The Relaxant Activity of Safranal in Isolated Rat Aortas is Mediated Predominantly via an Endothelium-Independent Mechanism - Vasodilatory mechanism of safranal -

Razavi, Bibi Marjan,Amanloo, Mojtaba Alipoor,Imenshahidi, Mohsen,Hosseinzadeh, Hossein KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.4

Objectives: Safranal is a pharmacologically active component of saffron and is responsible for the unique aroma of saffron. The hypotensive effect of safranal has been shown in previous studies. This study evaluates the mechanism for the vasodilatory effects induced by safranal on isolated rat aortas. Methods: To study the vasodilatory effects of safranal (0.2, 0.4 and 0.8 mM), we contracted isolated rat thoracic aorta rings by using $10^{-6}-M$ phenylephrine (PE) or 80-mM KCl. Dimethyl sulfoxide (DMSO) was used as a control. The vasodilatory effect of safranal was also evaluated both on intact and denuded endothelium aortic rings. Furthermore, to study the role of nitric oxide and prostacyclin in the relaxation induced by safranal, we incubated the aortic rings by using L-NAME ($10^{-6}M$) or indomethacin ($10^{-5}M$), each for 20 minutes. Results: Safranal induced relaxation in endothelium-intact aortic rings precontracted by using PE or KCl in a concentration-dependent manner, with a maximum relaxation of more than 100%. The relaxant activity of safranal was not eliminated by incubating the aortic rings with L-NAME ($EC_{50}=0.29$ vs. $EC_{50}=0.43$) or with indomethacin ($EC_{50}=0.29$ vs. $EC_{50}=0.35$), where $EC_{50}$ is the half maximal effective concentration. Also, the vasodilatory activity of safranal was not modified by endothelial removal. Conclusion: This study indicated that relaxant activity of safranal is mediated predominantly through an endothelium-independent mechanism.

The Relaxant Activity of Safranal in Isolated Rat Aortas is Mediated Predominantly via an Endothelium-Independent Mechanism - Vasodilatory mechanism of safranal -

Bibi Marjan Razavi,Mojtaba Alipoor Amanloo,Mohsen Imenshahidi,Hossein Hosseinzadeh 대한약침학회 2016 Journal of pharmacopuncture Vol.19 No.4

Objectives: Safranal is a pharmacologically active component of saffron and is responsible for the unique aroma of saffron. The hypotensive effect of safranal has been shown in previous studies. This study evaluates the mechanism for the vasodilatory effects induced by safranal on isolated rat aortas. Methods: To study the vasodilatory effects of safranal (0.2, 0.4 and 0.8 mM), we contracted isolated rat thoracic aorta rings by using 10-6-M phenylephrine (PE) or 80-mM KCl. Dimethyl sulfoxide (DMSO) was used as a control. The vasodilatory effect of safranal was also evaluated both on intact and denuded endothelium aortic rings. Furthermore, to study the role of nitric oxide and prostacyclin in the relaxation induced by safranal, we incubated the aortic rings by using L-NAME (10-6 M) or indomethacin (10-5 M), each for 20 minutes. Results: Safranal induced relaxation in endothelium- intact aortic rings precontracted by using PE or KCl in a concentration-dependent manner, with a maximum relaxation of more than 100%. The relaxant activity of safranal was not eliminated by incubating the aortic rings with L-NAME (EC50 = 0.29 vs. EC50 = 0.43) or with indomethacin (EC50 = 0.29 vs. EC50 = 0.35), where EC50 is the half maximal effective concentration. Also, the vasodilatory activity of safranal was not modified by endothelial removal. Conclusion: This study indicated that relaxant activity of safranal is mediated predominantly through an endothelium- independent mechanism.

Review on Clinical Trials of Black Seed (Nigella sativa) and Its Active Constituent, Thymoquinone

Tavakkoli, Alireza,Mahdian, Vahid,Razavi, Bibi Marjan,Hosseinzadeh, Hossein KOREAN PHARMACOPUNCTURE INSTITUTE 2017 Journal of pharmacopuncture Vol.20 No.3

Objectives: Nigella sativa (black seed or black cumin), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties. Among its many active constituents, thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa (N. sativa) seeds, and it is the constituent to which most properties of this herb are attributed. Methods: PubMed-Medline, Scopus, and Web of Science databases were searched to identify randomized control trials (RCTs) investigating the therapeutic effects of N. sativa and/or TQ. In this review, we investigated the clinical uses of N. sativa and TQ in the prevention and the treatment of different diseases and morbidity conditions in humans. Results: Black seed and TQ are shown to possess multiple useful effects for the treatment of patients with several diseases, such as inflammatory and auto-immune disorders, as well as metabolic syndrome. Also, other advantages, including antimicrobial, anti-nociceptive and anti-epileptic properties, have been documented. The side effects of this herbal medicine appear not to be serious, so it can be applied in clinical trials because of its many advantages. Conclusion: Some effects of N. sativa, such as its hypoglycemic, hypolipidemic and bronchodilatory effects, have been sufficiently studied and are sufficiently understood to allow for the next phase of clinical trials or drug developments. However, most of its other effects and applications require further clinical and animal studies.

Review on Clinical Trials of Black Seed (Nigella sativa ) and Its Active Constituent, Thymoquinone

Alireza Tavakkoli,Vahid Mahdian,Bibi Marjan Razavi,Hossein Hosseinzadeh 대한약침학회 2017 Journal of pharmacopuncture Vol.20 No.3

Objectives: Nigella sativa (black seed or black cumin), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties. Among its many active constituents, thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa (N. sativa) seeds, and it is the constituent to which most properties of this herb are attributed. Methods: PubMed-Medline, Scopus, and Web of Science databases were searched to identify randomized control trials (RCTs) investigating the therapeutic effects of N. sativa and/or TQ. In this review, we investigated the clinical uses of N. sativa and TQ in the prevention and the treatment of different diseases and morbidity conditions in humans. Results: Black seed and TQ are shown to possess multiple useful effects for the treatment of patients with several diseases, such as inflammatory and auto-immune disorders, as well as metabolic syndrome. Also, other advantages, including antimicrobial, anti-nociceptive and anti-epileptic properties, have been documented. The side effects of this herbal medicine appear not to be serious, so it can be applied in clinical trials because of its many advantages. Conclusion: Some effects of N. sativa, such as its hypoglycemic, hypolipidemic and bronchodilatory effects, have been sufficiently studied and are sufficiently understood to allow for the next phase of clinical trials or drug developments. However, most of its other effects and applications require further clinical and animal studies.

Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum

Najmeh Asrari,Rezvan Yazdian-Robati,Khalil Abnous,Bibi Marjan Razavi,Mrazieh Rashednia,Faezeh Vahdati Hasani,Hossein Hosseinzadeh 대한약침학회 2018 Journal of pharmacopuncture Vol.21 No.1

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/ day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum

Asrari, Najmeh,Yazdian-Robati, Rezvan,Abnous, Khalil,Razavi, BiBi Marjan,Rashednia, Mrazieh,Hasani, Faezeh Vahdati,Hosseinzadeh, Hossein KOREAN PHARMACOPUNCTURE INSTITUTE 2018 Journal of pharmacopuncture Vol.21 No.1

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

Effect of Crocus sativus L. stigma (saffron) against subacute effect of diazinon: histopathological, hematological, biochemical and genotoxicity evaluations in rats

Alireza Timcheh Hariri,Seyed Adel Moallem,Mahmoud Mahmoudi,Bahram Memar,Bibi Marjan Razavi,Hossein Hosseinzadeh 대한약침학회 2018 Journal of pharmacopuncture Vol.21 No.2

Objective: In this study, the effects of saffron stigma against subacute diazinon (DZN) toxicity on enzymes levels, biochemical, hematological, histopathological and genotoxicity indices were studied in rats. Methods: Vitamin E (200 IU/kg) and the aqueous extract of saffron (50, 100 and 200 mg/kg) were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The hematological and biochemical parameters were evaluated at the end of 4 weeks. Results: Reticulocytes counts, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine ami- notransferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase, CPK-MB, gama glutamyl transferase (GGT), uric acid and micronucleus indices were increased significantly but total protein and RBC cholinesterase activity were decreased in the DZN-treated group. Saffron prevented the effect of DZN on GGT (50 mg/kg), LDH, CPK and CPK-MB (100 and 200 mg/kg) levels. An increased uric acid and reduced protein levels by DZN were prevented by vitamin E and some doses of saffron. A significant reduction was observed in platelets, RBC, hemoglobin and hematocrit indices in the DZN group. Saffron and vitamin E prevented this reduction. Vitamin E and saffron did not reduce the effect of DZN on RBC cholinesterase activity. The extract and vitamin E could not prevent DZN genotoxicity in the micronucleus assay. Other biochemical parameters and pathological evaluation did not show any abnormality in tissues of all groups. Conclusion: This study shows that vitamin E and saffron reduce DZN induced hematological and biochemical toxicity. However, they do not prevent the genotoxicity induced by DZN.

Protective Effects of Aqueous and Ethanolic Extracts of Portulaca oleracea L. Aerial Parts on H_2O_2- Induced DNA Damage in Lymphocytes by Comet Assay

Javad Behravan,Fatemeh Mosafa,Negar Soudmand,Elahe Taghiabadi,Bibi Marjan Razavi,Gholamreza Karimi 사단법인약침학회 2011 Journal of Acupuncture & Meridian Studies Vol.4 No.3

The comet assay is a standard method for measuring DNA damage. In this study, the protective effects of ethanolic and aqueous extracts of Portulaca oleracea L. (P. oleracea)on human lymphocyte DNA lesions were evaluated with the comet assay. Lymphocytes were isolated from blood samples taken from healthy volunteers. Human lymphocytes were incubated in H_2O_2 (50,100, and 200 mM), aqueous extract (0.05, 0.1,0.5, 1, and 2.5 mg/ml), and ethanolic extracts (0.05, 0.1, 0.5, 1, and 2.5 mg/ml) of P. oleraceae aerial parts alone with a combination of H_2O_2 (100 mM) with either 1 or 2.5 mg/ml of both extracts at 4℃ for 30 minutes. The extent of DNA migration was measured using the alkaline single cell gel electrophoresis approach assay, and DNA damage was expressed as percentage tail DNA. We found that the aqueous extract of P. oleracea significantly inhibited DNA damage, while there was no effect of the ethanolic extract. These data suggest that the aqueous extract of P. oleracea can prevent oxidative DNA damage to human lymphocytes, which is likely due to antioxidant constituents in the extract.

Effect of Crocus sativus L. stigma (saffron) against subacute effect of diazinon: histopathological, hematological, biochemical and genotoxicity evaluations in rats

Hariri, Alireza Timcheh,Moallem, Seyed Adel,Mahmoudi, Mahmoud,Memar, Bahram,Razavi, Bibi Marjan,Hosseinzadeh, Hossein KOREAN PHARMACOPUNCTURE INSTITUTE 2018 Journal of pharmacopuncture Vol.21 No.2

Objective: In this study, the effects of saffron stigma against subacute diazinon (DZN) toxicity on enzymes levels, biochemical, hematological, histopathological and genotoxicity indices were studied in rats. Methods: Vitamin E (200 IU/kg) and the aqueous extract of saffron (50, 100 and 200 mg/kg) were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The hematological and biochemical parameters were evaluated at the end of 4 weeks. Results: Reticulocytes counts, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase, CPK-MB, gama glutamyl transferase (GGT), uric acid and micronucleus indices were increased significantly but total protein and RBC cholinesterase activity were decreased in the DZN-treated group. Saffron prevented the effect of DZN on GGT (50 mg/kg), LDH, CPK and CPK-MB (100 and 200 mg/kg) levels. An increased uric acid and reduced protein levels by DZN were prevented by vitamin E and some doses of saffron. A significant reduction was observed in platelets, RBC, hemoglobin and hematocrit indices in the DZN group. Saffron and vitamin E prevented this reduction. Vitamin E and saffron did not reduce the effect of DZN on RBC cholinesterase activity. The extract and vitamin E could not prevent DZN genotoxicity in the micronucleus assay. Other biochemical parameters and pathological evaluation did not show any abnormality in tissues of all groups. Conclusion: This study shows that vitamin E and saffron reduce DZN induced hematological and biochemical toxicity. However, they do not prevent the genotoxicity induced by DZN.