Crocus sativus, commonly known as Saffron, contains more than 150 volatile compounds and is considered to be the most expensive precious spice in the world. It is widely cultivated in Iran, the Indian region of Kashmir and in many areas of Southern Europe including Italy.
The part of the plant used is the stigma of the hand-picked flower and on which pollen is deposited; Saffron is nothing but the dried stigma of the violet crocus from which this expensive spice is derived. A stigma weighs on average 2 mg, and each flower has three stigmas, 150,000 flowers need to be carefully harvested one to one to get 1 kg of spice.
Saffron compositions, including crocetin, have shown very significant effects in depression therapy and in improving memory and learning. It has been demonstrated to bring benefits in coronary heart disease by inhibiting the oxidation of lipoproteins (1-2), neurodegenerative diseases (1-2-3), and functional recovery of the retina through an increase in blood flow (1-3).
Spice components are Crocina (responsible for color), picrococin (responsible for bitter taste) and safranal (responsible for odor and aroma).
- 1 Therapeutic targets
- 2 Crocus and cancer
- 3 Conclusion
- 4 Bibliography
In traditional Persian medicine saffron is used in depression therapy, and on this ancient indication, recent studies have been carried out to control the truth of this affirmation.
Shain Akhondzadeh et al. Of the University of Tehran, conducted a double-blind, randomised pilot study published in “Complement Alternative Medicine” 2004. Thirty patients with mild to moderate depression are recruited and are divided into two groups: the first group takes 30 mg / d of saffron in capsules while the second group takes 100 mg/die of imipramine, all for six weeks.
The conclusions of the study are interesting as a spice in improving depressive symptoms has been as effective as imipramine, the latter being burdened by side effects such as dry mouth and sedation (4).
A previous study of these Animal-Made Authors had given the same efficacy results as saffron on depression syndrome (5).
Another study structurally similar to the previous one is reported in Journal Ethnopharmacology 2005, in which 30 mg / d of saffron are tested against 20 mg / d of fluoxetine (the famous Prozac!) In 40 outpatients.
The results indicate that the efficacy of crocus sativus was similar to that of fluoxetine in the treatment of mild to moderate depression (6).
Other clinical trials comparing Crocus with placebo published in Phytotherapy Research 2005 and Phytomedicine 2006 (7-8) were performed. The results confirmed a steady and evident improvement in depression in the groups treated with saffron compared with placebo.
To conclude and confirm these findings we cite a recent work published on the Journal Affective Disorder 2015. This study evaluates the efficacy of crocin, the main constituent of saffron, as an adjunct treatment in patients with the major depressive disorder.
40 patients are recruited and divided into two groups.
A first group is treated with a modern generation antidepressant (fluoxetine 20 mg/day or sertraline 50 mg/day or citalopram 20 mg/day), and in addition to the drug therapy, two 15 mg crocin tablets are administered for a total of 30 mg/day.
In the second group of patients, the same drug therapy was administered, with the addition of two placebo tablets.
The results are very instructive as the scores of depression in the crocin-treated group are significantly better than those of the placebo-treated group (9).
This indicates that crocin works well even in combination with pharmacological therapies and, as teaching for clinical practice, patients with major depressive disorder who do not adequately respond to traditional treatments (frequently occurs) with the addition of precious spice to adequate doses. They may find improvements without resorting to high doses or associations of multiple medications with significant side effects.
A comforting news is that from a preclinical study performed in Iran has also found that crocus sativus petals, a part of this plant that is at significantly lower prices than stigma, shows antidepressant action (10).
Memory and learning effects
Much evidence suggests that saffron and its components are involved in the process of cognition. To date, few studies have been carried out with the aim of evaluating the effects of spice in a person suffering from memory disorders. In a first study published in the Journal Clinical Pharmacology Teheran 2010, the goal was to evaluate the effectiveness of the plant in the treatment of mild to moderate cognitive deficits.
Recalled 46 patients with mild or moderate Alzheimer’s are divided into two groups and treated for 16 weeks with 30 mg / d of saffron the first group and two placebo tablets the second group. After 16 weeks the saffron produced a significantly better cognitive function than the placebo and proved to be very safe and efficient in mild or moderate memory loss (11).
Subsequently, the same group of researchers carried out a wider experiment Appeared on “Psychopharmacology” 2010, in which 54 adults were enrolled, the average age of 55 years with mild Alzheimer’s And were subjected to a treatment of 22 weeks. The novelty of this study consisted of the fact that saffron was first compared to Donezepil.
Participants were randomly assigned to receive a capsule of Saffron at 30 mg/day (15 mg twice daily) or donepezil 10 mg/day (5 mg twice daily). At these doses at the end of the 22 weeks of the study, saffron showed the same efficacy as donezepil. Also, some adverse effects that occurred with the drug (vomiting) were absent in the group treated with saffron (12). The researchers insisted with a further study published in 2014 on “Human Psychopharmacology” in which they tested Saffron against memantine.
68 patients with moderate to severe Alzheimer’s disease have been recruited with a score on the Mini-Mental State Examination Of 8-14 (average score 30) and randomly administered memantine 20 mg/day or 30 mg / d of saffron in capsules for 12 months. Both treatment groups showed similar results! There was no significant difference between the two groups regarding the scores regarding the changes. (13) In simple words this precious spice has obtained the same results as two of the most powerful and used drugs in the last few years without adverse effects.
Mechanism of Action
A synthesis of the possible action mechanisms of saffron is necessary to make the reader understand substantial differences over traditional therapy.
Aggregation and amyloid deposition is the primary molecular process underlying Alzheimer’s disease and states current there are no drugs that can block these pathology outcomes.
First line: cognitively healthy elderly without subjective memory decline.
Second line: elderly with increased amyloid deposition and memory decline.
In one In vitro study published in Journal Agricultural and Food Chemistry 2006, it has been shown that safflower stigmas interact with this abnormal protein and prevent aggregation in the form of amyloid plaques (14). Other in vitro studies show that crocus sativus And crocetin (but not safranal) inhibit the acetylcholinesterase enzyme. The blockade of this enzyme destroying acetylcholine leads to an increase in acetylcholine itself and an improvement in cognitive functions. Experimental results suggest for oxidative stress a key role in the pathogenesis of various neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (15- 16-17-18). An alternative hypothesis to explain the beneficial effect of this potent spice on memory is based on its high antioxidant properties confirmed by a large number of studies (19-20-21).
Ocular Pathology: Maculopathy
Age-related macular degeneration is a neurodegenerative pathology Of the retina affecting subjects over 50 years of age and is the leading cause of irreversible deficit of central visual function. The most important risk factors are age, familiarity and highly oxidative cigarette smoking, and both oxidative stress and chronic inflammation play a significant role in the pathogenesis of the disease. The saffron with its active ingredients, Crocina and crocetin, has shown to have anti-apoptotic properties, i.e., prevents retinal cells from “suicide” (apoptosis) in the face of the oxidative damage of reactive oxygen species (22-23). It plays a significant role in retinal function by increasing the blood flow (3).
It also enhances the concentration of glutathione (26).
Maintaining adequate levels of glutathione through a saffron treatment can protect cells from oxidative damage and death (26).
In an Italian clinical study on “Investigative Ophthalmology and Visual Science” 2010, researchers submitted 25 patients with age-related macular degeneration, Related, to daily supplementation with 20 mg / day of saffron for three months, another group instead took placebo. The results show that short-term (90 days) shortening safflower significantly improves retinal sensitivity to light pulses at least at the beginning of the disease (27).
Two years later another Italian research group conducted another experimentation published On “Evidence-Based Complementary and Alternative Medicine” 2012, to evaluate whether the functional benefits observed in the short period of the previous study could be extended over a longer period of time. 29 mid-aged 55-85-year-olds were recruited Visual acuity greater than 0.3 (we are in the category of low vision) and are treated with 20 mg / d of saffron for 14 months.
After three months of treatment, visual acuity and retinal sensitivity were significantly improved and these improvements remained stable Throughout the period of observation of the study, proving that precious spice induces improvements even in the long run (25). Another major American school study published in the Journal of Ocular Pharmacology and Therapeutics 1999, studied the effect of spice on ischemic retinopathy and age-related macular degeneration. An important cause of these pathologies is the reduction of blood flow to the retina and the choroid.
Saffron has been shown to cause vasodilation and significantly increase blood flow to the retina and choroid, facilitating functional retinal recovery. Increased blood flow improves oxygenation by the intake of essential nutrients (3). To end the antioxidant and antiapoptotic activities of this precious spice have been proven to be able to also prevent experimental-induced cataracts with selenium subcutaneous inoculations in Wistar rats by inhibition of the lysis of water-soluble crystalline proteins (28).
There are very few spices that can stimulate spermatozoic maturation and motility, saffron is one of these together with pomegranate and dried tomatoes. In a study Published in the Urology Journal 2008, it’s examined the administration of saffron in 52 infertile men whose problem could not be solved surgically. They are treated with 50 mg of spice administered three times a week For a period of three months, seed analysis was performed before and after treatment.
The percentage of sperm with normal morphology was 26.50% before treatment, which increased to 33.90% after treatment; The mean percentage of A-class sperm spermatozoa was 5.32% before the treatment, which rose to 11.77% later. No significant increase was documented in the sperm count. In conclusion, the work demonstrated the efficacy of saffron as an antioxidant to improve morphology and sperm motility in infertile men (29).
Another study appeared on Phytotherapy Research 2011, Comes to entirely different conclusions. 260 infertile men are recruited, in which, in addition to the numerical reduction of sperm, there was also a decrease in progressive motility and normal forms: this condition is called oligo-steno-teratozoospermia and in most cases Is of an idiopathic nature, that is, they do not know the causes. Saffron is administered at 60 mg / day for 26 weeks to a group of 130 subjects and another equivalent group is given placebo. In this study, spice did not produce any statistically significant improvement in any seminal parameter, nor on morphology or sperm motility (30).
It is the personal opinion of those who write that probably the failure of saffron in this study is to be attributed to Multiple causes responsible for the seminal morphologic framework (scarcely-hypo mathsy-altered sperm) that physiologically escape the action of spice. That is to say, besides the truly unknown (idiopathic) causes, immune disorders, anatomical malformations of the reproductive system, vascular pathologies (eg varicocele), endocrine-metabolic pathologies such as hormonal deficits are described, in which case the potent antioxidant activity of precious spice is not It would find receptors on which to act.
The saffron with its powerful antioxidant power creates an environment that is much more favourable to sperm replication and maturation but has no authority to act on hormones, vascular alterations and immune systems.
For erectile dysfunction is meant the Persistent inability to achieve or maintain a sufficient erection to conduct a satisfactory sexual relationship. Saffron has been shown to have significant action on this issue. In a study published on “Phytomedicine” in 2009, the efficacy of saffron on Erectile Dysfunction is investigated in 20 patients who take spice in the form of a tablet for ten days 200 mg.
At the end of the treatment there was a statistically significant improvement in rigidity and tumescence of the penis. Saffron showed a positive effect on sexual function with an increase both in the number and duration of erectile events even after 10 days of intake (31). One particular study is reported in Journal Evid Based Complementary Alternative Medicin 2015, Saffron is used as a topical gel in diabetic patients. The hypothesis of work is interesting because diabetes is a major risk factor for erectile dysfunction.
Patients were randomly assigned to two groups of 25 subjects each. The intervention group was treated with saffron gel, the other with placebo. At the end of the study it was found that saffron gel compared to placebo significantly improved erectile dysfunction in diabetic patients (32).
Cardiovascular – Atherosclerosis
The antioxidants present in saffron can reduce the risk of heart disease. In a work published on “Indian Journal Medical Sciences” 1998, the protective effect of saffron in cardiovascular disease is tested. 20 patients are recruited, 10 of whom are in good health and 10 are diseased and are treated with 100 mg / day of saffron.
It is measured and studied The oxidation of lipoproteins (the process responsible for the formation of atherosclerotic plaque) is initially and after 3 and 6 weeks. There has been a gradual and constant decrease of the oxidative process: healthy patients dropped by 43% while in the 10 patients With cardiovascular disease had dropped by 36% (33).
Attention is drawn to the work published in Biochemistry Pharmacology 2005, in which the effect of the administration of crocetin on the development of atherosclerotic plaque in rabbits has been studied. Animals are divided into three groups and fed With three different diets for 8 weeks. A standard diet, a lipid-rich diet (HDL) and the last group fed a lipid-rich diet associated with crocetin.
The group (HDL) developed hypercholesterolemia and atherosclerosis While the crocetin-integrated group decreased its adverse health effects due to a lipid-rich diet. The results showed no significant differences in plasma lipid levels between the HDL group and the crocetin group, But the latter group of animals in the aorta artery showed a marked decrease in cholesterol, foamy cells and atherosclerotic lesions (33) and this is an apparent effect of the antioxidant power of this precious spice.
Crocus and cancer
In this field, unfortunately, we have no clinical studies but only experiments on animal models and tumor cell culture lines where spice has shown to possess excellent anti-tumor properties. Chrysocene is an essential saffron carotenoid constituent has proven to have a good potential as an anti-cancer agent in animal models and cell culture systems (34-35-37).
Interferes with tumor cell growth by inhibiting the synthesis of nucleic acids, improving the antioxidant system, inducing l ‘Apoptosis (suicide cell) and interfering with signaling pathways of growth factors (35-37). Saffron and its derivatives, particularly crocetin, have demonstrated significant tumor activity on the breast, pancreas, lung and leukaemia.
Crocetin has been shown to possess the ability to inhibit the proliferation of breast cancer cells (38). Incubation of 48-hour cancer cells with different concentrations of crocus extracts showed a dose-dependent inhibitory effect on proliferation of cells in test cell cultures. The effect was not related to the presence of estrogen receptors.
Crocetin inhibited DNA synthesis in pancreatic tumor cells (36). Overall, these studies indicate that spice is useful as an antiproliferative agent as it stops the cell cycle. Recently in an unpublished study, crocetin has shown in combination with small doses of cis-platinum (a potent chemotherapeutic) to inhibit cell proliferation And stimulate programmed death (apoptosis) of pancreatic tumor cells.
In an animal lung cancer model, Crocetin has had good anticancer activity. In a study published in “Molecular Cellular Biochemistry” 2006, a stem of albino carriers of the disease was treated in the first part of the survey with 20 mg/kg body weight of crocetin and subsequently with 50 mg/kg body weight Body of spice. After treating animals with benzo-a-pyrene (the most potent carcinogen in cigarette smoke!), Lipid peroxidation levels were visibly increased and almost returned to normal after crocetin treatment. Concentrations of antioxidants such as glutathione (one of the most potent ones) were significantly increased after treatment with spice (39-40) .
In two in vitro studies on leukemic human cell lines, crocetin showed significant cytotoxicity, i.e. capacity To create damage to the leukemic cell (41-42). Moreover, this peculiar cytotoxic property has also been observed in various other leukemic cell lines (43). Studies have also been made on skin cancer and uterine cervix, but discussion of such experimental data is outside the scope of this work. All these research tend to Clarify the mechanism of action of the plant and are fundamental to justify further in-depth studies before undertaking significant clinical studies.
In Ayurveda saffron is used for the treatment of chronic diseases such as asthma and arthritis, it has also proved useful in treating Colds and coughs. Ayurvedic medicines containing saffron are used to treat acne and various skin diseases. Ancient Ayurvedic texts give instructions on using the plant as aphrodisiac and stimulant.
Ancient sources also report nerve diseases such as convulsions or arterial hypertension or anti-aging activities. In this discussion, we attended to the study of few therapeutic targets established by clinical trials and analyses. It allows us to follow a “modern” mentality and not always accustomed to reasoning by analogy and symbols, to use the plant with a systematic method and to find relatively consistent clinical findings.
In our professional practice, we were amazed at the effectiveness of spice in Depressive syndromes where it often achieves very good results also in combination with pharmacological therapies and, beyond the skepticism of our traditional colleagues Should be encouraged and disseminated a knowledge and therapeutic application based on the scientific evidence we have in our possession.
Dott. Claudio Sandri
Translated by Ms Jeanne Marie Arcaini
Article bibliography at the following link.