Iranian Journal of Basic Medical Sciences
Volume:16 Issue: 1, Jan 2013

Islamic Traditional Medicine (ITM) is a holistic system of medicine. Saffron (Crocus sativus) is one of the most famous plants cultivated in Iran and has a wide range of activities such as oxytocic, anti-carcinogenic, exhilarant, anti-depressant, and anti-asthma effects. In addition, saffron can increase the bioavailability and enhance absorption of other drugs. This study comprises a bibliographical survey of 13 major ITM books regarding different medical aspects of this species. Ferdows al-Hekmah fi’l-Tibb (The Paradise of Wisdom in Medicine), Al-Hawi fi’l-Tibb (Comprehensive Book of Medicine), Kamel al-Sanaat al-Tibbyyah (Complete Book of the Medical Art), Al-Qanun fi’l-Tibb (Canon of Medicine), Zakhireh Kharazmshahi (Treasure of Kharazmshahi), and Makhzan al-Adwiah (Drug Treasure) are some of the most important ITM books used in this survey

Safranal, the main component of Crocus sativus essential oil, is thought to be the main cause of saffron unique odor. It is now about eighty years that this compound has been discovered and since then different scientific experiments have been done investigating its biological-pharmacological activities. Safranal effects in CNS have been more attractive to scientists and an escalating number of papers have been published regarding its neuropsychological effects. These promising properties of safranal propose its presence as a therapeutic agent in future, although there is a great need for further clinical trials and toxicological studies. In this review article, according to Scopus ®, Thomson Reuters Web of Knowledge®, Scientific Information Database (SID) ® and Pubmed ® all papers published until July 2012 were thoroughly discussed and a brief note of each study was prepared.

Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L.) aqueous extract (SAE) on the 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer in rat was investigated. MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum) and stomach of rats. Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca2+, tyrosine kinase activity and carcino-embryonic antigen) were not significant. SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner.

Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects such as antioxidant, anticancer and memory improving activities. Crocin tablets were evaluated for short-term safety and tolerability in healthy adult volunteers. The study was a randomized, double-blind, placebo-controlled design consisting of one month treatment of crocin tablets. Volunteers who fulfilled inclusion and exclusion criteria were randomized into 2 groups of 22 each (males and females) and received 20 mg crocin tablets or placebo. General measures of health were recorded during the study such as hematological, biochemical, hormonal and urinary parameters in pre and post-treatment periods. No major adverse events were reported during the trial. Crocin tablets did not change the above parameters except that it decreased amylase, mixed white blood cells and PTT in healthy volunteers after one month. This clinical safety evaluation showed a relatively safe and normal profile for crocin in healthy volunteers at the given doses within the trial period

The present study reports the development and validation of a sensitive and rapid extraction method beside high performance liquid chromatographic method for the determination of crocetin in human serum. The HPLC method was carried out by using a C18 reversed-phase column and a mobile phase composed of methanol/water/acetic acid (85:14.5:0.5 v/v/v) at the flow rate of 0.8 ml/min. The UV detector was set at 423 nm and 13-cis retinoic acid was used as the internal standard. Serum samples were pretreated with solid-phase extraction using Bond Elut C18 (200mg) cartridges or with direct precipitation using acetonitrile. The calibration curves were linear over the range of 0.05-1.25 μg/ml for direct precipitation method and 0.5-5 μg/ml for solid-phase extraction. The mean recoveries of crocetin over a concentration range of 0.05-5 μg/ml serum for direct precipitation method and 0.5-5 μg/ml for solid-phase extraction were above 70 % and 60 %, respectively. The intraday coefficients of variation were 0.37- 2.6% for direct precipitation method and 0.64 - 5.43% for solid-phase extraction. The inter day coefficients of variation were 1.69 – 6.03% for direct precipitation method and 5.13-12.74% for solid-phase extraction, respectively. The lower limit of quantification for crocetin was 0.05 μg/ml for direct precipitation method and 0.5 μg/ml for solid-phase extraction. The validated direct precipitation method for HPLC satisfied all of the criteria that were necessary for a bioanalytical method and could reliably quantitate crocetin in human serum for future clinical pharmacokinetic study

This study was designed to evaluate the cardioprotective effect of Crocus sativus L. (saffron) aqueous extract and safranal, the major constituent of the essential oil of saffron, on lipid peroxidation, biochemical parameters and histopathological findings in isoproterenol (ISO)-induced myocardial infarction in Wistar rats. The saffron extract (20, 40, 80 and 160 mg/kg/day IP) or control were administered for 9 days along with ISO (85 mg/kg, SC, at 24 hr interval) on 8th and 9th day in rats. Activities of creatine kinase-muscle, brain (CK-MB) and lactate dehydrogenase (LDH) were measured using standard commercial kits. The level of malondialdehyde in heart tissue was estimated with thiobarbituric acid reactive species test. For histopathological examination, hematoxylin and eosin (H&E) staining was used. ISO administration induced a statistically significant increase (P< 0.001) in serum LDH and CK-MB and a significant increase (P< 0.001) in the levels of thiobarbituric acid reactive substances (TBARs) in the heart as compared to vehicle control rats. Saffron pretreatment (20, 40, 80 and 160 mg/kg IP) or safranal pretreatment (0.025, 0.050, 0.075 ml/kg IP) for 8 days, significantly decreased (P< 0.001) the serum LDH and CK-MB and myocardial lipid peroxidation as compared to ISO- induced rats. Histological findings of the heart sections confirmed myocardial injury with ISO administration and preserved nearly normal tissue architecture with saffron or safranal pretreatment. Saffron and safranal may have cardioprotective effect in ISO-induced myocardial infarction through modulation of oxidative stress in such a way that they maintain the redox status of the cell

In this study, the effects of crocin against subchronic toxicity of diazinon (DZN) on systolic blood pressure (SBP) and heart rate (HR) were evaluated in rats. Rats were equally divided into 7 groups; control (corn oil), DZN (15 mg/kg), crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN), vitamin E (200 IU/kg plus DZN) and crocin (50 mg/kg) treated groups. Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week) and crocin (once a day) were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method), malondealdehyde (MDA) levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method); SBP and HR (tail cuff method) were evaluated at the end of 4th week. A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001). Crocin did not show any effects on cholinesterase activity.DZN increased MDA levels in aortic tissue (P< 0.001) in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01) and increased HR (P< 0.001) in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats

Quinolinic acid (QA)-mediated excitotoxicity has been widely used as a model for studying neurodegenerative disorders. Recent studies suggested that saffron (Crocus sativus) or its active metabolite, i.e. safranal, exerts pharmacological actions on central nervous system including anxiolytic, anticonvulsant, and neuroprotective properties. The present study aimed to investigate the effect safranal pretreatment on QA-induced oxidative damage in rat hippocampus. Under anesthesia, a guide cannula was stereotaxically inserted into left ventral hippocampus of rats. The rats were then given either saline or safranal (72.75, 145.5, and 291 mg/kg, IP) 30 min before administration of QA (300 nmol, intrahippocampal injection). The markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, as an index of lipid preoxidation), total sulfhydryl groups, antioxidant capacity of hippocampus (using FRAP assay), and oxidative DNA damage (%tail DNA, using comet assay) were measured in hippocampus. The QA induced a significant increase in TBARS levels and %tail DNA and remarkable decrease in antioxidant power (FRAP value) and total sulfhydryl content of hippocampus, in comparison with control animals. Systemic administration of safranal (291 mg/kg, IP), effectively and dose-dependently decreased the QA-induced lipid peroxidation (P<0.001) and oxidative DNA damage (P<0.001). Safranal also prevented the decrease of hippocampal thiol redox and antioxidant status (P<0.001) produced by QA. Safranal have protective effects on different markers of oxidative damage in hippocampal tissue following QA administration. Our findings might raise a possibility of potential therapeutic application of safranal for preventing and treating neurodegenerative disorders such as Alzheimer’s disease

Crocin is a constituent of saffron and has many biological functions. The present study aimed to investigate the effects of intraperitoneal (IP) injection of crocin on sciatic nerve regeneration in male Wistar rats. Fifty-four rats were divided into 9 groups: groups 1-4 (intact + normal saline and intact + crocin at doses of 5, 20 and 80 mg/kg, respectively); group 5 (sham surgery + normal saline); groups 6-9 (crush + normal saline and crush + crocin at doses of 5, 20 and 80 mg/kg, respectively). Normal saline and crocin were IP injected for 10 consecutive days after induction of a standard crush injury in left sciatic nerve. Footprints were obtained 1 day before and weekly after induction of nerve injury for evaluation of sciatic functional index (SFI). Blood samples were taken for evaluation of malondialdehyde (MDA) levels. Histopathological changes of sciatic nerve were investigated by light microscopy. Sciatic nerve crush-injured rats showed SFI values reduction, increased plasma MDA levels and produced Wallerian degeneration in sciatic nerve. Crocin at a dose of 5 mg/kg had no significant effects. At doses of 20 and 80 mg/kg, crocin accelerated the SFI recovery, decreased MDA levels and reduced Wallerian degeneration severity. The present study suggests that the neuroprotective effects afforded by crocin may be due in part to reduction of free radicals-induced toxic effects

Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Diabetes was induced by intraperitoneal (IP) injection of streptozotocin (STZ, 45 mg/kg). Transfer latency (TL) paradigm in elevated plus-maze (EPM) was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. STZ increased acquisition transfer latency (TL1) and retention transfer latency (TL2), and MDA, decreased transfer latency shortening (TLs) and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

Crocin, as the main carotenoid of saffron, has shown anti-tumor activity both in vitro and in vivo. Crocin might interact with cellular proteins and modulate their functions, but the exact target of this carotenoid and the other compounds of the saffron have not been discovered yet. Microtubular proteins, as one of the most important proteins inside the cells, have several functions in nearly all kinds of cellular processes. The aim of this study was to investigate whether crocin affects microtubule polymerization and tubulin structure. Microtubules were extracted from sheep brains after two cycles of temperature-dependant assembly-disassembly in the polymerization buffer (PMG). Then phosphocellulose P11 column was used to prepare MAP-free tubulin. Turbidimetric assay of microtubules was performed by incubation of tubulins at 37 ºC in PIPES buffer. To investigate the intrinsic fluorescence spectra of tubulins, the emission spectra of tryptophans was monitored. To test the interaction of crocin with tubulin in more details, ANS has been used. Crocin extremely affected the tubulin polymerization and structure. Ultraviolet spectroscopy indicated that crocin increased polymerization of microtubules by nearly a factor of two. Fluorescence spectroscopic data also pointed to significant conformational changes of tubulin. We showed that crocin increased tubulin polymerization and microtubule nucleation rate and this effect was concentration dependant. After entering cell, crocin can modulate cellular proteins and their functions. Concerning the results of this study, crocin would be able to affect several cell processes through interaction with tubulin proteins or microtubules.