Publications by authors named "Mohammad Hossein Boskabady"

168 Publications

Anti-inflammatory and Antioxidant Effects of Rosuvastatin on Asthmatic, Hyperlipidemic, and Asthmatic-Hyperlipidemic Rat Models.

Inflammation 2021 Jul 6. Epub 2021 Jul 6.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Statins could be of potential therapeutic effect in asthma due to their pleiotropic effects on inflammation process. This study aimed to examine the possible interaction of serum lipids, and evaluate the effect of rosuvastatin treatment on asthma. Seven groups of rats, namely control (C), asthmatic (A), hyperlipidemic (H), asthmatic-hyperlipidemic (AH), rosuvastatin (40 mg/kg)-treated asthmatic (AR), rosuvastatin-treated hyperlipidemic (HR), and rosuvastatin-treated hyperlipidemic-asthmatic (AHR) groups, were studied. Total and differential WBC counts, serum oxidative stress markers, and bronchoalveolar lavage fluid (BALF) levels of IL-6 and IL-10 were evaluated. In the A and AH groups, total and differential WBC counts, and IL-6 and IL-10 levels were higher than in the C group (p<0.05 to p<0.001). An increase in nitrite and malondialdehyde concentrations and a decrease in total thiol content and superoxide dismutase and catalase activities were observed in the A, H, and AH groups compared to the C group (p<0.05 to p<0.001). Beyond lipid lowering, rosuvastatin treatment reduced total and differential WBC counts in the A and AH groups (p<0.05 to p<0.001), IL-6 level in the AH group (p<0.05), and IL-10 level in all treated groups (p<0.05). Rosuvastatin reduced oxidative stress by decreasing nitrite and malondialdehyde concentrations, and increasing total thiol content in all treated groups as well as superoxide dismutase and catalase activities in the H and AH groups (p<0.05 to p<0.01). Rosuvastatin reduced airway inflammation and oxidation through regulating NOS and reducing pro-inflammatory cytokine and inflammatory cells, which indicate a novel insight into the pleiotropic effects of rosuvastatin in treatment of asthma.
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http://dx.doi.org/10.1007/s10753-021-01499-8DOI Listing
July 2021

Systemic inflammation and oxidative stress induced by inhaled paraquat in rat improved by carvacrol, possible role of PPARγ receptors.

Biofactors 2021 Jun 5. Epub 2021 Jun 5.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Control rats were exposed to saline aerosol, two groups were exposed to paraquat (PQ), 27 (PQ-L) and 54 (PQ-H) mg/m aerosols and six groups were treated with carvacrol, 20 (C-L) and 80 (C-H) mg/kg/day, pioglitazone, 5 (Pio-L) and 10 (Pio-H) mg/kg/day, C-L+Pio-L and dexamethasone, 0.03 mg/kg/day, for 16 days after the end of exposure to PQ-H. Different variables were measured after the end of treatment period. Total and differential white blood cells counts, nitrite, malondialdehyde, interleukin (IL)-10, and interferon-gamma levels were significant increased, but thiol, superoxide dismutase, catalase, IL-17, and tumor necrosis factor alpha were decreased in the blood due to both doses of PQ (p < 0.05-p < 0.001). Most measured parameters were significantly improved in treated groups with both doses of carvacrol, pioglitazone, the combination of C-L+Pio-L and dexamethasone compared to PQ-H group (p < 0.05-p < 0.001). Treatment with C-L+Pio-L showed significantly higher effects compared to each one alone (p < 0.05-p < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by carvacrol and pioglitazone. Higher effects of C-L+Pio-L than each one alone suggests carvacrol modulating PPAR-γ receptors.
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http://dx.doi.org/10.1002/biof.1761DOI Listing
June 2021

A qualitative and quantitative comparison of Crocus sativus and Nigella sativa immunomodulatory effects.

Biomed Pharmacother 2021 Aug 29;140:111774. Epub 2021 May 29.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The present article reviews and compares the immunomodulatory activities of Crocus sativus (C. sativus) and Nigella sativa (N. sativa) and their main bioactive compounds. Immunomodulatory effects of these plants, especially with respect to Th1 and Th2 cytokines, are discussed based on relevant articles, books, and conference papers published in English until the end of April 2020, that were retrieved from Web of Science, PubMed, Scopus and Google Scholar databases. C. sativus and its constituents increase immunoglobulin (Ig-)G, interleukin 2 (IL)-2, interferon gamma (IFN-γ), and IFN-γ/IL-4 ratio, but decreased IgM, IL-10 and IL-4 secretion. N. sativa extract and thymoquinone reduce the levels of IL-2, -4, -10, and -12, while enhance IFN-γ and serum IgG1 and 2a. The reviewed articles indicate that C. sativus and N. sativa and their constituents could be potentially considered promising treatments for disorders associated with immune-dysregulation such as asthma and cancer.
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http://dx.doi.org/10.1016/j.biopha.2021.111774DOI Listing
August 2021

and Pioglitazone Affect Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rats.

Mediators Inflamm 2021 4;2021:5575059. Epub 2021 May 4.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 9177948564.

The effects of () and pioglitazone (a PPAR- agonist) alone and in combination, on systemic inflammation and oxidative stress induced by inhaled paraquat (PQ) as a herbicide, which induced inflammation in rats, were examined. Rats were exposed to (1) saline (control) and (2) 54 mg/m PQ aerosols (8 times, every other day, each time for 30 min) without treatment or treated with (3 and 4) two doses of (200 and 800 mg/kg/day), (5 and 6) two doses of pioglitazone (5 and 10 mg/kg/day), (7) low doses of . + pioglitazone, (Pio-5+Z-200 mg/kg/day) or (8) dexamethasone (0.03 mg/kg/day) for 16 days, after the last PQ exposure. Different variables were measured at the end of the treatment period. Exposure to PQ significantly increased total and differential white blood cells (WBC) counts, serum levels of nitrite (NO), malondialdehyde (MDA), interleukin- (IL) 17, and tumor necrosis factor alpha (TNF-), but reduced thiol, superoxide dismutase (SOD), catalase (CAT), IL-10, and interferon-gamma (INF-) ( < 0.05 to < 0.001). Most measured parameters were significantly improved in groups treated with either doses of the extract, pioglitazone, Pio-5+Z-200 mg/kg/day, or dexamethasone compared to the PQ group ( < 0.05 to < 0.001). The combination of low doses of Pio-5+Z-200 mg/kg/day showed significantly higher effects compared to each one alone ( < 0.05 to < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by and pioglitazone. Higher effects of Pio-5+Z-200 mg/kg/day compared to each one alone suggest modulation of PPAR- receptors by the plant extract, but further studies using PPAR- antagonists need to be done in this regard.
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http://dx.doi.org/10.1155/2021/5575059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112915PMC
May 2021

Relaxant Effect of on Tracheal Smooth Muscle Mediated by the Effect on Beta-2 Adrenergic, Muscarinic Receptors and Calcium and Potassium Channels.

Evid Based Complement Alternat Med 2021 20;2021:6637990. Epub 2021 Apr 20.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

() showed anti-inflammatory, antioxidant, antibacterial, diuretic, vasodilatation, and wound-healing effects on fungal infections, cardiac disorders, digestive disorders, rheumatoid disease, and respiratory disorders such as bronchitis, bronchial nosocomial infections, and severe cough. To examine the bronchodilatory effect of , the relaxant effect of its extract on rat tracheal smooth muscle (TSM) and its possible mechanism was examined in this study. Male Wistar rats' TSM were divided into eight groups ( = 8 in each group). Four of these groups were TSM tissues, contracted with KCl (60 mM) incubated with atropine, glibenclamide, and indomethacin and nonincubated TSM, while the other four groups were TSM tissues contracted with methacholine (10 M) for 5 min, incubated with propranolol, chlorpheniramine, and diltiazem and nonincubated TSM. Cumulative concentrations of extract (12.5, 25, 50, 100, 20, and 400 g/ml) were then added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6, and 0.8 mM) as positive control and saline (1 ml) as negative control were also examined in nonincubated tissues. A concentration-dependent relaxant effect of on nonincubated TSM contracted with KCl (60 mM) or methacholine (10 M) ( < 0.01 and < 0.001) was observed. The relaxant effects of extract in the incubated tissues with glibenclamide, propranolol, diltiazem, atropine, and chlorpheniramine were significantly lower than those in the nonincubated tissues ( < 0.05 to < 0.001). EC values of extract in the incubated TSM with glibenclamide, propranolol, diltiazem, and atropine were significantly higher than those in the nonincubated tissues ( < 0.05 for diltiazem-incubated tissues and < 0.001 for other cases). extract displayed considerable relaxant effect on TSM comparable to the effect of theophylline. Beta-2 adrenoceptor stimulation and muscarinic receptor inhibition as well as potassium opening and calcium channels blocking effects are the possible mechanisms for the relaxant effects of the plant.
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http://dx.doi.org/10.1155/2021/6637990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081620PMC
April 2021

Human T-Cell Leukemia Virus Type 1 Changes Leukocyte Number and Oxidative Stress in the Lung and Blood of Female BALB/c Mice.

Adv Biomed Res 2021 30;10. Epub 2021 Jan 30.

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

Background: Human T-cell leukemia virus type 1(HTLV-1) infection is likely to induce nonneoplastic inflammatory pulmonary diseases. Therefore, an experimental study was conducted to evaluate the leukocytes' number alteration and oxidative stress in the lung and blood of HTLV-1-infected BALB/c mice, which could be of benefit for the recognition of HTLV-1 mechanism in the induction of pulmonary disorders.

Materials And Methods: Twenty female BALB/c mice were divided into two groups of control and HTLV-1-infected animals. The HTLV-1-infected group was inoculated with 10 MT-2 HTLV-1-infected cells. Two months later, the infection was confirmed using real-time polymerase chain reaction, and then lung pathological changes, total and differential inflammatory cell counts in the blood and bronchoalveolar lavage fluid (BALF), along with oxidative stress biomarker levels in the BALF and lung tissue were evaluated.

Results: In the HTLV-1-infected group, the peribronchitis score ( < 0.01), the number of total leukocytes, neutrophils, lymphocytes, and monocytes ( < 0.05) in the blood and BALF were increased. The number of eosinophils in the blood of the HTLV-1-infected group was higher than in the control group ( < 0.01), whereas the number of basophils of BALF was increased in the HTLV-1-infected group ( < 0.001). The lung and BALF oxidative stress results showed that the MDA level was increased, while the total thiol level and superoxide dismutase activity were decreased in the HTLV-1-infected group ( < 0.01).

Conclusion: The HTLV-1 infection seems to induce pulmonary inflammatory reactions by recruiting leukocytes as well as inducing oxidative stress in the lung tissue.
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http://dx.doi.org/10.4103/abr.abr_117_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095261PMC
January 2021

Thymoquinone Ameliorates Lung Inflammation and Pathological Changes Observed in Lipopolysaccharide-Induced Lung Injury.

Evid Based Complement Alternat Med 2021 30;2021:6681729. Epub 2021 Mar 30.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Anti-inflammatory, antioxidant, and immunomodulatory effects of thymoquinone (TQ) have been shown. The effects of TQ on lipopolysaccharide- (LPS-) induced inflammation and pathological changes in rats' lung were investigated in this study. Four groups of rats included (1) control (saline treated); (2) LPS (treated with 1 mg/kg/day i.p. for two weeks); and (3 and 4) 5 or 10 mg/kg TQ i.p. 30 min prior to LPS administration. Total and differential WBC counts in the blood and bronchoalveolar fluid (BALF), TGF-1, INF-, PGE2, and IL-4 levels in the BALF and pathological changes of the lung were evaluated. Total WBC count and eosinophil, neutrophil, and monocyte percentage were increased, but the lymphocyte percentage was reduced in the blood and BALF. The BALF levels of PGE2, TGF-1, and INF- were also increased, but IL-4 level was reduced due to LPS administration. LPS also induced pathological insults in the lung of rats ( < 0.05 to < 0.001 for all changes in LPS-exposed animals). Treatment with TQ showed a significant improvement in all changes induced by LPS ( < 0.05 to < 0.05). TQ showed a protective effect on LPS-induced lung inflammation and pathological changes in rats which suggested a therapeutic potential for TQ on lung injury.
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http://dx.doi.org/10.1155/2021/6681729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024078PMC
March 2021

Carvacrol and PPARγ agonist, pioglitazone, affects inhaled paraquat-induced lung injury in rats.

Sci Rep 2021 Apr 14;11(1):8129. Epub 2021 Apr 14.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day pioglitazone, low dose of pioglitazone + carvacrol and 0.03 mg/kg/day dexamethasone (Dexa) for 16 days after the end of PQ exposure were studied (n = 6 in each group). Lung pathological changes, tracheal responsiveness to methacholine and ovalbumin (OVA) as well as transforming growth factor beta (TGF-β) and interleukin (IL)-6 level in the lung tissue homogenize as well as TGF-β, IL-6, oxidant and antioxidant levels oxidant and antioxidants were increased in PQ group (p < 0.01 to p < 0.001). Lung pathological changes, tracheal responsiveness to methacholine and OVA as well as TGF-β, IL-6 oxidant and antioxidant levels were improved in all treated groups except lung pathological changes in treated group with low dose of pioglitazone (p < 0.05 to p < 0.001). The effects of low dose of pioglitazone and carvacrol alone were significantly lower than in the combination group of low dose of pioglitazone + carvacrol (p < 0.05 to p < 0.001). Carvacrol treatment improved inhaled PQ-induced lug injury similar to the effects of dexamethasone. The synergic effect of carvacrol and pioglitazone suggests PPAR-γ receptor mediated effects of carvacrol on inhaled PQ-induced lung injury.
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http://dx.doi.org/10.1038/s41598-021-87546-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047048PMC
April 2021

Carvacrol improves pulmonary function tests, oxidant/antioxidant parameters and cytokine levels in asthmatic patients: A randomized, double-blind, clinical trial.

Phytomedicine 2021 May 6;85:153539. Epub 2021 Mar 6.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Carvacrol effects on inflammatory mediators, lung pathology and tracheal responsiveness were indicated in animal models of pulmonary diseases.

Purpose: To evaluate carvacrol effects on respiratory symptoms, pulmonary function tests (PFT), oxidative stress markers and cytokine levels in asthmatic patients.

Study Design: This study was a randomized, placebo-controlled double-blind, clinical trial.

Methods: Thirty-three moderate asthmatic patients were divided to the two groups of: placebo group (n = 16) and carvacrol group (1.2 mg/kg/day, n = 17). Prepared capsules were taken for two months along, 3 times/day along with routine medications. Respiratory symptoms, PFT, and oxidative stress markers were evaluated before the treatment (step 0), and one (step I) and two months (step II) after the beginning of the treatment. However, cytokine levels in serum and supernatant of peripheral blood mononuclear cells (PBMC), and their gene expression were evaluated in step 0 and II.

Results: In carvacrol-treated group, respiratory symptoms significantly decreased after one- and two-month treatment with carvacrol compared to pre-treatment values (p < 0.05 to p < 0.001). Compared to step 0, PFT values were significantly increased in step I and II, in treated group with carvacrol (p < 0.05 to p < 0.001). Most oxidative stress markers were improved following carvacrol treatment (p < 0.05 to p < 0.001). Treatment with carvacrol for two-month also significantly improved cytokine levels in serum and supernatant of PBMC, compared to step 0 (p < 0.05 to p < 0.001). However, no significant changes were observed in the above-noted parameters in the placebo group.

Conclusion: Due to anti-inflammatory and antioxidant effect, carvacrol could be suggested as a therapeutic agent for asthma.
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http://dx.doi.org/10.1016/j.phymed.2021.153539DOI Listing
May 2021

Immediate and late systemic and lung effects of inhaled paraquat in rats.

J Hazard Mater 2021 08 12;415:125633. Epub 2021 Mar 12.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The immediate and the late effects of inhaled Paraquat (PQ) on systemic and lung inflammation and oxidative stress were investigated. Rats were exposed to saline (control group) and two doses of inhaled PQ (27 and 54 mg/m) and studied variables were measured: 1) one day after the end of PQ exposure as "immediate condition", 2) 16 days after the end of PQ exposure as "late condition". Total and differential white blood cells (WBC) counts, lipid peroxidation and nitrite were increased but thiol, superoxide dismutase and catalase in the blood and BALF as well as methacholine EC50 was reduced in both conditions in the animals exposed to PQ compared to control groups (p < 0. 05 to p < 0.001). Most studied parameters in the immediate condition were significantly higher than the late condition (p < 0.05 to p < 0.001). Systemic and lung inflammation and oxidative stress due to inhaled PQ in both the immediate and the late conditions were shown. Although most measured parameters in the immediate condition were higher, all variables were significantly different with the control group even in late condition, indicating a long-term effect of inhaled PQ toxicity, which may help in a more effective treatment of PQ poising in the future.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125633DOI Listing
August 2021

The effects of Nigella sativa on respiratory, allergic and immunologic disorders, evidence from experimental and clinical studies, a comprehensive and updated review.

Phytother Res 2021 Jun 17;35(6):2968-2996. Epub 2021 Jan 17.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Nigella sativa (N. sativa) seed had been used traditionally due to several pharmacological effects. The updated experimental and clinical effects of N. sativa and its constituents on respiratory, allergic and immunologic disorders are provided in this comprehensive review article. Various databases including PubMed, Science Direct and Scopus were used. The preventive effects of N. sativa on pulmonary diseases were mainly due to its constituents such as thymoquinone, thymol, carvacrol and alpha-hederin. Extracts and constituents of N. sativa showed the relaxant effect, with possible mechanisms indicating its bronchodilatory effect in obstructive pulmonary diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of N. sativa was demonstrated by mechanisms such as antioxidant, immunomodulatory and antiinflammatory effects. Bronchodilatory and preventive effects of the plant and its components on asthma, COPD and lung disorders due to exposure to noxious agents as well as on allergic and immunologic disorders were also shown in the clinical studies. Various extracts and constituents of N. sativa showed pharmacological and therapeutic effects on respiratory, allergic and immunologic disorders indicating possible remedy effect of that the plant and its effective substances in treating respiratory, allergic and immunologic diseases.
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http://dx.doi.org/10.1002/ptr.7003DOI Listing
June 2021

Immuno-modulatory effects of methanolic extract of Ferula szowitsiana on isolated human Th/Th/T cytokines levels, and their genes expression and nitric oxide production.

Cytokine 2021 02 2;138:155387. Epub 2020 Dec 2.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Anti-inflammatory and anti-oxidants activities of Ferula szowitsiana L. (F. szowitsiana) were shown in ancient texts and assayed by modern studies. However, immunomodulatory properties of the plant are poorly understood.

Methods: The effects of F. szowitsiana extract (10, 40 and 160 µg/ml), dexamethasone and vehicle were investigated on nitric oxide (NO) level, cell proliferation, and cytokines (IL-4, IL10 and IFN-γ) expression at gene and protein levels in non-stimulated and phytohaemagglutinin-stimulated human lymphocytes (n = 15 in each group).

Results: Cell proliferation, cytokines secretion, NO production and levels of genes expression were significantly inhibited but IFN-γ/IL-4 and IL-10/IL-4 ratios (T helper 1/Th2 and Treg/Th2 balances respectively) were increased by dexamethasone and all three concentrations of the extract compared to control group in stimulated lymphocytes (P < 0.001 for all cases). The effect of three concentrations of the extract in all experiments was significantly lower than dexamethasone (P < 0.001 for all cases).

Conclusion: The extract of F. szowitsiana concentration-dependently decreased NO level but increased Th/Th and T/Th ratios toward Th and T. These results suggest the therapeutic potential of the plant's extract in inflammatory diseases with dominant Th2 polarization such as asthma or cancers.
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http://dx.doi.org/10.1016/j.cyto.2020.155387DOI Listing
February 2021

Treadmill exercise ameliorates memory deficits and hippocampal inflammation in ovalbumin-sensitized juvenile rats.

Brain Res Bull 2020 12 28;165:40-47. Epub 2020 Sep 28.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The behavioral changes, including spatial learning and memory impairment as well as depressive- and anxiety-like behaviors in an animal model of asthma were demonstrated previously. On the other hand, there is increasing evidence that the anti-inflammatory actions of exercise are related to their neuroprotective properties against different insults in the brain. This study was aimed to explore the effects of moderate treadmill exercise on cognitive deficits and possible anti-inflammatory mechanisms in ovalbumin (OVA)-sensitized rats. The exercise groups were trained to run on the treadmill 30 min/day with an intensity of 12 m/min, 5 days/week for 4 weeks. Animals in the OVA groups were sensitized by two intraperitoneal (i.p.) injections of OVA (10 μg/injection) and challenged with OVA by inhalation during the treadmill running exercise period. Passive avoidance (PA) memory, levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in the hippocampus, total and differential white blood cell (WBC) count in the blood as well as pathological changes of the lung were then evaluated. OVA-sensitization was resulted in cognitive deficits in the PA task, along with increased total and differential WBC in blood and TNF-α in the hippocampus. However, exercise ameliorated these changes and increased the IL-10 level in the hippocampus, suggesting that moderate treadmill exercise can improve memory impairment in OVA-sensitized rats due to its anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.brainresbull.2020.09.016DOI Listing
December 2020

Paraquat-induced systemic inflammation and increased oxidative markers in rats improved by extract and carvacrol.

Avicenna J Phytomed 2020 Sep-Oct;10(5):513-522

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Paraquat (PQ) is a herbicide which induces oxidative stress and inflammation. Anti-inflammatory and anti-oxidant effects were shown for (Z) and carvacrol previously. The effects of Z hydroalcoholic extract and carvacrol on systemic inflammation and oxidative stress induced by inhaled PQ were examined in this study.

Materials And Methods: Six groups of male rats used in this study were as follows: control group exposed to normal saline aerosol, one group exposed to PQ 54 mg/m aerosol, animals exposed to PQ 54 mg/m and treated with Z (200 and 800 mg/kg/day) or carvacrol (20 and 80 mg/kg/day) for 16 days after the end of exposure to PQ. Exposure to PQ was performed 8 times, every other day, each time for 30 min. After the end of the treatment period, different variables were measured.

Results: Significant increases in nitrite (NO, malondialdehyde (MDA) and interleukin (IL)-6 serum levels but significant reduction of interferon-gamma (IFN-γ) serum levels as well as IFN-γ/IL-6 ratio were observed in PQ-exposed compared to control group (p<0.01 for MDA and IL-6, p<0.001 for other cases). Treatment with both doses of the extract and carvacrol specially at high dose, reduced MDA, NO, and IL-6 but increased IFN-γ and IFN-γ/IL-6 ratio compared to un-treated PQ exposed group (p<0.05 to p<0.001).

Conclusion: Treatment with and carvacrol improved systemic inflammation oxidative biomarkers induced by inhaled PQ which may indicate therapeutic potential of the plant and its constituent, carvacrol in systemic inflammation and oxidative biomarkers induced by inhaled PQ.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508324PMC
September 2020

Carvacrol and influenced the PPARγ agonist effects on systemic inflammation and oxidative stress induced by inhaled paraquat in rat.

Iran J Basic Med Sci 2020 Jul;23(7):930-936

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

Objectives: The effects of PPAR-γ agonist alone and in combination with carvacrol and on inhaled paraquat (PQ) induced-systemic inflammation and oxidative stress were examined.

Materials And Methods: Control group exposed to normal saline aerosol, one group exposed to 54 mg/m PQ aerosol and four groups exposed to PQ aerosol and treated with 5 mg/kg/day pioglitazone, pioglitazone + 200 mg/kg/day Z. extract, pioglitazone + 20 mg/kg/day carvacrol, and 0.03 mg /kg/day dexamethasone for 16 days after the end of exposure to PQ were studied. Exposure to normal saline or PQ was performed every other days for 30 min (8 times). Different variables were measured after the end of treatment period.

Results: PQ exposure significantly increased serum levels of NO, MDA and IL-6 but dexreased CAT and IFN-γ levels and IFN-γ/IL-6 ratio compared to control group (<0.01 to <0.001). Treatment with pioglitazone only improved serum level of MDA (<0.01). Treatment with combination of pioglitazone and carvacrol as well as treatment with dexamethasone improved all measured variables compared to PQ exposed group (<0.05 to <0.001). The effects of pioglitazone + Z. and pioglitazone + carvacrol on almost all measured variables were significantly higher than pioglitazone alone (<0.05 to <0.001).

Conclusion: The effects of combination therapy of pioglitazone with Z. or carvacrol on inhaled paraquat (PQ) induced-oxidative stress and systemic inflammation were higher than the effects of pioglitazone alone. These results suggested that the effects of the extract and carvacrol may mediated through PPAR-γ receptors.
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http://dx.doi.org/10.22038/ijbms.2020.45962.10648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395191PMC
July 2020

Zataria multiflora induced bronchodilatoion comparable to theophylline syrup in asthmatic patients.

Explore (NY) 2020 Jul 15. Epub 2020 Jul 15.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Objective: The bronchodilatory effect of hydro-ethanolic extract of Z. multiflora was examined in asthmatic patients.

Design: Pulmonary function tests (PFTs) were measured before and 15, 30, 60, 90, 120, 150, and 180 min after administration of the extract (20 mg/kg) in 18 asthmatics and after theophylline syrup (6 mg/kg) in 12 patients.

Main Outcome Measures: The extract of Z. multiflora significantly increased all PFT values, 30 to 180 min post-administration similar to the effect of theophylline (all, p<0.001). Increased PFT values due to the extract were significantly declined 180 min but the effects of theophylline were declined 150 min after administration (p<0.05 to p<0.001). Values of PFTs at baseline, 30 and 180 min after drugs administration were not singnificantly different between the extract and theophylline.

Conclusions: Z. multiflora showed a bronchodilatory effect in asthmatic patients comparable to theophylline effect but with a longer duration of action.
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http://dx.doi.org/10.1016/j.explore.2020.07.002DOI Listing
July 2020

The Relaxant Effect of Crocin on Rat Tracheal Smooth Muscle and Its Possible Mechanisms.

Iran J Pharm Res 2019 ;18(3):1358-1370

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Crocin, a component of saffron, showed hypotensive activity which is perhaps due to vascular smooth muscle relaxant effect. The relaxant effects of saffron on tracheal smooth muscle also could be due to its constituent, crocin. In the present study, the relaxant effects of crocin and its possible mechanisms on rat tracheal smooth muscle were investigated. The relaxant effects of three cumulative concentrations of crocin (30, 60, and 120 μM) or theophylline (0.2, 0.4, 0.6 mM) as positive control were examined on pre-contracted tracheal smooth muscle by methacholine or KCl in non-incubated or incubated conditions with different agents including atropine, chlorpheniramine, indomethacin, diltiazem, glibenclamide, and propranolol. In non-incubated tracheal smooth muscle, crocin showed significant relaxant effects on KCl induced muscle contraction ( < 0.001 for two higher concentrations). However, crocin did not show relaxant effect on methacholine induced tissue contraction. In incubated tissues with chlorpheniramine, indomethacin, diltiazem and propranolol, there were no significant differences in the relaxant effects of crocin between non-incubated and incubated tissues. However, the relaxant effects of crocin obtained in incubated tissues with atropine and glibenclamide were significant lower than non-incubated tracheal smooth muscle ( < 0.05 to < 0.001). The EC value obtained in incubated tissue with propranolol was significantly increased. Theophylline showed significant relaxant effect on both KCl and methacholine induced tissue contraction ( < 0.01 to < 0.001). A relatively potent relaxant effect of crocin on tracheal smooth muscle, lower than that of theophylline was shown. Muscarinic receptor blocking, potassium channels opening and ß-adrenoreceptors stimulation were also suggested as possible mechanisms of this effect.
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http://dx.doi.org/10.22037/ijpr.2019.1100713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934977PMC
January 2019

Zataria multiflora affects clinical symptoms, oxidative stress and cytokines in asthmatic patient: A randomized, double blind, placebo-controlled, phase II clinical trial.

Cytokine 2020 09 22;133:155169. Epub 2020 Jun 22.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Z. multiflora effect on clinical symptoms, pulmonary function tests (PFT), oxidative stress and cytokine levels in asthmatic patients were evaluated.

Methods: 36 asthmatic patients were divided to; placebo group (P), two groups treated with Z. multiflora extract (5 and 10 mg/kg/day, as Z5 and Z10, respectively), (n = 12 in each group). Medications were administered three times a day for two months and several parameters were evaluated before treatment (step 0), one (step 1) and two months (step 2) after treatment.

Results: Clinical symptoms and PFTs were significantly improved in Z5 and Z10 groups in steps 1 and 2 compared to step 0 (p < 0.05 to p < 0.001). Improvement of oxidative stress, cytokines levels and their gene expression after treatment with both doses of extract were observed in step 2 compared to step 0 (p < 0.05 to p < 0.001).

Conclusion: These results indicated therapeutic value of Z. multiflora for the management of asthma.
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http://dx.doi.org/10.1016/j.cyto.2020.155169DOI Listing
September 2020

The effect of Zataria multiflora on inflammatory cytokine and respiratory symptoms in veterans exposed to sulfur mustard.

Environ Sci Pollut Res Int 2020 Jun 20;27(18):22451-22460. Epub 2020 Apr 20.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran.

The effect of Zataria multiflora (Z. multiflora) on serum cytokine, chemokines, and respiratory symptoms in the veterans exposed to sulfur mustard (SM) more than two decades (27-30 years) ago was conducted in 2018. Thirty-four patients were randomly assigned to the placebo group (P, mean age (54.40 ± 5.51)) and two treated groups with Z. multiflora extract 5 and 10 mg/kg/day (Z5 and 10; mean age, 58.50 ± 3.60 and 55.18 ± 4.11, respectively). Serum levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), forced expiratory volume-one second (FEV), and respiratory symptoms including chest wheeze (CW), night wheeze (NW), night cough (NC), and cough and wheeze during exercise (ECW) were assessed at the baseline (phase 0), 1 and 2 months after starting treatment (phase I and II, respectively). The value of FEV was significantly increased in Z10 in phase I and II compared with that in phase 0 (p < 0.01 for both) and in Z5 in phase II compared with phase I and 0 (p < 0.001for both). All respiratory symptoms significantly decreased in Z5 and 10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). Serum levels of TNF-α and VEGF were decreased in Z5 and 10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). Serum levels of MCP-1 and EGF were decreased in Z10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). The percent change of respiratory symptoms, serum levels of cytokines during the treatment period, was significantly improved in the treated groups compared with that in the placebo group. Two months' of treatment with Z. multiflora improved cytokine levels, respiratory symptom, and FEV values in SM-exposed patients.
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http://dx.doi.org/10.1007/s11356-020-08855-5DOI Listing
June 2020

Effects of levothyroxine on lung inflammation, oxidative stress and pathology in a rat model of Alzheimer's disease.

Respir Physiol Neurobiol 2020 06 5;277:103437. Epub 2020 Apr 5.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: In this study, the effect of levothyroxine (L-T4) on tracheal responsiveness, lung inflammation, oxidative stress and pathological features in a rat model of Alzheimer's disease (AD), was evaluated.

Methods: An animal model of AD was established by intracerebroventricular injection of streptozotocin (STZ) (3 mg/kg) in rats. The rats were then treated for 3 weeks with L-T4 (10 and 100 μg/kg).

Results: In AD animals, tracheal responsiveness to methacholine and ovalbumin (p < 0.05), white blood cell (WBC) count (p < 0.05 to p < 0.01), malondialdehyde (MDA) concentration (p < 0.05) and inflammation score (p < 0.01) were increased, but superoxide dismutase (SOD) activity and total thiol content (for both cases p < 0.05) were decreased compared to the controls. Tracheal responsiveness to methacholine and MDA concentration (p < 0.05) were decreased in AD animals treated with T4 compared to the AD group. Bronchial inflammation in terms of total and some differential WBC in the BALF and inflammatory score, was significantly worsened in AD animals treated with high dose of T4 (p < 0.05 to p < 0.001) compared to the controls.

Conclusion: Alzheimer's disease may cause lung inflammation and treatment with low dose of T4 improved MDA level and lung inflammation.
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http://dx.doi.org/10.1016/j.resp.2020.103437DOI Listing
June 2020

Rosuvastatin Affects Tracheal Responsiveness, Bronchoalveolar Lavage Inflammatory Cells, and Oxidative Stress Markers in Hyperlipidemic and Asthmatic Rats.

Iran J Allergy Asthma Immunol 2019 Oct 12;18(6):624-638. Epub 2019 Oct 12.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Statins provide greater protection than predicted from just cholesterol-lowering effects, which is possibly mediated by other pleiotropic actions. This study aimed to examine the possible interaction effect of asthma on lipid profiles and evaluate the effect of rosuvastatin treatment on asthma. The animals were assigned into (1) control, (2) asthmatic, (3) hyperlipidemic, (4) asthmatic-hyperlipidemic, (5) rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic, (6) rosuvastatin-treated hyperlipidemic and (7) rosuvastatin-treated asthmatic-hyperlipidemic groups. Tracheal responsiveness to methacholine and ovalbumin, total and differential WBC (white blood cell) counts, and oxidative stress markers in bronchoalveolar lavage fluid (BALF) were evaluated. In the asthmatic and asthmatic-hyperlipidemic groups, tracheal responsiveness to ovalbumin, total WBC count, numbers of eosinophils, neutrophils, and monocytes were higher than the control group (p<0.001). A left-ward shift in the concentration-response curves to methacholine, an increase in nitrite and malondialdehyde concentrations, and a decrease in total thiol content, superoxide dismutase and catalase activities were also observed in the asthmatic and asthmatic-hyperlipidemic groups compared to control group (p<0.01 to p<0.001). Beyond lipid-lowering effect in the treated hyperlipidemic and asthmatic-hyperlipidemic groups, rosuvastatin treatment decreased tracheal responsiveness to methacholine, reduced total WBC count, the numbers of eosinophils, neutrophils, and monocytes, as well as decreased malondialdehyde concentration, and increased total thiol content, superoxide dismutase and catalase activities in treated asthmatic and asthmatic-hyperlipidemic groups (p<0.05 to p<0.001). The improving effect of rosuvastatin on asthmatic and asthmatic-hyperlipidemic animals was shown due to pleiotropic mechanisms including the effect on airway hyperresponsiveness, lung inflammation, and oxidative stress.
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http://dx.doi.org/10.18502/ijaai.v18i6.2175DOI Listing
October 2019

Calcium and potassium channels are involved in curcumin relaxant effect on tracheal smooth muscles.

Pharm Biol 2020 Dec;58(1):257-264

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Curcumin, the active component of L. (Zingiberaceae), exhibits a wide variety of biological activities including vasodilation and anti-inflammation. The relaxant effect of curcumin in tracheal smooth muscle (TSM) was not examined so far, thus, this study was designed to assess the relaxant effect of curcumin on rat TSM and examine the underlying mechanism(s) responsible for this effect. TSM was contracted by KCl (60 mM) or methacholine (10 μM), and cumulative concentrations of curcumin (12.5, 25, 50, and 100 mg/mL) or theophylline (0.2, 0.4, 0.6, and 0.8 mM, as positive control) were added to organ bath. The relaxant effect of curcumin was examined in non-incubated or incubated tissues with atropine (1 μM), chlorpheniramine (1 μM), indomethacin (1 μM), and papaverine (100 μM). In non-incubated TSM, curcumin showed significant relaxant effects on KCl-induced contraction in a concentration-dependent manner ( < 0.001 for all concentrations). The relaxant effects of curcumin 12.5, 25, and 50 mg/mL were significantly lower in atropine-incubated tissue compared to non-incubated TSM ( < 0.05 to  < 0.001). A significant difference was observed in EC between atropine-incubated (48.10 ± 2.55) and non-incubated (41.65 ± 1.81) tissues ( < 0.05). Theophylline showed a significant relaxant effect on both KCl and methacholine-induced contraction in a concentration-dependent manner ( < 0.001 for all cases). The results indicated a relatively potent relaxant effect of curcumin on TSM, which was less marked than the effect of theophylline. Calcium channel blocking and/or potassium channel opening properties of curcumin may be responsible for TSM relaxation.
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http://dx.doi.org/10.1080/13880209.2020.1723647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170316PMC
December 2020

A Randomized, Doubled-Blind Clinical Trial on the Effect of Zataria multiflora on Clinical Symptoms, Oxidative Stress, and C-Reactive Protein in COPD Patients.

J Clin Pharmacol 2020 07 23;60(7):867-878. Epub 2020 Mar 23.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

The effects of Zataria multiflora on clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein levels in chronic obstructive pulmonary disease (COPD) patients were evaluated. Forty-five patients were allocated to 3 groups: placebo group and 2 groups that received 3 and 6 mg/kg/day Z. multiflora extract (Z3 and Z6) for 2 months. Clinical symptoms, pulmonary function tests, oxidative stress, and serum C-reactive protein levels were evaluated pretreatment (step 0) and 1 (step I) and 2 (step II) months after treatment. Clinical symptoms including breathlessness and chest wheeze in Z3- and Z6-treated groups and sputum production only in the Z6-treated group were significantly improved 1 and 2 months after treatment compared with baseline values (P < .01 to P < .001). The FEV was significantly increased after 2 months of treatment with Z3 and Z6 (P < .05 to P < .01). Malondialdehyde and nitrite levels were significantly decreased after a 2-month treatment with Z6 compared with step 0 (P < .05 to P < .01). The thiol contents in the Z6 group as well as superoxide dismutase and catalase activities in both groups treated with the extract were significantly increased in step II compared with step 0 (P < .05 to P < .01). The C-reactive protein level at the end of the study was significantly reduced compared with the step 0 in both treated groups (P < .05 for both cases). Two-month treatment with Z. multiflora improved clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein in COPD patients. The results suggest that this herbal medicine could be of therapeutic value as a preventive drug for the treatment of COPD.
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http://dx.doi.org/10.1002/jcph.1586DOI Listing
July 2020

Hydro-Ethanolic Extract of Ameliorates Total and Differential WBC, Lung Pathology and Oxidative Biomarkers in Asthmatic Rats.

Iran J Pharm Res 2019 ;18(4):1947-1958

Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

The effects of ( ; PO) on total and differential WBC count, and oxidant/antioxidant biomarkers in bronchoalveolar lavage fluid (BALF) as well as on lung pathology in asthmatic rats were examined. Rats were randomly divided into; control group (C), asthma group, asthma groups treated with either (rats that received PO 1, 2 and 4 mg/mL) or dexamethasone 1.25 μg/mL (D), (n = 8 in each group). Total and differential white blood cells (WBC) count, nitrite (NO), nitrate (NO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and thiol levels in rats BALF were evaluated and lung pathological features were studied. Total WBC count, eosinophil, neutrophil and monocyte percentages, levels of NO, NO, MDA in the BALF and most pathological scores in the lung were increased but lymphocyte percentage, SOD, CAT and thiol levels were decreased in the BALF of asthmatic animals ( < 0.05 to < 0.001). Treatment with significantly reduced total WBC, neutrophil, eosinophil, monocyte, NO, and NO, MDA, interstitial fibrosis, emphysema, interstitial inflammation and epithelial damage, but increased lymphocyte, SOD, CAT and thiol levels compared to asthma group ( < 0.05 to < 0.001). Dexamethasone-treated rats also showed significant improvements in most parameters compared to asthma group ( < 0.05 to < 0.001). Our results demonstrated the ameliorative effects of on total and differential WBC count and oxidant-antioxidant biomarkers levels in BALF as well as lung pathological features in asthmatic rats, which propose the usage of this extract as a preventive anti-inflammatory treatment against asthma.
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http://dx.doi.org/10.22037/ijpr.2019.13712.11817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059043PMC
January 2019

Anti-oxidant and anti-inflammatory effects of auraptene on phytohemagglutinin (PHA)-induced inflammation in human lymphocytes.

Pharmacol Rep 2021 Feb 12;73(1):154-162. Epub 2020 Mar 12.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Inflammation is characterized as a defensive response of our body against endogenous or exogenous stimuli. Chronic inflammation and oxidative stress play an important role in the pathogenesis of various disorders such as asthma, cancers, and multiple sclerosis. Recently, diverse pharmacological activities of auraptene, a natural prenyloxycoumarin, were reported. In the present study, we aimed to evaluate the anti-oxidative and anti-inflammatory effects of auraptene on human isolated lymphocytes.

Method: The effects of auraptene (10, 30 and 90 μM) and dexamethasone (0.1 mM) were evaluated on cell viability, reactive oxygen species (ROS), and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione content (GSH) as well as the secretion of interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α in phytohemagglutinin (PHA)-stimulated human lymphocytes.

Results: Auraptene (10-90 μM) did not affect lymphocytes' viability after 48 h incubation. PHA markedly elevated ROS, MDA, IL-6, and TNF-α levels, while diminished the GSH content, and CAT and SOD activities in human lymphocytes (p < 0.001 for all cases). Treatment with auraptene (10-90 µM) significantly ameliorated ROS, MDA, IL-6, and TNF-α levels, and markedly increased GSH content, and CAT and SOD activities (p <  0.5-0.001).

Conclusion: Auraptene may possess promising healing effects in the different inflammatory disorders associated with activation of the acquired immune system such as multiple sclerosis and asthma.
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http://dx.doi.org/10.1007/s43440-020-00083-5DOI Listing
February 2021

Contribution of potassium channels, beta2-adrenergic and histamine H1 receptors in the relaxant effect of baicalein on rat tracheal smooth muscle.

Iran J Basic Med Sci 2019 Nov;22(11):1347-1352

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Baicalein, a compound extracted from a variety of herbs, showed various pharmacological effects. This study evaluated the relaxant effects of baicalein and its underlying molecular mechanisms of action on rat's isolated tracheal smooth muscle.

Materials And Methods: Tracheal smooth muscle were contracted by 10 μM methacholine or 60 mM KCl and the effects of cumulative concentrations of baicalein (5, 10, 20 and 40 mg/ml) and theophylline (0.2, 0.4, 0.6 and 0.8 mM) were evaluated. To examine the possible mechanism(s) of the relaxant effect of baicalein, its effect was also evaluated on incubated tissues with atropine, indomethacin, diltiazem, N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, propranolol and chlorpheniramine.

Results: A concentration-dependent and significant relaxant effect was seen for baicalein in non-incubated tissues contracted by KCl or methacholine (0.01 to 0.001). No significant difference was seen between the relaxant effects of high concentrations of baicalein and theophylline. The relaxant effects of all concentrations of baicalein in incubated tissues with glibenclamide, propranolol and chlorpheniramine were significantly lower than non-incubated tissues (0.05 to 0.001). Additionally, the EC values of baicalein in incubated tissue with propranolol was significantly higher than non-incubated condition (0.05).

Conclusion: A potent relaxant effect comparable to the effect of theophylline was shown for baicalein, which was probably mediated via inhibition of histamine (H1) receptors, stimulation of beta2-adrenergic receptors and potassium channels activation.
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http://dx.doi.org/10.22038/ijbms.2019.36377.8666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038427PMC
November 2019

The protective effect of Nigella sativa extract on lung inflammation and oxidative stress induced by lipopolysaccharide in rats.

J Ethnopharmacol 2020 May 6;253:112653. Epub 2020 Feb 6.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Ethnopharmacological Relevance: Oxidative stress during inflammation can increase inflammation and damage tissue. Nigella sativa L. (NS) showed many pharmacological properties including antioxidant and anti-inflammatory activities.

Aim Of The Study: In this study, the preventive effect of NS on lung inflammation and oxidative stress induced by lipopolysaccharide (LPS) in the rats was investigated.

Materials And Methods: Male rats were assigned to: Control, LPS (1 mg/kg, i.p.), LPS + NS (100, 200, 400 mg/kg, i.p.), (10 per group). Saline (1 ml/kg) was intra-peritoneal (i.p.) injected instead of LPS in the rats of the control group. LPS dissolved in saline and injected i.p. daily for 14 days. Treatment with NS extracts started two days before LPS administration and treatment continued during LPS administration. White blood cells (WBC), total and differential as well as oxidative stress index in bronchoalveolar fluid (BALF) and serum, TGF-β1, IFN-γ, PGE, and IL-4 levels in the BALF and lung histopathology were examined.

Results: LPS administration increased total WBC, eosinophils, neutrophils, basophils, and monocytes counts as well as oxidative stress markers in the BALF and serum as well as TGF-β1, IFN-γ, PGE, IL-4 levels in the BALF and pathological changes of the lung tissue. All of these effects were reduced by NS extract treatment dose-dependently.

Conclusion: These results suggested the protective effects of NS extract on lung inflammation and oxidative stress as well as its effect on lung pathology induced by LPS dose-dependently.
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http://dx.doi.org/10.1016/j.jep.2020.112653DOI Listing
May 2020

Rosuvastatin suppresses cytokine production and lung inflammation in asthmatic, hyperlipidemic and asthmatic-hyperlipidemic rat models.

Cytokine 2020 04 31;128:154993. Epub 2020 Jan 31.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Given the role that T lymphocytes play on the pathogenesis of allergic asthma, drugs targeting Th2 and Th17 cells may be a hopeful therapeutic strategy. This study aimed to evaluate the effect of rosuvastatin treatment on cytokine production and lung inflammation in allergic asthma.

Methods: The animals were assigned into control (C), asthmatic (A), hyperlipidemic (H), asthmatic-hyperlipidemic (AH), rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic (AR), rosuvastatin-treated hyperlipidemic (HR) and rosuvastatin-treated asthmatic-hyperlipidemic (AHR) groups (n = 6 in each group). The levels of IL-4, IFN-γ and IL-17, total and differential WBC counts in bronchoalveolar lavage fluid (BALF), Th1/Th2 balance, and pathological changes were evaluated.

Results: The BALF level of IL-4 in A, H and AH groups, and IL-17A in A and AH groups were significantly higher than that in C group (p < 0.05 to p < 0.001). IFN-γ level and Th1/Th2 balance (IFN‑γ/IL-4 ratio) in A and AH groups were significantly decreased (p < 0.05 to p < 0.01). Inflammatory cells infiltration, muscle hypertrophy and emphysema were also observed in A and AH groups. The BALF levels of IL-4 in AR, HR and AHR groups, IFN-γ level in HR group, and IL-17A level in AR and AHR groups showed a significant improvement compared to that of A, H and AH groups (p < 0.05 to p < 0.001). Rosuvastatin treatment increased Th1/Th2 balance in all treated groups (p < 0.05 to p < 0.01), decreased total WBC counts, neutrophilia, eosinophilia and lung inflammation in AR and AHR groups, and improved muscle hypertrophy and emphysema in AHR group.

Conclusions: Rosuvastatin treatment improved lung pathological changes by suppression of Th2 and Th17-mediated cytokines which was unrelated to its lipid-lowering activity. Therefore, rosuvastatin might be a candidate immunomodulatory drug for treatment of patients with allergic asthma.
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http://dx.doi.org/10.1016/j.cyto.2020.154993DOI Listing
April 2020

Treadmill exercise restores memory and hippocampal synaptic plasticity impairments in ovalbumin-sensitized juvenile rats: Involvement of brain-derived neurotrophic factor (BDNF).

Neurochem Int 2020 05 23;135:104691. Epub 2020 Jan 23.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levels of hippocampal BDNF in OVA-sensitized rats.
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http://dx.doi.org/10.1016/j.neuint.2020.104691DOI Listing
May 2020

Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma.

BMC Complement Altern Med 2019 Dec 4;19(1):349. Epub 2019 Dec 4.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Ocimum species (Lamiaceae) has been traditionally used for treatment of upper respiratory tract infections, bronchitis, coughs, sore throat, and wound healing. The Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum (O. basilicum) leaves was examined in ovalbumin sensitized animals.

Methods: Wistar rats were divided to six groups; non-sensitized, sensitized to ovalbumin, sensitized and treated with dexamethasone (1.25 μg/mL), and O. basilicum extract (0.75, 1.50 and 3.00 mg/mL) in drinking water for 21 days. The levels of interleukin 4 (IL-4), interferon gamma (IFN-γ), IFN-γ/IL-4 ratio, immunoglobulin E (IgE), phospholipase A (PLA) and total protein (TP) in BALF, and lung pathological changes were examined.

Results: A significant increase in IL-4, IgE, PLA and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats (P < 0.05 to P < 0.001). Treatment with O. basilicum extract resulted in decreased IL-4, IgE, PLA and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitized rats (P < 0.01 to P < 0.001). The plant significantly improved the pathological changes of sensitized rats (P < 0.05 to P < 0.01). The improvement effects of higher concentrations of the O. basilicum extract were significantly more than those of dexamethasone (P < 0.05 to P < 0.001).

Conclusion: The improvement effects of O. basilicum on pathological changes, immunological and inflammatory markers in sensitized rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the plant in asthma.
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http://dx.doi.org/10.1186/s12906-019-2765-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894265PMC
December 2019
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