共查询到20条相似文献,搜索用时 31 毫秒
1.
Swayam Prakash Srivastava Akansha Mishra Vikram Bhatia T. Narender Arvind K. Srivastava 《Medicinal chemistry research》2011,20(9):1732-1739
The ethanolic as well as aqueous extracts of the hard wood of Acacia catechu showed improvement on oral glucose tolerance post-sucrose load in normal rats and streptozotocin (STZ)-induced diabetic rats.
Around 22 and 27% improvement in glucose tolerance was observed post 7 and 14 days of feeding the ethanolic extracts, respectively,
on STZ-induced diabetic rats. Whereas around 17 and 26% improvement on glucose tolerance was observed post 7 and 14 days of
feeding the ethanolic extract in the high fructose high fat diet (HFD) fed-low dosed STZ-treated rats. The ethanolic extract
of A. catechu hard wood also showed marked anti-dyslipidemic activity on HFD fed Syrian golden hamster as evidenced by around 43 and 26%
decline in serum triglycerides and total cholesterol, respectively. The ethanolic and aqueous extracts also showed marked
inhibition on eye lens aldose reductase either from normal or STZ-induced diabetic rats. Further studies are warranted to
isolate and identify the active ingredients from the ethanolic and aqueous extracts of A. catechu hard wood. 相似文献
2.
Rohit Srivsatava Swayam Prakash Srivastava Natasha Jaiswal Akansha Mishra Rakesh Maurya Arvind Kumar Srivastava 《Medicinal chemistry research》2011,20(9):1656-1666
The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P < 0.01) in normal rats and shows around 17.7% (P < 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic
rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P < 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract
was also found to have antidyslipidemic activity as evident by 21.04% (P < 0.01) decline in serum triglycerides, 22.7% (P < 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P < 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to
eye lens aldose reductase (EC 1.1.1.21) with IC50 value of 7.07 μg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC50 2.35 μg/ml. The extract was also found inhibitory to α-glucosidase with IC50 value of 100 μg/ml as compared to known drug Acarbose which showed IC50 of around 25 μg/ml. 相似文献
3.
Objectives Acacia catechu heartwood contains significant amounts of polyphenolic compounds that exhibit powerful antioxidant activity. The purpose of this study was to evaluate the cytotoxicity of A. catechu heartwood extracts in a human epithelial carcinoma cell line (A431) and antitumour activity against DMBA/TPA induced squamous cell carcinoma in Balb/c mice. Methods Various extracts, including aqueous, ethyl acetate, chloroform and n‐hexane, were tested for cytotoxic properties on a human epithelial carcinoma cell line (A431) by using MTT, sulforhodamine B and lactate dehydrogenase leakage assays. The standardized A. catechu heartwood aqueous extract (AQCE) was further evaluated for antitumour activity against 7,12‐dimethylbenz[a]anthracene (DMBA)/12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) induced skin carcinoma in Balb/c mice. Key findings The results showed that administration of AQCE showed a dose‐dependent growth inhibition response, with an IC50 value of 78.56 µg/ml. Tumour incidence was significantly decreased (P < 0.001) to 30% with AQCE compared with 100% in the DMBA/TPA group. The AQCE was also found to significantly upregulate different antioxidant enzymes in skin and liver tissue. Conclusions The results suggest that AQCE may exert its chemopreventive activity by acting as an antioxidant. 相似文献
4.
Lonchocarpus cyanescens (LC) is a medicinal plant commonly used in combination with other recipes in the treatment of psychotic disorders in traditional
medicine. This study was designed to examine whether the aqueous and ethanolic extracts of LC possess antipsychotic property
in rats. The antipsychotic effects of the extracts were assessed using the amphetamine animal model of psychosis in rats.
The effect of the extracts on spontaneous motor activity was also studied in the open field test in mice. The extrapyramidal
side effect of catalepsy was tested based on the ability of the extracts to alter the duration of akinesia in mice placed
on a vertical wrapped string. Aqueous and ethanolic extracts of LC (25–400 mg/kg, i.p.) significantly (p < 0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p.) in rats, which suggest antipsychotic activity.
The extracts (25–400 mg/kg, i.p.) further produced a significant (p < 0.05) reduction in spontaneous motor activity of the animals in the open field test. However, in contrast to chlorpromazine,
a typical antipsychotic, the extracts did not induce cataleptic behaviour in the animals. Preliminary phytochemical screening
showed the presence of alkaloids, anthraquinones, cardiac glycosides, cyanogenetic glycosides, flavonoids, saponins, steroids
and tannins in the leaves of LC. The presence of these secondary metabolites was confirmed by thin-layer chromatography. Taken
together, these findings suggest that the extracts possess phytochemically active constituents with antipsychotic property.
Thus, this investigation provides evidence that may justify the ethnomedicinal applications of Lonchocarpus cyanescens as the major constituent of the recipe used for the management of psychosis in Nigeria. 相似文献
5.
《Pharmacological reports : PR》2014,66(5):799-803
BackgroundVarious mechanisms with a complex integrating paradigm have been implicated in diabetic complications. The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end products (AGEs) inhibitory activity of resveratrol (RSV) and its potential in the treatment of diabetic complications such as cataract and nephropathy.MethodsRSV was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit formation of AGEs. Anticataract activity of RSV was demonstrated using sugar induced lens opacity model in isolated cattle lens. Furthermore the involvement of RSV in streptozotocin-induced diabetic nephropathy was investigated by assessing the key markers of kidney function along with the formation of AGEs. The potent AR inhibitor, fidarestat was as a standard.ResultsRSV exhibited inhibitory activity against RLAR and RKAR with IC50 values of 4.99 μg/ml (21.9 μM) and 5.49 μg/ml (24.5 μM), respectively. It also showed a significant inhibition of AGEs formation in vitro. In sugar-induced lens opacity model, RSV displayed a significant protective effect preventing opacification and formation of polyols in cattle lens. RSV significantly improved glycaemic status and renal function in diabetic rats with a significant decrease in the formation of AGEs in the kidneys.ConclusionsThe results obtained in this study underline the potential of RSV as a possible therapeutic agent against long-term diabetic complications. 相似文献
6.
Nishant P. Visavadiya Badrish Soni Nirav Dalwadi 《Food and chemical toxicology》2009,47(10):2507-2515
An emerging consensus underscores the importance of oxidative events in vascular disease including excess production of reactive oxygen/nitrogen species (ROS/RNS), in addition to lipoprotein oxidation. Sesamum indicum has long been used extensively as a traditional food. The aim of present study was to evaluate antioxidant action of aqueous and ethanolic seed extracts from S. indicum using various in vitro ROS/RNS generated chemical and biological models. Results demonstrated that the graded-dose (25–1000 μg/ml) of aqueous and ethanolic extracts markedly scavenged the nitric oxide, superoxide, hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, showed metal chelating ability as well as reducing capacity in Fe3+/ferricyanide complex and ferric reducing antioxidant power assays. In biological models, both extracts were found to inhibit metal-induced lipid peroxidation in mitochondrial fractions, human serum and LDL oxidation models. In lipoprotein kinetics study, both extracts significantly (P < 0.05) increased lag phase time along with reduced oxidation rate and conjugated dienes production. Ethanolic extract of S. indicum showed higher amounts of total polyphenol and flavonoid content as compared to their counterpart. The IC50 values of both extracts were compared with respective antioxidant standards. Overall, ethanolic extract of S. indicum possess strong antioxidant capacity and offering effective protection against LDL oxidation susceptibility. 相似文献
7.
Context: The study was carried out to evaluate the effect of the aqueous fruit pericarp extract of Litchi chinensis (APLC) on parameters which leads to diabetic cataractogenesis and retinopathy in the streptozotocin-induced diabetic rats.Objective: The objective of the study is to evaluate the APLC for in vivo antioxidant activity and its role in inhibiting the polyol pathway and formation of advanced glycation end products (AGEs).Materials and methods: The diabetic animals were treated with L. chinensis for a period of 12 weeks. At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats. Cataract progression due to hyperglycemia was monitored by slit lamp bio microscope and classified into four stages. Fundoscope test and retinal histopathology were done for assessing retinopathy.Results: Statistically significant reduction in glucose, and elevation of protein content, SOD, CAT, and GSH levels and decreased levels of AR and PCO in lens homogenate and significant reduction in AGEs serum and lens homogenate were observed. Slit lamp examination, fundoscope, and histopathology showed improvement in retinal changes in APLC-treated rats compared to diabetic control animals.Conclusion: The treatment with APLC found to delay the progression of diabetic cataractogenesis and retinopathy, which might be due to its antioxidant activity, because of the presence of active phytochemicals in APLC. 相似文献
8.
Aussara Panya Petlada Yongpitakwattana Prapaphan Budchart Nunghathai Sawasdee Sucheewin Krobthong Atchara Paemanee Sittiruk Roytrakul Siriluk Rattanabunyong Kiattawee Choowongkomon Pa‐thai Yenchitsomanus 《Chemical biology & drug design》2019,93(2):100-109
The therapeutic activities of food‐derived bioactive proteins and peptides are attracting increased attention within the research community. Medicinal plants used in traditional medicines are an excellent source of bioactive proteins and peptides, especially those traditionally prepared by water extraction for use as tea or food supplement. In this study, novel bioactive peptides were isolated from enzymatic digests of 33 Thai medicinal plants. The inhibitory activity of each against dengue virus (DENV) infection was investigated. Of 33 plants, peptides from Acacia catechu extract demonstrated the most pronounced anti‐DENV activity. Half maximal inhibitory concentration of 0.18 μg/ml effectively inhibited DENV foci formation. Treatment with 1.25 μg/ml crude peptide extract could reduce virus production less than 100‐fold with no observable cell toxicity. Peptide sequences were determined by high‐performance liquid chromatography and liquid chromatography–tandem mass spectrometry. Two bioactive peptides isolated from Acacia catechu inhibited DENV foci formation >90% at the concentration of 50 μM; therefore, they are recommended for further investigation as antiviral peptides against DENV infection. 相似文献
9.
Sama Venkatesh B. Madhava Reddy G. Dayanand Reddy Ramesh Mullangi M. Lakshman 《Journal of natural medicines》2010,64(3):295-304
The antihyperglycemic and hypolipidemic activities of Helicteres isora Linn. (Sterculiaceae) root extracts were investigated in alloxan-induced diabetic rats and a possible mechanism of the blood
glucose lowering action was studied. Alloxan-induced diabetic rats experienced 69.13 and 51.14%, 22.60 and 21.89%, 30.12 and
19.96%, and 50.05 and 34.29% reduction in blood glucose, total cholesterol, triglycerides, and urea levels following oral
administration of butanol and aqueous ethanol extracts of H. isora root, respectively, at 250 mg/kg for 10 days. The beneficial effects of these extracts were supported by evidence from histological
examinations of the liver, pancreas, and kidney. Following the treatment with both extracts, the degenerative changes caused
by alloxan in pancreatic cells were restored, particularly with the butanol extract. Histological examination convincingly
showed the restoration of pancreatic islets, kidney glomeruli, and liver to its normal size. These results suggest that H. isora roots possess antidiabetic principles and can be useful for treatment of diabetes. 相似文献
10.
M.R.M. Rafiullah A.W. Siddiqui S.R. Mir M. Ali K.K. Pillai Surendar Singh 《Pharmaceutical biology》2013,51(2):95-99
AbstractThe effect of aqueous extracts of Syzygium cumini. Linn., Gymnema sylvestre. (Retz.) Schult., and Portulaca olearacea. Linn. were investigated in fasting normal and streptozotocin (STZ)-induced diabetic rats. The effects of extracts on oral glucose tolerance in normal fasting rats were also studied. The aqueous extracts of S. cumini. (200 mg/kg) and G. sylvestre. (200 mg/kg) decreased the blood glucose in normal rats significantly at 2 and 4 h of extract administration (p < 0.05, p < 0.01). The S. cumini. and G. sylvestre. extracts decreased the increase of glucose levels significantly (p < 0.05) at 90 and 180 min after the glucose load in glucose tolerance test. In STZ diabetic animals, the aqueous extracts of S. cumini. and G. sylvestre. decreased the blood glucose significantly (p < 0.05) at 4 h. The aqueous extract of P. olearacea. did not show any hypoglycemic activity. 相似文献
11.
Chlorogenic acid (5-O-caffeoylquinic acid, CA), a phenolic compound found ubiquitously in plants, has antidiabetic effect
in diabetic animal models. In this study, we investigated the inhibitory effect of CA on diabetic cataractogenesis. We evaluated
the aldose reductase (AR) activity during cataract development in 50% galactose-fed rats, an animal model of sugar cataract.
Galactose-fed rats were treated orally with CA (10 and 50 mg/kg body weight) once a day for 2 weeks. In vehicle-treated galactose-fed
rats, lens opacity was increased, and lens fiber swelling and membrane rupture were observed. In addition, AR protein was
highly expressed in lens epithelial cells and lens cortical fibers of galactose-fed rats. However, CA inhibited the rat AR
activity in vitro, and the administration of CA prevented the development of sugar cataract through the inhibition of AR activity. These observations
suggest that CA is useful for the treatment of sugar cataract. 相似文献
12.
J. Eliza M. Rajalakshmi S. J. Ignacimuthu P. Daisy 《Medicinal chemistry research》2011,20(7):1111-1118
Diabetes mellitus is a major health problem in developed and developing countries. Costus speciosus (C. speciosus) is widely used in Indian medicine to treat various diseases including diabetes. Hexane, Ethyl acetate, Methanol, and aqueous
crude extracts of C. speciosus administered to streptozotocin (STZ)-induced diabetic rats at the dose of 250, 400, 400, and 600 mg/kg, respectively, for
60 days. It was found that plasma glucose concentration was significantly (P < 0.05) decreased in all the extracts compared to control. Also hexane crude extract restored the altered tissue protein
and pancreatic DNA, plasma insulin, and plasma C-peptide levels to near normal. Based on the results of the bio-assays, hexane
extract fractionated on silica gel, and active principles have been isolated from the most active fractions. Thus, this study
shows that C. speciosus hexane extract and its compounds have an antihyperglycemic action, and are able to ameliorate the diabetic state, and probably
they can be used as an alternate therapy for diabetes. 相似文献
13.
Hyun Ah Jung Na Young Yoon Hyun Ju Bae Byung-Sun Min Jae Sue Choi 《Archives of pharmacal research》2008,31(11):1405-1412
As part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications, the rat
lens aldose reductase (RLAR) inhibitory effect of Coptidis Rhizoma (the rhizome of Coptis chinensis Franch) was evaluated. Its extract and fractions exhibited broad and moderate RLAR inhibitory activities of 38.9∼67.5 μg/mL.
In an attempt to identify bioactive components, six quaternary protoberberine-type alkaloids (berberine, palmatine, jateorrhizine,
epiberberine, coptisine, and groenlandicine) and one quaternary aporphine-type alkaloid (magnoflorine) were isolated from
the most active n-BuOH fraction, and the chemical structures therein were elucidated on the basis of spectroscopic evidence and comparison
with published data. The anti-diabetic complications capacities of seven C. chinensis-derived alkaloids were evaluated via RLAR and human recombinant AR (HRAR) inhibitory assays. Although berberine and palmatine were previously reported as prime
contributors to AR inhibition, these two major components exhibited no AR inhibitory effects at a higher concentration of
50 μg/ml in the present study. Conversely, epiberberine, coptisine, and groenlandicine exhibited moderate inhibitory effects
with IC50 values of 100.1, 118.4, 140.1 μM for RLAR and 168.1, 187.3, 154.2 μM for HRAR. The results clearly indicated that the presence
of the dioxymethylene group in the D ring and the oxidized form of the dioxymethylene group in the A ring were partly responsible
for the AR inhibitory activities of protoberberine-type alkaloids. Therefore, Coptidis Rhizoma, and the alkaloids contained
therein, would clearly have beneficial uses in the development of therapeutic and preventive agents for diabetic complications
and diabetes mellitus. 相似文献
14.
Mario Luiz Conte da FrotaJr. Elizandra Braganhol Andrés Delgado Canedo Fabio Klamt Miriam Anders Apel Beatriz Mothes Cléa Lerner Ana Maria Oliveira Battastini Amélia Teresinha Henriques José Cláudio Fonseca Moreira 《Investigational new drugs》2009,27(5):440-446
We have studied the apoptotic pathway activated in response to marine sponge extracts of Polymastia janeirensis. The effect on intracellular ROS production was also examined. Exposure of U138MG glioma cell line to doses higher than 5 μg/mL
has decreased glioma cell viability, with an IC50 <15 μg/mL for both aqueous and organic extracts. However, extracts at higher doses (50 and 100 μg/mL) have stronger cytotoxic
effects, decreasing more than 90% of glioma cell viability. The antioxidant Trolox? (100 μM) reversed the cell death percentage
induced by extracts at 10 and 25 μg/mL. The type of cell death induced by such high doses was predominantly necrosis, while
a high percentage of apoptotic glioma cells was found at 10 μg/mL. Moreover, inhibition of caspase-8 with Z-IETD (a caspase-8
inhibitor) had no effect on the amount of apoptosis induced by 10 μg/mL, but inhibition of caspase-9 with Z-LEHD (a caspase-9
inhibitor) decreased apoptosis. We also observed a dose-dependent increase in ROS production, and similarly to effects observed
on viability of glioma cells, and on cell death, higher doses also had more severe effects. Co-treatment with Trolox? significantly
reduced ROS production by extracts at doses lower than 50 μg/mL. This is a first report demonstrating that marine sponge extracts
of P. janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway. 相似文献
15.
Abdel-Sattar Essam Harraz Fathalla M. Al-Ansari Soliman M. A. El-Mekkawy Sahar Ichino Chikara Kiyohara Hiroaki Otoguro Kazuhiko Omura Satoshi Yamada Haruki 《Journal of natural medicines》2009,63(2):232-239
The antiplasmodial and antitrypanosomal activity of the methanol extracts of 42 plants collected from the Kingdom of Saudi
Arabia and some fractions obtained thereof were evaluated. The antiplasmodial activity was tested in vitro against chloroquine-resistant
strain (K1) and sensitive strain (FCR3), and the antitrypanosomal activity was tested in vitro against Trypanosoma brucei brucei GUTat 3.1 strain. For host cells, the cytotoxicity of the active extracts was also evaluated against the MRC5 human cell
line. Only extracts of three samples demonstrated good antiplasmodial activity (IC50 < 12.5 and > 1.56 μg/ml, score 2), the methanol extracts of Lycium shawii, Heliotropium zeylanicum and the petroleum ether-soluble fraction of the methanol extract of Caralluma tuberculata, while extracts of the remaining 42 plants were inactive (IC50 > 12.5 μg/ml, score 1). As for the antitrypanosomal activity, the methanol extract of Solanum schimperianum demonstrated the highest activity (IC50 0.061 μg/ml), followed by the petroleum ether-soluble fraction of the methanol extract of C. tuberculata (IC50 0.5 μg/ml). The chloroform-soluble fraction of the methanol extract of C. tuberculata was moderately active (IC50 3.5 μg/ml), with low cytotoxicity (IC50 62.6 μg/ml) and moderate selectivity index (SI 17.9). The methanolic extracts of 34 plants showed good activity with score
2 (IC50 < 12.5 and > 1.56 μg/ml), while the extracts of seven plants were inactive (IC50 > 12.5 μg/ml, score 1). 相似文献
16.
《Journal of pharmaceutical sciences》2023,112(9):2538-2551
Encapsulation of polyphenol-rich herbal extracts into nanoliposomes is a promising strategy for the development of novel therapeutic agents against type 2 diabetes mellitus. An attempt was made to encapsulate aqueous, ethanol, and aqueous ethanol (70% v/v) extracts of Senna auriculata (L.) Roxb., Murraya koenigii (L.) Spreng,. and Coccinia grandis (L.) Voigt into nanoliposomes and to screen acute bioactivities in vitro and in vivo. A wide spectrum of bioactivity was observed of which aqueous extracts encapsulated nanoliposomes of all three plants showed high bioactivity in terms of in vivo glucose-lowering activity in high-fat diet-fed streptozotocin induced Wistar rats, compared to respective free extracts. The particle size, polydispersity index, and zeta potential of the aforementioned nanoliposomes ranged from 179–494 nm, 0.362–0.483, and (–22) to (–17) mV, respectively. The atomic force microscopy (AFM) imaging reflected that the nanoparticles have desired morphological characteristics and Fourier-transform infrared (FTIR) spectroscopy analysis revealed successful encapsulation of plant extracts into nanoparticles. However, only the S. auriculata aqueous extract encapsulated nanoliposome, despite the slow release (9% by 30 hours), showed significant (p < 0.05) in vitro α-glucosidase inhibitory activity and in vivo glucose-lowering activity compared to free extract, proving worthy for future investigations. 相似文献
17.
Chandra Kirana Graham Peter Jones Ian Roland Record Graeme Howie McIntosh 《Journal of natural medicines》2007,61(2):131-137
Extract of Boesenbergia pandurata (Kaempferia pandurata) (Zingiberaceae) has been used as a replacement for K. rotunda, the main ingredient of a popular traditional tonic called “jamu” especially for women in Indonesia. From our previous study,
ethanolic extract of B. pandurata showed strong inhibitory effects on the growth of cancer cells, similar to ethanolic extract of Curcuma longa. C. longa and its bioactive compound, curcumin, have shown potential anticancer activity in in vitro and in vivo studies and have undergone
clinical trials. Panduratin A, a chalcone derivative isolated from B. pandurata, was found to inhibit the growth of MCF-7 human breast cancer and HT-29 human colon adenocarcinoma cells with an IC50 of 3.75 and 6.56 μg/ml, respectively. Panduratin A arrested cancer cells labelled with Annexin-V and propidium iodide in
the G0/G1 phase and induced apoptosis in a dose-dependent manner. In an animal model study, male Sprague–Dawley rats were
fed with AIN diet containing ethanolic extracts prepared from the equivalent of 4% by weight of dried rhizomes of B. pandurata and C. longa. Aberrant crypt foci (ACFs) were induced by two subcutaneous doses (15 mg/kg body weight) of azoxymethane (AOM) 1 week apart.
The rats were killed 10 weeks later, and the ACFs were assessed in the colon. At the dose given to rats, it appeared that
the extracts were not toxic. Total ACFs were slightly reduced by B. pandurata extract compared to control group but not significantly different. Extract of B. pandurata may have a protective effect against colon cancer but additional studies using different models, such as a breast cancer
model, need to be carried out. 相似文献
18.
da Frota ML Braganhol E Canedo AD Klamt F Apel MA Mothes B Lerner C Battastini AM Henriques AT Moreira JC 《Investigational new drugs》2009,27(1):13-20
Summary Marine sponges have been prominently featured in the area of cancer research. Here, we examined the anti-proliferative effects
of crude extracts (aqueous and organic) of the Brazilian marine sponge Polymastia janeirensis in the U138MG human glioma cell line. Moreover, we examined the effects of extracts on selective cytotoxicity in the glioma
cells in comparison with a normal cell culture. Exposure of glioma cells to treatments (24 h) resulted in cell number decrease
at all doses tested, with both aqueous and organic extracts (IC50 <20 and <30 μg/ml, respectively). Parallel to this result, sponge extracts reduced glioma cell viability (IC50 <15 μg/ml for both extracts). However, higher doses (50 and 100 μg/ml) induced a stronger cytotoxic effect when compared
to the lower dose tested (10 μg/ml), inhibiting more than 80% of cellular growth and viability. Propidium iodide uptake and
flow cytometry analysis further showed that sponge extracts caused necrosis in the glioma cell line at higher doses, while
a high percentage of apoptotic glioma cells were observed at 10 μg/ml. Moreover, apoptosis was prevented by the pan-caspase
inhibitor Z-VAD, suggesting that marine sponge extracts, at lower doses, induce caspase-dependent apoptosis in U138MG glioma
cells. Surprisingly the extracts herein tested were more effective than temozolomide, a potent inductor of apoptosis used
for the treatment of malignant gliomas. Furthermore, our results suggested a selectivity cytotoxic effect on glioma cell line
in comparison with a normal cell culture, since the effect on viability found in glioma cells was not observed in astrocyte
cultures with the lower dose (10 μg/ml). Thus, this marine sponge may be considered a good candidate for development of new
cancer medicines with antitumor activity against gliomas. 相似文献
19.
Luisa Mosti Paola Fossa Giulia Menozzi Letizia Trincavelli Maura Floreani 《Medicinal chemistry research》2008,17(9):587-603
In the last few years, much effort has been directed towards the synthesis of selective adenosine receptor (AR) antagonists
since they are attractive tools for pharmacological intervention in many pathophysiological conditions. During our studies
aimed at obtaining new nonclassical adenosine antagonists devoid of phosphodiesterase (PDE) inhibition, a series of 2-pyridones
and 2,5-quinolinediones (3a–f, 5a–f, 6a,c–f) has been synthesized as potential AR ligands. Binding affinities of the new compounds were determined for bovine and human
adenosine A1, A2A, and A3 receptors. Compound 5f showed good affinity (K
i = 7.8 μM) towards human A1AR but no selectivity (K
i = 7.0 μM) towards human A2AAR, whereas compound 6f showed more affinity towards human A2A (K
i = 16 μM) than A1 receptor (percentage inhibition at 10 μM concentration = 11). In the 1–100 μM range, the new compounds did not inhibit cardiac
PDE3 activity at all. Molecular modeling studies carried out on 5f and 6f support the pharmacological results and suggest 6f as a potential lead compound selective towards A2AAR. 相似文献
20.