Publications by authors named "Mandana Jafari"

15 Publications

  • Page 1 of 1

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Pak J Pharm Sci 2019 Sep;32(5):2167-2173

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 μg/mL and 6000 μg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 μg/mL and 1103±3.2 μg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.
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September 2019

Distinct genetic variation and heterogeneity of the Iranian population.

PLoS Genet 2019 09 24;15(9):e1008385. Epub 2019 Sep 24.

Cologne Center for Genomics, University of Cologne, Cologne, Germany.

Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, while close to neighboring populations, present distinct genetic variation consistent with long-standing genetic continuity, harbor high heterogeneity and different levels of consanguinity, fall apart into a cluster of similar groups and several admixed ones and have experienced numerous language adoption events in the past. Our findings render Iran an important source for human genetic variation in Western and Central Asia, will guide adequate study sampling and assist the interpretation of putative disease-implicated genetic variation. Given Iran's internal genetic heterogeneity, future studies will have to consider ethnic affiliations and possible admixture.
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http://dx.doi.org/10.1371/journal.pgen.1008385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759149PMC
September 2019

Cytotoxicity investigations of biogenic tellurium nanorods towards PC12 cell line.

IET Nanobiotechnol 2018 Dec;12(8):1144-1149

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

The authors evaluated the cytotoxicity underlying mechanisms of biogenic tellurium (Te) nanorods (NRs) produced by the strain Te on the PC12 cell line. The half-maximal inhibitory concentration (IC) value was estimated at 5.05 ± 0.07 ng/ml for biogenic Te NRs and 2.44 ± 0.38 ng/ml for KTeO, respectively. The viability of PC12 was inhibited concentration dependent at doses of 1, 2.5, 5, 10, and 20 ng/ml. Te NRs principally induced late apoptosis or necrosis at IC concentration, without effect on caspase-3 activities. Furthermore, Te NRs reduced glutathione and enhanced malondialdehyde levels, and also reduced superoxide dismutase and catalase activities. These findings revealed that biogenic Te NRs were less toxic than KTeO. Additionally, they induced cytotoxity towards the PC12 cell line through the activation of late apoptosis independent of the caspase pathway, and may also enhance oxidative stress in the nervous system.
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http://dx.doi.org/10.1049/iet-nbt.2018.5137DOI Listing
December 2018

Impact of Ondansetron on Withdrawal Signs, Fentanyl Requirement and Pain Relief in Opioid-addicted Patients under General Anesthesia.

Curr Clin Pharmacol 2019 ;14(3):232-241

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Background: Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies.

Objective: Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures.

Methods: Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults.

Results: We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron.

Conclusion: This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.
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http://dx.doi.org/10.2174/1574884714666190131122846DOI Listing
August 2020

Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.

Bioorg Med Chem 2019 01 4;27(2):305-314. Epub 2018 Dec 4.

Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (ICs less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.
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http://dx.doi.org/10.1016/j.bmc.2018.12.003DOI Listing
January 2019

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line.

IET Nanobiotechnol 2018 08;12(5):653-657

Sudent Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.
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http://dx.doi.org/10.1049/iet-nbt.2017.0295DOI Listing
August 2018

Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds.

Eur J Med Chem 2018 May 2;152:600-614. Epub 2018 May 2.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotective and anti-cholinesterase activities. Based on primary screening, two compounds (5 and 11) were subjected to further biological evaluations. In particular, compound 11 which was the most potent AChE inhibitor showed good inhibitory effect on Aβ-aggregation and intracellular ROS (reactive oxygen species) formation, as well as the ability of selective bio-metal chelation and neuroprotection against HO- and Aβ-induced cytotoxicity. In the light of these results, the applied hybridization approach introduced new promising lead compound with desired multifunctional properties, being useful in the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.ejmech.2018.04.058DOI Listing
May 2018

New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease.

Eur J Med Chem 2017 Oct 31;139:280-289. Epub 2017 Jul 31.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 7l with IC of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 7l had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against HO-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and Aβ aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery.
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http://dx.doi.org/10.1016/j.ejmech.2017.07.072DOI Listing
October 2017

Probiotic and antioxidant properties of selenium-enriched Lactobacillus brevis LSe isolated from an Iranian traditional dairy product.

J Trace Elem Med Biol 2017 Mar 23;40:1-9. Epub 2016 Nov 23.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

The present study was designed to isolate a highly selenium-tolerant lactobacillus strain from an Iranian traditional dairy product named as Spar. Different criteria such as tolerance to the low pH, simulated gastric juice (SGJ), simulated intestinal juice (SIJ) and bile salts tolerance as well as Caco-2 cell adhesion assay were examined to evaluate the probiotic potentials of the selected isolate. Furthermore, the antioxidant properties of the isolate cultivated in medium containing and free of SeO ions were evaluated using DPPH scavenging and reducing power assays. The isolate was identified using conventional identification and 16S rDNA gene sequencing methods as Lactobacillus brevis LSe. The obtained results showed that the isolate was able to tolerate high concentration of sodium selenite (3.16mM). By decreasing the pH of the SGJ from 6 to 3, the survival percent of L. brevis LSe was not significantly changed over the time (p>0.05). In addition, the survival percent of the isolate in the SIJ (pH 6 and pH 8) was not statistically altered after 3h, 6h and 24h of incubation (p>0.05). In the presence of bile salts (0.3% and 0.6%) the survival rate of L. brevis LSe was not significantly decreased (p>0.05).L. brevis LSe also demonstrated the satisfactory ability to adhere to Caco-2 cells which were similar to that of the reference strain L. plantarum. The obtained results of antioxidant evaluation showed that L. brevis LSe containing elemental Se exhibited significantly higher radical scavenging ability (36.5±1.31%) and reducing power (OD, 0.14) than L. brevis LSe cultured in selenite-free medium (p<0.05). To sum up, further investigations should be conducted to merit the probable potential health benefit of Se-enriched L. brevis LSe and its application as Se-containing supplements or fermented foods.
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http://dx.doi.org/10.1016/j.jtemb.2016.11.013DOI Listing
March 2017

Microwave-assisted biosynthesis of zinc nanoparticles and their cytotoxic and antioxidant activity.

J Trace Elem Med Biol 2017 Jan 3;39:116-123. Epub 2016 Sep 3.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

The present study was designed for microwave assisted synthesis of zinc nanoparticles (Zn NPs) using Lavandula vera leaf extract in the presence of ZnSO (1mM). The biogenic Zn NPs were then characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Thereafter, the cytotoxic effect of ZnSO and Zn NPs on different cell lines was investigated by MTT-based cytotoxicity assay and their antioxidant properties were assessed using DPPH scavenging activity and reducing power assay. The SEM micrograph showed that the Zn NPs had spherical shape with the size range of 30-80nm. For A549, MCF-7, HT-29, and Caco-2 cell lines treated with Zn NPs, the concentration necessary causing 50% cell death (IC) was found to be 22.3±1.1μgmL, 86±3.7μgmL, 10.9±0.5μgmL, and 56.2±2.8μgmL, respectively. In the case of ZnSO, the same results (IC) were observed at concentration of 81.6±1.3μgmL (A549), 121.0±2.4μgmL (MCF-7), 43.0±1.4μgmL (HT-29), and 85.7±2.3μgmL (Caco-2). The obtained results of antioxidant activity showed that the IC values of butylated hydroxyanisole (BHA) and Zn NPs were 44μgmLand 65.3μgmL, respectively, while ZnSO at concentration of 200μgmL exhibited only 10.9% DPPH radical scavenging effect. Moreover, the reducing power of Zn NPs and BHA were significantly higher than ZnSO (p<0.05). To sum up, application of L. vera leaf extract combined with microwave heating energy led to simple and fast formation of Zn nanostructures exhibited higher antioxidant and cytotoxic activity compared to soluble Zn ions. However, identification of the related mechanisms merit further studies.
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http://dx.doi.org/10.1016/j.jtemb.2016.09.001DOI Listing
January 2017

Microbial-assisted synthesis and evaluation the cytotoxic effect of tellurium nanorods.

Mater Sci Eng C Mater Biol Appl 2015 Apr 24;49:183-189. Epub 2014 Dec 24.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

The present study was designed to isolate bacterial strain capable of tellurium nanorods' (Te NRs) production followed by purification and evaluation of the cytotoxic effect of Te NRs. Among 25 environmental samples collected for screening of Te NR-producer bacterial strains one bacterial colony (isolated from hot spring and identified as Pseudomonas pseudoalcaligenes strain Te) was selected and applied for biosynthesis of Te NRs. Thereafter, an organic-aqueous partitioning system was applied for the purification of the biogenic Te NRs and the purified Te NRs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. The cytotoxic effect of biologically synthesized Te NRs and potassium tellurite on four cell lines of MCF-7, HT1080, HepG2 and A549 was then determined using the MTT assay method. The obtained results revealed lower toxicity for the rod-shaped biogenic tellurium nanostructures (~22nm diameter by 185nm length) compared to K2TeO3.
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http://dx.doi.org/10.1016/j.msec.2014.12.078DOI Listing
April 2015

The effect of Angipars on diabetic neuropathy in STZ-induced diabetic male rats: a study on behavioral, electrophysiological, sciatic histological and ultrastructural indices.

ScientificWorldJournal 2014 29;2014:721547. Epub 2014 Dec 29.

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Tahmassebabad Crossroad, Ebne-Sina Street, Kerman 76198-13159, Iran.

Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1 mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats.
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http://dx.doi.org/10.1155/2014/721547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295134PMC
June 2015

Preparation and evaluation of the effect of Fe3 O4 @piroctone olamine magnetic nanoparticles on matrix metalloproteinase-2: a preliminary in vitro study.

Biotechnol Appl Biochem 2014 Nov-Dec;61(6):676-82

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

In the present study, Fe3 O4 magnetic nanoparticles were synthesized by the coprecipitation of Fe(2+) and Fe(3+) ions and used as a nanocarrier for the production of piroctone-olamine-loaded Fe3 O4 nanoparticles (Fe3 O4 @PO NPs). The nanocrystalline structure of the prepared iron oxide species was confirmed by the X-ray diffraction spectroscopy method. Particle size distribution analysis showed that the size of Fe3 O4 @PO NPs was in the range of 5-55 nm. The magnetization curve of Fe3 O4 @PO NPs (with saturation magnetization of 28.2 emu/g) confirmed its ferromagnetic property. Loading of PO on the surface of Fe3 O4 NPs qualitatively verified by Fourier transform infrared spectrum obtained from Fe3 O4 @PO NPs. Cytotoxicity studies on the human fibrosarcoma cell line (HT-1080) revealed higher inhibitory effect of Fe3 O4 @PO NPs (50% cell death [IC50 ] of 8.1 µg/mL) as compared with Fe3 O4 NPs (IC50 of 117.1 µg/mL) and PO (IC50 of 71.2 µg/mL) alone. In the case of human normal fibroblast (Hs68), the viability percentage was found to be 75% in the presence of Fe3 O4 @PO NPs (120 µg/mL). Gelatin zymography showed 17.2% and 34.6% inhibition of matrix metalloproteinase-2 (MMP-2) in the presence of Fe3 O4 @PO and PO, respectively, at the same concentration of 40 µg/mL, whereas Fe3 O4 NPs did not inhibit MMP-2 at any concentration.
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http://dx.doi.org/10.1002/bab.1231DOI Listing
August 2015

One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines.

Eur J Med Chem 2014 May 16;78:151-6. Epub 2014 Mar 16.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. Electronic address:

A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine, pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic acid. The anti-tumor potential of title compounds was tested against several cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and 5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080 cells in comparison to the reference drug doxorubicin. Also, the cytotoxic activity of compounds 5d and 5n against MCF-7 was better than that of doxorubicin. Compound 5n with IC50 value of 4.3 μM was 4-fold more potent than doxorubicin. The structure-activity relationship study revealed that the introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved the cytotoxic activity against all tested cell lines.
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http://dx.doi.org/10.1016/j.ejmech.2014.03.049DOI Listing
May 2014

Date fruit extract is a neuroprotective agent in diabetic peripheral neuropathy in streptozotocin-induced diabetic rats: a multimodal analysis.

Oxid Med Cell Longev 2011 1;2011:976948. Epub 2011 Dec 1.

Department of Basic Neuroscience, Neuroscience Research Center, Kerman Medical University, Kerman 76198-13159, Iran.

Background: To study the effects of an aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae) diet on diabetic polyneuropathy (DPN) in streptozotocin- (STZ-) induced diabetic rats.

Methods: The effects of a date fruit extract (DFE) diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with a nondiabetic control group, diabetic control group (sham), and vehicle group with respect to the following parameters: open field behavioral test, motor nerve conduction velocity (MNCV), and morphological observations.

Results: In the model of STZ-induced of diabetic neuropathy, chronic treatment for 6 weeks with DFE counteracted the impairment of the explorative activity of the rats in an open field behavioral test and of the conduction velocity of the sciatic nerve (MNCV). In addition, pretreatment with DFE significantly reversed each nerve diameter reduction in diabetic rats.

Conclusion: DFE treatment shows efficacy for preventing diabetic deterioration and for improving pathological parameters of diabetic neuropathy in rats, as compared with control groups.
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http://dx.doi.org/10.1155/2011/976948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236446PMC
May 2012