. No significant changes were observed for glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Data demonstrate the beneficial potential of AELr to be employed for therapeutic purposes. However, further studies are required to validate the pharmacological application of this plant extract to develop as a phytotherapeutic formulation.

Phenolic Composition, Toxicity Potential, and Antimicrobial Activity of Licania rigida Benth (Chrysobalanaceae) Leaf Extracts.

This study was conducted to evaluate the phenolic composition, toxicity, and antimicrobial activity of Licania rigida Benth, an underexploited wild Licania species. L. rigida leaf fractions (ethyl alcohol and ethyl acetate) were analyzed for their phenolic compound and flavonoid total, and high-performance liquid chromatography/ultraviolet spectra chromatographic profiles. Regarding the extract biological effects, toxicity was measured by acute oral toxicity in Wistar rats, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method, and apoptosis indicators with DAPI in VERO cells, whereas well-agar diffusion and broth microdilution assays were applied to evaluate the antimicrobial ability. The phytochemical analysis resulted in significant amounts of phenolic compounds and total flavonoids in the extract and fraction, with flavonol-3-O-glycosylates as the main constituent. Regarding the extract and fraction antimicrobial activity, the results showed a significant effect against gram-positive bacteria and fungi, among which Staphylococcus epidermidis and Candida krusei displayed more susceptibility. No toxicity effects were observed in animals. Concerning the cytotoxicity assay, only the highest dose tested exhibited a minimal toxic effect on the analyzed cell lines. These results are relevant considering the increase of multiresistant microorganisms to conventional treatments applied. Therefore, investigating the pharmacological properties of the genus Licania is promising in the search for new sources of antimicrobial compounds.

Seasonal and pluviometric effects on the phenolic compound composition and antioxidant potential of Licania macrophylla Benth (Chrysobalanaceae), a medicinal plant from the Amazon rainforest

Abstract Licania macrophylla is a medicinal plant from the Amazon. It is mainly used in the form of a decoction and has been reported to contain several phenolic compounds. However, the effect of seasonality on the phenolic composition and antioxidant potential of this plant has not been well studied, especially in the Amazon region, an area affected by the rainy and less-rainy seasons. Therefore, we evaluated the seasonality of these aromatic compounds and the antioxidant potential of the extracts from L. macrophylla stem bark. We also determined the correlation between the extraction methods used and precipitation levels during each period for 1 year. The total flavonoid and phenolic content, DPPH-scavenging potential, percentage of phosphomolybdenum complex reduction, and iron-reducing power were quantified. The levels of phenolic compounds were the highest in June, whereas those of flavonoids were the highest in September and October; however, these differences were not significant. The extracts from April, November, and June showed the best results for DPPH scavenging, phosphomolybdenum reduction, and iron reduction power, respectively. Significant differences in the phenolic content and DPPH-scavenging activity were observed between the more- and less-rainy seasons. The total phenolic content was positively correlated with FRAP and DPPH, whereas flavonoid levels were negatively correlated.

A new prenylated coumestan from the roots of Campylotropis hirtella.

A new prenylated coumestan, campylohirtin A (1), along with fifteen phenolic known compounds (2‒16) and four other known compounds (17‒20), was obtained from the 95% ethanol extract of roots of Campylotropis hirtella. Their structures were elucidated based on extensive spectroscopic analysis (1 D and 2 D-NMR, MS, UV and IR). In vitro antimalarial activities of compounds 1-3, 5-14 and 16 were evaluated by ß-hematin formation inhibition assay. Compared with the positive control chloroquine diphosphate, compounds 8, 11 and 16 exhibited strong antimalarial activity with the IC50 values of 69.9, 33.2 and 75.4 µM, respectively. Compounds 1-3, 5-7 and 12 showed moderate antimalarial activities with IC50 values ranging from 134.6 µM to 578.6 µM.[Formula: see text].

Chrysobalanus icaco: A review of its phytochemistry and pharmacology.

The genus Chrysobalanus is one of the classes of medicinal plants used in the treatment and management of several diseases. This study is aimed at providing up-to-date information on the phytochemical composition and pharmacological uses of Chrysobalanus icaco. Current literature on the Chrysobalanus species was obtained by searching electronic databases such as PubMed, Google Scholar and Web of Science. Of the species in this genus, four have been reported in the literature, but only one (C. icaco) has been extensively studied. C. icaco is rich in several minerals, including potassium, magnesium, calcium and sodium. The plant also contains a host of phytochemicals, such as flavonoids, diterpenes and triterpenes, which have been shown to have pharmacological activity. It can be concluded that C. icaco is a good source of phytochemicals that contribute to its therapeutic uses. However, bioassay-guided isolation of its bioactive compounds is necessary for promoting the development of drugs from this medicinal plant.

O uso de plantas medicinais para o tratamento do Diabetes Mellitus Tipo II ­ Revisão de literatura / The use of medicinal plants for treatment of type II Diabetes Mellitus ­ Literature review

O Diabetes mellitus tipo II (DM II) é uma síndrome metabólica com uma das maiores prevalências mundiais. A Organização Mundial da Saúde (OMS, 2019) estima que até 2045 teremos aproximadamente 629 milhões de diabéticos adultos no planeta. Além disso, a Federação Internacional de Diabetes (IDF, 2019) estima que o gasto anual global com tratamentos para diabetes adultos em 2017 foi de U$850 bilhões de dólares. Com números tão expressivos buscam-se tratamentos naturais efetivo, eficaz e baixo custo para tal distúrbio. Inúmeras plantas já estão sendo utilizadas como coadjuvante no tratamento do DM II por possuírem ação antidiabética. Porém, há uma incidência na procura de ampliar o acervo de plantas medicinais com compostos hipoglicemiantes. Portanto, este presente trabalho destaca plantas como Croton cajucara Benth, Licania rígida Benth e Morus nigra L. e seus compostos hipoglicemiantes como alternativa em potencial para tratamento desta síndrome metabólica. Os resultados demonstraram a importância das mesmas para a terapêutica do DM II com estudos que comprovem a ação, garantia da eficácia e segurança em sua utilização.

Diabetes mellitus type II (DM II) is a metabolic syndrome with one of the highest prevalence worldwide. The World Health Organization (WHO, 2019) estimates that by 2045 we will have approximately 629 milion adult diabetics on the planet. In addition, the International Diabetes Federation (IDF, 2019) estimates that the annual global expenditure on treatments for adult diabetes in 2017 was $ 850 bilion dollars. With such expressive numbers, effective, efficient and lowcost natural treatments are sought for such disorder. Numerous plants are already being used as an adjuvant in the treatment of DM II because they have an anti-diabetc action. However, there is an incidence in the search to expand the collection of medicinal plants with hypoglicemic compounds. Therefore, this present work highligths plants such as Croton cajucara Benth, Licania rigida Benth and Morus nigra L., and their hypoglycemic compounds as a potential alternative for the treatment of this metabolic syndrome. The results demonstrated the importance of the same for the treatment of DM II with studies that prove the action, guarantee of the efficacy and safety in its use.

Effect of an aqueous extract of Chrysobalanus icaco on the adiposity of Wistar rats fed a high-fat diet.

INTRODUCTION: Objective: the purpose of this study was to investigate the effects of Chrysobalanus icaco on adiposity and its mechanism of action in the gene and protein expression of acetyl-CoA carboxylase (ACC), a key enzyme in lipogenesis. Method: Wistar rats were divided into a regular or control group (CG) and a high-fat diet (HFD) group. HFD was treated with saline or aqueous extract of Chrysobalanus icaco (AECI) for four weeks. Body weight and food intake were assessed. Subcutaneous, retroperitoneal and periepididymal adipose tissue samples were collected and weighed. Adipocytes from periepididymal tissue were isolated and analyzed. The gene and protein expression of ACC in subcutaneous tissue was determined. Results: AECI showed no effect on intake or body weight. However, the weight of the fat pads and the gene and protein expression of ACC were lower, and glucose tolerance was improved. Conclusion: the aqueous extract of Chrysobalanus icaco proved beneficial for the treatment of obesity, preventing fat storage and improving glycemic homeostasis.

INTRODUCCIÓN: Objetivo: el objetivo de este estudio fue investigar los efectos del extracto acuoso de Chrysobalanus icaco (AECI) en la adiposidad y su mecanismo de acción en la expresión génica y proteica de la acetil-CoA-carboxilasa (ACC), una enzima clave para la lipogénesis. Métodos: se usaron ratones macho Wistar que se asignaron a una dieta estándar de control (CG) o a una rica en grasa (HFD). La HFD se trató con solución salina o con extracto acuoso de Chrysobalanus icaco (AECI) durante cuatro semanas. Se evaluaron el peso corporal y el consumo alimentario. Se aislaron y analizaron muestras de tejido adiposo subcutáneo, retroperitoneal y periepididímico. Se determinó la expresión génica y proteica de ACC en el tejido subcutáneo. Resultados: el AECI no mostró ningún efecto sobre la ingesta de alimento y tampoco sobre el peso corporal. Sin embargo, el tratamiento con AECI redujo el peso de los tejidos adiposos y la expresión génica y proteica de ACC, y mejoró también la tolerancia a la glucosa. Conclusión: Chrysobalanus icaco (AECI) resultó ser beneficioso para el tratamiento de la obesidad, previniendo el almacenamiento de grasa y mejorando la homeostasis glucémica.

Acute and repeated dose 28-day oral toxicity of Chrysobalanusicaco L. leaf aqueous extract.

Chrysobalanus icaco L. is a native plant of Brazil used as a food source and traditionally for the treatment of various diseases. The aim of study was performed the phytochemical analysis by UPLC-DAD-ESI-QTOF-MS/MS, and evaluated acute and repeated dose oral toxicities of the C. icaco L. leaf aqueous extract (AECi). The acute toxicity study was performed using a dose of AECi 2000 mg/kg, while the repeated dose toxicity study, the AECi was administered daily at doses of 100, 200 and 400 mg/kg, for 28 days. Behavior and mortality of animals were observed during the test period and body weight, as well water and eating consumption. Hematological, biochemical parameters and histopathological examinations were carried out. Phytochemical analysis of the AECi revealed the presence of flavonoids and tannins. Oral single dose of 2000 mg/kg of AECi resulted in no mortalities or abnormal clinical signs. Studies of repeated dose toxicity promoted a reduction in the body weight of treated animals and an increase of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in both, males and females. Histopathological analyzes showed alterations in the livers of animals treated with AECi. Thus, this study recommends the population take care when using this species, especially during prolonged periods.

Chemical composition, nutritional properties, and antioxidant activity of Licania tomentosa (Benth.) fruit.

Licania tomentosa is a Brazilian plant species that produces edible fruits, yet there is little information available concerning their nutritional and/or bioactive composition. This study aimed to evaluate the nutritional and polyphenol composition of L. tomentosa fruits (pulp and seeds) and measure antioxidant activity in ethanolic extracts.The pulp and seeds were excellent sources of fiber (25.62%-41.70%) as well as minerals and vitamins. L. tomentosa contained no lectins or protease inhibitors (chymotrysin and trypsin) and 12 polyphenol compounds were identified in the seed extracts with a predominance of flavonoids. The seeds also presented antioxidant activities using the DPPH (SC5010.30-15.87 µg/mL), TBARS (IC50 18.46-20.84 µg/mL), and FRAP (RC50 0.203-0.309 µg/mL) assays. Due to its nutrient and antioxidant content, L. tomentosa may be used for food applications.

Genetic fingerprinting of the Brazilian medicinal plant Chrysobalanus icaco L. (Chrysobalanaceae)

Chrysobalanus icaco L. (Chrysobalanaceae) is a medicinal species widely used in Brazil mainly to treat diabetes. Despite the medicinal importance of C. icaco, genetic information of this genus remains limited. Thus, our aim was to evaluate the influence of the genetic basis of C. icaco by determining its chemotypes. 25 C. icaco genotypes were collected from 15 sites in Belém, Marajó and Northeastern mesoregions of Pará state, Brazil. The genotypes were selected by evaluating the plant morphological characteristics such as fruit color and plant habit. The DNA fingerprinting profile was performed using PCR based RAPD technique and appropriate statistical methods were used. RAPD markers were used for evaluation of genetic diversity and molecular characterization of the C. icaco, using a total of 18 decamer primers. These primers produced 85 amplification products, with an average of 4.7 bands per primer and 99.2% polymorphism. The genotypes are genetically distinct, forming variable clusters in number and constitution by different methods. By the morphological characteristics considered, there is a tendency of clustering based on the color of the ripe fruit. We found the secondary metabolite content depends not on environmental condition, but rather on C. icaco genome. Therefore, it may have implications for ethnopharmacological use of the chemotypes.

Caracterización química y actividad biológica de las hojas y semillas de Chrysobalanus icaco L. (Icaco) / Chemical characterization and biological activity of leaves and seeds of Chrysobalanus icaco L. (icaco)

Introducción: Chrysobalanus icaco L. (Chrysobalanaceae) es un arbusto utilizado en la fitoterapia tradicional latinoamericana, pero en la provincia de Chiriquí se ha registrado el uso de su fruto para hacer conservas, no de forma medicinal. Objetivo: Caracterizar los metabolitos secundarios presentes en las hojas y semillas de Chrysobalanus icaco y evaluar su actividad biológica in vitro. Métodos: Los metabolitos secundarios presentes en los extractos de las hojas, semilla inmadura y madura de Chrysobalanus icaco, se detectaron a través de tamizaje fitoquímico y purificación por técnicas cromatográficas. Posteriormente se evaluó el contenido de polifenoles totales y la actividad antioxidante total de la infusión de las hojas, semillas y pulpa de esta especie, así como la actividad antibacteriana in vitro. Resultados: En las hojas se identificaron por tamizaje fitoquímico, flavonoides, glucósidos cardiotónicos, triterpenos y esteroides. Para la semilla inmadura se encontró presencia mayoritaria de mezclas de azucares, mientras que para la semilla madura se detectaron ácidos grasos en el endocarpio (almendra). Los datos de polifenoles totales en extractos de Icaco mostraron alto contenido de estos metabolitos en la infusión de hojas secas, y la inhibición del radical DPPH fue mayor también para las hojas secas de icaco, seguido de la infusión de semilla inmadura. Por otro lado, la infusión de hojas secas y el licuado de la pulpa fueron los que mostraron una mayor inhibición contra la cepa de Staphylococcus spp. en el ensayo de actividad antibacteriana. Conclusión: Las hojas secas de Chrysobalanus icaco mostraron alto contenido de polifenoles, asociado a su potencial actividad antioxidante y antibacteriana. Además, se aportaron nuevos datos de composición química de la semilla, se observó que los azúcares detectados inicialmente en la semilla inmadura se pierden considerablemente con la maduración del fruto.

Introduction: Chrysobalanus icaco L. (Chrysobalanaceae) is a shrub used in Latin American traditional phytotherapy, but in the province of Chiriquí its fruit has been reported to be used in food preserves, not for medicinal purposes. Objective: Characterize the secondary metabolites present in Chrysobalanus icaco leaves and seeds and evaluate their in vitro biological activity. Methods: The secondary metabolites present in extracts from leaves and immature and mature seeds of icaco were detected by phytochemical screening and purification with chromatographic techniques. Evaluation was then conducted of total polyphenolic content and total antioxidant activity of the leaf, seed and pulp infusion as well as its antibacterial activity in vitro. Results: Phytochemical screening of the leaves found flavonoids, cardiotonic glycosides, triterpenes and steroids. Sugar mixtures were the most abundant components in immature seeds, whereas fatty acids were found in the endocarp (almond) of mature seeds. Total polyphenolic data about icaco extracts showed high contents of these metabolites in the dry leaf infusion. DPPH radical inhibition was also greater for icaco dry leaves, followed by immature leaf infusion. The dry leaf infusion and the pulp shake displayed the greatest inhibition against the Staphylococcus spp. strain in the antibacterial activity test. Conclusion: Icaco dry leaves exhibited a high polyphenolic content, associated to their antioxidant and antibacterial activity. Fresh data were also contributed about the chemical composition of the seed. It was observed that the sugars initially detected in immature seeds are considerably lost as the fruit ripens.

Proteomic characterization of medicinal plants used in the treatment of diabetes.

Several plants have been studied for their medicinal properties, especially concerning the management of chronic diseases, such as diabetes, aiming at a more accessible form of treatment. In this context, the aim of this study was to characterize plant proteins used in folk medicine as hypoglycemic agents for the treatment of diabetes, namely "abajerú" (Chrysobalanus icaco) and "cow's paw" (Bauhinia forficata and Bauhinia variegata). The species were differentiated by proteome characterization. Proteins were in-solution digested using trypsin by the filter-assisted sample preparation (FASP) method. Peptides were then analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for protein characterization. In total, 131 proteins were identified. The main biological functions of these proteins were cellular respiration, transport, metabolism and photosynthesis. Insulin-like proteins were not detected, but proteins involved in controlling glucose levels were. The results are of value in the proteomic characterization of phytotherapeutic plants, and may serve as baseline for the assessed species in Brazil, where a lack of knowledge in this regard is observed.

Mass Spectral Similarity Networking and Gas-Phase Fragmentation Reactions in the Structural Analysis of Flavonoid Glycoconjugates.

Flavonoids represent an important class of natural products with a central role in plant physiology and human health. Their accurate annotation using untargeted mass spectrometry analysis still relies on differentiating similar chemical scaffolds through spectral matching to reference library spectra. In this work, we combined molecular network analysis with rules for fragment reactions and chemotaxonomy to enhance the annotation of similar flavonoid glyconjugates. Molecular network topology progressively propagated the flavonoid chemical functionalization according to collision-induced dissociation (CID) reactions, as the following chemical attributes: aglycone nature, saccharide type and number, and presence of methoxy substituents. This structure-based distribution across the spectral networks revealed the chemical composition of flavonoids across intra- and interspecies and guided the putatively assignment of 64 isomers and isobars in the Chrysobalanaceae plant species, most of which are not accurately annotated by automated untargeted MS2 matching. These proof of concept results demonstrate how molecular networking progressively grouped structurally related molecules according to their product ion scans, abundances, and ratios. The approach can be extrapolated to other classes of metabolites sharing similar structures and diagnostic fragments from tandem mass spectrometry.

Anti-inflammatory activity of herb products from Licania rigida Benth.

PURPOSE: The objective of the present study was to evaluate the systemic anti-inflammatory activity of the hydroalcoholic extract of the leaves of Licania rigida Benth (EHFLR) on models of systemic inflammation in mice. METHODS: The quantitative chemical profiles of phenolic acids and flavonoids were performed by High-Performance Liquid Chromatography (HPLC). Systemic anti-inflammatory activity was determined from carrageenan and dextran-induced paw edema models and the animals were orally treated (p.o.) with EHFLR at doses of 25, 50, 100 mg/kg, indomethacin (10 mg/kg) for carrageenan-induced paw edema and promethazine (6 mg/kg) for dextran-induced paw edema. The possible mechanisms involved in the anti-inflammatory action of the extract were evaluated by the paw edema models induced by histamine and arachidonic acid, and by the model of carrageenan-induced peritonitis, where vascular permeability and leukocyte migration to the peritoneal cavity were evaluated. RESULTS: The results of the HPLC identified the presence of phenolic acids and flavonoids, with chlorogenic acid (1.16%) and Caempferol (0.81%) as the main constituents. From the results, it was concluded that the extract has an LD50 ≥5000 mg/kg when administered orally in mice as this dose did not trigger deaths in any of the observed groups. EHFLR (25 mg/kg) showed a significant antiderematogenic effect on histamine and arachidonic acid-induced paw edema at the third hour of the tests, with a percentage of inhibition of 46.64% and 18.33%, respectively. The extract (25 mg/kg, p.o.) also significantly reduced vascular permeability and leukocyte migration in the peritoneal cavity. CONCLUSIONS: It is concluded that EHFLR exerts a systemic anti-inflammatory action, which seems to depend, at least in part, on the inhibition of arachidonic acid metabolism and the action of vasoactive amines. In addition, the extract reduced the leukocyte migration in the peritoneal cavity, indicating that its action may be linked to the inhibition of pro-inflammatory cytokines.

The new plant Parinari kerstingii Engl.: Toxicity studies and anti-inflammatory properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Parinari kerstingii Engl. extract is traditionally used for the treatment of inflammation, bronchopneumonia, feverish pains, and breast cancer. However, there have not been any scientific reports regarding the medicinal properties of this plant, and no experiments have been done to ascertain the safety of the extract. AIM OF THE STUDY: The objective of this work was to evaluate the toxicity of Parinari kerstingii Engl. extracts as an herbal remedy and to investigate its anti-inflammatory potential in vivo. MATERIALS AND METHODS: Sprague-Dawley albino male rats were used in these experiments. 100, 300 and 600 mg/kg of body weight doses of Parinari kerstingii Engl. water extract (PKWE) were used for a 14 day toxicity study. For the anti-inflammatory studies, the carrageenan-induced paw edema model was used to investigate the effect of four fractions of Parinari kerstingii Engl. ethanol extract [petroleum ether (fraction A), ethyl acetate (fraction B), n -butanol (fraction C) and water (fraction D)] on the paw size of rats and to investigate the inhibitory effects of Parinari kerstingii Engl. water (PKWE) and Parinari kerstingii Engl. ethanol extract (PKEE). RESULTS: The administration of 100 mg/kg and 300 mg/kg of body weight doses of Parinari kerstingii Engl. water extract showed no sign of toxicity. However, the 600 mg/kg of body weight dose showed a very significant increase in creatinine concentration. All the fractions of Parinari kerstingii Engl. extract demonstrated anti-inflammatory effects, as shown by a significant reduction in carrageenan-induced paw edema and by a significant decrease in the production of IL-1, TNF-α, COX-2, NF-кB, and PGE2. Moreover, fraction A and B showed enhanced in vivo anti-inflammatory effects compared to aspirin. Furthermore, PKEE was demonstrated to be more effective than PKWE. CONCLUSION: We present the first report on the plant Parinari kerstingii Engl. Based on our findings, PKWE at a dose of up to 300 mg/kg of body weight for 14 days is considered safe, and our anti-inflammatory results support its traditional use. Overall, Parinari kerstingii Engl. has been demonstrated to be a potential drug candidate. Thus, further experiments, such as isolation/structural elucidation of the phytochemicals and biological screening of this plant, need to be done.

Cocoplum (Chrysobalanus icaco L.) decreases doxorubicin-induced DNA damage and downregulates Gadd45a, Il-1ß, and Tnf-α in vivo.

DNA damage and inflammation are promising targets in disease prevention studies. Since these pathways have shown to be modulated by dietary components, investigating the molecular effects of food becomes relevant. This study aimed at investigating the protective effects of cocoplum (Chrysobalanus icaco L.) against doxorubicin (DXR)-induced damage. Rats were treated with cocoplum (100, 200 or 400mg/kg/day) for 14days, associated or not with DXR (15mg/kg b.w.). Tissue-targeted comet assay and the oxidative stress parameters oxidized/reduced glutathione and catalase were investigated in liver, kidney, and heart. The expressions of DNA damage/repair (Gadd45a, Parp1, Xrcc2) and proinflammatory genes (Il-1ß, Il-6, Nf-κb, Tnf-α) were performed by real-time quantitative PCR. Cocoplum decreased DNA damage and the expressions of Gadd45a, Il-1ß, and Tnf-α induced by DXR. These findings demonstrate that cocoplum fruits possess antigenotoxic and anti-inflammatory effects against DXR-induced damage and encourage other in vivo/clinical studies with this fruit.