Reprinted with the kind permission of Life Extension.
By Jennifer Provos
As more positive data accumulates about the health benefits of the Mediterranean diet, researchers are uncovering new applications for the spice saffron, which is a Mediterranean diet constituent.
In multiple studies, scientists are finding that saffron has the unique ability to both slow and reverse cancer growth!1
Saffron’s cancer-preventive properties include inhibiting the promotion of tumors and preventing chemical modifications to DNA that can activate cancer genes or induce new cancer-causing mutations.2-4
Additionally, saffron has been shown to help reduce the harmful effects produced by chemotherapy drugs.
Chemo drugs can induce genetic damage that may lead to new cancers, making standard chemotherapy a double-edged sword and limiting its effectiveness.5 Research has found that the abundant carotenoids in saffron offer direct protection against chemotherapy-induced DNA damage.5
Along with its chemoprevention abilities, saffron contains a host of beneficial, biologically active compounds that have been shown to protect heart and blood vessel tissue,6 ease the impact of diabetes and other metabolic disorders,7 and slow or even reverse cognitive and mood disorders associated with aging.8
This spice with ancient origins is finding new use in the battle against the onslaughts of aging.
Saffron consists of the dried dark red or yellow “stigmas” of the crocus flower, Crocus sativus.9 In addition to its culinary uses, saffron has a long history as a potent component of traditional medical systems.2,5,10-13
Like most plant derivatives, saffron contains a multitude of bioactive molecules, many of which have been shown to have specific benefits in the body. Chief among these molecules are crocin, crocetin, and safranal, members of the carotenoid family of molecules that also includes forms of vitamin A.4,14
These compounds have been shown to exert multiple favorable effects in laboratory studies, including improved oxygen diffusion (which enhances lung performance and brain oxygenation), improved treatment of atherosclerosis and arthritis, protection of liver tissue against damage by chemical toxins, and protection of bladder tissue against chemical damage.3
Let’s now take a closer look at how saffron and its constituents beneficially effect cancer, heart disease, metabolic disorders, and cognitive disorders.
Comprehensive Cancer Chemoprevention
Cancer is one of the world’s leading causes of death, killing about 8 million people each year.2,10,14 While the bulk of mainstream medical research has been aimed at treating cancers once they appear,12 wiser researchers search for natural molecules that might derail the development of cancer very early in its development. This admirable goal is known as chemoprevention, as opposed to chemotherapy.
In this search, saffron has emerged as a contender for effective chemoprevention because it acts at multiple stages in the complex set of events that lead to a full-blown tumor.10,15,16 Let’s look at how saffron works as a chemopreventive agent one stage at a time:
Saffron and its constituents start working long before a cell undergoes transformation into a malignant cancer cell.
The first step in cancer development, or carcinogenesis, is some kind of trigger that initiates malignant transformation. This may be an environmental toxin, a stray oxygen radical, or invasion with certain viruses. Saffron components have been shown to help prevent carcinogenesis caused by each of these triggers.
In one study, the saffron derivatives crocin and diglucosylcrocetin were shown to inhibit tumor cell markers emerging on the surface of virally infected cells in laboratory experiments.17 In another study, when hamsters were orally treated with saffron prior to administration of a powerful chemical carcinogen, tumor formation was completely prevented, demonstrating its ability to prevent the initial stage of cancer.18
Saffron extracts and specific components have also been shown to potently prevent DNA damage caused by free radicals, radiation, and inflammation, thereby reducing the risk of new cancer formation.5,19
Inhibits The Rapid Spread Of Cancer Cells
Once a cell has been triggered to become malignant, it then proliferates, or reproduces rapidly and without normal controls, to produce a developing tumor. Studies show that saffron is able to suppress—and in some cases reverse—the proliferation of certain human cancer cells in culture.
For example, one compelling study found that colon cancer cells that were treated with either saffron extract—or its major component, crocin—displayed sharp and significant reductions in proliferation, to as low as 2.8% of the rate seen in untreated cells.4 A similar reduction in proliferation was demonstrated in non-small cell lung cancer and breast cancer cells in culture. 4,9 It is important to note that in none of these studies did saffron or its constituents display damage to healthy, normal cells.4,9
Crocetin, another major saffron constituent, has been found to inhibit proliferation of pancreatic cells in culture as well.20And in live animal studies, crocetin produced marked regression of pancreatic tumors that were induced when aggressive pancreatic cancer cells were directly injected into mice. Importantly, in this study, the crocetin was given orally, and only after the tumors were already detectable, demonstrating crocetin’s potent ability not only to slow, but to reverse cancer growth!20
WHAT YOU KNEED TO KNOW
- Saffron, the ancient spice from the Middle East and Asia, contains a host of beneficial, biologically active compounds.
- In particular, saffron and its extracts demonstrate anticancer effects, making saffron a promising cancer chemopreventive agent.
- In addition to preventing and mitigating cancer development and progression, saffron provides protection for heart and blood vessel tissue, eases the impact of diabetes and other metabolic disorders, and slows or reverses cognitive and mood disorders associated with aging.
- Saffron’s multiple beneficial effects act at levels fundamental to the proper function of all body cells, making it a true “whole-body” supplement and validating its centuries-old use as a protector of human health
Triggers Programmed Cell Death
Another important way in which developing cancer cells can be stopped in their tracks is through the mechanism known asapoptosis, or programmed cell death. All normal body cells contain a genetic program that induces the cell to die under specific conditions. This is a vital means of removing damaged cells and preventing overgrowth of normal tissues. Cancer cells, however, typically lose their responsiveness to the apoptosis signal, effectively becoming “immortal,” and hence, deadly.
Saffron has been shown to trigger apoptosis in a variety of cancer cell lines, which is seen as an essential component of any cancer-control or cancer-prevention method.11,19-21 In fact, all three major components of saffron—crocin, crocetin, and safranal—have shown powerful apoptosis-inducing properties.2,22,23
If a cancer cell survives attempts to quash it by blocking proliferation or apoptosis, it may go on to produce specialized molecules that help it degrade the protein matrix between healthy cells, allowing it to invade otherwise-healthy tissue.24 This is how cancers spread locally, and it is also a major mechanism in metastasis, the spread of malignant cells throughout the body.25-27
The saffron constituent crocetin has now been shown to downregulate production of one such protein-degradation molecular type, known as matrix metalloproteinase.24 This action has been shown to prevent breast cancer cells from penetrating and invading both local tissues and those in other parts of the body by metastasis.24
Still another means by which growing tumors are able to thrive is through the induction of new blood vessel growth, a process known as angiogenesis. Considerable scientific effort has been devoted to developing drugs that can block angiogenesis, thereby starving a developing tumor of the nutrients and oxygen it needs to sustain growth.28
Recent studies support the use of saffron extracts in reducing levels of a vital signaling molecule called vascular endothelial growth factor (VEGF), which markedly reduces new blood vessel formation in the tumor mass.29
Studies Show Saffron Prevents The Deadliest Human Cancers
As you just read, extensive data has provided persuasive evidence that saffron can prevent, mitigate, and even reverse many of the changes that lead a healthy cell to turn cancerous. As a result, a growing body of literature now supports the use of saffron for the prevention of several of the most aggressive and deadly human cancers, including liver, lung, and stomach cancers.
Liver cancer is an increasing public health threat, partly the result of the growing number of toxins in our environment and partly the result of increasing prevalence of the hepatitis C virus, especially in people born in the Baby Boom generation.30
In rats given a powerful chemical that produces liver cancer, a two-week pretreatment course of saffron significantly reduced the number and size of cancerous nodules developing in the animals’ livers.15 Sub-microscopic study of the affected cells showed that saffron achieved this effect by sharply reducing the levels of oxidant and inflammatory signaling that contributes to malignant cell growth and also by inducing apoptosis, which helped to stop tumors from growing.15
Lung cancer is another major cancer that continues to be a leading cause of death, even as rates of smoking decline. Saffron extracts have now been used to reduce the viability of lung cancer cells in culture, inducing cell death by apoptosis.31
In studies of stomach cancer, another rapidly increasing cancer worldwide, crocetin enhanced apoptosis and slowed tumor progression, while boosting blood levels of protective compounds that further suppress cancer development.32 In one study, a water extract of saffron produced similar effects in an animal model of stomach cancer. 33
To date, saffron, its extracts, and its individual components crocin, crocetin, and safranal have demonstrated compelling preventive effects against cancers of the lung, liver, colon, breast, pancreas, stomach, bone, and blood.9,32,34-39 Saffron has an impressive safety profile, with no evidence of toxic effects on healthy tissues or harmful effects on blood coagulation.5,40
Saffron And Metabolic Disorders
Saffron has been shown to have powerful effects against diabetes and its side effects. High blood sugar levels are dangerous because they increase glycation, which results in the oxidation and inflammation that damages body tissues.41-43 Saffron extracts help bring blood sugar levels under control by enhancing glucose uptake and improving insulin sensitivity in muscle tissue. 44 This is vital because muscle cells are the largest users of glucose in the body.
Subscribe to the World's Most Popular Newsletter (it's free!)
The benefits of this effect have been validated in numerous animal studies. When diabetic rats were fed saffron or its components safranal or crocin, they experienced significant reductions in fasting blood sugar levels.45-47 Some studies have demonstrated significant improvements in lipid profiles as well, with reductions in cholesterol and triglycerides.48
As a result of saffron’s effect on glucose-induced oxidant damage, saffron has shown great promise for preventing the debilitating effects associated with diabetes, including diabetic neuropathy, diabetic encephalopathy, and diabetic nephropathy.
Although the mechanism behind diabetic neuropathy (damage to nerve fibers) is unclear, it appears to involve sugar-induced oxidant damage to nerve cells.49 A study of human brain cells in culture showed that saffron extract markedly decreases the sugar toxicity that causes the damage.49
In extreme cases, diabetics may develop a brain condition called diabetic encephalopathy, which is thought to arise from the same causes as diabetic neuropathy. In an animal study, saffron supplementation (the human equivalent dose of 448 to 896 mg per day) not only improved cellular antioxidant systems, but more importantly, decreased cognitive deficits associated with the condition.50
Diabetics also develop substantial risk for kidney disease, or diabetic nephropathy, again in part a result of glucose-induced oxidant damage. One study demonstrated that when diabetic rats were pretreated with the saffron constituent crocin, they experienced improvement in kidney function.51
And, in a startling study, supplementation with the saffron constituent safranal reduced oxidative lung damage in diabetic rats, helping to reduce lung distress.52
Underlying the development of diabetes often is metabolic syndrome, which is a common result of Western dietary and lifestyle habits. Metabolic syndrome (the combination of obesity, high blood sugar, lipid abnormalities, and hypertension) is an important risk factor for cardiovascular diseases, and hence represents an important point for interventions to reduce cardiovascular death.53
Numerous studies have demonstrated that saffron supplementation in humans with metabolic syndrome has many beneficial effects:
- It reduces levels of “heat shock proteins,” which are markers of cellular stress,53
- It reduces snacking and increases the sense of fullness after a meal (satiety),54
- It can prevent metabolic syndrome development in patients taking olanzapine, a common drug used in psychiatry.55
Saffron And Cardiovascular Disease
Saffron, a major component of the Mediterranean diet, has been linked with some of the beneficial effects associated with the diet—including lower rates of cardiovascular disease.6 In fact, saffron offers dual protection for your heart: It helps to protect against cardiovascular disease and it helps reduce the damage that occurs if a heart attack does happen.
Scientists are now uncovering some of the major mechanisms by which saffron protects cardiovascular tissue. Cardiovascular disease results in part from multiple factors that lead to inflammation, oxidant damage, and loss of tissue and organ function. As you’ve read, saffron is able to potently reduce oxidant stress and inflammation. But its cardiovascular benefits don’t stop there.
Recent studies have demonstrated saffron’s potential for protecting against heart attacks and strokes by reducing blood pressure and improving blood lipid profiles.56,57 Crocin markedly decreases blood concentrations of triglycerides and total and low-density (“bad”) cholesterol, while raising levels of high-density (“good”) cholesterol.57 In some animal studies, blood cholesterol was reduced by as much as 50%. 6 A recent study published in Phytotherapy Research demonstrated for the first time that crocetin could also significantly reduce mean blood pressure in hypertensive rats. 58
In a mechanism similar to the common calcium channel blocking drugs, saffron inhibits the inflow of calcium into smooth muscle cells in artery walls and in heart muscle tissue, a process known to constrict arteries and raise blood pressure.59-62
In addition, studies have shown that crocin can reduce both visible and molecular evidence of heart attack in laboratory rats by rebalancing the oxygen status of individual heart muscle cells.63,64 Remarkably similar effects have been demonstrated using both crocetin and saffron itself to protect heart tissue from damaging low blood flow.65,66
And in experimentally induced heart attacks, saffron supplementation in animals was shown to significantly reduce the size of the infarction, or area of dying tissue that occurs during a heart attack.67
It is common for people to experience heart rhythm disturbances (arrhythmias) following a heart attack. Saffron extracts have been shown to reduce susceptibility to life-threatening arrhythmias by remodeling the structure of the heart’s normal pacemaker (the atrioventricular node, or “AV node”). 68
SAFFRON PROTECTS AGAINST THE DANGERS OF CHEMOTHERAPY
While saffron offers strong cancer-preventing properties and has been found to be a promising chemopreventive agent, an additional benefit is saffron’s ability to help reduce the harm produced by modern chemotherapy drugs.
A major problem with existing chemotherapy medications is that they are often capable of inducing precisely the kind of genetic damage that can lead to new cancers, making standard chemotherapy a double-edged sword and limiting its effectiveness.5 Research has found that the abundant carotenoids in saffron may offer direct protection against chemotherapy-induced DNA damage.5
In one study, when mice were pretreated with saffron at doses equivalent to 224 to 896 mg per day in humans, it significantly inhibited DNA damage caused by the chemotherapy drugs cisplatin, cyclophosphamide, and mitomycin-C. This prevented the breaks in DNA strands that can lead to fresh, cancer-causing mutations.5
Laboratory studies have also shown that the saffron constituent crocetin enhances the effects of common chemotherapy drugs such as vincristine and cisplatin.35,93
And in an exciting new development, it now appears that saffron-derived constituents can substantially enhance the effectiveness of protein-based vaccines, which are being developed to treat specific kinds of cancers. Used in this way as “adjuvants,” saffron-derived saponin molecules increase both blood-based and cellular responses to anticancer vaccines.94
Saffron And Strokes
Saffron has also been demonstrated to have beneficial effects in stroke victims. The most common form of stroke is an ischemic stroke, which can be thought of as a heart attack of the brain, because like a heart attack, it is also caused by a sharp reduction or interruption of blood flow.69,70
When blood flow is restored to the brain, it unfortunately leads to something called “reperfusion injury,” which is tissue damage that occurs when the blood supply returns to the area as a result of oxidative damage and inflammation. This is the main factor in brain damage following an ischemic stroke.
A study done on rat models of ischemic stroke demonstrated that crocin reduced the damaging effects of oxidant molecules produced when blood flow was restored, which can ultimately help to limit the negative effects of the stroke.71
In a compelling validation of the benefits of this effect, another study published in Phytotherapy Research demonstrated that both the herb itself and its constituent crocin improved spatial cognitive performance in rats following an experimental stroke.72
Saffron And Your Brain
Because oxidation, inflammation, and glucose damage are harmful to brain health, scientists are turning to saffron as a potential neuroprotective agent against both neurodegenerative diseases and mood disorders such as depression, which affects upwards of one-fifth of the US population.73-76
Animal studies reveal antidepressant effects of saffron extracts on performance in behavioral models of depression,77 and for symptoms of obsessive-compulsive disorder (OCD).84
Human studies using low doses of saffron have produced even more impressive results as follows:
- Saffron (30 mg per day) significantly reduced depression scores on a standard rating scale when compared to placebo,73,78,79
- Saffron (30 mg per day) was found to be similar in effectiveness to the standard antidepressant drugs imipramine andfluoxetine in the treatment of mild to moderate depression,80,81
- Saffron (30 mg per day) reduced erectile dysfunction, a common side effect produced by treatment with the antidepressant drug fluoxetine,82
- Saffron (30 mg per day) was more effective than placebo in relieving symptoms of premenstrual syndrome when used over two menstrual cycles.83
Loss of cognitive function is one of the most common, most feared consequences of aging. Studies show that saffron has promise in preventing or ameliorating some of those effects. A 16-week trial of saffron (30 mg per day) showed that the supplement was superior to placebo in patients with early, probable Alzheimer’s disease. The same dose, for 22 weeks, proved similar in effect to the prescription drugs memantine and donepezil in a comparable population.85,86
In laboratory models of neurodegenerative diseases such as Alzheimer’s, saffron and its extracts demonstrate protection against excitotoxicity, the overactivity of certain kinds of nerve cells that produces long-term degeneration of brain tissue. 87And animal studies have shown that saffron supplementation can antagonize the cognitive effects of Alzheimer’s disease induced by chemical treatments.88,89
The ancient spice saffron has been used for millennia as a treatment and preventive agent against cancer, heart disease, metabolic conditions, and other conditions we now recognize as symptoms of aging.12,90-92
Modern science is vindicating these uses, demonstrating that saffron and its constituent molecules protect a myriad of body tissues and organs against the fundamental processes that induce aging, such as oxidant damage, inflammation, toxic exposures, and high glucose.
In particular, saffron is showing promising chemopreventive properties against many different forms of cancer. Many of the same mechanisms that make it so potent against cancer also make it a powerful tool in reducing the impact of diabetes and the metabolic syndrome, of cardiovascular disease and stroke, and of depression and neurodegenerative disorders.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at1-866-864-3027.
- Dhar A, Mehta S, Dhar G, et al. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009 Feb;8(2):315-23.
- Gutheil WG, Reed G, Ray A, Anant S, Dhar A. Crocetin: an agent derived from saffron for prevention and therapy for cancer. Curr Pharm Biotechnol. 2012 Jan;13(1):173-9.
- Giaccio M. Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr. 2004;44(3):155-72.
- Aung HH, Wang CZ, Ni M, et al. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol. 2007 Sep;29(3):175-80.
- Premkumar K, Thirunavukkarasu C, Abraham SK, Santhiya ST, Ramesh A. Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice. Hum Exp Toxicol. 2006 Feb;25(2):79-84.
- Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent. 2011 Spring;6(2):59-61.
- Elgazar AF, Rezq AA, Bukhari HM. Anti-hyperglycemic effect of saffrom extract in alloxan-induced diabetic rats. Eur J Biol Sci. 2013; 5(1):14-22.
- Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of saffron (Crocus sativus) and its constituents: a review. Drug Res (Stuttg). 2014 May 21.
- Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res. 2007 Jan-Feb;27(1a):357-62.
- Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med (Maywood). 2002 Jan;227(1):20-5.
- Tavakkol-Afshari J, Brook A, Mousavi SH. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxicol. 2008 Nov;46(11):3443-7.
- Samarghandian S, Borji A. Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharmacognosy Res.2014 Apr;6(2):99-107.
- Kim SH, Lee JM, Kim SC, Park CB, Lee PC. Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines. Biochem Cell Biol. 2014 Apr;92(2):105-11.
- Available at: http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed December 19, 2014.
- Amin A, Hamza AA, Bajbouj K, Ashraf SS, Daoud S. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology. 2011 Sep 2;54(3):857-67.
- Zhang Z, Wang CZ, Wen XD, Shoyama Y, Yuan CS. Role of saffron and its constituents on cancer chemoprevention.Pharm Biol. 2013 Jul;51(7):920-4.
- Molnar J, Szabo D, Pusztai R, et al. Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates. Anticancer Res. 2000 Mar-Apr;20(2a):861-7.
- Manoharan S, Wani SA, Vasudevan K, et al. Saffron reduction of 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Asian Pac J Cancer Prev. 2013;14(2):951-7.
- Bajbouj K, Schulze-Luehrmann J, Diermeier S, Amin A, Schneider-Stock R. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines. BMC Complement Altern Med. 2012;12:69.
- Dhar A, Mehta S, Dhar G, et al. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009 Feb;8(2):315-23.
- Hoshyar R, Bathaie SZ, Sadeghizadeh M. Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. DNA Cell Biol. 2013 Feb;32(2):50-7.
- Malaekeh-Nikouei B, Mousavi SH, Shahsavand S, Mehri S, Nassirli H, Moallem SA. Assessment of cytotoxic properties of safranal and nanoliposomal safranal in various cancer cell lines. Phytother Res. 2013 Dec;27(12):1868-73.
- Bolhassani A, Khavari A, Bathaie SZ. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects.Biochim Biophys Acta. 2014 Jan;1845(1):20-30.
- Chryssanthi DG, Dedes PG, Karamanos NK, Cordopatis P, Lamari FN. Crocetin inhibits invasiveness of MDA-MB-231 breast cancer cells via downregulation of matrix metalloproteinases. Planta Med. 2011 Jan;77(2):146-51.
- Ma C, Rong Y, Radiloff DR, et al. Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev . 2008 Feb 1;22(3):308-21.
- Oskarsson T. Extracellular matrix components in breast cancer progression and metastasis. Breast. 2013 Aug;22 Suppl 2:S66-72.
- Stewart DA, Cooper CR, Sikes RA. Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reprod Biol Endocrinol . 2004 Jan 7;2:2.
- Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors. Accessed December 19, 2014.
- Mousavi M, Baharara J, Shahrokhabadi K. The synergic effects of crocus sativus L. and low frequency electromagnetic field on VEGFR2 gene expression in human breast cancer cells. Avicenna J Med Biotechnol. 2014 Apr;6(2):123-7.
- Nave RL. Baby boomers and the hepatitis C boom. Ann Emerg Med. 2013 Dec;62(6):19a-21a.
- Samarghandian S, Tavakkol Afshari J, Davoodi S. Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction. Appl Biochem Biotechnol. 2011 May;164(2):238-47.
- Bathaie SZ, Hoshyar R, Miri H, Sadeghizadeh M. Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer. Biochem Cell Biol. 2013 Dec;91(6):397-403.
- Bathaie SZ, Miri H, Mohagheghi MA, Mokhtari-Dizaji M, Shahbazfar AA, Hasanzadeh H. Saffron aqueous extract inhibits the chemically-induced gastric cancer progression in the wistar albino rat. Iran J Basic Med Sci. 2013 Jan;16(1):27-38.
- Samarghandian S, Borji A, Farahmand SK, Afshari R, Davoodi S. Crocus sativus L. (saffron) stigma aqueous extract induces apoptosis in alveolar human lung cancer cells through caspase-dependent pathways activation. Biomed Res Int. 2013;2013:417928.
- Li X, Huang T, Jiang G, Gong W, Qian H, Zou C. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol Lett. 2013 Aug 29;221(3):197-204.
- Geromichalos GD, Papadopoulos T, Sahpazidou D, Sinakos Z. Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study. Food Chem Toxicol. 2014 Sep 17;74c:45-50.
- Harrington M. Saffron offers protection from liver cancer. Lab Anim (NY). 2011 Oct;40(10):289.
- Garcia-Olmo DC, Riese HH, Escribano J, et al. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer. 1999;35(2):120-6.
- Bakshi H, Sam S, Rozati R, et al. DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev. 2010;11(3):675-9.
- Lopez-Corral L, Humphray S, Murray L, et al. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Leukemia. 2014 Apr;28(4):539-43.
- Negre-Salvayre A, Salvayre R, Augé N, Pamplona R, Portero-Otín M. Hyperglycemia and glycation in diabetic complications. Antioxid Redox Signal. 2009 Dec;11(12):3071-109
- Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res . 2004 Sep 1;63(4):582-92.
- Osawa T, Kato Y. Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci. 2005 Jun;1043:440-51.
- Kang C, Lee H, Jung ES, et al. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms. Food Chem. 2012 Dec 15;135(4):2350-8.
- Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food. 2013 Mar;16(3):206-10.
- Bajerska J, Mildner-Szkudlarz S, Podgorski T, Oszmatek-Pruszynska E. Saffron (Crocus sativus L.) powder as an ingredient of rye bread: an anti-diabetic evaluation. J Med Food. 2013 Sep;16(9):847-56.
- Maeda A, Kai K, Ishii M, Ishii T, Akagawa M. Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice. Mol Nutr Food Res. 2014 Jun;58(6):1177-89.
- Shirali S, Zahra Bathaie S, Nakhjavani M. Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res. 2013 Jul;27(7):1042-7.
- Mousavi SH, Tayarani NZ, Parsaee H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells. Cell Mol Neurobiol. 2010 Mar;30(2):185-91.
- Samarghandian S, Azimi-Nezhad M, Samini F. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Biomed Res Int. 2014;2014:920857.
- Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Hum Exp Toxicol. 2014 Jun 12.
- Samarghandian S, Afshari R, Sadati A. Evaluation of lung and bronchoalveolar lavage fluid oxidative stress indices for assessing the preventing effects of safranal on respiratory distress in diabetic rats. ScientificWorldJournal.2014;2014:251378.
- Shemshian M, Mousavi SH, Norouzy A, et al. Saffron in metabolic syndrome: its effects on antibody titers to heat-shock proteins 27, 60, 65 and 70. J Complement Integr Med. 2014;11:43-9.
- Gout B, Bourges C, Paineau-Dubreuil S. Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. Nutr Res. 2010 May;30(5):305-13.
- Fadai F, Mousavi B, Ashtari Z, et al. Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry. 2014 Jul;47(4-5):156-61.
- Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. The effect of chronic administration of saffron (Crocus sativus) stigma aqueous extract on systolic blood pressure in rats. Jundishapur J Nat Pharm Prod. 2013 Nov;8(4):175-9.
- Xu GL, Yu SQ, Gong ZN, Zhang SQ. Study of the effect of crocin on rat experimental hyperlipemia and the underlying mechanisms. Zhongguo Zhong Yao Za Zhi. 2005 Mar;30(5):369-72.
- Higashino S, Sasaki Y, Giddings JC, et al. Crocetin, a carotenoid from gardenia jasminoides ellis, protects against hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. Phytother Res. 2014 Sep;28(9):1315-9.
- Liu N, Yang Y, Mo S, Liao J, Jin J. Calcium antagonistic effects of Chinese crude drugs: preliminary investigation and evaluation by 45 Ca. Appl Radiat Isot. 2005 Aug;63(2):151-5.
- Boskabady MH, Shafei MN, Shakiba A, Sefidi HS. Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother Res. 2008 Mar;22(3):330-4.
- Simonetti G, Mohaupt M. Calcium and blood pressure. Ther Umsch. 2007 May;64(5):249-52.
- Kiowski W, Bolli P, Erne P, Hulthén UL, Bühler FR . Mechanisms of action of calcium antagonists in hypertension. J Cardiovasc Pharmacol. 1987;10 Suppl 10:S23-8.
- Goyal SN, Arora S, Sharma AK, et al. Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine. 2010 Mar;17(3-4):227-32.
- Sachdeva J, Tanwar V, Golechha M, et al. Crocus sativus L. (saffron) attenuates isoproterenol-induced myocardial injury via preserving cardiac functions and strengthening antioxidant defense system. Exp Toxicol Pathol. 2012 Sep;64(6):557-64.
- Joukar S, Najafipour H, Khaksari M, et al. The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction. Cardiovasc Toxicol. 2010 Mar;10(1):66-71.
- Yan J, Qian Z, Sheng L, et al. Effect of crocetin on blood pressure restoration and synthesis of inflammatory mediators in heart after hemorrhagic shock in anesthetized rats. Shock. 2010 Jan;33(1):83-7.
- Bharti S, Golechha M, Kumari S, Siddiqui KM, Arya DS. Akt/GSK-3beta/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats. Eur J Nutr. 2012 Sep;51(6):719-27.
- Khori V, Alizadeh AM, Yazdi H, et al. Frequency-dependent electrophysiological remodeling of the AV node by hydroalcohol extract of Crocus sativus L. (saffron) during experimental atrial fibrillation: the role of endogenous nitric oxide. Phytother Res. 2012 Jun;26(6):826-32.
- Chen YC, Wu JS, Yang ST, et al. Stroke, angiogenesis and phytochemicals. Front Biosci (Schol Ed). 2012;4:599-610.
- Vasiliadis AV , Ziki? M. Current status of stroke epidemiology in Greece: a panorama. Neurol Neurochir Pol. 2014 November-December;48(6):449-57.
- Zheng YQ, Liu JX, Wang JN, Xu L. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 2007 Mar 23;1138:86-94.
- Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res. 2012 Mar;26(3):381-6.
- Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res. 2005 Feb;19(2):148-51.
- El-Alfy AT, Abourashed EA, Matsumoto RR. Nature against depression. Curr Med Chem. 2012;19(14):2229-41.
- Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr.2007;157(13-14):315-9.
- Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013 Nov;11(6):377-83.
- Wang Y, Han T, Zhu Y, et al. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med. 2010 Jan;64(1):24-30.
- Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine.2006 Nov;13(9-10):607-11.
- Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):439-42.
- Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816].BMC Complement Altern Med. 2004 Sep 2;4:12.
- Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol.2005 Feb 28;97(2):281-4.
- Modabbernia A, Sohrabi H, Nasehi AA, et al. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl). 2012 Oct;223(4):381-8.
- Agha-Hosseini M, Kashani L, Aleyaseen A, et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Bjog. 2008 Mar;115(4):515-9.
- Georgiadou G, Tarantilis PA, Pitsikas N. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder. Neurosci Lett. 2012 Oct 18;528(1):27-30.
- Akhondzadeh S, Shafiee Sabet M, Harirchian MH, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl). 2010 Jan;207(4):637-43.
- Farokhnia M, Shafiee Sabet M, Iranpour N, et al. Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer’s disease: a double-blind randomized clinical trial. Hum Psychopharmacol. 2014 Jul;29(4):351-9.
- Berger F, Hensel A, Nieber K. Saffron extract and trans-crocetin inhibit glutamatergic synaptic transmission in rat cortical brain slices. Neuroscience. 2011 Apr 28;180:238-47.
- Khalili M, Hamzeh F. Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer’s disease in male rats. Iran Biomed J. 2010 Jan-Apr;14(1-2):59-65.
- Naghizadeh B, Mansouri MT, Ghorbanzadeh B, Farbood Y, Sarkaki A. Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats. Phytomedicine. 2013 Apr 15;20(6):537-42.
- Rathore B, Ali Mahdi A, Nath Paul B, Narayan Saxena P, Kumar Das S. Indian herbal medicines: possible potent therapeutic agents for rheumatoid arthritis. J Clin Biochem Nutr. 2007 Jul;41(1):12-7.
- SamSchmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr. 2007;157(13-14):315-9.
- Javadi B, Sahebkar A, Emami SA. A survey on saffron in major islamic traditional medicine books. Iran J Basic Med Sci. 2013 Jan;16(1):1-11.
- Zhong YJ, Shi F, Zheng XL, et al. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms. Acta Pharmacol Sin. 2011 Dec;32(12):1529-36.
- Castro-Diaz N, Salaun B, Perret R, et al. Saponins from the Spanish saffron Crocus sativus are efficient adjuvants for protein-based vaccines. Vaccine. 2012 Jan 5;30(2):388-97.