An in silico investigation of phytochemicals as potential inhibitors against non-structural protein 1 from dengue virus 4

Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4.

Parthenolide promotes apoptotic cell death and inhibits the migration and invasion of SW620 cells

BACKGROUND/AIMS: Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. METHODS: SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death. The wound healing, Transwell migration, and Matrigel invasion assays were performed to investigate the effect of PT on cell migration/invasion. Western blotting was used to establish the signaling pathway of apoptosis and cell migration/invasion. RESULTS: PT exerts antiproliferative effect and induces apoptotic cell death of SW620 cells. In addition, PT prevents cell migration and invasion in a dose-dependent manner. Moreover, PT markedly suppressed migration/invasion-related protein expression, including E-cadherin, β-catenin, vimentin, Snail, cyclooxygenase-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 in SW620 cells. PT also inhibited the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and activated apoptosis terminal factor (caspase-3) in a dose-dependent manner. CONCLUSIONS: Our results suggest that PT is a potential novel therapeutic agent for aggressive CRC treatment.

Weekly azathioprine pulse versus daily azathioprinein the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study.

Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the effi cacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically signifi cant and comparable (P = 0.366). Patients on WAP had a higher incidence of adverse effects (P = 0.02). Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Papel do partenolídeo na redução do potencial maligno de células de câncer colorretal / [Role of parthenolide in reducing the malignant potential of colorectal cancer cells]

câncer colorretal constitui uma das principais causas de câncer no Brasil e no mundo. O microambiente inflamatório desempenha um importante papel na iniciação, promoção e progressão deste tipo de câncer. O TNF-α é um componente deste microambiente e conhecido por ativar via NF-κB. Neste contexto, o partenolídeo, uma lactona sesquiterpênica, com importante função anti-inflamatória por inibir a via NF-κB,apresenta-se como uma promissora molécula anticâncer por prevenir progressão no ciclo celular, migração, invasão e sobrevivência de células tumorais. No entanto, seus efeitos no câncer colorretal necessitam ser melhor definidos. O objetivo do presenteestudo foi analisar a ação do partenolídeo na reversão de características pró-tumoraisem células derivadas de câncer colorretal, Caco-2, HT-29 e HCT-116. Nossos resultados mostram que a atividade de NF-κB está diferencialmente ativa entre asdiferentes linhagens de células de câncer colorretal e que a resposta citotóxica ao tratamento com partenolídeo está relacionada com essa ativação. O partenolídeo foi capaz de prevenir a ativação da via NF-κB induzida por TNF-α através da redução da fosforilação do IκBα nas linhagens Caco-2 e HT-29, porém parece ter outro alvo inibitório nas células HCT-116, pois estas não apresentaram redução na translocação nuclear de NF-κB...

Colorectal cancer is one the main cancer types in Brazil and world. Inflammatorymicroenvironmet plays an important role in the initiation, promotion and progression of this cancer. TNF-a is an important constituent of this microenvironment, which is known as activator of NF-κB pathway. In this context, the parthenolide, a esquiterpene lactone that have anti-inflammatory function through NF-κB inhibition, presents promising anticancer properties for preventing cell cycle progression, migration,invasion and cell survival. However, the effects on colorectal cancer need to be best understood. This study aims to analyze the parthenolide action reversing pro-tumor characteristics of Caco-2, HT-29 and HCT-116 colorectal cancer cells. Our results shown the NF-κB pathway is differentially active among cell types of colorectal cancerand citotoxic response to parthenolide treatment has relationship with this level of activation. Parthenolide was able to prevent the TNF-α induced-activation NF-κB pathway through to decrease IκBα phosphorilation in Caco-2 and HT-29, but seem have another inhibitory target in HCT-116 cells, because it did not observed reduction of NF-κB nuclear in these cells...

Actividad antioxidante y antiinflamatoria del extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "Santa María". Ayacucho, 2014 / Antioxidant and anti-inflammatory activity of the hydroalcoholic extract of the flowers of Tanacetum parthenium L. Sch. Beep. "Santa Maria". Ayacucho, 2014

Los procesos inflamatorios no controlados producen daño celular donde los radicales libres están presentes y representan un peligro para la vida del paciente, en este contexto la búsqueda de moléculas de origen vegetal son incesantes por su aceptación cultural, una mejor compatibilidad con el cuerpo humano y menos efectos secundarios. El objetivo fue determinar la actividad antioxidante y antiinflamatoria del extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria", empleando la técnica in vitro del DPPH y el modelo in vivo de edema plantar inducida por carragenina en ratas Wistar. Se llevó a cabo en los laboratorios de la Escuela de Farmacia y Bioquímica de la Universidad Nacional de San Cristóbal de Huamanga, Ayacucho, Perú. La muestra fue recolectada en la ciudad de Huancayo, región Junin. Se ensayó concentraciones de 1, 2 y 3% en ungüentos base como vehículo semisólido usando el estándar de referencia diclofenaco gel 1%. El extracto hidroalcohólico contiene fenoles y taninos, flavonoides, faetonas y/o cumarinas, triterpenos y/o esteroides y aminoácidos. La concentración de extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria" con mayor actividad antiinflamatoria fue al 3%, con un porcentaje de desinflamación del84.6% {porcentaje de inflamación de 15.4%) y con un ABC de 6,214 mllt2. La concentración de extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria" con mayor actividad antioxidante fue a 100 ¡Jg/ml, con un porcentaje de 63,9%. Se concluye que el extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maría" tiene poca actividad antioxidante in vitro pero buena actividad antiinflamatoria in vivo estadísticamente similar al diclofenaco por lo que constituyen una fuente potencial para el tratamiento antiinflamatorio tópico.

Rapid screening of tannase producing microbes by using natural tannin

Use of natural tannin in the screening of tannase producing microbes is really promising. The present work describes about the possibility and integrity of the newly formulated method over the previously reported methods. Tannin isolated from Terminalia belerica Roxb. (Bahera) was used to differentiate between tanninolytic and nontanninolytic microbes. The method is simple, sensitive and superior for the rapid screening and isolation of tannase-producing microbes.

[Medicinal plants used in treatment of rhematologic diseases: a systematic review]

The rheumatologic diseases like osteoarthritis, rheumatoid arthritis, lowback pain and fibromyalgia are very common. The synthetic drugs available for treatment of these diseases have low efficacy and considerable adverse effects. Numerous approaches are used as alternatives and complementary to synthetic drugs to treat these diseases. One of the approaches is use of herbal medications. Here, the effects of medicinal plants and herbal active constituents used in treatment of these diseases including gammalinolenic acid, glucosamine, devil's claw [Harpagophytum procumbens], Ocimum species, Salix species, feverfew [Tanacetum parthenium], Tripterygium wilfordii, Uncaria species, nettle [Urtica dioica], ginger [Zingiber officinale], turmeric [Curcuma longa], chicory [Cichorium intybus], dog rose [Rosa canina] and avocado/soybean unsaponifiables obtained from search for english articles published in the databases PubMed and SCOPUS from 1966 to the end of 2011 using the keywords including the scientific, common and traditional names of plants are reviewed. Limited research has been conducted on the antirheumatic effects of these plants and active constituents so far. Thus it seems that further research to determine the mechanisms of action, drug interactions, efficacy and safety of medicinal plants and herbal active constituents potentially useful in treatment of these diseases are warranted

Synergistic Effect of Parthenolide in Combination with 5-Fluorouracil in SW480 Cells

BACKGROUND/AIMS: Parthenolide (PT) is responsible for the bioactivities of Feverfew. Besides its potent anti-inflammatory effect, this compound has recently been reported to induce apoptosis in cancer cells. Unfortunately, many of the therapies that use 5-fluorouracil (5-FU) alone or in combination with other agents are likely to become ineffective due to drug resistance. In the present study, we investigate the antitumor effect of PT combined with 5-FU on colorectal cancer cells. METHODS: SW480 cell was employed as a representative of human colorectal carcinoma (CRC) cells. We performed MTT, annexin-V assay, and Hoechst 33258 staining to measure the synergistic effect. Western blotting was used to demonstrate apoptotic pathway. RESULTS: Our result demonstrated that PT inhibited the viability of colorectal cancer cells and had synergistic anti-proliferation in combination with 5-FU. After combined treatment of 5-FU and PT, enhanced apoptotic cell death is observed using annexin-V FITC assay and it was revealed by the condensed chromatin and fragmented DNA. Compared with 5-FU or PT alone, the apoptosis of colorectal cancer cells treated with PT and 5-FU enhanced the activation of caspase-8, caspase-3. CONCLUSIONS: Combined treatment with PT may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells.

Characterization and application of tannase produced by Aspergillus niger ITCC 6514.07 on pomegranate rind

Extracellular tannase and gallic acid were produced optimally under submerged fermentation at 37 0C, 72 h, pH 5.0, 10 percent(v/v) inoculum and 4 percent(w/v) of the agroresidue pomegranate rind (PR) powder by an Aspergillus niger isolate. Tannic acid (1 percent) stimulated the enzyme production by 245.9 percent while with 0.5 percent glucose, increase was marginal. Tannase production was inhibited by gallic acid and nitrogen sources such as NH4NO3, NH4Cl, KNO3, asparatic acid, urea and EDTA. The partially purified enzyme showed temperature and pH optima of 35 0C and 6.2 respectively which shifted to 40 0C and 5.8 on immobilization in alginate beads. Activity of the enzyme was inhibited by Zn+2, Ca+, Mn+2, Mg+2, Ba+2and Ag+. The immobilized enzyme removed 68.8 percent tannin from juice of aonla/myrobalan (Phyllanthus emblica), a tropical fruit, rich in vitamin C and other essential nutrients. The enzymatic treatment of the juice with minimum reduction in vitamin C is encouraging as non enzymatic treatments of myrobalan juice results in vitamin C removal.

Development of enteric coated tablets from spray dried extract of feverfew (Tanacetum parthenium L) / Desenvolvimento de comprimidos de revestimento entérico de extrato de produto seco por aspersão de matricária (Tanacetum parthenium L)

Tanacetum parthenium (feverfew) is an herb that is commercialized worldwide as a therapeutic treatment for migraine. Its pharmacological effect is mainly due to the presence of the sesquiterpene lactone parthenolide as well as of flavonoids. So far, there are no studies on standardization of pre-formulations or phytomedicines containing this herb. The present study aimed at developing a pre-formulation using a standardized spray-dried extract of feverfew and further designing and standardizing enteric coated tablets. In this work, the spray-dried extract of feverfew was evaluated for its parthenolide, santin and total flavonoid content, parthenolide solubility, particle size, tapped density, hygroscopicity, angle of repose and moisture content. Tablets containing the spray-dried extract were tested for their average weight, friability, hardness, and disintegration time. The total flavonoid and parthenolide contents in the spray-dried extract were 1.31 percent and 0.76 percent w/w, respectively. The spray-dried extract presented consistent pharmacotechnical properties and allowed its tableting by direct compression. Tablet properties were in accordance with the proposed specifications. The procedures described herein can be used to prepare and evaluate pre-formulations of feverfew with adequate properties for the development of a high-quality phytomedicine.

Tanacetum parthenium (tanaceto) é uma planta medicinal comercializada no mundo todo para tratamento de enxaqueca. Seu efeito farmacológico é creditado principalmente à lactona sesquiterpênica partenolídeo e flavonóides. Até o momento não existem estudos sobre a padronização de pré-formulações ou o desenvolvimento de fitoterápicos com tanaceto. Logo, o objetivo deste trabalho foi obter comprimidos de revestimento entérico a partir de extrato seco e padronizado de tanaceto. Neste trabalho, o extrato seco do tanaceto obtido pelo método de spray drying foi avaliado quanto ao teor de partenolídeo, presença da santina, teor de flavonóides totais, solubilidade do partenolídeo, tamanho de partícula, ângulo de repouso, densidade, análise higroscópica e teor de umidade. A partir do extrato seco obtiveram-se comprimidos que foram revestidos em leito de jorro. Os comprimidos revestidos foram avaliados com relação ao peso médio, friabilidade, dureza e desintegração. O teor de flavonóides totais e de partenolídeo no extrato seco foram 1,31 por cento e 0,76 por cento (p/p), respectivamente. O extrato seco apresentou características farmacotécnicas satisfatórias permitindo a obtenção de comprimidos pelo método de compressão direta. As propriedades dos comprimidos revestidos estão de acordo com as especificações da literatura. Os procedimentos utilizados nesse trabalho podem ser utilizados para obter extrato seco e fitoterápicos de T. parthenium com alto padrão de qualidade.

Efficiency of composting parthenium plant and neem leaves in the presence and absence of an oligochaete, Eisenia fetida

Parthenium plants and neem leaves were composted using the epigeic earthworm, Eisenia fetida [worm-worked compost] to study the growth and reproductive indices of earthworm involved in the process of composting. Similarly, parthenium plants and neem leaves were composted without worms [worm-unworked compost]. Efficacy of the resulting composts in supporting the growth of plant was tested with the germination and growth of Vigna radiate seedlings. The results showed that higher parthenium amendment significantly reduced the growth and reproduction of Eisenia fetida compared with control. The two-way ANOVA results showed a significant difference in the growth rate of worms when exposed to different amended concentrations of parthenium plants and neem leaves at different durations as fixed factors. The following compost parameters were not significantly different when compared with control: pH, nitrogen, phosphorus, iron for parthenium worm-worked compost; nitrogen, phosphorus, magnesium, iron, organic carbon and carbon/nitrogen ratio for neem worm-worked compost; nitrogen, phosphorus and organic carbon for parthenium worm-unworked compost and pH, nitrogen, phosphorus, zinc and carbon/nitrogen ratio for neem worm-unworked compost. Between parthenium plant composts and neem leaves composts, significant differences were not observed in any of the plant biometric parameters. The results obtained from the present study indicated that the parthenium composting at low amendments with cow dung may help its eradication for better utilization

A new approach to microbial production of gallic acid / Uma nova abordagem para produção microbiana de ácido gálico

In a new approach to microbial gallic acid production by Aspergillus fischeri MTCC 150, 40gL-1 oftannic acid was added in two installments during the bioconversion phase of the process (25gL-1 and 15gL-1 at 32 and 44h respectively). The optimum parameters for the bioconversion phase were found to be temperature: 35ºC, pH: slightly acidic (3.3-3.5), aeration: nil and agitation: 250 rpm. A maximum of 71.4 percent conversion was obtained after 71h fermentation with 83.3 percent product recovery. The yield was 7.35 g of gallic acid per g of biomass accumulated and the fermenter productivity was 0.56 g of gallic acid produced per liter of medium per hour.

Em uma nova abordagem para produção de ácido gálico por Aspergillus fischeri MTCC 150, adiciona-se 40 g.L-1 de ácido tânico em dois momentos da fase de bioconversão do processo (25 g.L-1 e 15 g.L-1 a 32h e 44h, respectivamente). Os parâmetros ótimos para a fase de bioconversão foram: temperatura 35ºC, pH levemente ácido (3,3 a 3,5), nenhuma aeração e agitação 250 rpm. Um máximo de 71,4 por cento de conversão foi obtido após 71h de fermentação, com 83,3 por cento de recuperação do produto. O rendimento foi 7,35g de ácido gálico por g de biomassa acumulada e a produtividade do fermentador foi 0,56g de ácido gálico por litro de meio por hora.

Parthenium dermatitis treated with azathioprine weekly pulse doses.

BACKGROUND: Parthenium dermatitis is a serious problem in India. Corticosteroids are the mainstay of treatment but the prolonged use of corticosteroids can cause serious side effects. Azathioprine used in daily doses has been shown to be effective. AIM: We have evaluated the effectiveness of azathioprine weekly pulse doses for the treatment of parthenium dermatitis. METHODS: Twelve patients, ten males and two females, aged between 39 and 65 years (mean +/- SD = 53.5 +/- 8.7) having air-borne contact dermatitis to Parthenium hysterophorus for 3-19 years (mean = 6.33) were included in the study. The diagnosis in each patient was confirmed by patch-testing. The severity of the disease was determined by clinical severity score (CSS) on the basis of erythema, itching, type of lesions, and areas of body involved. RESULTS: The pretreatment CSS in these patients varied from 29.7 to 55.5 (mean +/- SD: 40.40 +/- 7.95). After clinical and laboratory evaluation, the patients were treated with 300-mg azathioprine once-weekly doses for 6 months. Clinical and laboratory evaluations were repeated at weeks 1, 2, and then every 4 weeks until the end of therapy to evaluate the therapeutic response and side effects. The response was excellent (80-100% clearance of disease) in seven (58.33%) patients and good (60% clearance) in five (41.66%) patients. The post-treatment CSS decreased from the mean +/- SD of 40.4 +/- 7.95 to 10.9 +/- 8.43 (P = 0.002). There were no significant side effects of the therapy. CONCLUSIONS: In this preliminary open study, azathioprine in weekly pulse doses has been found to be effective without any serious adverse effects in the treatment of parthenium dermatitis. The cost of therapy with this regimen is reduced by 60%.

new guaianolide from Tanacetum fruticulosum Leded

A new guaianolide, 3 beta, 4 beta -epoxy-8 alpha -isobutyryloxyguaia - 1[10], 11[13] - dien - 12,6 alpha -olide [Carlaolide] [1] from Tanacetum fruticulosum was isolated, and it's structure was elucidated on the basis of spectroscopic data

Pharmacologic misadventures with herb-drug interactions

This article review and discuss the complimentary and alternative medicine (CAM), where it all began, practices and ideas self- defined by their users as preventing and treating illnesses or promoting health and well-being.

Exposure to Parthenium hysterophorous pollen extract leads to bronchospasm in stable patients of bronchial asthma.

Role of Parthenium hysterophorous as an allergen evoking bronchial hyper-responsiveness was assessed in twenty five adult patients with stable asthma and ten healthy controls. Assessment was made with the help of skin prick and bronchial provocation tests (BPT) using a commercially available Pathenium extract. Eleven patients (44%) of the study group had a positive skin reaction and 4 (16%) showed a significant fall in FEV1 and PEFR (p < 0.05) on bronchial provocation. In the control group only one patient (10%) had a positive skin test while there was none with a positive bronchial challenge. There was a significant fall in the mean values of FEV1 and PEFR over base line after the BPT in patients of asthma than controls. It is concluded that a significant proportion of bronchial asthma patients are sensitized to Parthenium hysterophorous and it may act as a cofactor in seasonal exacerbation of their symptoms.

Tratamiento alternativo de dismenorrea primaria con Ruta chalepensis (ruda), Tagetes lucida (pericón), Chrysanthemun parthenium (altamisa) versus ibuprofen / Alternative treatment of primary dysmenorrhea with Ruta chalepensis (rue), Tagetes lucida (pericón), Chrysanthemun parthenium (altamisa) versus ibuprofen

Esta investigación fue realizada con el propósito de determinar el efecto clínico de la Tagetes lúcida, Chrysanthemun parthénium y Ruta chalepensis comparadas con ibuprofen en el tratamiento de dismenorrea primaria. Basado en el conocimiento de estudios realizados in vitro e in vivo y al uso popular de estas hiervas. El estudio doble ciego fue realizado en el Centro de Salud de la zona 1 de Villa Nueva durante los meses de febrero a mayo de 1996. Participando 60 pacientes entre las edades de 11 a 25 años, dedicadas a distintas actividades (estudiantes, amas de casa y empleadas), escogidas al azar, conformando una muestra de 30 pacientes en el grupo estudio tratadas con tintura de ruda, altamisa y pericón y 30 pacientes en el grupo control con tratamiento de ibuprofen (400mg). De la población estudiada las pacientes comprendidas entre los 16 20 años fueron las más afectadas por la dismenorrea primaria (42%), al igual que las solteras (81%). Se observó que la mayoría de las pacientes recurren a la automedicación (90%), asociando además el uso de plantas medicinales (20%). En la modificación del dolor el ibuprofen actúa en mayor número de pacientes (35%) durante el primer día de tratamiento asegurando un alivio más rápido en la paciente y por tanto su bienestar general. Mientras la tintura alcanza esa mejoría hasta el segundo día de dosificación. En el último día de tratamiento con ambos medicamentos se obtuvo una total mejoría del cuadro clínico de la población estudiada. Se observó una mayor frecuencia de efectos secundarios provocados por el ibuprofen (53%), siendo epigastralgia el más frecuentemente observado. Las pacientes tratadas con tintura presentaron menor frecuencia de efectos adversos (47%), los más frecuentes fueron cefalea y nausea. Debido a que se trató un proceso agudo y por corto tiempo, se tomó este dato como relevante pues es necesario determinar mediante estudios farmacológicos, efectos a largo plazo provocados por el uso prolongado de estas plantas. No se encontró diferencia de la eficacia de tintura comparada con el ibuprofen en el tratamiento de dismenorrea primaria, al aplicar x2 con una alfa de 0.05.