Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Bioaccessibility Measurement and Safety Evaluation of Elements in Decoction of Zhebawei Traditional Chinese Medicines / 中国药学杂志

OBJECTIVE: To study the bioaccessibility and evaluate the safety of inorganic elements in decoction of "Zhebawei" traditional Chinese medicines (TCMs). METHODSE: The bioaccessibility of inorganic elements in decoction of "Zhebawei" TCMs was measured based on in vitro digestion and inductively coupled plasma atomic emission spectrometer (ICP-AES) and the safety of these elements were evaluated by comparing with the safe limits issued by the FAO and WHO. RESULTS: The bioaccessibility of the inorganic elements was less than 1, and varied among different elements of the same herbal medicine or for the same element among different herbal medicines. Cd, V, Se, Cr, Sn, and As were not detected in the dialysate of some TCMs' decoction after in vitro digestion because of the total content being low or undetected in decoction. The result of safety evaluation showed that the daily intakes of Ni, Fe, Mn, Se, Cu, Zn, Co, V, Cr from the decoction of "Zhebawei" TCMs were all within safe limits. The daily intakes of Cd and Sn did not exceed the level of personal acceptable daily intake instituted by the FAO and WHO. The total content in the decoction of Rhizoma Corydalis was more than the level of personal acceptable daily intake instituted by FAO and WHO, however the amount in the dislysate of "Zhebawei" TCMs' decoction after in vitro digestion were under the standard. The analysis of total content may exaggerate the risk of toxicity. CONCLUSION: The results will provide the basis for further researches such as bioavailability and safety of inorganic elements in "Zhebawei" TCMs, and will provide references for ensuring the rational use of TCM according to the analysis of inorganic elements.

Caracterização quí­mica de tomate roxo e estudo da metabolização de flavonoides in vitro e in vivo / Chemical characterization of purple tomato and in vitro and in vivo study of metabolism of flavonoids

Tendo em vista a importância dos compostos bioativos (CBAs) para a promoção da saúde, foram desenvolvidos, a partir de cruzamentos do tomate cereja com espécies selvagens, os tomates laranja (rico em ß-caroteno) e roxo (rico em antocianinas), por meio da técnica de introgressão de alelos. Diante disso, o objetivo deste trabalho foi caracterizar o perfil de compostos bioativos e voláteis dos tomates enriquecidos e avaliar a estabilidade e metabolização de flavonoides do tomate roxo durante digestão in vitro e em modelo animal. Os tomates foram caracterizados quanto ao conteúdo de compostos fenólicos totais; capacidade antioxidante por DPPH e ORAC; ácidos orgânicos; açúcares solúveis; perfil de carotenoides por CLAE/DAD; flavonoides por CLAE/DAD e LC/ESI/MS/MS e compostos voláteis por CG/MS. Avaliou-se ainda a estabilidade dos flavonoides da casca do tomate roxo por simulação da digestão in vitro, utilizando o Simulator of the Human Intestinal Microbial Ecosystem (SHIME), bem como a formação de AGCC por GC-MS, e excreção em ratos Wistar, com posterior identificação dos compostos fenólicos por LC/Q-TOF/MS. O tomate roxo apresentou aumento no conteúdo de fenólicos totais, capacidade antioxidante e vitamina C, com destaque para casca. A rutina foi o principal flavonol identificado em todos os frutos, e na casca do tomate roxo foi encontrado alto teor de petunidina (p-coumaroil)-rutinosídeo-hexosídeo, além da superexpressão de outros flavonoides como a quercetina-3-O-rutinosídeo e kaempferol. Não houve alteração no perfil de flavonoides do fruto laranja. Este, por sua vez, apresentou acúmulo de ß-caroteno, importante pró-vitamina A, ao passo que o tomate roxo também teve seus conteúdos de ß-caroteno e licopeno aumentados. Os frutos apresentaram perfil de compostos voláteis diferentes entre si, o que foi relacionado à degradação dos diferentes CBAs característicos de cada um. O extrato fenólico da casca de tomate roxo, submetido à digestão in vitro, se manteve estável na primeira porção, relativo às condições estomacais. Contudo, o conteúdo de flavonoides apresentou redução significativa (p<0,05) nas porções que simulam as condições do duodeno e do colón, com a formação de catabólitos pela ação da microbiota intestinal e/ou pela degradação química espontânea. Foi observado o aparecimento de novos ácidos fenólicos não presentes inicialmente na matriz, dentre eles o ácido 3-O-metilgálico e o ácido homovanílico, supostamente derivados da degradação da petunidina e da quercetina, respectivamente. Houve aumento na produção total de AGCC, com excessão do butirato. Na urina dos animais foram detectados diversos outros compostos fenólicos derivados do metabolismo de fase II, dentre eles o ácido hipúrico e o 3-O-metilcatecol. Nas fezes foram identificados cerca de metade dos compostos presentes na fermentação in vitro. Dessa forma, o melhoramento convencional pode ser uma alternativa para o enriquecimento, com CBAs, de alimentos amplamente consumidos pela população, como o tomate. Além disso, durante a passagem pelo trato gastrointestinal, os flavonoides presentes na casca do tomate roxo sofrem intensa degradação pela microbiota intestinal, com formação de catabólitos com reconhecido potencial benefício à saúde

Considering the importance of bioactive compounds (BACs) for health promotion, the orange (ß-carotene-rich) and purple (anthocyanin-rich) tomatoes were developed from cherry tomato interspecific crossing with wild species, using the technique of allele introgression. The objective of this work was to characterize the profile of bioactive and volatile compounds of enriched tomatoes, and to evaluate the stability and metabolism of purple tomato's flavonoids during in vitro and in vivo digestion. The tomatoes were characterized by its content of total phenolic compounds; antioxidant capacity (DPPH and ORAC); organic acids; soluble sugars; carotenoids (HPLC/DAD); flavonoids (HPLC/DAD and LC/ESI/MS/MS) and volatile compounds (GC/MS). The stability of the flavonoids from purple tomato peel was assessed by using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), as well as the formation of AGCC by GC-MS, and metabolism and excretion in Wistar rats, with subsequent identification of phenolic compounds by LC/Q-TOF/MS. The purple tomato showed an increase in the total phenolic content, antioxidant capacity and vitamin C, with highlight for the peel. The rutin was the main flavonol identified in all fruits, and it was found high content of petunidin (p-coumaryl)-rutinoside-hexoside in the purple tomato peel, in addition to overexpression of other flavonoids such as quercetin-3-O-rutinoside and kaempferol. There was no change in the flavonoid profile of the orange fruit. This one, in turn, presented accumulation of ß-carotene, important pro-vitamin A, while the purple tomato also showed an increase in its ß-carotene and lycopene contents. The fruits presented different volatile compounds profile among them, which was related to the degradation of the different BACs composition of each one. In the in vitro digestion, the phenolic extract of the purple tomato peel remained stable in the first portion, relative to the stomach conditions. However, the content of flavonoids presented a significant reduction (p<0.05) in the portions simulating the duodenum and colon, with the formation of catabolites by the action of intestinal microbiota and/or spontaneous chemical degradation. It was observed the appearance of new phenolic acids that was not initially present in the matrix, among them 3-O-methylgalic acid and homovanilic acid, supposedly derived from the degradation of petunidin and quercetin, respectively. There was an increase in the total production of SCFAs, with the exception of butyrate. In the urine of the animals several other phenolic compounds derived from phase II metabolism were detected, among them hippuric acid and 3-O-methylcatechol. About half of the compounds present in the in vitro fermentation were identified in the feces. Conventional breeding may be an alternative for the enrichment, with BACs, of foods that are widely consumed by the population, such as tomatoes. In addition, during the passage through the gastrointestinal tract, the flavonoids present in the purple tomato peel are severely degraded by the intestinal microbiota, with formation of catabolites with recognized potential health benefit

Fate of polyphenols in pili (Canarium ovatum Engl.) pomace after in vitro simulated digestion

Objective: To evaluate the stability and bioavailability of polyphenols in pili (Canarium ovatum Engl.) pomace during simulated in vitro digestion. Methods: Freeze-dried pili pomace was subjected to in vitro digestion simulating con-ditions in the stomach, small intestine and colon. Total polyphenols, anthocyanins, flavonoids and condensed tannins, and its antioxidant activity– 1,1-diphenyl-2-picrylhydrazyl, 2,20-azinobis-3-ethylbenzothiozoline-6-sulfonic acid, and ferric reducing antioxidant power were measured using standard spectrophotometric methods. Results: In vitro digestion of pili pomace resulted in reduction of phenolic compounds. Condensed tannins and anthocyanins were released in the gastric and intestinal stages, while total polyphenols and flavonoids after fermentation simulating colonic conditions. Antioxidant values of the bioavailable fractions showed that more than 90% of activity was lost during simulated digestion. Conclusions: Findings indicate that pili pomace is a promising functional ingredient for food and dietary supplements which can furnish potentially bioavailable phenolic anti-oxidants to the body.

Fate of polyphenols in pili (Canarium ovatum Engl.) pomace after in vitro simulated digestion

Objective To evaluate the stability and bioavailability of polyphenols in pili (Canarium ovatum Engl.) pomace during simulated in vitro digestion. Methods Freeze-dried pili pomace was subjected to in vitro digestion simulating conditions in the stomach, small intestine and colon. Total polyphenols, anthocyanins, flavonoids and condensed tannins, and its antioxidant activity – 1,1-diphenyl-2-picrylhydrazyl, 2,2′-azinobis-3-ethylbenzothiozoline-6-sulfonic acid, and ferric reducing antioxidant power were measured using standard spectrophotometric methods. Results In vitro digestion of pili pomace resulted in reduction of phenolic compounds. Condensed tannins and anthocyanins were released in the gastric and intestinal stages, while total polyphenols and flavonoids after fermentation simulating colonic conditions. Antioxidant values of the bioavailable fractions showed that more than 90% of activity was lost during simulated digestion. Conclusions Findings indicate that pili pomace is a promising functional ingredient for food and dietary supplements which can furnish potentially bioavailable phenolic antioxidants to the body.

Acetylcholinesterase Inhibitory Activity After in vitro Gastrointestinal Digestion of Infusions of Mentha Species.

Aims: To study the acetylcholinesterase inhibitory activity of Mentha infusions before and after the gastrointestinal digestion and to correlate this activity with the chemical compounds present in these infusions. Place and Duration of Study: Fresh Mentha x piperita, M. spicata, M. pulegium were bought in a local supermarket. These plants were composed of leaves, stems and flowers for the identification, which was carried out in Plant Biotechnology Centre, Faculty of Sciences, University of Lisbon. The chemical identification of the infusions and the enzymatic tests were carried out in the Center of Chemistry & Biochemistry, Faculty of Science University of Lisbon from September 2010 till June 2011. Methodology: The compounds present in the infusions were identified by LC-MS. The enzyme activity assay was carried out using a spectrophotometric method. The digestive simulation was accomplished using enzymatic juices prepared in the laboratory and Caco-2 cells lines simulating the intestine barrier. Results: All the Mentha infusions contained rosmarinic acid. M. spicata infusion contained also eriocitrin and eriodictyol. The IC50 values for acetylcholinesterase inhibitory activity of the infusions, before digestion, stayed between 0.72 and 1.9 mg/mL. These activities are statistically different at p<.05. These activities can be explained by the presence of the phenolic compounds mentioned. Rosmarinic acid has an IC50 equal to 0.439 mg/mL (1.22 mM), eriocitrin and eriodictyol have IC50 equal to 0.439 mg/mL (0.29 mM) and 0.256 mg/mL (0.89 mM) respectively. The presence of these two flavonoids, eriocitrin and eriodictyol, can account for the higher activity detected for M. spicata. The gastric juice or the pancreatic juices used to simulate the gastrointestinal digestion did not originate any difference in the chemical composition of the infusions (analysed by HPLCDAD). This was also corroborated by the enzymatic tests. The Caco-2 cells did not originate any modification in the enzymatic activity of the infusions. The analysis of the cell homogenate revealed the presence of rosmarinic acid and the phenolic compounds, although in minor amount. Conclusion: Mentha infusions have the capacity to inhibit acetylcholinesterase, due to the presence of rosmarinic acid, eriocitrin and eriodictyol The composition of the Mentha herbal teas was not modified by the gastro-intestinal juices, or by the intestinal cell line.

ASSESSMENT OF IRON BIOAVAILABILITY OF IRON BIOFORTIFIED MAIZE USING IN VITRO DIGESTION/CACO-2 CELL CULTURE MODEL / 营养学报

Objective To assess iron bioavailability of three iron-biofortified maizes using an in vitro digestion/ Caco-2 cell culture model. Method Three maize varieties rich in iron (Zhongtie 2, 3 and 4) and two maize varieties with lower content of iron (Zhengda 818 and 619) were pulverized, and the content of iron and phosphorus in each maize variety was measured. After digestion the iron bioavailability per g food was determined by using Caco-2 cell ferritin formation per mg cell protein as indicator. Results The iron content (33.250 mg/kg), iron bioavailability and the iron bioavailability per g food of Zhongtie 2 maize was the highest among all varieties, but its phosphorus content was lower. The maize varieties with the next higher iron bioavailability were Zhongtie 3 and Zhengda 818, and the lowest was Zhengda 619. Conclusion Zhongtie 2 maize contained the hightest content and bioavailability of iron,so it was optimal to use for the following human trials.

STUDY ON ANGIOTENSIN CONVERTING ENZYME INHIBITORY PEPTIDES FROM DIGESTION OF SOY PROTEIN IN VITRO / 营养学报

Objective: To investigate if angiotensin converting enzyme inhilitory(ACEI) peptides would be produced from SPI digested by a batch digestion system using enzymes similar to digestive enzymes in humans.Method: Simulate the conditions of human gastrointestinal digestion in a model digestion system in vitro and produce soy peptides from SPI digested using pepsin and pancreatin.In addition to monitoring ACEI activity in the total soy protein digest,the possibility of generating soy peptide fractions with more potent activity than the unfractionated digest was investigated by measuring activity of fractions obtained after ultrafitration,anion exchange,and RP-HPLC.Results: The generation of ACEI activity in SPI was determined after sequential digestion with pepsin and pancreatin.The inhibitory activity was highest within the first 20 min at pepsin digestion and decreased upon subsequent digestion with pancreatin.An IC50 value of 0.28?0.06 mg/ml was determined after 180 min of digestion,while no ACEI activity was measured for the undigested SPI at 0.73 mg/ml.Chromatographic fractionation of the SPI digest resulted in IC50 values of active fractions ranging from 0.13?0.03 to 0.93?0.08 mg/ml.Conclusion: Many different peptides with ACEI activities were produced after pepsin-pancreatin digestion of SPI in vitro and lead to the speculation that physiological gastrointestinal digestion could also yield ACE inhibitory peptides from SPI.