Publications by authors named "Ahmad Ghorbani"

97 Publications

Levetiracetam promoted rat embryonic neurogenesis via NMDA receptor-mediated mechanism in vitro.

Life Sci 2021 Nov 2;284:119923. Epub 2021 Sep 2.

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Aims: Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with neuroprotective properties and novel mechanisms of action. Some evidence suggests that LEV may impact adult neurogenesis, but the results are controversial. The present study was aimed to evaluate the effects of LEV on the proliferation and differentiation of rat embryonic neural stem cells (NSCs) and to explore the role of GABA or NMDA receptors.

Main Methods: NSCs were isolated from rat fetal ganglionic eminence at embryonic day 14.5. The effects of LEV on viability, proliferation, neurosphere formation, and neuronal or astroglial differentiation of NSCs were assessed using resazurin, BrdU incorporation, immunocytochemistry, quantitative real-time PCR, and western blotting. Additionally, we addressed the relationship between treatment with NMDA and GABA receptor antagonists (MK801 and saclofen, respectively) in combination with LEV on these parameters.

Key Findings: The data showed that LEV (50 μM) significantly increased the number (p < 0.01) and diameter of neurospheres (p < 0.05), enhanced proliferation (p < 0.01), and promoted neuronal differentiation, as revealed by significantly increased expressions of DCX and NeuN. The expressions of astroglial markers, GFAP and Olig2, were markedly reduced. The addition of MK801 (10 μM) significantly diminished neurospheres growth (p < 0.001), decreased the number of proliferating cells (p < 0.01), and reduced the number of new neurons (p < 0.001) but increased the astroglial cells (p < 0.001) induced by LEV. Co-treatment with saclofen (25 μM) did not significantly affect LEV-induced NSCs proliferation and differentiation.

Significance: Our findings suggest that LEV may enhance rat embryonic neurogenesis mainly through an NMDA receptor-mediated mechanism.
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http://dx.doi.org/10.1016/j.lfs.2021.119923DOI Listing
November 2021

Effects of climate variables on the incidence of scorpion stings in Iran for five years.

J Venom Anim Toxins Incl Trop Dis 2021 30;27:e20200110. Epub 2021 Jun 30.

Toxicology Research Center, Medical Basic Sciences Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Toxicology Research Center Medical Basic Sciences Institute Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran.

Background: Although scorpionism is recorded worldwide, some regions such as Iran present a higher incidence. Due to the great prevalence of scorpion stings in Khuzestan province, southwestern Iran, the present study examined the relationship between different climate parameters and the scorpion sting rate in this area from April 2010 to March 2015.

Methods: In this cross-sectional descriptive-analytical study, we considered all scorpion sting cases recorded in the Department of Infectious Diseases, Ahvaz Jundishapur University of Medical Sciences. Data were analyzed using statistics, frequency distribution and Pearson's correlation coefficient.

Results: A total of 104,197 cases of scorpion stings was recorded from 2010 to 2015. The cumulative incidence of scorpion sting was 2.23%. The spatial distribution of scorpion stings showed that most cases occurred in the Dehdez district (4,504 scorpion stings/100,000 inhabitants) and the Masjed Soleyman county (4,069 scorpion stings/100,000 inhabitants). A significant association was found between climate factors (temperature, evaporation rate, sunshine duration, humidity, and precipitation) and the scorpion sting rate. An increase in rainfall and humidity coincided with a reduction in scorpion stings whereas an increase in temperature, evaporation, and sunshine duration was accompanied by a growth of scorpion stings. No significant correlation was found between wind velocity/direction and the incidence rate of stings. Moreover, the seasonal peak incidence of scorpion stings was recorded in summer (an average of 8,838 cases) and the lowest incidence was recorded during winter (an average of 1,286 cases). The annual trend of scorpion sting cases decreased during the period from 2010 to 2015.

Conclusion: Climate variables can be a good index for predicting the incidence of scorpion stings in endemic regions. Since they occur mostly in the hot season, designing preventive measures in the counties and districts with a high incidence of scorpion stings such as Dehdez and Masjed Soleyman can minimize mortality and other burdens.
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http://dx.doi.org/10.1590/1678-9199-JVATITD-2020-0110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252957PMC
June 2021

Protective effect of on 6-hydroxydopamine-induced toxicity in SH-SY5Y cell line.

Avicenna J Phytomed 2021 May-Jun;11(3):238-246

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Several experimental studies have shown neuroprotective and antioxidant effects for . The present study was designed to assess the effect of on 6-hydroxydopamine (6-OHDA)-induced toxicity in SH-SY5Y cells.

Materials And Methods: SH-SY5Y cells were treated with ethanolic extract of for 24 hr and then, exposed to 6-OHDA (250 μM) for another 24 hr. MTT (3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide) assay was used for evaluation of cell viability. Moreover, the rate of apoptosis was measured using propidium iodide (PI) staining. The amount of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) was also measured using 2', 7'-dichlorofluorescin diacetate (DCFDA) fluorometric method. Determination of glutathione (GSH) and superoxide dismutase (SOD) activity was done by colorimetric assay using DTNB [5, 5'-Dithiobis (2-nitrobenzoic acid)] and pyrogallol respectively.

Results: While 6-OHDA significantly increased ROS and apoptosis (p<0.001), the extract of significantly reduced ROS and cell apoptosis at concentrations ranging from 6.25 to 25 μg/mL (p<0.01 and p<0.001 respectively). Also, the extract significantly reduced MDA level in comparison with 6-OHDA (p<0.001). The GSH level and SOD activity were increased by the extract.

Conclusion: Findings of the current study showed that exerts it effect through inhibiting oxidative stress parameters and it can be considered a promising candidate to be used in combination with the conventional medications for the treatment of neurodegenerative disorders, such as Parkinson's disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140215PMC
May 2021

Optogenetic stimulation of entorhinal cortex reveals the implication of insulin signaling in adult rat's hippocampal neurogenesis.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Dec 6;111:110344. Epub 2021 May 6.

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day). The expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors, and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors, and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, are mediated by insulin increase in the dentate gyrus and subsequently activation of its downstream signaling pathway.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110344DOI Listing
December 2021

Protective effects of a standardized extract of on pancreas and liver in streptozotocin-induced diabetic rats.

Res Pharm Sci 2021 Feb 30;16(1):71-78. Epub 2020 Dec 30.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

Background And Purpose: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of . The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of rhizomes on streptozotocin-induced diabetic rats.

Experimental Approach: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the extract (IGE).

Findings/results: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level.

Conclusion And Implication: These findings suggest that rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.
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http://dx.doi.org/10.4103/1735-5362.305190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074805PMC
February 2021

Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies.

Pharmacology 2021 13;106(5-6):233-243. Epub 2021 Apr 13.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents.

Summary: Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.
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http://dx.doi.org/10.1159/000515032DOI Listing
July 2021

Fibroblast Growth Factor 1 Gene-Transfected Adipose-Derived Mesenchymal Stem Cells Modulate Apoptosis And Inflammation In The Chronic Constriction Injury Model of Neuropathic Pain.

Iran J Pharm Res 2020 ;19(4):151-159

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. This study aimed to investigate the potential anti-apoptotic and anti-inflammatory effects of adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs ) on chronic constriction injury (CCI) of the rat's sciatic nerve. The rats that underwent CCI were treated with AD-MSCs and AD-MSCs . Bax, Bcl2, and caspases 3, the major contributors of apoptosis, and inflammatory markers including Iba-1, IL1-β, and MMP-2 were evaluated in the lumbar portion (L4-L6) of the spinal cord through western bloating at days 3 and 14. The ratio of Bax/Bcl2, cleaved caspases 3, MMP-2, IL-1β, and Iba1, was elevated in CCI animals compared to sham-operated animals and decreased following treatment with both AD-MSCs and AD-MSCs . However, the effect of AD-MSCs was significantly higher than AD-MSCs. These data suggest that the administration of AD-MSCs through modulating apoptosis and neuroinflammation could be considered a promising medicine for treating neuropathic pain.
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http://dx.doi.org/10.22037/ijpr.2020.113223.14176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019860PMC
January 2020

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Phytother Res 2021 Jun 23;35(6):3365-3376. Epub 2021 Feb 23.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and β-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/β-catenin pathway and therefore prolongs the survival of rats with HCC.
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http://dx.doi.org/10.1002/ptr.7056DOI Listing
June 2021

Effects of hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Drug Chem Toxicol 2021 Jan 17;44(1):75-83. Epub 2018 Dec 17.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.
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http://dx.doi.org/10.1080/01480545.2018.1533024DOI Listing
January 2021

Evaluation Potential Antidiabetic Effects of in Streptozotocin-Induced Diabetic Rats.

J Pharmacopuncture 2020 Sep;23(3):158-164

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: The aim of the present work was to evaluate the possible beneficial effects of on blood glucose, lipids, and diabetes-related changes in the liver and kidney of streptozotocin-induced diabetic rats.

Methods: Male Wistar rats were randomly allocated into four groups (n = 6) normal control rats, diabetic control rats, diabetic rats treated for 4 weeks with root (400 mg/kg/day), and diabetic rats treated with aerial parts (400 mg/kg/day).

Results: Induction of diabetes significantly (p < 0.05) increased the levels of fasting blood glucose (FBG), triglyceride, total cholesterol, low-density lipoprotein (LDL), blood urea nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Diabetes also increased (p < 0.05) oxidative stress in the kidney and liver (decrease of thiol and increase of superoxide dismutase). The root and aerial parts of significantly reduced the level of LDL (p < 0.05) and restored the content of thiol (p < 0.05) and superoxide dismutase (p < 0.01) in the kidney and liver. had no significant effect on the levels of FBG, BUN, AST, and ALT. The root of also reduced the serum level of total cholesterol (p < 0.05) and prevented the progression of hyperglycemia.

Conclusion: These findings suggest that may improve diabetic dyslipidemia by reducing serum LDL. Further studies are needed to confirm our findings.
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http://dx.doi.org/10.3831/KPI.2020.23.3.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540228PMC
September 2020

Combined use of platelet-rich plasma and adipose tissue-derived mesenchymal stem cells shows a synergistic effect in experimental spinal cord injury.

J Chem Neuroanat 2020 12 7;110:101870. Epub 2020 Oct 7.

Pharmacological Research Center of Medical Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Spinal cord injury (SCI) as a crippling disability causes tissue degeneration via neuron loss and fiber disruption. Some researchers have tried to reverse or minimize these changes. Platelet-rich plasma (PRP) is a biological product derived from peripheral blood containing a variety of growth factors. PRP has been extensively used in regenerative medicine. On the other hand, via secreting neuroprotective growth factors, mesenchymal stem cells (MSCs) have shown a promising potential in repairing central nervous system deficits. This study investigated the therapeutic effect of the combined use of MSCs and PRP in a rat model of SCI. We used real time-PCR method for evaluation of Bcl-2, Bax and caspase 3 expressions, TUNEL test for apoptotic cell death assessment, and neurofilament NF200 immunohistochemistry for examination of axonal regeneration. The results showed that co-treatment with MSCs and PRP efficiently alleviated the evaluated categories. Significant differences were observed in expression of Bcl-2 and caspase3, but not Bax, apoptotic index and the number of NF200 positive axons (for all P ≤ 0.01) between co-treatment animals compared with those treated with only MSCs or PRP. In conclusion, this study showed that combination of MSCs and PRP synergistically promotes their therapeutic effects in the SCI.
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http://dx.doi.org/10.1016/j.jchemneu.2020.101870DOI Listing
December 2020

Neural synchronization between the anterior cingulate and orbitofrontal cortices during effort-based decision making.

Neurobiol Learn Mem 2020 11 30;175:107320. Epub 2020 Sep 30.

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, School of Medicine, Tehran, Iran. Electronic address:

Optimal decision making reflects the ability to choose the most advantageous option for various alternatives so that the anterior cingulate cortex is an important area involved in effort-based decision making. The current study aimed to investigate the functional connectivity between the ACC (anterior cingulate cortex) and the orbitofrontal cortex (OFC) during effort-based decision-making. A T-maze decision-making task with different rewards (large vs. small reward) and costs (high vs. low effort) was used, and simultaneously, local field potentials (LFP) from the ACC and OFC were also recorded in male Wistar rats. During the effort-based decision making, when the animals preferred the higher over, the lower reward, neural synchronization was observed in theta/low beta (4-20 Hz) frequency bands between both of the areas. Also, neural synchronization was not significant when the animals chose a lower reward. High gamma (80-100 Hz) synchrony between the areas was also observed; however, it was not dependent on the animal's decision. In this regard, the present findings revealed that neural synchronization and functional connectivity between the ACC and OFC in the low-frequency range (theta/low beta) is essential during the effort-based decision making.
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http://dx.doi.org/10.1016/j.nlm.2020.107320DOI Listing
November 2020

Biomedical Waste Management by Using Nanophotocatalysts: The Need for New Options.

Materials (Basel) 2020 Aug 9;13(16). Epub 2020 Aug 9.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea.

Biomedical waste management is getting significant consideration among treatment technologies, since insufficient management can cause danger to medicinal service specialists, patients, and their environmental conditions. The improvement of waste administration protocols, plans, and policies are surveyed, despite setting up training programs on legitimate waste administration for all healthcare service staff. Most biomedical waste substances do not degrade in the environment, and may also not be thoroughly removed through treatment processes. Therefore, the long-lasting persistence of biomedical waste can effectively have adverse impact on wildlife and human beings, as well. Hence, photocatalysis is gaining increasing attention for eradication of pollutants and for improving the safety and clearness of the environment due to its great potential as a green and eco-friendly process. In this regard, nanostructured photocatalysts, in contrast to their regular counterparts, exhibit significant attributes such as non-toxicity, low cost and higher absorption efficiency in a wider range of the solar spectrum, making them the best candidate to employ for photodegradation. Due to these unique properties of nanophotocatalysts for biomedical waste management, we aim to critically evaluate various aspects of these materials in the present review and highlight their importance in healthcare service settings.
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http://dx.doi.org/10.3390/ma13163511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476041PMC
August 2020

Effect of rutin on oxidative DNA damage in PC12 neurons cultured in nutrients deprivation condition.

Iran J Basic Med Sci 2020 Mar;23(3):390-395

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Rutin is a flavonoid with potent antioxidant property, which exhibited cytoprotective effects in several models of neuronal injury. This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation (SGD) as an in vitro model of neurodegeneration and ischemia.

Materials And Methods: The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin or α-tocopherol (positive control) and then further incubated for 12 hr in SGD condition. Then, cell viability, DNA fragmentation, lipid peroxidation, generation of reactive oxygen species (ROS), and the expression of proteins involved in apoptosis were determined.

Results: The SGD condition significantly decreased viability of the cells, which was accompanied by a significant rise in the generation of ROS and lipid peroxidation. Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation. In addition, rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins (Bax, caspase-3, caspase-9) and increasing the level of anti-apoptotic protein Bcl-2.

Conclusion: This study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition. Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders.
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http://dx.doi.org/10.22038/IJBMS.2020.31832.7657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229504PMC
March 2020

Scorpion stings in pregnancy: an analysis of outcomes in 66 envenomed pregnant patients in Iran.

J Venom Anim Toxins Incl Trop Dis 2020 Apr 30;26:e20190039. Epub 2020 Apr 30.

Department of Obstetrics and Gynecology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Scorpionism is one of the most important health problems in tropical regions, which unfortunately results in thousands of deaths annually. Pregnant women are potential victims in areas with high scorpion-sting prevalence. Limited medical data are available on the effects of scorpion envenomation in pregnant women. This study aimed to examine the effect of scorpion envenomation on pregnancy outcomes in 66 cases.

Methods: The present descriptive/analytical cross-sectional study was performed on 66 scorpion-envenomed pregnant women referred to the clinical toxicology unit of Ahvaz Razi Hospital in Iran during 2015-2017. The variables assessed in all cases, via questionnaire and hospital medical records, were: age, patient residency, gestational week, status of the fetus, laboratory anomalies, clinical severity of envenomation, sting site and scorpion species. Pregnancy outcome (miscarriage, stillbirth, preterm birth, normal delivery) and status of the newborns were also evaluated. Data were analyzed using SPSS software (version 24.0).

Results: The following pregnancy outcomes were recorded from envenomed pregnant women: miscarriage = 1.5% (n = 1), stillbirth = 4.5% (n = 3), preterm birth = 10.6% (n = 7), normal birth = 83% (n = 55). Among participants whose pregnancy led to birth, 11(17.7%) cases had prenatal-neonatal complications. Neonatal complications, including Apgar score less than 8 points at 5 min, were found in 7 (11.3%) preterm birth cases and in 4 (6.4%) normal birth cases, along with birth weight below 2500 g in normal births. A significant relationship was found between adverse pregnancy outcomes and bite location, as well as scorpion species, but no relationship was found with other variables.

Conclusion: Envenomation significantly contributes to preterm birth. Moreover, the location of bites and the type of scorpion species have a decisive role in the pregnancy outcome of scorpion-envenomed pregnant women.
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http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204829PMC
April 2020

Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway.

Curr Mol Pharmacol 2021 ;14(1):79-87

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies.

Objective: The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells.

Methods: The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting.

Results: Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide.

Conclusion: Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.
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http://dx.doi.org/10.2174/1874467213666200512075507DOI Listing
January 2021

Anti-Hypolipidemic and Anti-Oxidative Effects of Hydroalcoholic Extract of on the Hepatosteatosis Induced with High-Fat Diet in Rats.

Malays J Med Sci 2020 Feb 27;27(1):57-69. Epub 2020 Feb 27.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: The aim of the current study is to evaluate the antihyperlipidemic and anti-oxidative effects of hydro-alcoholic extract of marjoram (HAEM) in rats fed with a high-fat diet (HFD).

Methods: In the experimental study, the rats were randomly divided into four groups of five rats in each and fed with high-fat diet for 12 weeks as follows: One group (normal diet group) was fed with a standard diet, one group was fed with HFD, and two groups were fed with HFD and orally fed with 150 and 450 mg/kg/day HAEM. The serum samples and liver tissues were used for measuring the biochemical and oxidative parameters and histopathological studies. HFD induced hepatosteatosis in rats as evidenced by the altered liver enzymes activity, serum lipid profile and oxidative status.

Results: Serum lipid profile (triglyceride, cholesterol and low-density lipoprotein) in rats fed with HFD + HAEM (150 and 450 mg/kg/day) was significantly decreased. Furthermore, the evaluation of oxidative stress showed a reduction of the malondialdehyde (MDA) level and an increase in ferric-reducing anti-oxidant power. Meanwhile, liver enzyme activities declined in response to HAEM.

Conclusion: Using the HAEM could be a future therapeutic agent in treating hepatosteatosis and reducing oxidative damages of HFD in the liver.
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http://dx.doi.org/10.21315/mjms2020.27.1.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053549PMC
February 2020

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review.

Curr Pharm Des 2020 ;26(15):1729-1741

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM's invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.
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http://dx.doi.org/10.2174/1381612826666200131100630DOI Listing
November 2020

Preparation and Applications of Superparamagnetic Iron Oxide Nanoparticles in Novel Drug Delivery Systems: An Overview.

Curr Med Chem 2021 ;28(4):777-799

Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Nanocarriers, as drug delivery frameworks, have been intended to enhance the pharmacological and restorative properties of traditional medications. The consolidation of medical atoms as nanocarriers can function as the drug that is required against corruption, as well as offer the desired potential outcomes in regards to targeting and controlled discharge. In the present overview article, applications of magnetic nanoparticles (MNPs) in medication conveyance are outlined. The MNPs have increased the excitement due to their biocompatibility - low poisonous quality, and their capacity to be handled in a magnetic field, which enables their applications as drug-bearing vehicles. The simplicity of surface modification of these particles can provide opportunities for targeting the moieties that are linked to the particle surface. We trust that the intriguing particles will gain further attention alongside achievements in the current ones in the near future.
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http://dx.doi.org/10.2174/0929867327666200123152006DOI Listing
March 2021

Rosmarinic Acid Protects Adipose Tissue-Derived Mesenchymal Stem Cells in Nutrient-Deficient Conditions.

Prev Nutr Food Sci 2019 Dec 31;24(4):449-455. Epub 2019 Dec 31.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 91779-44553, Iran.

One of the major challenges for stem cell therapy of ischemic organs is that the transplanted cells are confronted with nutrient deficiency and oxidative stress. Previous studies have indicated that pretreatment of stem cells with cytoprotective phytochemicals improves their therapeutic potential. This study was aimed to investigate whether rosmarinic acid can enhance survival of adipose tissue-derived stem cells (ASCs) in nutrient-deficient culture as an model of ischemia. The ASCs were isolated from subcutaneous adipose tissue of male adult Wistar rats and incubated for 24 h with rosmarinic acid in nutrient-deficient (glucose- and serum-deprived, GSD) culture medium. In a separate experiment, ASCs were pre-incubated for 4 h with rosmarinic acid and then exposed to GSD conditions for 24 h. The viability of ASCs was determined using thiazolyl blue tetrazolium bromide assays. The effect of rosmarinic acid on the cell cycle was evaluated using propidium iodide staining. GSD conditions significantly decreased the viability of ASCs and enhanced the generation of reactive oxygen species (ROS), lipid peroxidation, sub-G1 cell populations, and necrosis. Both pre-incubation and incubation of ASCs with 0.75~6 μM rosmarinic acid significantly increased cell viability in GSD conditions. Rosmarinic acid further decreased the level of ROS, lipid peroxidation, the percent of cells in sub-G1 stage, and necrosis in GSD conditions. These findings suggest that rosmarinic acid enhances survival of ASCs cultured in nutrient-deficient conditions through promoting antioxidant effects. Therefore, rosmarinic acid may help preserve ASCs survival after they are transplanted into ischemic organs.
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http://dx.doi.org/10.3746/pnf.2019.24.4.449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941722PMC
December 2019

Effects of ethanolic extract of oleo-resin in a rat model of streptozotocin-induced diabetes.

Res Pharm Sci 2019 Apr 8;14(2):138-145. Epub 2019 Mar 8.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

Previous studies have shown that some plants in the genus of (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.
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http://dx.doi.org/10.4103/1735-5362.253361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791176PMC
April 2019

Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS).

EXCLI J 2019 30;18:576-590. Epub 2019 Jul 30.

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Glioblastoma multiforme (GBM), like the devastating type of astrocytic tumors, is one of the most challenging cancers to treat owing to its aggressive nature. Auraptene, as a prenyloxy coumarin from citrus species, represents antioxidant and antitumor activities; however, the underlying antitumor mechanisms of auraptene against GBM remain unclear. The present study aimed to evaluate the cytotoxic and apoptogenic effects of auraptene, as a promising natural product, and the possible signaling pathways affected in human malignant GBM (U87) cells. Reactive oxygen species (ROS) production significantly decreased in the first 2, and 6 hours after treatment with auraptene however, ROS levels increased in other incubation times (8 and 24 hours), dramatically. N-acetyl-cysteine (NAC) markedly attenuated auraptene-induced ROS production, and consequently reversed auraptene-induced cytotoxicity in 8 and 24 hours after treatment, as well. Induction of apoptosis occurred in the first 24- and 48-hours concentration-dependently. The qRT-PCR showed an up-regulation in p21, CXCL3, and a down-regulation in Cyclin D1 genes expression. Western blot analysis confirmed the up-regulation of the Bax/Bcl-2 ratio protein levels concentration-dependently. Hence, this study collectively revealed that the increase in ROS level is at least one of the mechanisms associated with auraptene-induced GBM cell toxicity as well as the induction of apoptosis through Bax/Bcl-2 modulation and genes expression involved that contribute to the cytotoxicity of auraptene in U87 cells. So, auraptene might be utilized as a potential novel anti-GBM agent after further studies.
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http://dx.doi.org/10.17179/excli2019-1136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785765PMC
July 2019

Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

Avicenna J Phytomed 2019 Jul-Aug;9(4):334-346

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Glioblastoma multiforme (GBM) is the deadliest type of primary brain tumors, and the survival of patients is estimated to be only about one year. This study, for the first time, investigated the cytotoxic effects of auraptene on U87 GBM cell line.

Materials And Methods: The cellular toxicity was measured by the MTT assay following 24 and 48-hr treatment with different concentrations of auraptene (0-400μg/ml). Apoptosis was evaluated by sub-G1 peak in cell cycle analysis of propidium-iodide- stained nuclei. Moreover, to determine the Ba, , , , , and genes expression, we used real-time polymerase chain reaction (RT-PCR).

Results: The results revealed that auraptene reduced the viability of U87 cells concentration- and time-dependently with IC values of 108.9 and 79.17μg/ml obtained for 24 and 48-hr treatments, respectively. Also, sub-G1 population was significantly increased following 24 (p<0.05 and p<0.001) and 48 (p<0.001) hours of treatment. The quantitative real-time RT-PCR showed an up-regulation in , , , and but a down-regulation in and genes expression.

Conclusion: This study showed that auraptene triggered apoptosis probably through Bax/Bcl-2 regulation, blocked cell cycle progression and inhibited proliferation in U87 GBM cells. Taken together, auraptene can be utilized as an effective natural medicine against GBM, after complementary studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612248PMC
July 2019

Pharmacological properties of Janisch.

Heliyon 2019 Jun 23;5(6):e01986. Epub 2019 Jun 23.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Medicinal herbs have been increasingly used worldwide for diseases prevention and treatment. Janisch. is a perennial shrub of the Polygonaceae family. Genus includes more than 60 species growing around the world which are used in foods and traditional medicines. is believed to be able to improve different kinds of disorders including diabetes, hypertension, jaundice and cancer. In recent years, this medicinal plant has been a subject of many experimental studies to document its health-beneficial properties. These studies have revealed antidiabetic, anticancer, nephroprotective, cardioprotective, and hepatoprotective properties of The presence of flavonoids (e.g. epicatechin and quercetin) and anthraquinones (e.g. chrysophanol, physcion, and emodin) in justifies its health-beneficial effects. Nevertheless, possible therapeutic applications and safety of this plant still need to be elucidated in further clinical studies.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595136PMC
June 2019

Acute and sub-acute toxicity evaluation of the root extract of Janisch.

Drug Chem Toxicol 2020 Nov 2;43(6):609-615. Epub 2019 Jul 2.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Despite the widespread use of in herbal medicine, no study has yet examined its toxicity. The aim of this study is to evaluate the acute and sub-acute toxicity of hydroalcoholic extract of root. In acute toxicity experiment, female and male mice ( = 5/group/sex) were orally administrated with the extract at single doses of 300, 2000 and 3000 mg/kg and observed for 14 days. In the sub-acute study, the extract was orally administered daily at doses of 100 and 400 mg/kg to male rats ( = 8) for 4 weeks. During the acute toxicity test, there were no deaths or any signs of toxicity observed after administration of the extract at 300 mg/kg, which was the no-observed-adverse-effect level (NOAEL). The extract at a dose of 3000 mg/kg led to the death of one female and one male mouse (LD > 3000 mg/kg). In sub-acute toxicity experiment, the extract induced no mortality or significant changes in body weight, general behaviors, hematological parameters, serum biochemical factors (related to the kidney and liver function), and histopathology of the heart, liver, kidney, and brain up to the highest dose tested of 400 mg/kg (NOAEL). High-performance liquid chromatography-mass spectrometry revealed the presence of phenolic compounds, flavonoids, alkanes, and anthraquinones in the extract. In conclusion, short-term use of root does not appear to produce significant toxicity up to a dose of 400 mg/kg.
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http://dx.doi.org/10.1080/01480545.2018.1561713DOI Listing
November 2020

Therapeutic Potential of Curcumin in the Treatment of Glioblastoma Multiforme.

Curr Pharm Des 2019 ;25(3):333-342

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite standard multimodality treatment, the highly aggressive nature of GBM makes it one of the deadliest human malignancies. The anti-cancer effects of dietary phytochemicals like curcumin provide new insights to cancer treatment. Evaluation of curcumin's efficacy against different malignancies including glioblastoma has been a motivational research topic and widely studied during the recent decade. In this review, we discuss the recent observations on the potential therapeutic effects of curcumin against glioblastoma. Curcumin can target multiple signaling pathways involved in developing aggressive and drug-resistant features of glioblastoma, including pathways associated with glioma stem cell activity. Notably, combination therapy with curcumin and chemotherapeutics like temozolomide, the GBM standard therapy, as well as radiotherapy has shown synergistic response, highlighting curcumin's chemo- and radio-sensitizing effect. There are also multiple reports for curcumin nanoformulations and targeted forms showing enhanced therapeutic efficacy and passage through blood-brain barrier, as compared with natural curcumin. Furthermore, in vivo studies have revealed significant anti-tumor effects, decreased tumor size and increased survival with no notable evidence of systemic toxicity in treated animals. Finally, a pharmacokinetic study in patients with GBM has shown a detectable intratumoral concentration, thereby suggesting a potential for curcumin to exert its therapeutic effects in the brain. Despite all the evidence in support of curcumin's potential therapeutic efficacy in GBM, clinical reports are still scarce. More studies are needed to determine the effects of combination therapies with curcumin and importantly to investigate the potential for alleviating chemotherapy- and radiotherapy-induced adverse effects.
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http://dx.doi.org/10.2174/1381612825666190313123704DOI Listing
February 2020

Flavonoids for preserving pancreatic beta cell survival and function: A mechanistic review.

Biomed Pharmacother 2019 Mar 8;111:947-957. Epub 2019 Jan 8.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Although the currently available antidiabetic medications are effective in managing hyperglycemia, vascular complications are common in diabetic patients. Cohort studies have shown preserved beta cell function has a protective role against the development of diabetic complications. Accordingly, beta cell mass and function are important pharmacological targets in the field of diabetes. Growing number of evidence supports the efficacy of flavonoids (e.g., quercetin, kaempferol, luteolin, and epicatechin) for prevention and attenuation of diabetes consequences. The focus of this paper is to give an overview regarding the effects of flavonoids on pancreatic beta cells. Experiments on insulin-releasing cell lines, isolated pancreatic islets, and diabetic animal models have shown that flavonoids strengthen the survival processes and insulin secretory capacity of beta cells. The proposed mechanisms by which flavonoids preserve beta cells survival (against cytokines, glucotoxicity, and lipotoxicity) include inhibition of NF-κB signaling, activation of PI3K/Akt pathway, inhibition of nitric oxide generation, and decrease of reactive oxygen species levels. Improving mitochondrial bioenergetic function and stimulating pathways of insulin secretion (e.g., PLC/PKC and/or cAMP/PKA signaling) are mechanisms by which flavonoids improve the secretory capacity of beta cells. These beneficial effects of flavonoids are of great importance because may protect beta cells of diabetic patients before dramatic dysfunction and degeneration.
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http://dx.doi.org/10.1016/j.biopha.2018.12.127DOI Listing
March 2019

A Randomized Controlled Trial of a Herbal Compound for Improving Metabolic Parameters in Diabetic Patients with Uncontrolled Dyslipidemia.

Endocr Metab Immune Disord Drug Targets 2019 ;19(7):1075-1082

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: The aim of this randomized controlled trial was to investigate the effects of a polyherbal compound consisting of Aloe vera, black seed, fenugreek, garlic, milk thistle, and psyllium on diabetic patients with uncontrolled dyslipidemia.

Methods: Fifty patients with type 2 diabetes who had dyslipidemia in spite of statin therapy were randomly allocated to two groups: control group (n = 25) receiving a conventional therapy with hypolipidemic and hypoglycemic drugs and intervention group (n = 25) receiving both the conventional therapy and the herbal compound (one sachet twice daily) for 12 weeks. Each sachet contained 300 mg of Aloe vera leaf gel, 1.8 g of black seed, 300 mg of garlic, 2.5 g of fenugreek seed, 1 g of psyllium seed, and 500 mg of milk thistle seed.

Results: The levels of serum triglyceride, total cholesterol, low-density lipoprotein, and HbA1c showed a significant in-group improvement in the intervention group. However, the effects of the herbal compound on fasting blood glucose remained insignificant. The compound had no unwanted effect on the kidney function parameters (urea, creatinine) and serum liver enzymes (alanine aminotransferase and aspartate transaminase).

Conclusion: The tested herbal compound, as an add-on to statin therapy, was effective in lowering the serum lipids in diabetic patients with uncontrolled dyslipidemia.
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http://dx.doi.org/10.2174/1871530319666190206213420DOI Listing
March 2020

Effect of Capparis spinosa Extract on Metabolic Parameters in Patients with Type-2 Diabetes: A Randomized Controlled Trial.

Endocr Metab Immune Disord Drug Targets 2019 ;19(1):100-107

Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Experimental studies have reported beneficial effects of Capparis spinosa L., a perennial shrub from the Capparidaceae family, on the glycemic status and serum lipids in diabetic animals.

Objective: The aim of the present randomized triple-blind placebo-controlled clinical trial was to investigate the safety and efficacy of C. spinosa oxymel on blood glucose, lipid profile, and other diagnostic indexes of metabolic syndrome in patients with poorly controlled type 2 diabetes.

Method: The C. spinosa oxymel was prepared by adding hydroalcoholic extract of C. spinosa fruit to simple oxymel (a mixture of grape vinegar and lactulose). Thirty diabetic patients with metabolic syndrome whose glycemic status was not controlled despite receiving full doses of oral hypoglycemic agents did not want to start insulin therapy and were randomly allocated to three groups to receive placebo, simple oxymel, or C. spinosa oxymel (10 mL/thrice daily for 3 months). All patients continued conventional therapy with hypolipidemic, antihyperlipidemic, and antihypertensive drugs during the study.

Results: C. spinosa oxymel significantly decreased the body weight and body mass index at the end of the study compared to the baseline. While the patients in the placebo and simple oxymel groups displayed further increase in the level of FBG or PPBG, administration of C. spinosa oxymel inhibited the progression of hyperglycemia. Nevertheless, there was not a significant difference between placebo and intervention groups regarding HbA1c at the end of the study. C. spinosa oxymel had no significant effect on the serum cholesterol but inhibited the progression of hypertriglyceridemia during the study. There were no significant changes in creatinine, microalbuminuria, AST, ALT, and ALP values following C. spinosa treatment, suggesting that it had no unwanted effects on kidney and liver function.

Conclusion: The results suggest that although C. spinosa oxymel cannot enhance the effects of hypoglycemic and hypolipidemic drugs, it can prevent further increase of blood glucose and triglycerides in patients with poorly controlled diabetes.
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http://dx.doi.org/10.2174/1871530318666180821131201DOI Listing
May 2019

assessment of alendronate toxic and apoptotic effects on human dental pulp stem cells.

Iran J Basic Med Sci 2018 Sep;21(9):905-910

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Osteonecrosis of the jaw, as an exposed necrotic bone in the oral cavity, is one of the adverse effects of bisphosphonates, which have an affinity for bone minerals. This study investigates the cytotoxic effects of alendronate (ALN) as a nitrogen-containing bisphosphonate, on human dental pulp stem cells (hDPSCs).

Materials And Methods: The mesenchymal stem cells (MSCs), obtained from third molar tooth pulps were characterized by immunophenotyping assay in order to identify surface markers to evaluate their expression. To detect multipotency hDPSCs, they were differentiate into osteocytes and adipocytes. Cell proliferation was measured by MTT assay. PI staining of DNA fragmentation by flowcytometry (sub-G1 peak) was performed for determination of apoptotic cells and Bax, Bcl-2, and cleaved caspase 3 expressions. Protein expression was detected by Western blotting.

Results: As the results revealed, ALN decreased viable cells (in 0.8-100 µM) after 72 hr and 168 hr (<0.001), significantly. ALN could lower cell proliferation in hDPSCs in a concentration and time-dependent manner. Sub-G1 peak as an indicator of flowcytometry histogram of treated cells by ALN, showed apoptosis was involved in ALN-induced cytotoxicity. Expressions of cleaved caspase 3 and Bax protein, as pro-apoptotic proteins, were increased and Bcl-2 protein as anti-apoptotic protein was decreased in response to increases in the concentration of ALN (0.8-25 µM).

Conclusion: Long-term effects of ALN on cell proliferation and apoptosis in hDPSCs can result in either initiation or potentiation of ALN-induced osteonecrosis.
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http://dx.doi.org/10.22038/IJBMS.2018.22877.5816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272077PMC
September 2018
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