فهرست مطالب

Avicenna Journal of Phytomedicine - Volume:5 Issue:5, 2015
  • Volume:5 Issue:5, 2015
  • تاریخ انتشار: 1394/06/14
  • تعداد عناوین: 12
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  • Amin Mokhtari-Zaer, Mohammad Reza Khazdair, Mohammad Hossein Boskabady Pages 365-375
    Saffron, Crocus sativus L. (C. sativus) is rich in carotenoids and used in traditional medicine for treatment of various conditions such as coughs, stomach disorders, amenorrhea, asthma and cardiovascular disorders. These therapeutic effects of the plant are suggested to be due to its relaxant effect on smooth muscles. The effect of C. sativus and its constituents on different smooth muscles and the underlying mechanisms have been studied. Several studies have shown the relaxant effects of C. sativus and its constituents including safranal, crocin, crocetin and kaempferol on blood vessels. In addition, it was reported that saffron stigma lowers systolic blood pressure. The present review highlights the relaxant effects of C. sativus and its constituents on various smooth muscles. The possible mechanisms of this relaxing effect including activation of ß2-adrenoceptors, inhibition of histamine H1 and muscarinic receptors and calcium channels and modulation of nitric oxide (NO) are also reviewed.
    Keywords: Crocus sativus, Saffron, Crocin, Smooth muscle, Relaxant effect, Possible mechanisms
  • Mohammad Reza Khazdair, Mohammad Hossein Boskabady, Mahmoud Hosseini, Ramin Rezaee, Aristeidis M. Tsatsakis Pages 376-391
    Saffron or Crocus sativus L. (C. sativus) has been widely used as a medicinal plant to promote human health, especially in Asia. The main components of saffron are crocin, picrocrocin and safranal. The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively. Saffron has been suggested to be effective in the treatment of a wide range of disorders including coronary artery diseases, hypertension, stomach disorders, dysmenorrhea and learning and memory impairments. In addition, different studies have indicated that saffron has anti-inflammatory, anti-atherosclerotic, antigenotoxic and cytotoxic activities. Antitussive effects of stigmas and petals of C. sativus and its components, safranal and crocin have also been demonstrated. The anticonvulsant and anti-Alzheimer properties of saffron extract were shown in human and animal studies. The efficacy of C. sativus in the treatment of mild to moderate depression was also reported in clinical trial. Administration of C. sativus and its constituents increased glutamate and dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system to reduce withdrawal syndrome. Therefore, in the present article, the effects of C. sativus and its constituents on the nervous system and the possible underlying mechanisms are reviewed. Our literature review showed that C. sativus and its components can be considered as promising agents in the treatment of nervous system disorders.
    Keywords: Crocus sativus, Nervous system, safranal, Crocin, Saffron
  • Amir Erfanparast, Esmaeal Tamaddonfard, Mina Taati, Milad Dabbaghi Pages 392-402
    Objective
    Crocin and safranal are the main components of saffron, and have many biological functions such as anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of crocin, safranal, morphine, diclofenac and naloxone in combined and separately on formalin-induced orofacial pain in rats.
    Materials And Methods
    Subcutaneous injection of a diluted formalin solution (50 µl, 1.5%) into the upper lip region produced a biphasic pattern of pain response (a neurogenic phase: 0-3 min and an inflammatory phase: 15-33 min). The time each animal spent face rubbing with ipsilateral forepaw was recorded and considered as an index of nociception
    Results
    Intraperitoneal injections of crocin (12.5 and 25 mg/kg), safranal (0.25 and 0.5 mg/kg), diclofenac (5 and 10 mg/kg) and morphine (1 and 2 mg/kg) suppressed the second phase of pain. The second phase of pain was also reduced when low (ineffective) doses of crocin (6.25 mg/kg) and safranal (0.125 mg/kg) were co-administered with low doses of diclofenac (2.5 mg/kg) and morphine (0.5 mg/kg). The more antinociceptive effects were observed when the medium doses of the above-mentioned chemicals used together. Naloxone prevented morphine-induced antinociception, but did not inhibit the suppressive effects of crocin and safranal. Safranal at a high dose (0.5 mg/kg) suppressed locomotor activity.
    Conclusion
    The present results showed antinociceptive effects for crocin and safranal in inflammatory pain. Opioid receptors may not be involved in the antinociceptive effect of crocin and safranal. Crocin and safranal increased diclofenac-induced antinociception.
    Keywords: Crocin, safranal, Diclofenac, Orofacial pain, Rats
  • Siamak Asri-Rezaei, Esmaeal Tamaddonfard, Behnaz Gasemsoltani-Momtaz, Amir Erfanparast, Sima Gholamalipour Pages 403-412
    Objectives
    Crocin is one of constituents of saffron and has antioxidant property. Zinc chloride is one of the common compounds of zinc with antioxidant activity. The present study was aimed to investigate separate and combined treatment effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in diabetic rats.
    Materials And Methods
    Diabetes was induced by intraperitoneal (i.p.) injection of 50 mg/kg of streptozotocin (STZ) and was confirmed by blood glucose levels higher than 250 mg/dL. After confirmation of diabetes, injections (i.p.) of crocin and zinc chloride were performed for six weeks. At the end of the experiment, blood levels of zinc, glucose, insulin, malodialdehyde (MDA), and total antioxidant capacity (TAC) were measured.
    Results
    Crocin (25 and 50 mg/kg) and zinc chloride (5 mg/kg) significantly recovered the decreased levels of zinc, insulin, and TAC and improved the increased levels of glucose and MDA in STZ-induced diabetic rats. In a combination treatment performed with an ineffective dose of crocin (12.5 mg/kg) and a low dose of zinc chloride (1.25 mg/kg), improving effects were observed on the above-mentioned biochemical parameters.
    Conclusions
    The results indicated that separate and combined treatments with crocin and zinc chloride produced improving effects on the blood levels of zinc, glucose, insulin, MDA and TAC in STZ-induced diabetic rats.
    Keywords: Crocin, Rats, Diabets, Zinc
  • Bentolhoda Mousavi, Seyedeh Zahra Bathaie, Farbod Fadai, Zabihollah Ashtari, Neda Ali Beigi, Sara Farhang, Sara Hashempour, Nasim Shahhamzei, Hamid Heidarzadeh Pages 413-419
    Objectives
    Saffron is the stigma of Crocus sativus L., which has the potentials to play a role in the treatment of many diseases. Although many researches are now going on this precious spice, there are few data on saffron safety in human, especially in patients with chronic mental illnesses. This study aimed to evaluate the short-term safety and tolerability of both saffron and crocin (its major constituent) in adult patients with schizophrenia.
    Materials And Methods
    The capsules of saffron aqueous extract (SAE) and crocin were used to evaluate short-term safety and tolerability in patients with schizophrenia. A double-blind, placebo-controlled study was performed on patients with schizophrenia. The patients were all male and were divided into three 22-patient groups. While receiving their normal treatment, they also received a 12 week treatment with SAE (15 mg twice daily), crocin (15 mg twice daily) or placebo.
    Results
    A total of 61 patients completed the trial; none of them reported a serious side effect. WBC count increased significantly in patients receiving saffron aqua extract (SAE), but it was within the normal range and had no clinical significance. Other hematologic components, markers of thyroid, liver and kidney or inflammation markers had no statistically significant difference among the groups.
    Conclusions
    This study showed that SAE and crocin in doses of 15 mg twice daily were safely tolerated in patients with schizophrenia.
    Keywords: Saffron Aqueous Extract, Crocin, Clinical trial, Safety assessment, Schizophrenia
  • Mahdi Esmaeilizadeh, Mahin Dianat, Mohammad Badavi, Alireza Samarbaf-Zadeh, Bahareh Naghizadeh Pages 420-426
    Objective
    Oxidative stress damages cells and brings about the pathogenesis of ischemia/reperfusion injury. This study was carried out to investigate the preconditioning and cardio protective potential effects of crocin and vitamin E by the eNOS and iNOS express gene in ischemia/reperfusion in rats.
    Material and Methods
    Male rats were divided into seven groups, namely: sham, control group and experimental groups treated with crocin(10, 20 and 40 mg/kg), vitamin E (100 mg/kg) and combination of crocin (40 mg/kg) with vitamin E (100 mg/kg) that were gavaged The heart was removed and relocated to a Langendorff apparatus and subjected to global ischemia and then the left ventricular end diastolic pressure (LVEDP) were measured as a hemodynamic parameter. Total RNA was extracted from heart frozen tissues. RT-PCR technique was performed by specific primers designed for nitric oxide gene and the results were assessed by agarose gel electrophoresis.
    Results
    Results after ischemia and reperfusion showed that crocin 40 mg/kg produced a significant improvement of LVEDP as a mechanical function (P<0.05), associated with a reduction of iNOS release (P<0.05). The eNOS mRNA levels were significantly higher in crocin-treated 40 mg/kg compared to controls treated by RT-PCR technique. The combination of crocin and vitamin E have shown more effective on the reduction of iNOS release (P<0.01).
    Conclusion
    In the isolated rat heart, protective effect of crocin, may possibly be explained by regulating eNOS and iNOS expressions. The Results resultsconfirmed the hypothesis that cardioprotective effect of crocin is partly mediated by nitric oxide. This could explain the cardioprotective action of crocin following ischemia and reperfusion.
    Keywords: Ischemia, reperfusion injury, Crocin, Vitamin E iNOS protein, eNOS protein, rat
  • Tayyebeh Kermani, Seyyed Hadi Mousavi, Maryam Shemshian, Abdolreza Norouzy, Mohsen Mazidi, Atefeh Moezzi, Toktam Moghiman, Majid Ghayour-Mobarhan, Gordon. A. Ferns Pages 427-433
    Objectives
    We have investigated the effect of a saffron supplement, given at a dose of 100 mg/kg, on prooxidant-antioxidant balance (PAB) in individuals with metabolic syndrome.
    Materials And Methods
    A randomized, placebo-controlled trial design was used in 75 subjects with metabolic syndrome who were randomly allocated to one of two study groups: (1) the case group received 100mg/kg saffron and (2) the placebo control group received placebo for 12 weeks. The serum PAB assay was applied to all subjects before (week 0) and after (weeks 6 and 12) the intervention.
    Results
    There was a significant (p=0.035) reduction in serum PAB between week 0 to week 6 and also from week 0 to week 12.
    Conclusion
    Saffron supplements can modulate serum PAB in subjects with metabolic syndrome, implying an improvement in some aspects of oxidative stress or antioxidant protection.
    Keywords: Metabolic syndrome, prooxidant, antioxidant balance, Saffron
  • Azar Hosseini, Seyed Hamed Mousavi, Anis Ghanbari, Fatemeh Homaei-Shandiz, Hamid-Reza Raziee, Masoud Pezeshki-Rad, Seyed Hadi Mousavi Pages 434-440
    Objective
    Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated.
    Materials And Methods
    Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided into two different groups. Both groups received chemotherapy regimen. Patients in group one were treated with saffron capsule (50 mg, twice daily) during chemotherapy periods whereas patients in group two received placebo. A sum of the longest diameter were calculated and compared for all lesions in IV contrast CT scan before and after the treatment.
    Results
    from 13 patients included in this study, six patients quit and seven continued until the end. In saffron-treated group, two patients showed partial and complete response (50%) whereas in placebo group, no response was seen. Also, two deaths in placebo and one in saffron group occurred.
    Conclusion
    This research suggests that saffron might be useful in patients suffering from liver metastasis. However, further investigations with larger sample size are required.
    Keywords: Saffron, Cancer, Liver Metastases
  • Bamdad Riahi-Zanjani, Mahdi Balali-Mood, Elaheh Mohammadi, Hassan Badie-Bostan, Bahram Memar, Gholamreza Karimi Pages 441-449
    Objectives
    The aim of the present study was to investigate immunotoxic effect of safranal (SAF), a main component of Crocus sativus essential oil, using Balb/c mice.
    Materials And Methods
    SAF was administered intraperitoneally at doses of 0.1, 0.5 and 1 ml/kg for 3 weeks. Hystopathological examination of spleen and bone marrow, cellularity of spleen, delayed type of hypersensitivity (DTH) response, hemagglutination titer (HA), cytokine production and lymphocyte proliferation assay were studied in various groups of animals.
    Results
    Spleen cellularity for SAF groups (0.1 ml/kg SAF: 6.68 [± 0.88] × 107, 0.5 ml/kg SAF: 8.16 [± 1.33] × 107, 1 ml/kg SAF: 6.12 [± 0.59] × 107) did not significantly differ as compared to vehicle control (8.52 [± 1.36] × 107; p > 0.05). In addition, SAF at all doses could not produce any significant changes in hematological parameters, HA titer, DTH and lymphoproliferation responses, as well as in release of cytokines by isolated splenocytes (p > 0.05). Despite a few studies demonstrating some immunomodulatory effects for saffron extract, SAF as a major constituent of saffron did not induce any marked effects in immune system parameters of mice.
    Conclusion
    Contrary to the toxicological studies which have indicated that SAF is more toxic than other active constituents in saffron stigma, at least it was found to be safe to mice immune system and has no toxicity on humoral and cellular immune responses.
    Keywords: safranal, Immunotoxic effect, Cellular immunity, Humoral immunity
  • Esmaeal Tamaddonfard, Sina Tamaddonfard, Salar Pourbaba Pages 450-457
    Objectives
    Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist.
    Materials And Methods
    A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test.
    Results
    Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity.
    Conclusion
    The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.
    Keywords: Crocin, Morphine, Naloxone, Orofacial pain, Rats
  • Bahareh Amin, Alireza Nakhsaz, Hossein Hosseinzadeh Pages 458-468
    Objective
    The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration.
    Material And Methods
    In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively.
    Results
    Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin.
    Conclusion
    Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.
    Keywords: Crocus sativus L, Crocetin, Crocin, Forced swimming test (FST), Tail suspension test (TST)
  • Amir Farshid, Esmaeal Tamaddonfard Pages 469-478
    Objectives
    Crocin and safranal, the major constituents of saffron, exert neuroprotective effects. In the present study, we investigated the effects of crocin and safranal (alone or in combination with insulin) on peripheral neuropathy in diabetic rats.
    Materials And Methods
    Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg of streptozotocin (STZ) and confirmed by blood glucose level higher than 250 mg/dl. After confirmation of diabetes, crocin (30 mg/kg, i.p.), safranal (1 mg/kg, i.p.) (alone or in combination with insulin) and insulin (5 IU/kg, s.c.) were administered for eight weeks. Neuropathic pain was evaluated using acetone drop test. Histopathological changes of sciatic nerve were evaluated using light microscope. Blood glucose levels and sciatic nerve malondialdehyde (MDA) contents were also measured.
    Results
    STZ caused cold allodynia, edema and degenerative changes of sciatic nerve, hyperglycemia and an elevation of sciatic nerve MDA levels. Crocin, safranal and insulin improved STZ-induced behavioral, histopathological and biochemical changes. Combined treatments produced more documented improving effects.
    Conclusion
    The results of the present study showed neuroprotective effects of crocin, safranal and insulin in a rat model of diabetic neuropathy. In addition, crocin and safranal enhanced the neuroprotective effect of insulin. The neuroprotective effects of theses chemical compounds could be associated with their anti-hyperglycemic and antioxidant properties.
    Keywords: Crocin, safranal, Insulin, Diabetic neuropathy, Rats