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Saffron, Prostate, Exercise, and Cognitive Impairment


March 2015

By Life Extension

Crocetin from saffron: an active component of an ancient spice.

The known properties of saffron (Crocus sativus, L.) and its components have been examined. Recently, hormone like effects in green algae and the anti-cancerogenic and anti-toxic effects, have been observed. In particular, the effects of crocetin, a carotenoids (8,8’-diapo-8,8’-carotenoic acid) present in saffron and characterized by a diterpenic and symmetrical structure with seven double bonds and four methyl groups, have been taken into consideration. It has been found that this compound enhances the oxygen diffusivity through liquids, such as plasma. As a consequence of this property, it has been observed that crocetin increases alveolar oxygen transport and enhances pulmonary oxygenation. It improves cerebral oxygenation in hemorrhaged rats and positively acts in the atherosclerosis and arthritis treatment. It inhibits skin tumor promotion in mice (i.e., with benzo(a)pyrene); it has an inhibitory effect on intracellular nucleic acid and protein synthesis in malignant cells, as well as on protein-kinase-C and prorooncogene in INNIH/3T3 cells. This is most likely due to its anti-oxidant activity. Furthermore, crocetin protects against oxidative damage in rat primary hepatocytes. It also suppresses aflatoxin B1-induced hepatotoxic lesions and has a modulatory effect on aflatoxin, B1 cytotoxicity, and DNA adduct formation on C3H10/T1/2 fibroblast cells. It also has a protective effect on the bladder toxicity, induced by cyclophosphamide. The experiments reported in the scientific literature and the interesting results obtained have been carried out in vitro or on laboratory animals, but not yet on man.

Crit Rev Food Sci Nutr. 2004;44(3):155-72

Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice.

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)­—using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.

Hum Exp Toxicol. 2006 Feb;25(2):79-81

Cardiovascular effects of saffron: an evidence-based review.

Herbal medicine can be a valuable source of assistance for traditional medicine. There are a number of herbs that can be used in conjunction with modern medicine. Herbs can also be taken to aid recovery from serious diseases. Although one should never aim to treat diseases such as cardiovascular disease solely with herbal medicine, the value of herbs used in tandem with modern medicine cannot be ignored. Saffron has been reported to help lower cholesterol and keep cholesterol levels healthy. Animal studies have shown saffron to lower cholesterol by as much as 50%. Saffron has antioxidant properties; it is, therefore, helpful in maintaining healthy arteries and blood vessels. Saffron is also known to have anti-inflammatory properties, which are beneficial to cardiovascular health. The people of Mediterranean countries, where saffron use is common, have lower than normal incidence of heart diseases. From saffron’s cholesterol lowering benefits to its anti inflammatory properties, saffron may be one of the best supplements for cardiac health. This paper reviews the studies regarding the beneficial effects of saffron in cardiovascular health.

J Tehran Heart Cent. 2011 Spring;6(2):59-61

Clinical applications of saffron (Crocus sativus) and its constituents: a review.

Commonly known as saffron, Crocus sativus L and its active components have shown several useful pharmacological effects such as anticonvulsant, antidepressant, anti-inflammatory, antitumor, radical scavenger effects, learning and memory improving effects, etc. There has been an increasing body of data on saffron use in medical databases within the last 20 years. In the current review, the strengths and weaknesses of some of the clinical trials about different pharmacological effects of saffron will be discussed C. sativus extract has been studied in 8 anti-depressant clinical trials in comparison to placebo or some antidepressant drugs, in which saffron showed effectiveness as an antidepressant drug. Clinical trials on anti-Alzheimer effect of saffron demonstrated that it was more effective than the placebo, and as effective as donepezil. 2 clinical trials on antipruritic and complexion promoter in skin care effects of saffron both confirmed that saffron was more efficient than the placebo. In another clinical trial, it was proved that in addition to the weight loss treatment, saffron could reduce snacking frequency. Clinical trials conducted on women with premenstrual syndrome showed that saffron could reduce suffering symptoms more than the placebo and similar to standard treatments.Furthermore, additional clinical trials on effects of saffron on erection dysfunction, allergies, cardiovascular and immune system as well as its safety, toxicity and human pharmacokinetics are reviewed herein.

Drug Res (Stuttg). 2014 May 21

Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines.

Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.

Food Chem Toxicol. 2008 Nov;46(11):3443-7

Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients.

Conventional and newly emerging treatment procedures such as chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reversing the outcome of cancer diseases to any drastic extent, which has led researchers to investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties Crocus sativus L., commonly known as saffron, is the raw material for one of the most expensive spice in the world, and it has been used in folk medicine for centuries. Chemical analysis has shown the presence of more than 150 components in saffron stigmas. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients, possible mechanisms for these activities are discussed. More direct evidence of anticancer effectiveness of saffron as chemo-preventive agent may come from trials that use actual reduction of cancer incidence as the primary endpoint. This review discusses recent literature data and our results on the cancer chemopreventive activities of saffron and its main ingredients.

Pharmacognosy Res. 2014 Apr;6(2):99-107

Role of saffron and its constituents on cancer chemoprevention.

CONTEXT: Cancer dramatically impacts human life expectancy and quality of life. Natural substances from vegetables, herbs and spices could be beneficial in the prevention or treatment of a variety of cancers. Crocus sativus (Iridaceae), which has been used as a folk medicine for treating diseases for ages, showed obvious cancer chemoprevention potential. OBJECTIVE: This article focuses on the effects of Crocus sativus and its main ingredients, such as crocin, on cancer therapeutics. METHODS: We reviewed research data from saffron, a spice derived from the flower of Crocus sativus, and its constituents using the major databases, namely, Web of Science, SciFinder and PubMed. RESULTS AND CONCLUSION: Saffron possesses free radical-scavenging properties and antitumor activities. Significant cancer chemopreventive effects have been shown in both in vitro and in vivo models. Based on current data, saffron and its ingredients could be considered as a promising candidate for clinical anticancer trials.

Pharm Biol. 2013 Jul;51(7):920-4

Saffron reduction of 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis.

Asian Pac J Cancer Prev. 2013;14(2):951-7

Saffron and natural carotenoids: Biochemical activities and anti-tumor effects.

Saffron, a spice derived from the flower of Crocus sativus, is rich in carotenoids. Two main natural carotenoids of saffron, crocin and crocetin, are responsible for its color. Preclinical studies have shown that dietary intake of some carotenoids have potent anti-tumor effects both in vitro and in vivo, suggesting their potential preventive and/or therapeutic roles in several tissues. The reports represent that the use of carotenoids without the potential for conversion to vitamin A may provide further protection and avoid toxicity. The mechanisms underlying cancer chemo-preventive activities of carotenoids include modulation of carcinogen metabolism, regulation of cell growth and cell cycle progression, inhibition of cell proliferation, anti-oxidant activity, immune modulation, enhancement of cell differentiation, stimulation of cell-to-cell gap junction communication, apoptosis and retinoid-dependent signaling. Taken together, different hypotheses for the antitumor actions of saffron and its components have been proposed such as a) the inhibitory effect on cellular DNA and RNA synthesis, but not on protein synthesis; b) the inhibitory effect on free radical chain reactions; c) the metabolic conversion of naturally occurring carotenoids to retinoids; d) the interaction of carotenoids with topoisomerase II, an enzyme involved in cellular DNA-protein interaction. Furthermore, the immunomodulatory activity of saffron was studied on driving toward Th1 and Th2 limbs of the immune system. In this mini-review, we briefly describe biochemical and immunological activities and chemo-preventive properties of saffron and natural carotenoids as an anticancer drug.

Biochim Biophys Acta. 2014 Jan;1845(1):20-30

Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.

Food Chem. 2012 Dec 15;135(4):2350-8

Saffron (Crocus sativus L.) powder as an ingredient of rye bread: an anti-diabetic evaluation.

In this study, a most consumer-acceptable rye bread (RB) containing saffron (S) powder (RB+S) was designed to verify its anti-diabetic properties, and to compare these effects with those of RB and S separately, matched to a similar dose of bioactive components, used in the high-fat (HF) diet in streptozotocin (STZ)-induced Wistar rats. After baking, beneficial antioxidant and sensory properties for RB enriched with 0.12% S were achieved. Twenty-four severely diabetic rats (fasting blood glucose (FBG) ≥350 mg/dL) were randomized to incorporate either 0.08% of pure S, or RB enriched with 0.12% S (the diet provided 0.08% of S), or RB alone into their diet for 5 weeks. As controls, nontreated, HF-feeding STZ-induced rats (positive control-HF/STZ) and rats receiving normal laboratory diet (negative control-C) were used. A significant FBG-lowering effect was observed (47%, 53%, and 54% reduction vs. HF/STZ; P<.05) after S, RB, and RB+S treatment. Improvements in the rats’ glycemia were achieved by b-cell regeneration and increases in insulin secretion. Only in the S and RB+S group of rats, a significant (P<.05) increase in relative pancreas (vs. HF/STZ) was noted. A significant (P<.05) reduction in the concentration of thiobarbituric acid-reactive substances (TBARS) was achieved, whereas the ferric-reducing ability of plasma (FRAP) was not changed after S, RB and RB+S treatment (vs. HF/STZ). Triglyceride (TG) concentrations after S, RB, and RB+S treatment were significantly decreased (P<.05) versus HF/STZ. Both S and RB can be used in diabetic therapy, but no additional metabolic effect was achieved after consumption of RB+S.

J Med Food. 2013 Sep;16(9):847-56