Polygonum cuspidatum Loaded Nanostructured Lipid Carriers for Dual Inhibition of TNF-α- and IL-6 Cytokines and Free Radical Species.

The main objective of this study was the testing of natural compounds, such as Polygonum cuspidatum (PgnC) loaded into nanostructured lipid carriers (NLC), which can act as a "double-edged sword" aimed at simultaneously combating dangerous free radicals and inhibiting pro-inflammatory cytokines. Resveratrol-rich PgnC extract was paired with another phytochemical, Diosgenin (DSG), in NLC. The lipid nanocarriers carrying both herbals (NLC-DSG-PgnC) had spherical diameters (100 ± 2 50 nm), a polydispersity index of ~0.15, and electrokinetic potentials greater than -46.5 mV. Entrapment efficiencies of 65% for PgnC and 87% for DSG were determined by chromatographic and UV-Vis spectroscopy assays. Cell cytotoxicity analysis proved that 50 µg/mL of NLC-PgnC and dual-NLC ensured a biocompatible effect like the untreated cells. The dual-NLC assured a much slower in vitro release of DSG and PgnC (67% PgnC and 48% DSG) than the individual-NLC (78% PgnC and 47% DSG) after 4 h of experiments. NLC encapsulating PgnC presented a superior ability to capture cationic radicals: 74.5 and 77.9%. The chemiluminescence results pointed out the non-involvement of DSG in stopping oxygenated free radicals, while the antioxidant activity was maintained at a level higher than 97% for dual-NLC. NLC-DSG-PgnC ensured a promising capacity for inhibition of pro-inflammatory cytokine IL-6, ranging from 91.9 to 94.9%.

The synergistic effect of Angelica sinensis (Oliv.) Diels and Rehmannia glutinosa (Gaertn.) DC. on antioxidant activity and protective ability against cell injury.

Oxidative stress-induced dysfunction of nerve cells has been implicated as a crucial cause of cell death in neurodegenerative diseases. In Asian countries, herbs, such as Angelica sinensis (Oliv.) Diels (DG) and Rehmannia glutinosa (Gaertn.) DC. (SDH), have long be considered to have antiaging abilities. The herbs act as neuro protectants that rescue nerve cells from oxidative stress damage and apoptosis. Thus, developing herbal formulas can potentially lead to new treatments for neurodegenerative diseases. In this study, we compared the effective active components and antioxidant properties of extractive of DG and SDH (DG-SDH) when formulated at different ratios. DG-SDH formulated at a ratio of 3:2 (DG-SDH [3:2]) produced the highest content of polysaccharides, polyphenols, and flavonoids. It also showed the best ability in removing DPPH and hydroxyl free radicals compared to single herb or other compounding ratio. The antioxidant activity of DG-SDH (3:2) showed best synergistic effects in scavenging activity assays of DPPH free radicals and hydroxyl free radicals. DG-SDH (3:2) could increase the cell viability of SHSY-5Y cells, PC-12 cells, and BV-2 cells. In particular, DG-SDH (3:2) protected SHSY-5Y cells from H2 O2 -induced cell injury by inhibiting excessive expression of reactive oxygen species (ROS), reducing the rate of apoptosis and restoring mitochondrial membrane potential. Actin-Tracker Green and DAPI staining and fluorescence microscope observation confirmed that DG-SDH (3:2) helped in preserving cell morphology under oxidative stress. These findings support that DG-SDH (3:2) promote the neuroprotection against hydrogen peroxide and can serve as a novel therapy for neurodegenerative diseases. PRACTICAL APPLICATIONS: This is the first study to investigate DG and SDH interaction between effective ingredients. These findings support that DG-SDH (3:2) has the best synergistic effects in antioxidant activity and promote the neuroprotection against hydrogen peroxide. Hence, DG-SDH (3:2) will be an excellent candidate to be developed as a functional food ingredients or nutraceuticals for neurodegenerative diseases.

Manufacturing micro/nano chitosan/chondroitin sulfate curcumin-loaded hydrogel in ionic liquid: A new biomaterial effective against cancer cells.

Chitosan/chondroitin sulfate (CHT/CS) curcumin-charged hydrogels were prepared through polyelectrolytic complexation (PEC) following two methodologies (PEC-CUR and PEC-T-CUR) and were applied on apoptosis of HeLa, HT29 and PC3 cancer cells. PEC-T-CUR (ionic liquid (IL) mixed using ultraturrax homogenizer) results show to be far better than for PEC-CUR (IL mixed using magnetic stirring), with IC50 being improved 5.13 times to HeLa cancer cells (from 1675.2 to 326.7 µg mL-1). PECs produced by this methodology presented favorable characteristics, such as particle size, hydrophobicity, pH swelling. Beyond this, the IL was quantitatively recovered in both cases. CUR entrapment levels were hugely loaded into PEC at around 100%. Swelling, dissolution/degradation, and pHpzc assays showed that PECs may positively act in several environments, releasing the CUR, the CHT and CS as well. Characterization through FTIR, SEM, TEM, TGA, DSC, and WAXS confirmed CUR presence in both types of PECs, and cytotoxic studies showed the significant anticancer effects of CUR-containing PECs.

Equivalencia terapéutica in vitro de tabletas de enalapril maleato 20 mg de producción nacional / In vitro therapeutic equivalence of 20 mg enalapril maleate tablets of national production

Los ensayos de equivalencia terapéutica tienen como objetivo demostrar que los medicamentos genéricos aportan la misma cantidad de principio activo en comparación con el medicamento innovador. El objetivo de la investigación fue evaluar la equivalencia terapéutica del medicamento enalapril maleato en tabletas de 20 mg, según la clasificación biofarmacéutica que le corresponde, ya que este es un medicamento representativo de la clase III, para demostrar que tienen un perfil de tolerabilidad adecuado y que son eficaces para su prescripción médica. Por otro lado, al demostrarse la equivalencia terapéutica se puede recurrir con toda seguridad al medicamento genérico y reducir los costos de los tratamientos, con lo cual la población tendrá una oferta de medicamentos confiables, seguros y a precios económicos. Se utilizó un medicamento innovador y tres de los ocho medicamentos genéricos de fabricación y comercialización nacional, a los cuales se les determinó perfiles de disolución (F2: 45.41, 92.42, 71.04), uniformidad de contenido (AV: 7.37, 2.97, 2.50) y valoración de principio activo (%: 107.14, 98.89, 101.71) para determinar la cantidad de principio activo en las muestras. Los análisis se realizaron con base en los criterios establecidos en la Farmacopea de los Estados Unidos. Se aplicó un modelo estadístico independiente, y se estableció que dos de los tres lotes analizados de los medicamentos genéricos son equivalentes terapéuticos con el lote del medicamento innovador. Con las pruebas de disolución in vitro realizadas a lo largo de este estudio, se puede concluir que los tres lotes analizados de dos medicamentos genéricos pueden ser considerados intercambiables con respecto al lote del medicamento innovador.

The therapeutic equivalence essays to demonstrate that generic medicine can provide the same amount of active ingredient compared to the innovative medicine. The objective of this research was to evaluate the therapeutic equivalence of enalapril maleate 20 mg, according to the biopharmaceutical classification, given that this is a representative class III drug. This to demonstrate that it has an acceptable tolerability profile and that it is effective for medical prescription. Once the therapeutic equivalence is stablished, the use of therapeutic bioequivalence products can reduce treatment costs, so that the general public can have access to reliable, safe and affordable medicines. For this study an innovative medicine and three of the eight generic medicines of national manufacture and commercialization were used for each medicine, the dissolucion profiles (F2: 45.41, 92.42, 71.04), the uniformity of content (AV: 7.37, 2.97, 2.50) and percentage of active ingredient (%: 107.14, 98.89, 101.71) were determined. The essays were performed based on the criteria established in The United States Pharmacopeia and were satisfactory in all the analyzed batches. An independent statistical model was carried out it was established, that two of the three analyzed batches for generic medicine are therapeutic equivalents with the batch of the innovative drug. In vitro dissolution tests obtained throughout this study, concluded that the three analyzed batches of two generic medicines can be considered interchangeable in respect to the batch of the innovative medicine.

Non-covalent formulation of active principles with dendrimers: Current state-of-the-art and prospects for further development.

During the last three decades, dendrimers, nano-sized highly-branched fractal-like symmetrical macromolecules, have been intensively studied as promising candidates for application as drug-delivery carriers. Among other important characteristics arising from their unique and highly-controlled architecture, size and surface properties, the possibility of hosting guest molecules in internal voids represents a key advantage underlying the potential of dendrimers as non-covalent drug-encapsulating agents. The impressive amount of accumulating experimental results to date allows researchers to identify the most important and promising theoretical and practical aspects of the use of dendrimers for this purpose. This review covers the main factors, phenomena, and mechanisms involved in this drug-vectorization approach, including mechanisms of non-covalent dendrimer-drug association, dendrimer-dendrimer interactions, as well as biological properties relevant to the host dendrimers. A discussion is then provided to illustrate some successful existing formulation strategies as well as to propose some new possible ones to optimize further development of the field.

The Medicinal Usage and Restriction of Ginseng in Britain and America, 1660-1900.

This article demonstrates the medicinal usage of ginseng in the West from 1660 to 1914. Asian[Korea] ginseng was first introduced into England in the early 17th century, and North American ginseng was found in the early 18th century. Starting from the late 17th century doctors prescribed ginseng to cure many different kinds of ailments and disease such as: fatigue general lethargy, fever, torpidity, trembling in the joints, nervous disorder, laughing and crying hysteria, scurvy, spermatic vessel infection, jaundice, leprosy, dry gripes and constipation, strangury, yellow fever, dysentery, infertility and addictions of alcohol, opium and tobacco, etc. In the mid-18th century Materia Medica began to specify medicinal properties of ginseng and the patent medicines containing ginseng were widely circulated. However, starting in the late 18th century the medicinal properties of ginseng began to be disparaged and major pharmacopoeias removed ginseng from their contents. The reform of the pharmacopoeia, influenced by Linnaeus in botany and Lavoisier in chemistry, introduced nomenclature that emphasized identifying ingredients and active constituents. Western medicine at this period, however, failed to identify and to extract the active constituents of ginseng. Apart from the technical underdevelopment of the period, the medical discourses reveal that the so-called chemical experiment of ginseng were conducted with unqualified materials and without proper differentiation of various species of ginseng.

The Medicinal Usage and Restriction of Ginseng in Britain and America, 1660–1900 / 의사학

This article demonstrates the medicinal usage of ginseng in the West from 1660 to 1914. Asian[Korea] ginseng was first introduced into England in the early 17th century, and North American ginseng was found in the early 18th century. Starting from the late 17th century doctors prescribed ginseng to cure many different kinds of ailments and disease such as: fatigue general lethargy, fever, torpidity, trembling in the joints, nervous disorder, laughing and crying hysteria, scurvy, spermatic vessel infection, jaundice, leprosy, dry gripes and constipation, strangury, yellow fever, dysentery, infertility and addictions of alcohol, opium and tobacco, etc. In the mid-18th century Materia Medica began to specify medicinal properties of ginseng and the patent medicines containing ginseng were widely circulated. However, starting in the late 18th century the medicinal properties of ginseng began to be disparaged and major pharmacopoeias removed ginseng from their contents. The reform of the pharmacopoeia, influenced by Linnaeus in botany and Lavoisier in chemistry, introduced nomenclature that emphasized identifying ingredients and active constituents. Western medicine at this period, however, failed to identify and to extract the active constituents of ginseng. Apart from the technical underdevelopment of the period, the medical discourses reveal that the so-called chemical experiment of ginseng were conducted with unqualified materials and without proper differentiation of various species of ginseng.

Bioinformatics Analysis on Proteomics of Rat Bone Marrow Mesenchymal Stem Cells Intervened by Active Principle Region of Yang-Xin Tong-Mai Formula / 世界科学技术-中医药现代化

This study was aimed to analyze the bioinformatics of proteomics of rat bone marrow mesenchymal stem cells (MSCs) intervened by active principle region of Yang-Xin Tong-Mai Formula (apr-YTF). The latest versions of bioinformatics tools including DAVID (http://david.abcc.ncifcrf.gov/) and GO (http://www.geneontology.org/) were combined to assign a precise function to rat bone marrow MSCs intervened by apr-YTF. KEGG and VISANT were assigned with a precise function to rat bone marrow MSCs intervened by apr-YTF. The results showed that a total of 102 biological processes were mainly involved, with 35 cellular components and 6 molecular functions. These proteins interacted in 3 signal transduction pathways. It was concluded that the following proteins and signal transduction pathways played an important role in the process of apr-YTF inducing BMSCs differentiation into cardiomyocytes. Presenilin-1 and Presenilin-2 were in the Notch signaling pathway. And syntaxin-4 protein was in soluble N-ethylmaleimide sensitive fusion protein attachment protein (SNARE). The apr-YTF played a role on MSCs from multiple sites, with multiple links through different biological processes. The bioinformatics of proteomics can predict action mechanism of traditional Chinese medicine (TCM) from the holism concept. The validation in combination with molecularbiology was a good way for TCM modernization.

The active principle region of Buyang Huanwu decoction induced differentiation of bone marrow-derived mesenchymal stem cells into neural-like cells: Superior effects over original formula of Buyang Huanwu decoction.

The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction (active principle region of decoction for invigorating yang for recuperation). After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula.

Determinação de óleos essenciais de alfavaca (Ocimum gratissimum L. ), orégano (Origanum vulgare L. ) e tomilho (Thymus vulgaris L.) / Determination of essential oils of basil (Ocimum gratissimum L. ), oregano (Ocimum gratissimum L. ) and thyme (Thymus vulgaris L.)

O presente trabalho teve como objetivo a caracterização de plantas frescas e secas (comerciais) de alfavaca, orégano e tomilho, a obtenção dos óleos essenciais através do método de arraste a vapor e a quantificação dos compostos químicos por CG/EM. As plantas frescas e as secas comerciais foram submetidas às análises de umidade, extrato etéreo, proteína, fibra bruta, cinzas, extrato não nitrogenado, valor calórico, teor de óleo essencial e identificação dos compostos majoritários através da cromatografia gasosa-espectrometria de massas. Dentre a caracterização obtida os resultados na base seca mostraram-se promissores, sendo o teor de proteína e de cinzas na alfavaca seca comercial com 17,34 g 100 g-1 e 8,12 g 100 g-1, respectivamente; a fibra bruta no orégano seco comercial com 15,65 g 100 g-1; o extrato etéreo, o extrato não nitrogenado e o valor calórico no tomilho seco comercial com 9,30 g 100 g-1, 52,72 g 100 g-1 e 356,74 Kcal 100 g-1, respectivamente. Obteve-se o maior rendimento de óleo essencial na alfavaca seca comercial com 1,02%, enquanto a alfavaca fresca apresentou o menor rendimento, com apenas 0,13%. Na alfavaca fresca encontrou-se 87,38% de eugenol e 6,27% de timol, enquanto na alfavaca seca comercial observou-se redução no eugenol (71,12%) e aumento do timol (13,28%). No orégano fresco foram quantificados quatro picos o γ-terpineno (33,45%), 4-terpineol (25,59%), timol (14,21%) e carvacrol (2,30%). Já no óleo essencial de orégano seco comercial houve redução no γ-terpineno (28,73%) e aumento no 4-terpineol (27,58%), timol (19,71%) e carvacrol (3,67%). No óleo essencial do tomilho fresco foram quantificados três picos o borneol (66,66%), timol (13,41%) e linalol (3,24%). Por outro lado, no óleo essencial do tomilho seco comercial houve redução no borneol (37,90%) e aumento no timol (20,61%) e linalol (10,34%). Pode-se concluir que as folhas secas comerciais analisadas de alfavaca, orégano, e tomilho apresentam potencial para o enriquecimento dos alimentos ou para a obtenção dos óleos essenciais.

This study aimed to characterize commercial fresh and dry medicinal plants (basil, oregano and thyme), to obtain essential oil by the steam distillation method and to quantify chemical compounds by means of GC/MS. The fresh and dry plants were subjected to the following analyses moisture, ether extract, protein, crude fiber, ash, non-nitrogenous extract, caloric value, essential oil content and identification of major compounds by gas chromatography-mass spectrometry. Considering the obtained characterization, the following results on dry basis proved promising: protein and ash content in commercial dry basil with 17.34 g 100 g-1 and 8.12 g 100 g-1, respectively; crude fiber in commercial dry oregano with 15.65 g 100 g-1; ether extract, non-nitrogenous extract and caloric value in commercial dry thyme with 9.30 g 100 g-1, 52.72 g 100 g-1 and 356.74 Kcal 100 g-1, respectively. The highest essential oil yield was obtained for commercial dry basil with 1.02% and the lowest yield was obtained for fresh basil with only 0.13%. Chromatography indicated 87.38% eugenol and 6.27% thymol in fresh basil. For commercial dry basil, the chromatogram showed a reduction in eugenol (71.12%) and an increase in thymol (13.28%). Four peaks were quantified for fresh oregano the γ-terpinene (33.45%), 4-terpineol (25.59%), thymol (14.21%) and carvacrol (2.30%). For the essential oil of commercial dry oregano, there was a decrease in γ-terpinene (28.73%) and an increase in 4-terpineol (27.58%), thymol (19.71%) and carvacrol (3.67%). In the chromatogram of the essential oil of fresh thyme, three peaks were quantified: borneol (66.66%), thymol (13.41%) and linalool (3.24%). On the other hand, in the chromatogram of the essential oil of commercial dry thyme, there was a decrease in borneol (37.90%) and an increase in thymol (20.61%) and linalool (10.34%). It can be concluded that commercial dry leaves of basil, oregano and thyme are feasible to enrich foods or to obtain essential oils.

Study on anticancer active principle in lignum Caesalpinia sappan / 肿瘤研究与临床

Objective To search for the anticancer active substance from Caesalpinia sappan wood extractions. Methods Crude extracts were extracted from Caesalpinia sappan wood with different solvents.Liquid chromatography was applied to analyze the content of each essential component in the extraction fractions. Trypan blue exclusion test was performed to detect the growth suppression rate of human bladder carcinoma cell line T24 treated by the extraction fractions at different time course (20,40,60,80,100 min).The main component positively correlated with the cell suppression rate was separated out using repeated chromatography, thus the anticancer active monomer was obtained, with purity over 98 ％. The chemical constitution was determined using NMR (nuclear magnetic resonance), mass spectrum and infrared spectrum methods. T24 cell line, human ovarian cancer cell line SKOV3, mice sarcoma S180 and hepatic carcinoma H22 cell were chosen as target subjects, with mitomycin, hydroxycamptothecin as positive control drug, the inhibitory activity of the monomer was tested by trypan blue chromophobia method. Results Among the extraction fractions, R12 has a positive correlation with the cell suppression rate (r100 min=0.941, P＜0.001).Brazilin is the key component in R12.The inhibition rate of brazilin could reach 90.89 ％,98.65 ％,99.82 ％ and 100.00 ％ on T24,SKOV3,S180 and H22 respectively in 40 min at the concentration of 1.2 mg/ml,and its effect is much superior to that of the control drug mitomycin and hydroxycamptothecin. Conclusion Brazilin is one of the essential anticancer principles in Caesalpinia sappan wood.

Current status of Indian medicinal plants with antidiabetic potential：a review

In India, indigenous remedies have been used in the treatment of diabetes mellitus since the time of Charaka and Sushruta. Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. The ethnobotanical information reports that about 800 plants may possess anti-diabetic potential. Out of several Indian medicinal plants 33 plants were reviewed. The most effective antidiabetic Indian medicinal plants are Acacia arabica, Aegle marmelose, Agrimonia eupatoria, Allium cepa, Allium sativum, Aloe vera, Azadirachta indica, Benincasa hispida, Beta vulgaris, Caesalpinia bonducella, Citrullus colocynthis, Coccinia indica, Eucalyptus globules, Ficus bengalenesis, Gymnema sylvestre, Hibiscus rosasinesis, Ipomoea batatas, Jatropha curcus, Mangifera indica, Momordica charantia, Morus alba, Mucuna pruriens, Ocimum sanctum, Pterocarpus marsupium, Punica granatum, Syzigium cumini, Tinospora cordifolia, Trigonella foenum graecum. A wide array of plant derived active principles representing numerous chemical compounds has demonstrated activity consistent with their possible use in the treatment of diabetes.

Antineoplasic activity of Agaricus brasiliensis basidiocarps on different maturation phases

The fungus Agaricus brasiliensis is a Basidiomycete studied because of its immunomodulation and/or antitumor substances. The objective of this study was to verify the Agaricus brasiliensis antineoplasic activity in vivo on different basidiocarp maturation phases on Sarcoma 180 cells implanted in mice. Sarcoma cells were implanted in mice and after seven days mice were divided in three groups. The first group was treated with saline solution, the second group was treated with closed basidiocarp extract solution and the third group was treated with opened basidiocarp extract solution. After 30 days of being daily orally treated with these three solutions all animals suffered euthanasia, and the splenic index, tumor mass and volume were determined. No significant differences of the tumor growth inhibition in function of the different basidiocarp maturation phases for the Agaricus brasiliensis strain were observed. The in vivo basidiocarp antineoplasic average activity was 89.22 percent.

Antineoplasic activity of Agaricus brasiliensis basidiocarps on different maturation phases.

The fungus Agaricus brasiliensis is a Basidiomycete studied because of its immunomodulation and/or antitumor substances. The objective of this study was to verify the Agaricus brasiliensis antineoplasic activity in vivo on different basidiocarp maturation phases on Sarcoma 180 cells implanted in mice. Sarcoma cells were implanted in mice and after seven days mice were divided in three groups. The first group was treated with saline solution, the second group was treated with closed basidiocarp extract solution and the third group was treated with opened basidiocarp extract solution. After 30 days of being daily orally treated with these three solutions all animals suffered euthanasia, and the splenic index, tumor mass and volume were determined. No significant differences of the tumor growth inhibition in function of the different basidiocarp maturation phases for the Agaricus brasiliensis strain were observed. The in vivo basidiocarp antineoplasic average activity was 89.22%.