Biotechnological, Nutritional, and Therapeutic Applications of Quinoa (Chenopodium quinoa Willd.) and Its By-Products: A Review of the Past Five-Year Findings.

This study aimed to provide an updated critical review of the nutritional, therapeutic, biotechnological, and environmental aspects involved in the exploitation of Chenopodium quinoa Willd and its biowastes. Special attention was devoted to investigations of the therapeutic and nutritional properties of different parts and varieties of quinoa as well as of the use of the biowaste resulting from the processing of grain. Studies published from 2018 onward were prioritized. Extracts and fractions obtained from several Chenopodium quinoa matrices showed antioxidant, antidiabetic, immunoregulatory, neuroprotective, and antimicrobial effects in in vitro and in vivo models and some clinical studies. The activities were attributed to the presence of phytochemicals such as polyphenols, saponins, peptides, polysaccharides, and dietary fibers. Quinoa wastes are abundant and low-cost sources of bioactive molecules for the development of new drugs, natural antioxidants, preservatives, dyes, emulsifiers, and carriers for food and cosmetics applications. Among the demands to be fulfilled in the coming years are the following: (1) isolation of new bioactive phytochemicals from quinoa varieties that are still underexploited; (2) optimization of green approaches to the sustainable recovery of compounds of industrial interest from quinoa by-products; and (3) well-conducted clinical trials to attest safety and efficacy of extracts and compounds.

Short-term effects of sodium arsenite (AsIII) and sodium arsenate (AsV) on carbohydrate metabolism in the perfused rat liver.

The actions of arsenite and arsenate on carbohydrate metabolism in the once-through perfused rat liver were investigated. The compound inhibited lactate gluconeogenesis with an IC50 of 25 µM. It also increased glycolysis and fructolysis at concentrations between 10 and 100 µM. This effect was paralleled by strong inhibition of pyruvate carboxylation (IC50 = 4.25 µM) and by a relatively moderate diminution in the ATP levels. The inhibitory action of arsenate on pyruvate carboxylation and lactate gluconeogenesis was 103 times less effective than that of arsenite. For realistic doses and concentrations («1 mM), impairment of metabolism by arsenate can be expected to occur solely after its reduction to arsenite. Arsenite, on the other hand, can be regarded as a strong short-term modifier of lactate gluconeogenesis and other pathways. The main cause of the former is inhibition of pyruvate carboxylation, a hitherto unknown effect of arsenic compounds.

Characterization and bioactivities of coffee husks extract encapsulated with polyvinylpyrrolidone.

Coffee processing generates large amounts of residues of which a portion still has bioactive properties due to their richness in phenolic compounds. This study aimed to obtain a coffee husks extract (CHE) and to encapsulate it (ECHE) with polyvinylpyrrolidone using a one-step procedure of solid dispersion. The extraction and encapsulation yields were 9.1% and 92%, respectively. Thermal analyses revealed that the encapsulation increased the thermal stability of CHE and dynamic light scattering analyses showed a bimodal distribution of size with 81% of the ECHE particles measuring approximately 711 nm. Trigonelline and caffeine were the main alkaloids and quercetin the main phenolic compound in CHE, and the encapsulation tripled quercetin extraction. The total phenolics content and the antioxidant activity of ECHE, assayed with three different procedures, were higher than those of CHE. The antioxidant activity and the bioaccessibility of the phenolic compounds of ECHE were also higher than those of CHE following simulated gastrointestinal digestion (SGID). Both CHE and ECHE were not toxic against Alliumcepa cells and showed similar capacities for inhibiting the pancreatic α-amylase in vitro. After SGID, however, ECHE became a 1.9-times stronger inhibitor of the α-amylase activity in vitro (IC50 = 8.5 mg/mL) when compared to CHE. Kinetic analysis revealed a non-competitive mechanism of inhibition and in silico docking simulation suggests that quercetin could be contributing significantly to the inhibitory action of both ECHE and CHE. In addition, ECHE (400 mg/kg) was able to delay by 50% the increases of blood glucose in vivo after oral administration of starch to rats. This finding shows that ECHE may be a candidate ingredient in dietary supplements used as an adjuvant for the treatment of diabetes.

Comparative study of the antioxidant and anti-inflammatory effects of the natural coumarins 1,2-benzopyrone, umbelliferone and esculetin: in silico, in vitro and in vivo analyses.

The aim of this work was to compare the anti-inflammatory and antioxidant effects of three natural coumarins: 1,2-benzopyrone, umbelliferone and esculetin. The antioxidant capacity of coumarins was evaluated using both chemical and biological in vitro assays. Chemical assays included DPPH and ABTS∙+ radical scavenging as well as ferric ion reducing ability power (FRAP) assay. Inhibition of mitochondrial ROS generation and lipid peroxidation in brain homogenates were used as biological in vitro assays. The experimental method of carrageenan-induced pleurisy in rats was used for the in vivo investigation of the anti-inflammatory activity. In silico molecular docking analysis was undertaken to predict the affinity of COX-2 to the coumarins. Considering the antioxidant capacity, esculetin was the most efficient one as revealed by all employed assays. Particularly, the mitochondrial ROS generation was totally abolished by the compound at low concentrations (IC50 = 0.57 µM). As for the anti-inflammatory effects, the COX-2 enzyme presented good affinities to the three coumarins, as revealed by the molecular docking analyses. However, considering the in vivo anti-inflammatory effects, 1,2-benzopyrone was the most efficient one in counteracting pleural inflammation and it potentiated the anti-inflammatory actions of dexamethasone. Umbelliferone and esculetin treatments failed to reduce the volume of pleural exudate. Overall, therefore, our results support the notion that this class of plant secondary metabolites displays promising effects in the prevention and/or treatment of inflammation and other diseases associated with oxidative stress, although the singularities regarding the type of the inflammatory process and pharmacokinetics must be taken into account.

Effects of a high-fat low-carbohydrate diet under different energy conditions on glucose homeostasis and fatty liver development in rats and on gluconeogenesis in the isolated perfused liver.

The beneficial effects of high-fat low-carbohydrate (HFLC) diets on glucose metabolism have been questioned and their effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of an HFLC diet under different energy conditions on glucose homeostasis, fatty liver development, and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for 4 weeks under three conditions: ad libitum (hypercaloric), isocaloric, and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity was not altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver.

A Critical Appraisal of the Most Recent Investigations on Ora-Pro-Nobis (Pereskia sp.): Economical, Botanical, Phytochemical, Nutritional, and Ethnopharmacological Aspects.

Pereskia aculeata Miller and Pereskia grandfolia Haw, known as 'ora-pro-nobis', are unconventional vegetables belonging to the Cactaceae family, native to the Americas and common in the northeast and southeast regions of Brazil. This review attempts to present a balanced account of both the methods used for obtaining extracts from the diverse parts of the plants and the results that were obtained in terms of their applicability to foods and other products with biological activities. Attention will also be devoted to the properties of their bioactives and their applications to real food products. Methods for obtaining extracts from the diverse parts of the plants will be analyzed, as well as the chemical nature of the bioactives that were hitherto identified. Next, the applicability of ora-pro-nobis in either its integral form or in the form of extracts or other products (mucilages) to the production of food and dietary supplements will be analyzed. The species have been extensively investigated during the last few decades. But, the determination of chemical structures is frequently incomplete and there is a need for new studies on texture determination and color evaluation. Further studies exploring the fruit and flowers of P. aculeata are also required.

Exploring the α-amylase-inhibitory properties of tannin-rich extracts of Cytinus hypocistis on starch digestion.

Cytinus hypocistis(L.) L. is an edible parasitic plant that grows within the roots of its host. In addition to its use as famine food in the past, it is also tradidionally used for treating several illnesses such as intestinal problems, inflammations, tumors, and bleeding. This species is rich in hydrolysable tannins, compounds often associated with inhibiting starch digestion. Therefore, the present work investigated how effectively C. hypocistis tannin-rich extracts inhibited enzymes involved in starch digestion and if such effect also occurs in vivo. The latter premise was approached using the starch tolerance test in mice. Two optimized hydroethanolic extracts were used, a heat-assisted and an ultrasound-assisted extract, with known hydrolysable tannin content. Both extracts demonstrated potent inhibition of α-amylase. Inhibitions were of the mixed type with inhibitor constants in the 15 µg/mL range. The inhibition of the intestinal α-glucosidase was at least ten times less effective. The inhibition of the α-amylase was negatively affected by in vitro gastrointestinal digestion and bovine serum albumin. In vivo, both extracts inhibited starch digestion at doses between 100 and 400 mg/mL in healthy mice. The highest doses of the ultrasound and heat extracts diminished the peak glucose levels in the starch tolerance test by 46 and 59.3%, respectively. In streptozotocin diabetic mice, this inhibition occurred only at the dose of 400 mg/mL. Under this condition, diminution of the peak glucose concentration in the starch tolerance test was equal to 36.7% and 48.8% for the ultrasound and heat extracts, respectively. Maltose digestion was not inhibited by the C. hypocistis extracts. Qualitatively and quantitatively, thus, the actions of both extracts were similar. The results allow adding a new biological property to C. hypocistis, namely, the ability to decrease the hyper-glycemic excursion after a starch-rich meal, propitiating at the same time a diminished caloric intake.

Improving Enzymatic Saccharification of Peach Palm (Bactris gasipaes) Wastes via Biological Pretreatment with Pleurotus ostreatus.

The white-rot fungus Pleurotus ostreatus was used for biological pretreatment of peach palm (Bactris gasipaes) lignocellulosic wastes. Non-treated and treated B. gasipaes inner sheaths and peel were submitted to hydrolysis using a commercial cellulase preparation from T. reesei. The amounts of total reducing sugars and glucose obtained from the 30 d-pretreated inner sheaths were seven and five times higher, respectively, than those obtained from the inner sheaths without pretreatment. No such improvement was found, however, in the pretreated B. gasipaes peels. Scanning electronic microscopy of the lignocellulosic fibers was performed to verify the structural changes caused by the biological pretreatments. Upon the biological pretreatment, the lignocellulosic structures of the inner sheaths were substantially modified, making them less ordered. The main features of the modifications were the detachment of the fibers, cell wall collapse and, in several cases, the formation of pores in the cell wall surfaces. The peel lignocellulosic fibers showed more ordered fibrils and no modification was observed after pre-treatment. In conclusion, a seven-fold increase in the enzymatic saccharification of the Bactris gasipaes inner sheath was observed after pre-treatment, while no improvement in enzymatic saccharification was observed in the B. gasipaes peel.

Harmful effects of chlorhexidine on hepatic metabolism.

Chlorhexidine (CHX) is an over-the-counter antiseptic amply used by the population. There are reports that CHX acts in mitochondria as an uncoupler and inhibitor. The purpose of this study was to investigate the short-term effects of CHX on hepatic metabolic pathways linked to energy metabolism in the perfused rat liver. The compound inhibited both glucose synthesis and the urea cycle. Oxygen consumption was raised at low concentrations (up to 10 µM) and diminished at higher ones. A pronounced diminution in the cellular ATP content was observed. Conversely, CHX stimulated glycolysis and enhanced leakage of cellular enzymes (lactate dehydrogenase and fumarase). In isolated mitochondria, this antiseptic inhibited pyruvate carboxylation, oxidases, and oxygen uptake at very low concentrations (2 µM) and promoted uncoupling. The results described herein raise great concerns about the safety of CHX, as the observed effects can induce hypoglycemia, lactic acidosis, ammonemia as well as cell membrane disruption.

Inhibition of Gluconeogenesis by Boldine in the Perfused Liver: Therapeutical Implication for Glycemic Control.

The alkaloid boldine occurs in the Chilean boldo tree (Peumus boldus). It acts as a free radical scavenger and controls glycemia in diabetic rats. Various mechanisms have been proposed for this effect, including inhibited glucose absorption, stimulated insulin secretion, and increased expression of genes involved in glycemic control. Direct effects on glucose synthesis and degradation were not yet measured. To fill this gap, the present study is aimed at ensuring several metabolic pathways linked to glucose metabolism (e.g., gluconeogenesis) in the isolated perfused rat liver. In order to address mechanistic issues, energy transduction in isolated mitochondria and activities of gluconeogenic key enzymes in tissue preparations were also measured. Boldine diminished mitochondrial ROS generation, with no effect on energy transduction in isolated mitochondria. It inhibited, however, at least three enzymes of the gluconeogenic pathway, namely, phosphoenolpyruvate carboxykinase, fructose-bisphosphatase-1, and glucose 6-phosphatase, starting at concentrations below 50 µM. Consistently, in the perfused liver, boldine decreased lactate-, alanine-, and fructose-driven gluconeogenesis with IC50 values of 71.9, 85.2, and 83.6 µM, respectively. Conversely, the compound also increased glycolysis from glycogen-derived glucosyl units. The hepatic ATP content was not affected by boldine. It is proposed that the direct inhibition of hepatic gluconeogenesis by boldine, combined with the increase of glycolysis, could be an important event behind the diminished hyperglycemia observed in boldine-treated diabetic rats.

Purple tea: chemical characterization and evaluation as inhibitor of pancreatic lipase and fat digestion in mice.

A variety of the classic green tea plant, Camellia sinensis, was developed and is exclusive to Kenya. Due to high content of anthocyanin polyphenols in its leaves, the beverage obtained from this variety is purple in color and is the origin of the name purple tea. This work had two main purposes. The first one was to identify and quantify the major anthocyanin polyphenols in a hot water aqueous extract of the purple tea leaves. The second one was to test the hypothesis if this extract is capable of inhibiting triglyceride absorption considering that anthocyanin polyphenolics have been frequently associated to antilipidemic effects. Parallel experiments were always done with a similar green tea extract for comparison purposes. The antioxidant, anti-inflammatory, and cytotoxic activities of both tea varieties are similar. The purple tea extract, however, was strongly inhibitory toward the pancreatic lipase (minimal IC50 = 67.4 µg mL-1), whereas the green tea preparation was a weak inhibitor. Triglyceride digestion in mice was inhibited by the purple tea extract starting at 100 mg kg-1 dose and with a well-defined dose dependence. Green tea had no effect on triglyceride digestion at doses up to 500 mg kg-1. The latter effect is probably caused by several components in the purple tea extract including non-anthocyanin and anthocyanin polyphenols, the first ones acting solely via the inhibition of the pancreatic lipase and the latter by inhibiting both the lipase and the transport of free fatty acids from the intestinal lumen into the circulating blood. The results suggest that the regular consumption of Kenyan purple tea can be useful in the control of obesity.

Avaliação morfológica do cólon proximal de ratos diabéticos suplementados com extrato de Agaricus blazei murrill / Morphological evaluation of the proximal colon of diabetic rats supplemented with agaricus blazei murrill extract / Evaluación morfológica del colon proximal de ratas diabéticas suplementadas con extracto de agaricus blazei murrill

O diabetes mellitus tipo I é resultado da absoluta deficiência de insulina, estando associado à anormalidades no metabolismo. Transtornos no trato gastrointestinal, tais como vômitos, disfagia e diarreia são frequentes no diabetes, sendo relacionados a alterações na morfologia intestinal e no sistema nervoso entérico. Compostos ricos em antioxidantes vem sendo utilizados como prevenção ou tratamento do diabetes. Agaricus blazei Murrill possui grande interesse farmacológico pelas propriedades anti-inflamató- rias, hipoglicêmicas e antioxidantes. Neste trabalho, avaliamos a integridade estrutural da parede e inervação intrínseca do cólon proximal em modelo experimental de diabetes induzido por estreptozotocina, tratados ou não com A. blazei. Ratos Wistar foram dividi- dos em grupos: normoglicêmicos (N), diabéticos (D) e com suplementação (NB e DB) por gavagem do extrato hidroalcoólico de Agaricus blazei (200mg/Kg), por 120 dias. Amostras do cólon proximal foram destinadas à técnicas histológicas para análise mor- fométrica da túnica mucosa, profundidade das criptas, muscular da mucosa, muscular ex- terna e parede total, número de células caliciformes e avaliação morfoquantitativa da pop- ulação mioentérica. O diabetes promoveu redução da muscular externa e muscular da mucosa com aumento na profundidade das criptas e área nuclear neuronal. O extrato promoveu hipertrofia da mucosa e muscular da mucosa. Houve manutenção na espessura da parede total, número de células caliciformes e na população neuronal mioentérica no diabetes e na suplementação. Conclui-se que o diabetes induzido por estreptozotocina e a suplementação com o extrato de Agaricus blazei causam ajustes morfológicos nas túnicas intestinais, sem interferir na parede e inervação mioentérica do cólon proximal, preservando a morfofisiologia absortiva e motora deste segmento

Type I diabetes mellitus is a result of absolute insulin deficiency and is associated with abnormalities in metabolism. Disorders in the gastrointestinal tract, such as vomiting, dysphagia and diarrhea are common in diabetes, being related to changes in intestinal morphology and enteric nervous system. Antioxidant rich compounds have been used as prevention or treatment of diabetes. Agaricus blazei Murrill is highly pharmacologically interested in anti-inflammatory, hypoglycemic and antioxidant properties. In this work, we evaluated the structural integrity of the wall and intrinsic innervation of the proximal colon in an experimental model of streptozotocin-induced diabetes, treated or not with A. blazei Wistar rats were divided into groups: normoglycemic (N), diabetic (D) and supplementation (NB and DB) by gavage of the hydroalcoholic extract of Agaricus blazei (200mg / kg) for 120 days. Samples of the proximal colon were used for histological techniques for morphometric analysis of the mucosa, depth of the crypts, muscularis mucosa, external muscular and total wall, number of goblet cells and morpho-quantitative evaluation of the myenteric population. Diabetes promoted reduction of muscularis mucosa and external muscular with increased depth of the crypts and nuclear neuronal area. The extract promoted mucosa and muscular of the mucosa hypertrophy. There were maintenance of total wall thickness, number of goblet cells and in the myenteric neuronal population in diabetes and supplementation. It is concluded that streptozotocin-induced diabetes and supplementation with Agaricus blazei extract cause morphological adjustments in the intestinal tunica, without interfering with the wall and myenteric innervation of the proximal colon, preserving the absorptive and motor morphophysiology of this segment.

La diabetes mellitus tipo I es el resultado de la deficiencia absoluta de insulina y se asocia con anomalías en el metabolismo. Los trastornos del tracto gastrointestinal, como vómitos, disfagia y diarrea son frecuentes en la diabetes, estando relacionados con cambios en la morfología intestinal y en el sistema nervioso entérico. Los compuestos ricos en antioxidantes se han utilizado como prevención o tratamiento de la diabetes. Agaricus blazei Murrill está muy interesado farmacológicamente en propiedades antiinflamatorias, hipoglucémicas y antioxidantes. En este trabajo, se evaluó la integridad estructural de la pared e inervación intrínseca del colon proximal en un modelo experimental de diabetes inducida por estreptozotocina, tratada o no con ratas A. blazei Wistar, divididas en grupos: normoglucémico (N), diabético (D) y suplementación (NB y DB) por sonda del extracto hidroalcohólico de Agaricus blazei (200mg/kg) por 120 días. Se utilizaron muestras del colon proximal para técnicas histológicas de análisis morfométrico de la mucosa, profundidad de las criptas, mucosa muscular, pared externa muscular y total, número de células caliciformes y evaluación morfo-cuantitativa de la población mientérica. La diabetes promovió la reducción de la muscular de la mucosa y de la muscular externa con el aumento de la profundidad de las criptas y del área neuronal nuclear. El extracto promovió la hipertrofia mucosa y muscular de la mucosa. Hubo mantenimiento del espesor total de la pared, número de células caliciformes y en la población neuronal mientérica en diabetes y suplementación. Se concluye que la diabetes inducida por estreptozotocina y la suplementación con extracto de Agaricus blazei causan ajustes morfológicos en la túnica intestinal, sin interferir con la pared e inervación mientérica del colon proximal, conservando la morfofisiología absortiva y motora de este segmento.

A Critical Appraisal of the Most Recent Investigations on the Hepatoprotective Action of Brazilian Plants.

Conventional treatments for liver diseases are often burdened by side effects caused by chemicals. For minimizing this problem, the search for medicines based on natural products has increased. The objective of this review was to collect data on the potential hepatoprotective activity of plants of the Brazilian native flora. Special attention was given to the modes of extraction, activity indicators, and identification of the active compounds. The databases were Science direct, Pubmed, and Google Academic. Inclusion criteria were: (a) plants native to Brazil; (b) studies carried out during the last 15 years; (c) high-quality research. A fair number of communications met these criteria. Various parts of plants can be used, e.g., fruit peels, seeds, stem barks, and leaves. An outstanding characteristic of the active extracts is that they were mostly obtained from plant parts with low commercial potential, i.e., by-products or bio-residues. The hepatoprotective activities are exerted by constituents such as flavonoids, phenolic acids, vitamin C, phytosterols, and fructose poly- and oligosaccharides. Several Brazilian plants present excellent perspectives for the obtainment of hepatoprotective formulations. Very important is the economical perspective for the rural producers which may eventually increase their revenue by selling increasingly valued raw materials which otherwise would be wasted.

Full Exploitation of Peach Palm (Bactris gasipaes Kunth): State of the Art and Perspectives.

The peach palm (Bactris gasipaes Kunth) is a palm tree native to the Amazon region, with plantations expanding to the Brazilian Southwest and South regions. This work is a critical review of historical, botanical, social, environmental, and nutritional aspects of edible and nonedible parts of the plant. In Brazil, the importance of the cultivation of B. gasipaes to produce palm heart has grown considerably, due to its advantages in relation to other palm species, such as precocity, rusticity and tillering. The last one is especially important, as it makes the exploitation of peach palm hearts, contrary to what happens with other palm tree species, a non-predatory practice. Of special interest are the recent efforts aiming at the valorization of the fruit as a source of carotenoids and starch. Further developments indicate that the B. gasipaes lignocellulosic wastes hold great potential for being upcycled into valuable biotechnological products such as prebiotics, enzymes, cellulose nanofibrils and high fiber flours. Clean technologies are protagonists of the recovery processes, ensuring the closure of the product's life cycle in a "green" way. Future research should focus on expanding and making the recovery processes economically viable, which would be of great importance for stimulating the peach palm production chain.

Resveratrol biotransformation and actions on the liver metabolism of healthy and arthritic rats.

AIMS: to investigate the effects of resveratrol on glycogen catabolism and gluconeogenesis in perfused livers of healthy and arthritic rats. The actions of resveratrol-3-O-glucuronide (R3G) and the biotransformation of resveratrol into R3G was further evaluated in the livers. MAIN METHODS: arthritis was induced with Freund's adjuvant. Resveratrol at concentrations of 10, 25, 50, 100 and 200 µM and 200 µM R3G were introduced in perfused livers. Resveratrol and metabolites were measured in the outflowing perfusate. Respiration of isolated mitochondria and activity of gluconeogenic enzymes were also evaluated in the livers. KEY FINDINGS: resveratrol inhibited glycogen catabolism when infused at concentrations above 50 µM and gluconeogenesis even at 10 µM in both healthy and arthritic rat livers, but more sensitive in these latter. Resveratrol above 100 µM inhibited ADP-stimulated respiration and the activities of NADH- and succinate-oxidases in mitochondria, which were partially responsible for gluconeogenesis inhibition. Pyruvate carboxylase activity was inhibited by 25 µM resveratrol and should inhibit gluconeogenesis already at low concentrations. Resveratrol was significantly metabolized to R3G in healthy rat livers, however, R3G formation was lower in arthritic rat livers. The latter must be in part a consequence of a lower glucose disposal for glucuronidation. When compared to resveratrol, R3G inhibited gluconeogenesis in a lower extension and glycogen catabolism in a higher extension. SIGNIFICANCE: the effects of resveratrol and R3G tended to be transitory and existed only when the resveratrol is present in the organ, however, they should be considered because significant serum concentrations of both are found after oral ingestion of resveratrol.

The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity.

Berberine is a plant alkaloid to which antihyperglycemic properties have been attributed. It is also known as an inhibitor of mitochondrial functions. In this work short-term translation of the latter effects on hepatic metabolism were investigated using the isolated perfused rat liver. Once-through perfusion with a buffered saline solution was done. At low portal concentrations berberine modified several metabolic pathways. It inhibited hepatic gluconeogenesis, increased glycolysis, inhibited ammonia detoxification, increased the cytosolic NADH/NAD+ ratio and diminished the ATP levels. Respiration of intact mitochondria was impaired as well as the mitochondrial pyruvate carboxylation activity. These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis, mediated by both energy metabolism and pyruvate carboxylation inhibition, represent most likely a significant contribution to its clinical efficacy as an antihyperglycemic agent. However, safety concerns also arise because all effects occur at similar concentrations and there is a narrow margin between the expected benefits and toxicity. Even mild inhibition of gluconeogenesis is accompanied by diminutions in oxygen uptake and ammonia detoxification and increases in the NADH/NAD+ ratio. All combined, desired and undesired effects could well in the end represent a deleterious combination of events leading to disruption of cellular homeostasis.

Alpha-tocopherol-loaded polycaprolactone nanoparticles improve the inflammation and systemic oxidative stress of arthritic rats.

Background and aim: The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison. Experimental procedure: Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction. Results: Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs. Conclusion: Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.

The rapid transformation of triclosan in the liver reduces its effectiveness as inhibitor of hepatic energy metabolism.

Triclosan (5-chloro-2'-[2,4-dichlorophenoxi]-phenol) is a polychlorinated biphenolic antimicrobial, utilized as antiseptic and preservative in hygiene products and medical equipment. Triclosan causes mitochondrial dysfunction (uncoupling, inhibition of electron flow), as demonstrated in isolated rat liver mitochondria. These actions in the mitochondria could compromise energy-dependent metabolic fluxes in the liver. For this reason, the present work aimed at investigating how these effects on isolated mitochondria translate to the whole and intact hepatocyte. For accomplishing this, the isolated perfused rat liver was utilized, a system that preserves both microcirculation and the cell-to-cell interactions. In addition, the single-pass triclosan hepatic transformation was also evaluated by HPLC as well as the direct action of triclosan on gluconeogenic enzymes. The results revealed that triclosan decreased anabolic processes (e.g., gluconeogenesis) and increased catabolic processes (e.g., glycolysis, ammonia output) in the liver, generally with a complex pattern of concentration dependences. Unlike the effects on isolated mitochondria, which occur in the micromolar range, the effects on intact liver required the 10-5 to 10-4 M range. The most probable cause for this behavior is the very high single-pass transformation of triclosan, which was superior to 95% at the portal concentration of 100 µM. The concentration gradient along the sinusoidal bed is, thus, very pronounced and the response of the liver reflects mainly that of the periportal cells. The high rates of hepatic biotransformation may be a probable explanation for the low acute toxicity of triclosan upon oral ingestion.

Production of fungal laccase on pineapple waste and application in detoxification of malachite green.

The main purpose of this work was to use pineapple crowns as substrate for optimizing laccase production by Trametes versicolor in lab-scale experiments. One-factor-at-the-time analysis and response surface methodology were used to optimize production. A single laccase with molecular weight of 45 kDa was the main protein produced. A maximal laccase activity of 60.73 ± 1.01 U/g was obtained in 7-day cultures, representing a 6.7-fold increase compared to non-optimized conditions. The optimized conditions were temperature: 28 °C; initial moisture: 90%; glucose: 8.38%; yeast extract: 2.86%. Combining activity and stability, the best conditions for using this laccase during the long periods required by large-scale processes are pH 4.0-5.0 and temperature of 40-50 °C. Under these conditions, the crude laccase was efficient in detoxifying the dye malachite green with a KM of 14.33 ± 1.94 µM and a Vmax of 0.482 ± 0.029 µM/min with 0.1 units/mL. It can be concluded that pineapple crown leaves can be effectively used as substrate by T. versicolor for producing laccase under solid-state culture conditions. Laccase is an industrially relevant enzyme and its production with concomitant valorization of pineapple crowns as substrate offers highly interesting perspectives.

The inhibitory action of purple tea on in vivo starch digestion compared to other Camellia sinensis teas.

In order to contribute to improve knowledge about the actions of Camellia sinensis extracts on starch digestion, several varieties were compared. The latter were green, oolong, white, black, and purple teas. The results are hoped to contribute to our understanding of the mode of action and potency of the various tea preparations as possible adjuvants in the control of post-prandial glycemia. The extracts were prepared in way similar to their form of consumption. All extracts decreased starch digestion, but the purple tea extract was the strongest inhibitor, their inhibitory tendency started at the dose of 50 mg/kg and was already maximal with 250 mg/kg. Maltose tolerance was not significantly affected by the extracts. Glucose tolerance was not affected by purple tea, but black tea clearly diminished it; green tea presented the same tendency. Purple tea was also the strongest inhibitor of pancreatic α-amylase, followed by black tea. The green tea, oolong tea, and white tea extracts tended to stimulate the pancreatic α-amylase at low concentrations, a phenomenon that could be counterbalancing its inhibitory effect on starch digestion. Based on chemical analyses and molecular docking simulations it was concluded that for both purple and black tea extracts the most abundant active component, epigallocatechin gallate, seems also to be the main responsible for the inhibition of the pancreatic α-amylase and starch digestion. In the case of purple tea, the inhibitory activity is likely to be complemented by its content in deoxyhexoside-hexoside-containing polyphenolics, especially the kaempferol and myricetin derivatives. Polysaccharides are also contributing to some extent. Cyanidins, the compounds giving to purple tea its characteristic color, seem not to be the main responsible for its effects on starch digestion. It can be concluded that in terms of postprandial anti-hyperglycemic action purple tea presents the best perspectives among all the tea varieties tested in the present study.