Biochanin A as a modulator of the inflammatory response: An updated overview and therapeutic potential.

Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.

Multi-response optimal hot pressurized liquid recovery of extractable polyphenols from leaves of maqui (Aristotelia chilensis [Mol.] Stuntz).

Multi-response optimization of hot pressurized liquid extraction (HPLE) was applied for the first time to obtain maqui (Aristotelia chilensis [Mol.] Stuntz) leaf extracts. The total polyphenol content (TPC), the antioxidant capacity (AC) as well as the total polyphenol purity of the maqui leaf extracts were accurately predicted (RSD < 8%) at the evaluated extraction scales. The optimum HPLE conditions that prioritized TPC and AC equally (OPT1) recovered ~3 times more TPC (205.14 mg GAE/g leaves) than maqui leaf extracts obtained by maceration, while the extract that prioritized purity over TPC and AC presented the highest purity (36.29%) and an EC50 ~3 times lower than currently reported values. It was found by multi-response optimization that maqui leaves and HPLE are among the best natural sources and extraction techniques, respectively, to recover protocatechuic acid, quercetin, and catechin.

Phenolic composition, antioxidant capacity and α-glucosidase inhibitory activity of raw and boiled Chilean Araucaria araucana kernels.

The Araucaria araucana kernels are a traditional food in southern Chile and Argentina. The aim of this work was to determine the composition of the phenolic-enriched extracts (PEEs) of the boiled kernels as well as their antioxidant capacity, inhibitory activity on metabolic syndrome-associated enzymes and effect on postprandial oxidative stress in a simulated gastric digestion model. The PEEs composition was assessed by HPLC-DAD-MS/MS. The main PEEs constituents were catechin and epicatechin in the unbound form, while hydroxybenzoic acids occurred mainly in the bound form. The unbound phenolics from boiled kernels showed significant correlations with DPPH, FRAP, TEAC (Pearson's r of 0.481, 0.331 and 0.417, respectively) and lipid peroxidation (r = 0.381) and were more active than the bound phenolics. The extracts were highly active against α-glucosidase (IC50: 0.33-3.15 µg/mL) and reduced lipoperoxidation. Traditional processing increases the flavan-3-ol content. Our results suggest that this traditional food has potential health promoting properties.

Brazilian fruits of Arecaceae family: An overview of some representatives with promising food, therapeutic and industrial applications.

The Arecaceae family is widely distributed and comprises about 2600 species, in which 48 of them are native to Brazil and occurs in transition biomes between the Amazon, Cerrado and Caatinga. In addition to being used as a source of food and subsistence, they are also rich in lipophilic bioactive compounds, mainly carotenoids, polyunsaturated fatty acids, tocopherols and vitamin A. Moreover, they have considerable content of phenolic compounds, fibers and minerals. Therefore, the objective of this review is to present the physical-chemical and nutritional aspects, the main bioactive compounds, the biological properties and the innovative potential of four Brazilian palm-tree fruits of the Arecaceae family. Due to the presence of bioactive compounds, these fruits have the potential to promote health and can be used to prevent chronic non-communicable diseases, such as obesity, type 2 diabetes and others. Furthermore, these raw materials and their by-products can be used in the development of new food, chemical, pharmaceutical and cosmetic products. To ensure better use of these crops, promote their commercial value, benefit family farming and contribute to the country's sustainable development, it is necessary to implement new cultivation, post-harvest and processing techniques. Investing in research to publicize their potential is equally important, mainly of the ones still little explored, such as the buritirana.

Effect of the nixtamalization process on the protein bioaccessibility of white and red sorghum flours during in vitro gastrointestinal digestion.

Protein bioaccessibility is a major concern in sorghum (Sorghum bicolor L. Moench) due to potential interactions with tannins affecting its nutritional value. Technological treatments such as boiling or alkaline cooking have been proposed to address this problem by reducing tannin-protein interactions. This research aimed to evaluate the impact of nixtamalization in the protein bioaccessibility from two sorghum varieties (red and white sorghum) during in vitro gastrointestinal digestion. Nixtamalization increased protein bioaccessibility in the non-digestible fraction (NDF) (5.26 and 26.31% for red and white sorghum, respectively). However, cooking showed a higher permeation speed of protein from red sorghum flours at the end of the intestinal incubation (9.42%). The SDS-PAGE profile of the digested fraction (DF) at 90 min of intestinal incubation indicated that, for red sorghum, cooking allows the formation of α and γ-kafirins while nixtamalization increase α-kafirin release. Principal Components Analysis (PCA) showed the association between nixtamalization and dissociation of δα kafirin complexes and increased protein content in the digestible fraction. In silico interactions indicated the highest biding energies for (+)-catechin and kafirin fractions (ß-kafirin: -7.0 kcal/mol; γ-kafirin: -5.8 kcal/mol, and δ-kafirin: -6.8 kcal/mol), suggesting a minor influence of depolymerized proanthocyanidin fractions with sorghum proteins as a result of the nixtamalization process. In conclusion, nixtamalization increased the bioaccessibility of sorghum proteins, depolymerizing condensed tannins, and breaking protein-tannin complexes. Such technological process improves the nutrimental value of sorghum, supporting its inclusion in the human diet.

Effect of the pre-treatment and the drying process on the phenolic composition of raisins produced with a seedless Brazilian grape cultivar.

The grape is an important fruit regarding economic and health benefit parameters, because of its large consumption around the world and their bioactive phenolic compounds. The drying process of BRS Morena grapes, whether pre-treated or not with olive oil for producing raisins, resulted in qualitative and quantitative changes in their phenolic composition (anthocyanins, flavonols, stilbenes, hydroxycinammic acid derivatives, flavan-3-ols and proanthocyanidins). The raisins with the pre-treatment preserved more anthocyanins and proanthocyanidins than the raisins not pre-treated. Moreover, the total dehydration time accelerated by approximately 40% in the raisins pre-treated. Therefore, the production of raisins of BRS Morena grapes pre-treated with olive oil as a natural surfactant constitutes an interesting process from both the industrial and health points of view, because of the remarkable reduction in the processing time and the preservation of high concentrations of flavonoids, which have important claims to health benefits from biological activities.

In vitro health promoting properties of antioxidant dietary fiber extracted from spent coffee (Coffee arabica L.) grounds.

Antioxidant dietary fiber extracted from spent coffee grounds (FSCG) was evaluated as a potential functional food ingredient when incorporated in a food model (biscuits), and digested in vitro under simulated human gastrointestinal conditions. FSCG added to biscuits increased its total dietary fiber, antioxidant capacity after in vitro digestion, bioaccessibility of phenolic compounds (gallic acid and catechin) and amino acids. Furthermore, advanced glycation end products (AGEs), involved in chronic diseases, decreased up to 6-folds in the biscuits containing FSCG when compared with the traditional biscuit. The digestible fraction of biscuits containing the highest amount of FSCG (5 g) displayed the higher inhibiting α-glucosidase activity, correlating with the bioaccessibility of ascorbic acid and catechin. Our study seems to indicate that anti-diabetic compounds may be released in the small intestine during FSCG digestion, where biscuits containing FSCG may be able to beneficially regulate sugar metabolism thereby helping in producing foods friendly for diabetes.

Fermented non-digestible fraction from combined nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chips modulate anti-inflammatory markers on RAW 264.7 macrophages.

Chronic non-communicable diseases (NCDs) are low-level inflammation processes affected by several factors including diet. It has been reported that mixed whole grain and legume consumption, e.g. corn and common bean, might be a beneficial combination due to its content of bioactive compounds. A considerable amount would be retained in the non-digestible fraction (NDF), reaching the colon, where microbiota produce short-chain fatty acids (SCFAs) and phenolic compounds (PC) with known anti-inflammatory effect. The aim of this study was to estimate the anti-inflammatory potential of fermented-NDF of corn-bean chips (FNDFC) in RAW 264.7 macrophages. After 24 h, FNDFC produced SCFAs (0.156-0.222 mmol/l), inhibited nitric oxide production > 80% and H2O2 > 30%, up-regulated anti-inflammatory cytokines (I-TAC, TIMP-1) > 2-fold, and produced angiostatic and protective factors against vascular/tissue damage, and amelioration of tumor necrosis factor signalling and inflammatory bowel disease. These results confirm the anti-inflammatory potential derived from healthy corn-bean chips.

Bioaccessibility and antioxidant activity of free phenolic compounds and oligosaccharides from corn (Zea mays L.) and common bean (Phaseolus vulgaris L.) chips during in vitro gastrointestinal digestion and simulated colonic fermentation.

Corn (Zea mays L.) and common beans (Phaseolus vulgaris L.) are alternative suitable ingredients for snacks, because of their content of bioactive compounds such as phenolic compounds (PC) and oligosaccharides (OS). However, there is no information about the transformation of these compounds associated with food matrix during gastrointestinal digestion. Therefore, the objective of this work was to simulate the whole digestion process (mouth to colon) to estimate bioaccessibility and small intestine permeability of free PC and OS, and the antioxidant capacity of free PC. Digested nixtamalized corn-cooked common bean chips exhibited significant different quantities of free PC and OS, and higher antioxidant activity compared to methanolic extract. The free PC showed high values of apparent permeability coefficients (0.023-0.729×10-3), related with their absorption in the small intestine. Both free PC and OS were retained in the non-digestible fraction of chips (10.24-64.4%) and were able to reach the colon. Our results suggest the digestion potential to increase chip bioactive compounds and antioxidant activity. Additional studies are required to evaluate their in vivo effects.

Chemical characterization and protective effect of the Bactris setosa Mart. fruit against oxidative/nitrosative stress.

Bactris setosa Mart. is a Brazilian tree from the palm family (Arecaceae), whose fruits are scientifically underexploited. Here, we report, for the first time, the identification and quantification of phenolic compounds and carotenoids in the pulp, seed, and peel extracts of B. setosa fruits and their in vitro biological activity. The anthocyanins cyanidin deoxyhexose hexoside and cyanidin hexoside and other phenolic compounds were detected mainly in the peel but also in the pulp extracts. All-trans-lutein was the unique carotenoid identified and quantified, and only in the peel extract. All extracts were able to scavenge reactive oxygen and nitrogen species (ROS and RNS, respectively), to modulate human neutrophils' oxidative burst and to protect Caco-2 cells against oxidative damage, the peel extract being the most efficient. This study indicates that extracts from B. setosa fruits, especially the peel extract, are a source of bioactive compounds with promising antioxidant and anti-inflammatory properties.

Spent coffee grounds, an innovative source of colonic fermentable compounds, inhibit inflammatory mediators in vitro.

Spent coffee grounds (SCG), rich in dietary fiber can be fermented by colon microbiota producing short-chain fatty acids (SCFAs) with the ability to prevent inflammation. We investigated SCG anti-inflammatory effects by evaluating its composition, phenolic compounds, and fermentability by the human gut flora, SCFAs production, nitric oxide and cytokine expression of the human gut fermented-unabsorbed-SCG (hgf-NDSCG) fraction in LPS-stimulated RAW 264.7 macrophages. SCG had higher total fiber content compared with coffee beans. Roasting level/intensity reduced total phenolic contents of SCG that influenced its colonic fermentation. Medium roasted hgf-NDSCG produced elevated SCFAs (61:22:17, acetate, propionate and butyrate) after prolonged (24h) fermentation, suppressed NO production (55%) in macrophages primarily by modulating IL-10, CCL-17, CXCL9, IL-1ß, and IL-5 cytokines. SCG exerts anti-inflammatory activity, mediated by SCFAs production from its dietary fiber, by reducing the release of inflammatory mediators, providing the basis for SCG use in the control/regulation of inflammatory disorders. The results support the use of SGC in the food industry as dietary fiber source with health benefits.

Guaraná (Paullinia cupana) seeds: Selective supercritical extraction of phenolic compounds.

Approximately 70% of the Brazilian production of guaraná (Paullinia cupana) seeds is absorbed by the beverage industries. Guaraná has several pharmacological properties: energy stimulant, antimicrobial, chemoprophylactic, antigenotoxic, antidepressive, anxiolytic, and anti-amnesic effects. Supercritical carbon dioxide extraction of bioactive compounds from guaraná seeds was carried out and optimized by an orthogonal array design (OA9(3(4))). The factors/levels studied were: modifier(s) (ethanol and/or methanol), extraction time (20, 40, and 60min), temperature (40, 50, and 60°C), and pressure (100, 200, and 300bar). The statistical design was repeated with increasing proportions of modifiers. The percentage of modifier used was proportional to the amount of polar compounds extracted. The best conditions for the supercritical extraction, based on the content of polyphenols, epicatechin/catechin quantification, yield and operating cost, proved to be: 40% ethanol:methanol during 40min, under 40°C, and 100bar. The temperature had a significant effect on the total phenolic content.

Anti-inflammatory and antinociceptive activities of Croton urucurana Baillon bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana (Euphorbiaceae) is popularly used in Brazil to treat inflammatory processes, pain, and gastric ulcers. AIM OF STUDY: To evaluate the anti-inflammatory and antinociceptive properties of the methanol extract from the bark of C. urucurana (MECu) in mice and identify its chemical constituents. MATERIALS AND METHODS: The extract was characterized by UHPLC-DAD-ESI-Q-TOF-MS/MS. Extract doses of 25, 100, and 400mg/kg were employed in the biological assays. Evaluation of anti-inflammatory activity was based on paw edema and leukocyte recruitment into the peritoneal cavity of mice, both induced by carrageenan. Abdominal writhing caused by acetic acid and duration of formalin-induced paw-licking were the models employed to evaluate antinociceptive activity. RESULTS: Ten compounds were identified in the extract: (+)-gallocatechin (1), procyanidin B3 (2), (+)-catechin (3), (-)-epicatechin (4), tembetarine (5), magnoflorine (6), taspine (7), methyl-3-oxo-12-epi-barbascoate (8), methyl-12-epi-barbascoate (9), and hardwickiic acid (10). This is the first report of compounds 2, 4, 6, 7, and 10 in C. urucurana and compound 5 in the genus Croton. In addition to inhibiting paw edema and leukocyte recruitment (particularly of polymorphonuclear cells) into the peritoneal cavity of mice, MECu reduced the number of abdominal writhings induced by acetic acid and the duration of formalin-induced paw licking. CONCLUSIONS: The methanol extract of C. urucurana bark exhibited anti-inflammatory and antinociceptive properties, corroborating its use in folk medicine. These effects may be related to the presence of diterpenes, alkaloids, and flavonoids.

Bioactive potential of Vitis labrusca L. grape juices from the Southern Region of Brazil: phenolic and elemental composition and effect on lipid peroxidation in healthy subjects.

Grapes are rich in polyphenols with biologically active properties. Although the bioactive potential of grape constituents are frequently reported, the effects of Brazilian Vitis labrusca L. grape juices ingestion have not been demonstrated in humans. This study identified the phenolic and elemental composition of red and white grape juices and the effect of organic and conventional red grape juice consumption on lipid peroxidation in healthy individuals. Concentrations of anthocyanins, flavanols and phenolic acids and the in vitro antioxidant activity were significantly higher in the organic juice. The macro-elements K, Ca, Na and Mg were the most abundant minerals in all juices. The acute consumption of red grape juices promoted significant decrease of lipid peroxides in serum and TBARS levels in plasma. It is concluded that red V. labrusca L. grape juices produced in Southern Brazil showed lipid peroxidation inhibition abilities in healthy subjects, regardless of the cultivation system.

Evaluation of anti-inflammatory activity of hydroethanolic extract of Dilodendron bipinnatum Radlk.

ETHNOPHARMACOLOGICAL RELEVANCE: Dilodendron bipinnatum Radlk. (Sapindaceae), popularly known as "mulher-pobre", is a native tree of the Pantanal of Mato Grosso, Brazil. The stem bark of Dilodendron bipinnatum is used by the population, in the forms of decoction and maceration in the treatment of inflammatory conditions. There is no information in the literature demonstrating the anti-inflammatory activity of Dilodendron bipinnatum and its respective mechanism of action. This study aimed to evaluate the anti-inflammatory activity and mechanism of action of the hydroethanolic extract of the stem bark of Dilodendron bipinnatum (HEDb) using in vivo and in vitro experimental models. MATERIALS AND METHODS: The stem bark of Dilodendron bipinnatum was macerated in 70% hydroethanolic solution (1:3, w/v) for 7 days, filtered, concentrated on a rotary evaporator and the residual solvent removed in oven at 40°C, thus obtaining HEDb. Cytotoxicity of HEDb in RAW 264.7 was assessed by the Alamar blue assay. in vivo anti-inflammatory activity of HEDb was evaluated with carrageenan and dextran-induced paw edemas and lipopolysaccharide (LPS)-induced peritonitis in mice. Effects of HEDb on the inflammatory cytokines (TNF-α, IL-1ß and IL-10) concentrations in the peritoneal fluid were evaluated using commercial ELISA kits. The in vitro anti-inflammatory activity was evaluated using RAW 264.7 cells stimulated with LPS and/or INF-γ, while a Griess method was employed to determine nitric oxide (NO) concentrations in the peritoneal lavage and in the supernatants of RAW 264.7 cells. Preliminary phytochemical analysis was carried out using classical methods and secondary metabolites detected on HEDb were analyzed and confirmed by high performance liquid chromatography (HPLC). RESULTS: HEDb showed very low cytotoxicity with IC50>200±0.38 µg/mL. HEDb effectively inhibited paw edema by carrageenan in the 2nd hour at 20 mg/kg (36%, p<0.001), and by dextran in the 1st hour at 100 mg/kg (46%, p<0.01), after induction with the phlogistic agents. Furthermore, HEDb reduced total leukocytes and neutrophils migration at all doses tested producing maximum effect at 20 mg/kg (45% and 64%, p<0.001 respectively). HEDb also attenuated increases in the concentrations of the pro-inflammatory cytokines (IL-1ß and TNF-α) and increased the level of the anti-inflammatory cytokine IL-10 in the peritonitis model. However, it had no effect on NO production in activated RAW 264.7 cells. Preliminary phytochemical analysis revealed the presence of phenolic compounds, chalcones, flavones, flavonones, flavonoids, saponins and coumarins. HPLC analyses identified some tannins, with epigallocatechin gallate being the major compound. CONCLUSIONS: Our findings provide evidence for the popular use of the stem bark of Dilodendrum bipinnatum in inflammation. Its anti-inflammatory action was due, at least in part, to the inhibition of cell migration, of the inflammatory mediators and Th1 cytokines and an increase in Th2 cytokines, without affecting NO pathway. It can be suggested that tannins account at least in part for the anti-inflammatory activity of HEDb.

Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. MATERIALS AND METHODS: The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. RESULTS: The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. CONCLUSION: Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.