Green chemical synthesis of gold nanoparticles by using Penicillium aculeatum and their scolicidal activity against hydatid cyst protoscolices of Echinococcus granulosus.

Hydatid disease is a helminth infection with various clinical complications caused by the larval stage of the dog tapeworm Echinococcus granulosus. The scolicidal agents have been broadly applied for inactivation of the fertile cysts up to now, but these scolicidal agents have several side effects on patients. Therefore, this study aimed to explore the scolicidal activity of green synthesized gold nanoparticles (AuNPs) utilizing mycelia-free culture filtrate of Penicillium aculeatum against hydatid cyst protoscolices of E. granulosus. The size and morphology of AuNPs were affirmed by UV-visible spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and dynamic light scattering (DLS) analysis. The Fourier transform infrared (FT-IR) analysis of AuNPs showed the presence of possible functional groups responsible for the bioreduction and capping. The AuNPs were formed relatively uniform with spherical shape and superior monodispersity with the average diameter of 60 nm. Consequently, various concentrations (0.05, 0.1, 0.2, and 0.3 mg/mL) of green synthesized AuNPs and different exposure times (10, 30, 60, and 120 min) were used against hydatid cyst protoscolices. Statistically, the difference between the scolicidal effects of AuNPs were seen extremely significant for all four concentrations and at various exposure times in comparison to the control group (P < 0.0001). The most mean protoscolex elimination ratio was 94% (0.3 mg/mL AuNPs and 120-min exposure time). The current investigation indicated that applying biogenic AuNPs may be considered as a potential scolicidal agent for cystic hydatid disease. However, further studies are required to evaluate the efficacy of AuNPs in vivo.

Naghibione; A Novel Sesquiterpenoid with Antiplasmodial Effect from Dorema hyrcanum Koso-Pol. Root, a Plant Used in Traditional Medicine.

Some Dorema species are used in Persian traditional medicine. In the present study the total extract from the roots of Dorema hyrcanum Koso-Pol. was investigated for its in-vitro (pLDH assay) and in-vivo (Peters' 4-days suppressive test) antiplasmodial effects and assessed for cytotoxicity against the normal cell line MDBK (MTT test). The IC50 values for a chloroquine- sensitive (3D7) and a chloroquine- resistant (K1) strain of Plasmodium falciparum were 28.64 and 9.79 µg/mL, respectively. The inhibition percentage of the rodent parasite, Plasmodium berghei, on day 4 in mice was 77.9% and IC50 value on Madin-Darby bovine kidney cells (MDBK cells) was 59.84 µg/mL. The total extract was subjected to a bioassay-guided fractionation protocol based on the in-vivo model which resulted in the isolation of an acetophenon (compound 1), one new sesquiterpenoid; naghibione (compound 2) and two known sesquiterpenoid derivatives (compounds 3, 4). Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments and ESI-MS. All compounds were evaluated for in-vivo antiplasmodial effect and the results revealed that naghibione showed good suppression activity, inhibiting 68.1 % of the parasite growth.

Antiplasmodial Activity and Cytotoxicity of Plants Used in Traditional Medicine of Iran for the Treatment of Fever.

Malaria is the most serious parasitic disease and one of the oldest recorded diseases in the world. Because of the resistance of malaria parasites to current drugs, it is necessary to discover new antiplasmodial drugs. Traditional medicine is one of the important sources of new antiplasmodial drugs. In this study, twenty methanolic extracts from different parts of sixteen medicinal plants used in traditional medicine of Iran for the treatment of "Nobeh fever" and/ or fever were screened for in-vivo antiplasmodial activity against Plasmodium berghei and cytotoxic effect on Madin-Darby bovine kidney cells (MDBK). Eleven species (55%) were found to have antiplasmodial activity. Methanolic extract from Rosa damascena Mill. reduced parasitemia by 57.7% compared to untreated control mice at intra-peritoneal (i.p.) injection doses of 10 mg/Kg per day for 4 days. This is the first report that mentioned in-vivo antiplasmodial activity of Rosa damascena Mill.

Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.

Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin) and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) µg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies.

Microbial mediated preparation, characterization and optimization of gold nanoparticles

The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 ºC and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl4 solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl4, pH of medium and temperature of shaker incubator. The R² value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hot and cold temperaments are the basic concepts of Iranian traditional medicine (ITM). Nevertheless, studies on the functional mechanisms of medicinal herbs based on hot and cold temperaments are not very extensive. This study aimed to evaluate the effects of diets containing hot or cold temperament seeds according to ITM on some hormonal and neuromediator parameters with a regulatory role in thermogenesis and energy metabolism in acute (24 hr) and subacute (7-day) experiments that were performed on rats. MATERIALS AND METHODS: Each experiment was performed on 42 male Wistar rats, which were randomly divided into 7 groups. while 1 group received usual diet (controls), 6 other groups were fed with a diet containing 10% seeds, namely, anise, fennel, or ajowan (hot temperament groups) or cucumber, pumpkin, or watermelon (cold temperament groups), respectively. The levels of the rats׳ serum free thyroxin (FT4), free triiodothyronin (FT3), triiodothyronin (T3), thyroxin (T4), corticosterone and urine vanillylmandelic acid (VMA) were analyzed. RESULTS: After 24 hours, a significant decrease in FT3 was observed in groups that were fed anise or fennel seeds. However, a significant increase in T3 was observed in the ajowan seed-fed group, and no changes in other parameters were observed in this group. On the 7th day, FT4 was significantly increased in fennel seed-fed group; T3 was significantly increased in the anise, fennel, ajowan and watermelon seed-fed groups; corticosterone was significantly increased in the watermelon and pumpkin seed-fed groups; and VMA was significantly increased in the fennel seed-fed group and significantly decreased in the cucumber seed-fed group. CONCLUSION: Alterations induced by hot and cold temperament seeds in measured hormonal and neuromediator levels that have a regulatory role in thermogenesis and the body׳s energy metabolism revealed that hot and cold temperament characteristics of studied seeds may most likely be related to their intervention in the body׳s energy metabolism, in that hot temperament seeds may increase energy metabolism and cold temperament ones may decrease it.

Cytotoxic activity evaluation of some medicinal plants, selected from Iranian traditional medicine Pharmacopoeia to treat cancer and related disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: By studying the Iranian Traditional Medicine (ITM) Pharmacopoeia, we have collected information about medicinal plants which had been used to manage cancer-like disorders over eight hundred years, from medieval to the early modern era. Exploring the ITM herbal knowledge, the selected species have been subjected to MTT assay for examining their in vitro cyototoxic activity. MATERIALS AND METHODS: Cancer was reviewed through the ITM and some terminologies were acquired. Five ITM Pharmacopoeia in Arabic and Persian languages from 10th to 18th century AD were explored. These Pharmacopoeia contained the ITM plants which were used to cure cancer and cancer-like diseases. The ITM names were matched with the scientific names. Then the medicinal plants were collected, authenticated and were evaluated for cytotoxic activity using MTT assay, against MCF-7, HepG-2, A-549 and HT-29 cell lines. Finally, the apoptosis induction ability of the most cytotoxic medicinal plant was investigated by activated caspase 3 inspection in MCF-7 cell line. RESULTS: Six species of the evaluated medicinal plants revealed cytotoxic activity. The most cytotoxicity was observed in Tanacetum polycephalum subsp. argyrophyllum (K.Koch) Podlech with IC50 values of 28.3 µg mL(-1), 53.9 µg mL(-1) and 43.3 µg mL(-1) against MCF-7, A-549 and HT-29 cell lines, respectively. Caspase 3 activation was also observed in MCF-7 cells by Tanacetum polycephalum subsp. argyrophyllum. This is the first time that the cytotoxic activity of this species has been reported. CONCLUSION: In the present study, some reliable references of ITM have been introduced and though many technical difficulties, linguistic problems and some other hindrances were encountered during the study, using traditional medicine texts for medicinal plant selection could be considered as a helpful starting point in the field of cancer drug discovery.

Natural sesquiterpen lactones as acetylcholinesterase inhibitors.

Background and the purpose of the study: The amount of elder people who suffer from Alzheimer disease is continuously increasing every year. Cholinesterase inhibitors have shown to be effective in alleviating the symptoms of the disease, thus opening a field of research for these treatments. Herbal products, owning a reputation as effective agents in many biological studies are now drawing attention for inhibiting acetylcholinesterase, in other words, Alzheimer disease. In the present study, the ability of three sesquiterpene lactones from Inula oculus-christi and I. aucheriana to inhibit AChE has been evaluated through Ellman assay. Materials and Methods: Gaillardin and pulchellin C were obtained from I. oculus-christi and britannin from I. aucheriana by chromatographic methods. They were dissolved in methanol in concentration of 3 mg/mL and the AChEI activity of the compounds was determined by Ellman method using Acethylthiocholine iodide as the substrate and 5, 5'-dithiobis-2-nitrobenzoic acid as the reagent, in 96-well plates at 405 nm. Results: AChEI activity of the examined compounds was obtained as 67.0, 25.2 and 10.9% in concentration of 300 µg/L for gaillardin, britannin and pulchellin C, respectively. Conclusion: Among the three sesquiterpene lactones, gaillardin with 67% inhibition of AChE could be considered a good candidate for future Alzheimer studies.

The effects of selected hot and cold temperament herbs based on Iranian traditional medicine on some metabolic parameters in normal rats.

This study was aimed to evaluate the effects of diets containing some hot and cold temperament herb seeds according to Iranian traditional medicine (ITM) on some metabolic parameters in acute (24 h) and sub-acute (7 day) experiments that were performed on rats. For each experiment, effects of diets containing 10% herb seeds in category of hot (anise, fennel, ajowan) and cold (cucumber, watermelon, pumpkin) temperaments were analyzed on body weight gain, food intake, water consumption, urine output, serum glucose (SG) and insulin levels of rats. In the acute experiment, anise or fennel fed groups showed a significant decrease in food intake and there were not any changes in other parameters. The hot temperament groups in comparison with the cold temperament ones showed a significant decrease in food intake and a significant increase in SG level. In the sub-acute experiment, anise and fennel fed groups had a significant decrease in body weight gain on the 4thday. On the 7th day, the anise fed group experienced a significant decrease in body weight gain and a significant increase in SG levels. The groups that were fed hot temperament diets compared to the ones that consumed cold temperament diets showed a significant decrease in body weight gain and food intake rates and a considerable increase in SG levels. Considering the findings of this study, one can conclude that it is possible that hot temperament herbs such as anise and fennel be useful for humans for certain conditions such as weight control.

Herbal Remedies Connected to Malaria like Fever in Iranian Ancient Medicinal Books- Brief Review Article.

Malaria is a major international public health problem. Drug-resistant parasites have made treatment and control of malaria more difficult. Therefore, safe, affordable and effective new drugs are urgently needed. Traditional medicine is an important source for new drugs. Determining the ancient medicinal books was the first step of this study for finding malaria or disease that has symptoms like malaria. Then the plants that used to treat "Ghebbe Khalesseh fever" were listed. Finally, recent antimalarial researches were explored. About 31 plants were identified. Information from these resources is valuable for the selection of plants for antiplasmodial screening programs.

Microbial mediated preparation, characterization and optimization of gold nanoparticles.

The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 °C and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl4 solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl4, pH of medium and temperature of shaker incubator. The R(2) value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

Cytotoxic activity and apoptosis induction by gaillardin.

Cytotoxic activity of gaillardin, a sesquiterpene lactone isolated from Inula oculus-christi L. (Asteraceae), was assessed in the human breast adenocarcinoma cell line MCF-7, human hepatocellular carcinoma cell line HepG-2, human non-small cell lung carcinoma cell line A-549, and human colon adenocarcinoma cell line HT-29, resulting in IC50 values of 6.37, 6.20, 4.76, and 1.81 microg/mL, respectively, in the microculture tetrazolium-formazan MTT assay. In vitro apoptosis-inducing properties of gaillardin were also evaluated in MCF-7 cells with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. The results suggest gaillardin as a candidate for further studies in cancer therapy

Fungus-mediated synthesis of gold nanoparticles: a novel biological approach to nanoparticle synthesis.

The biological effects of nanoparticles and their uses as molecular probes are research areas of growing interest. The present study demonstrates an eco-friendly biosynthesis of gold nanoparticles. The pure colonies of penicillium aurantiogriseum, penicillium citrinum, and penicillium waksmanii were cultured in fluid czapek dox broth. Then, their supernatants were examined for the ability to produce gold nanoparticles. In this step, 1 mM solution of AuCl added to the reaction matrixes separately. The reactions were performed in a dark environment at 28 degrees C. After 24 hours, it was observed that the color of the solutions turned to dark purple from light yellow. Synthesized gold nanoparticles were characterized by using UV-Visible Spectroscopy, Nano Zeta Sizer, Scanning Electron Microscopy and Fourier transformed infrared spectroscopy. The results showed that the gold nanoparticles were formed fairly uniform with spherical shape with the Z-average diameter of 153.3 nm, 172 nm and 160.1 nm for penicillium aurantiogriseum, penicillium citrinum, and penicillium waksmanii, respectively. The Fourier transformed infrared spectra revealed the presence of different functional groups to gold nanoparticles which were present in the fungal extract. The current approach suggests that the rapid synthesis of nanoparticles would be proper for developing a biological process for mass scale production.

In vitro and in vivo antimalarial evaluations of myrtle extract, a plant traditionally used for treatment of parasitic disorders.

Based on the collected ethnobotanical data from the Traditional Medicine and Materia Medica Research Center (TMRC), Iran, Myrtus communis L. (myrtle) was selected for the assessment of in vitro and in vivo antimalarial and cytotoxic activities. Methanolic extract of myrtle was prepared from the aerial parts and assessed for antiplasmodial activity, using the parasite lactate dehydrogenase (pLDH) assay against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. The 4-day suppressive test was employed to determine the parasitemia suppression of the myrtle extract against P. berghei in vivo. The IC50 values of myrtle extract were 35.44 µg/ml against K1 and 0.87 µg/ml against 3D7. Myrtle extract showed a significant suppression of parasitaemia (84.8 ± 1.1% at 10 mg/kg/day) in mice infected with P. berghei after 4 days of treatment. Cytotoxic activity was carried out against mammalian cell lines using methyl thiazol tetrazolium (MTT) assay. No cytotoxic effect on mammalian cell lines up to 100 µg/mL was shown. The results support the traditional use of myrtle in malaria. Phytochemical investigation and understanding the mechanism of action would be in our upcoming project.

Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are an important element of medical system. These resources are usually regarded as part of cultural traditional knowledge. We present for the first time the results of an ethnobotanical survey in Kohghiluyeh va Boyer Ahmad province of Iran, conducted between 2008 and 2010. This information could be the basis of an evidence based investigation to discover new drugs. MATERIALS AND METHODS: Ethnobotanical data were analyzed by use-reports in addition important indices like relative frequency of citation (RFC) and cultural importance index (CI) were calculated. Totally 23 informants were interviewed. RESULTS: Our study reports 138 traditionally used plant species, belonging to 52 plant families from this province. Asteraceae and Lamiaceae are the dominant locally used families. The highest number of species and application were reported for digestive system disorder, metabolic disorder and respiratory system, respectively. The part of the plant most frequently used was the aerial part (31.9%), leaves (14.8%) and fruits (11.7%). The plants are used both for medicinal and non-medicinal purposes. Daphne mucronata Royle. and Teucrium polium L. have the largest value of relative frequency of citation and cultural importance index, respectively. CONCLUSION: Kohghiluyeh va Boyer Ahmad has good ethnobotanical potential for medicinal plants. This study is the first contribution to the ethnobotany of this region. We have gathered from this province some considerable knowledge about local medicinal plants for treating common health problem that is ready to be further investigated in the laboratory.

Evaluating the effect of zingiber officinalis on nausea and vomiting in patients receiving Cisplatin based regimens.

Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study.

Sesquiterpene lactones from Inula oculus-christi.

Inula oculus-christi L. (Compositae) extract was chromatographed and three sesquiterpene lactones ergolide, gaillardin and pulchellin C were isolated. The structures of these compounds were determined by analysis of their spectroscopic data, and their crystal structures were defined using X-ray crystallography; the isolation of ergolide and pulchellin C is reported for the first time from this species. These three compounds were evaluated for their in vitro cytotoxic activity against MDBK, MCF7 and WEHI164 cells; ergolide and gaillardin exhibited lower and significantly different IC50 values compared with pulchellin C (p<0.001).

New cucurbitane-type triterpenoids from Bryonia aspera.

Phytochemical investigation of the chloroform extract of BRYONIA ASPERA roots resulted in the isolation and structure elucidation of two new cucurbitacins (1, 2) together with eight known cucurbitane derivatives (6-13), the pentacyclic triterpene bryonolic acid (5) and two hydroxybenzoic acid amides (3, 4). Their structures were elucidated by spectroscopic analysis, including 2D NMR techniques.

Screening of antiplasmodial properties among some traditionally used Iranian plants.

ETHNOPHARMACOLOGICAL RELEVANCE: An investigation of plants was undertaken through interviews and literature surveys on plants used to treat malaria or cancer or microbial diseases in Iran. AIM OF STUDY: In vitro and in vivo antiplasmodial tests were carried out on selected plants traditionally used in Iran. MATERIALS AND METHODS: Thirty-two plants were extracted with methanol and tested for their in vitro (pLDH assay) activity against Plasmodium falciparum, in vivo activity against Plasmodium berghei and assessed for any cytotoxicity against the human cancer cell line MCF7 and the normal cell MDBK. RESULTS: Extracts from four plants, Buxus hyrcana Pojark. (Buxaceae), Erodium oxyrrhnchum M. Bieb. (Geraniaceae), Glycyrrhiza glabra L. (Fabaceae) and Ferula oopoda (Boiss and Bushe) Boiss. (Apiaceae) were found to have significant antiplasmodial activity (IC50 ranging from 4.7 to 26.6 microg/ml). These findings lend support to the use of Buxus hyrcana and Glycyrrhiza glabra in traditional medicine. The chloroformic fraction also was active against K1 and 3D7 strains. The chloroformic fraction was studied at 10 mg per kg body weight mouse per day. This fraction reduced parasitaemia by 86.1% compared to untreated control mice. CONCLUSION: Glycyrrhiza glabra showed antiplasmodial activity and has selectivity for Plasmodium falciparum and Plasmodium berghei when tested on mammalian cells. This is the first report that mentioned in vitro and in vivo antiplasmodial activity of Glycyrrhiza glabra.