Saffron

Saffron/Drug Interactions:

  • AlcoholAlcohol: Based on animal study, a saffron extract or constituent (crocin) prevented ethanol or acetaldehyde (metabolite)-induced inhibition of long-term potentiation in the rat dentate gyrus (130; 131; 132).
  • Alzheimer's agentsAlzheimer's agents: Based on clinical study, saffron extract was as effective as donepezil for Alzheimer's disease (108). Based on in vitro study, trans-crocin-4, the digentibiosyl ester of crocetin, and dimethylcrocetin, inhibited Abeta fibrillogenesis (133).
  • AnalgesicsAnalgesics: Based on animal study, crocin attenuated pain in the formalin-induced pain model (134). In mice, intraperitoneal injection of saffron extracts resulted in antinociceptive activity against acetic acid-induced writhing (135).
  • Antianxiety drugsAntianxiety drugs: Based on animal study, intraperitoneal saffron aqueous extract had anxiolytic effects (12). Crocins also had anxiolytic effects in animal models (11).
  • Antiasthma drugsAntiasthma drugs: Based on in vitro study, a mixture of saffron and seven other herbs inhibited histamine release from stimulated rat peritoneal mast cells (136).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on in vitro and animal evidence, constituents of saffron may both induce and inhibit platelet aggregation (88; 89; 90; 137).
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Based on human and animal study, saffron had antidepressant effects (110; 111; 112; 113; 138).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Based on human and animal study, saffron had antidepressant effects (110; 111; 112; 113; 138).
  • Antidiabetic agentsAntidiabetic agents: Based on animal study, crocetin improved insulin sensitivity (91; 92; 139).
  • AntihistaminesAntihistamines: Based on in vitro study, a mixture of saffron and seven other herbs inhibited histamine release from stimulated rat peritoneal mast cells (136).
  • AntihypertensivesAntihypertensives: Based on animal study, saffron extracts had hypotensive effects in both normotensive and hypertensive rats (140; 141).
  • Anti-inflammatory agentsAnti-inflammatory agents: Anti-inflammatory effects of crocetin have been shown in various animal models, including experimental colitis and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema (41; 142; 135).
  • Antilipemic agentsAntilipemic agents: Based on animal (high-fat) study, saffron and its constituent crocin had hypolipidemic effects (59). Triglycerides and total cholesterol were reduced. In a high-cholesterol-diet animal model, crocin decreased blood total cholesterol, LDL cholesterol, and triglycerides, and increased levels of HDL cholesterol (143).
  • Antineoplastic agentsAntineoplastic agents: Based on several in vitro and in vivo studies, saffron and several of its constituents may exert antitumor and cytotoxic properties and inhibit DNA and RNA synthesis (144; 145; 7; 119; 146; 147; 148; 149; 25; 27; 150; 151; 152; 153; 154; 155; 156; 23; 157; 158; 159). Based on in vitro study, saffron may protect against side effects of antineoplastic agents (i.e., daunorubicin) (160; 161; 162; 163).
  • AntitussivesAntitussives: Based on animal evidence, Crocus sativus stigma extracts may reduce the number of coughing episodes (10).
  • Cardiovascular agentsCardiovascular agents: Based on in vitro evidence, aqueous-ethanol extract from Crocus sativus has shown potent inhibitory effects on the calcium channel of guinea pig heart (164).
  • CisplatinCisplatin: Based on in vivo evidence, pretreatment with saffron may significantly inhibit the genotoxicity of cisplatin (165). Based on animal study, treatment with Crocus sativus extract prevented cisplatin-induced decreases in body weight, hemoglobin levels, and leukocyte counts, and prolonged lifespan (166). In animals, a combination of intraperitoneal cysteine, vitamin E, Crocus sativus, and Nigella sativa extracts had a protective effect against cisplatin-induced liver and kidney toxicity (167). Also in animals, crocin protected against cisplatin-induced acute renal failure and oxidative stress (168).
  • CyclophosphamideCyclophosphamide: Based on in vivo evidence, pretreatment with saffron may significantly inhibit the genotoxicity and bladder toxicity induced by cyclophosphamide (165; 169).
  • Drugs that may lower seizure thresholdDrugs that may lower seizure threshold: Based on animal study, safranal attenuated experimental absence seizures in acute experimental seizure models (170; 171; 172).
  • Fertility agentsFertility agents: Based on human study, saffron improved sperm morphology and motility (115).
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: Based on animal study, crocetin reduced experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) (41).
  • GemcitabineGemcitabine: It has been suggested that saffron-derived compounds may interfere with the effects of gemcitabine against pancreatic cancer when used in combination (173). Further details are lacking.
  • Hepatotoxic agentsHepatotoxic agents: Based on animal study, intravenous crocetin had hepatoprotective effects in a hemorrhagic shock model (53). In an aflatoxin B1 hepatotoxicity model, crocetin pretreatment resulted in a decrease in elevations of liver enzymes as well as hepatotoxic lesions (174; 175).
  • Hypnotic agentsHypnotic agents: Based on animal study, intraperitoneal saffron aqueous extract had hypnotic effects (12).
  • ImmunosuppressantsImmunosuppressants: Based on in vitro evidence, a glycoconjugate from saffron corms may promote significant macrophage activation (176). Also in vitro, crocin was an inhibitor of T cell activation (177).
  • Impotence agentsImpotence agents: Based on animal evidence, crocin increased mounting frequency, intromission frequency, and erection frequency behaviors and reduced ejaculation latency, intromission latency, and mount latency parameters, whereas safranal, another compound of saffron spice, did not show these effects (178).
  • Mitomycin CMitomycin C: Based on in vivo evidence, pretreatment with saffron may significantly inhibit the genotoxicity of mitomycin C; while no changes were observed in hepatic glutathione S-transferase (GST) activity of saffron alone, saffron pretreatment attenuated the inhibitory effects of the genotoxins on GST activity (165).
  • Nephrotoxic agentsNephrotoxic agents: Based on animal study, saffron extracts and constituents had antioxidant effects in the kidney and protected against cisplatin-induced acute renal failure (179; 168; 167).
  • Neurologic agentsNeurologic agents: In animal study, a saffron or its constituents prevented inhibition of long-term potentiation in the rat dentate gyrus (130; 131; 132), reduced extracellular hippocampal levels of glutamate and aspartate (180), attenuated cerebral ischemia-induced oxidative damage (181), reduced oxidative injury to cerebral microvessels (182), protected levels of glutathione and dopamine (69), and decreased multiple sclerosis symptoms, increased antioxidant status, and decreased leukocyte infiltration (68; 69).
  • NoradrenalineNoradrenaline: Based on in vitro study, crocetin had protective effects against noradrenaline in primary cultures of cardiac myocytes (183; 184). Protective effects against cardiac hypertrophy were also demonstrated in animal study (185).
  • OpiatesOpiates: Based on animal study, saffron, and its constituent safranal, reduced morphine withdrawal symptoms (67). Based on animal study, crocin increased morphine-induced antinociception (134).
  • PentylenetetrazolPentylenetetrazol: Based on animal study, safranal had protective effects against pentylenetetrazol-induced seizures (172).
  • ScopolamineScopolamine: Based on animal study, crocins and saffron extracts counteracted the delay-dependent recognition memory deficits in the normal rat and attenuated scopolamine-induced performance deficits in the radial water maze test (186; 66).
  • SedativesSedatives: Based on animal study, an alcohol extract of Crocus sativus had sedative effects (187).
  • UrethaneUrethane: Based on in vivo evidence, pretreatment with saffron may significantly inhibit the genotoxicity of urethane; while no changes were observed in hepatic glutathione S-transferase (GST) activity of saffron alone, saffron pretreatment attenuated the inhibitory effects of the genotoxins on GST activity (165).

    • Saffron/Herb/Supplement Interactions:

  • Alzheimer's herbsAlzheimer's herbs: Based on clinical study, saffron extract was as effective as donepezil for Alzheimer's disease (108). Based on in vitro study, trans-crocin-4, the digentibiosyl ester of crocetin, and dimethylcrocetin, inhibited Abeta fibrillogenesis (133).
  • AnalgesicsAnalgesics: Based on animal study, crocin attenuated pain in the formalin-induced pain model (134). In mice, intraperitoneal injection of saffron extracts resulted in antinociceptive activity against acetic acid-induced writhing (135).
  • Antiasthma herbs and supplementsAntiasthma herbs and supplements: Based on in vitro study, a mixture of saffron and seven other herbs inhibited histamine release from stimulated rat peritoneal mast cells (136).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on in vitro and animal evidence, constituents of saffron may both induce and inhibit platelet aggregation (88; 89; 90; 137).
  • Antidepressants, monoamine oxidase inhibitors (MAOIs)Antidepressants, monoamine oxidase inhibitors (MAOIs): Based on human and animal study, saffron had antidepressant effects (110; 111; 112; 113; 138).
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Based on human and animal study, saffron had antidepressant effects (110; 111; 112; 113; 138).
  • AntihistaminesAntihistamines: Based on in vitro study, a mixture of saffron and seven other herbs inhibited histamine release from stimulated rat peritoneal mast cells (136).
  • Anti-inflammatory herbsAnti-inflammatory herbs: Anti-inflammatory effects of crocetin have been shown in various animal models, including experimental colitis and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema (41; 142; 135).
  • AntilipemicsAntilipemics: Based on animal (high-fat) study, saffron and its constituent crocin had hypolipidemic effects (59). Triglycerides and total cholesterol were reduced. In a high-cholesterol-diet animal model, crocin decreased blood total cholesterol, LDL cholesterol, and triglycerides, and increased levels of HDL cholesterol (143).
  • AntineoplasticsAntineoplastics: Based on several in vitro and in vivo studies, saffron and several of its constituents may exert antitumor and cytotoxic properties and inhibit DNA and RNA synthesis (144; 145; 7; 119; 146; 147; 148; 149; 25; 27; 150; 151; 152; 153; 154; 155; 156; 23; 157; 158; 159). Based on in vitro study, saffron may protect against side effects of antineoplastic agents (i.e., daunorubicin) (160; 161; 162; 163).
  • AntioxidantsAntioxidants: Based on in vitro, animal, and human evidence, constituents of saffron may exert antioxidant effects (188; 189; 190; 191; 192; 193).
  • AntitussivesAntitussives: Based on animal evidence, Crocus sativus stigma extracts may reduce the number of coughing episodes (10).
  • AnxiolyticsAnxiolytics: Based on animal study, intraperitoneal saffron aqueous extract had anxiolytic effects (12). Crocins also had anxiolytic effects in animal models (11).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: Based on in vitro evidence, aqueous-ethanol extract from Crocus sativus has shown potent inhibitory effects on the calcium channel of guinea pig heart (164).
  • Fertility agentsFertility agents: Based on human study, saffron improved sperm morphology and motility (115).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Based on animal study, crocetin reduced experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) (41).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Based on animal study, intravenous crocetin had hepatoprotective effects in a hemorrhagic shock model (53). In an aflatoxin B1 hepatotoxicity model, crocetin pretreatment resulted in a decrease in elevations of liver enzymes as well as hepatotoxic lesions (174; 175).
  • Herbs/supplements that lower seizure thresholdHerbs/supplements that lower seizure threshold: Based on animal study, safranal attenuated experimental absence seizures in acute experimental seizure models (170; 171; 172).
  • Hypnotic agentsHypnotic agents: Based on animal study, intraperitoneal saffron aqueous extract had hypnotic effects (12).
  • HypoglycemicsHypoglycemics: Based on animal study, crocetin improved insulin sensitivity (91; 92; 139).
  • HypotensivesHypotensives: Based on animal study, saffron extracts had hypotensive effects in both normotensive and hypertensive rats (140; 141).
  • ImmunostimulantsImmunostimulants: Based on in vitro evidence, a glycoconjugate from saffron corms may promote significant macrophage activation (176). Also in vitro, crocin was an inhibitor of T cell activation (177).
  • ImmunosuppressantsImmunosuppressants: Based on in vitro evidence, a glycoconjugate from saffron corms may promote significant macrophage activation (176). Also in vitro, crocin was an inhibitor of T cell activation (177).
  • Impotence agentsImpotence agents: Based on animal evidence, crocin increased mounting frequency, intromission frequency, and erection frequency behaviors and reduced ejaculation latency, intromission latency, and mount latency parameters, whereas safranal, another compound of saffron spice, did not show these effects (178).
  • Kainic acidKainic acid: In anesthetized rats, safranal reduced extracellular hippocampal levels of glutamate and aspartate in animals treated with kainic acid (a constituent of seaweed) (180).
  • Nephrotoxic agentsNephrotoxic agents: Based on animal study, saffron extracts and constituents had antioxidant effects in the kidney and protected against cisplatin-induced acute renal failure (179; 168; 167).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: In animal study, a saffron or its constituents prevented inhibition of long-term potentiation in the rat dentate gyrus (130; 131; 132), reduced extracellular hippocampal levels of glutamate and aspartate (180), attenuated cerebral ischemia-induced oxidative damage (181), reduced oxidative injury to cerebral microvessels (182), protected levels of glutathione and dopamine and reduced levels of thiobarbituric acid reactive substance (TBARS) (69), and decreased multiple sclerosis symptoms, increased antioxidant status, and decreased leukocyte infiltration (68).
  • SedativesSedatives: Based on animal study, an alcohol extract of Crocus sativus had sedative effects (187).

    • Saffron/Food Interactions:

  • Insufficient available evidence.

    • Saffron/Lab Interactions:

  • Blood glucose and insulin levelsBlood glucose and insulin levels: Based on animal study, crocetin improved the insulin resistance induced by a high-fat diet (91). Also, hepatic non-esterified fatty acid uptake and oxidation were increased, triglyceride clearance in plasma was accelerated, lipoprotein lipase activity in liver was enhanced, and the accumulation of certain lipids were reduced in liver and muscle. Crocetin also improved insulin sensitivity in fructose-fed rats (92). In in vitro study, crocetin prevented advanced glycation end products-induced vascular endothelial cell apoptosis (44). In rat adipocytes in vitro, crocetin attenuated induced insulin insensitivity and disordered tumor necrosis factor-alpha and adiponectin expression (139).
  • Blood lipidsBlood lipids: Based on animal (high-fat) study, saffron and its constituent crocin had hypolipidemic effects (59). Triglycerides and total cholesterol were reduced. In a high-cholesterol-diet animal model, crocin decreased blood total cholesterol, LDL cholesterol, and triglycerides, and increased levels of HDL cholesterol (143).
  • Blood pressureBlood pressure: Based on animal study, an aqueous saffron extract had hypotensive effects in both normotensive and hypertensive rats (140). Based on animal study, an extract of petals from Crocus sativus had hypotensive effects in anesthetized rats (141).
  • Body weightBody weight: Based on animal study, treatment with Crocus sativus extract prevented cisplatin-induced decreases in body weight (166).
  • Clotting panelClotting panel: Based on in vitro and animal evidence, constituents (crocein) of saffron and saffron extract itself may inhibit platelet aggregation (88; 89; 90). Based on in vitro study, bulbs of Crocus sativus var. cartwrightianus contained constituents that both induced and inhibited platelet aggregation (137).
  • HemoglobinHemoglobin: Based on animal study, treatment with Crocus sativus extract prevented cisplatin-induced decreases in hemoglobin levels (166) and effected hemoglobin levels in other animal studies (63).
  • HistamineHistamine: In in vitro study, a mixture of eight herbs (chamomile, saffron, anise, fennel, caraway, licorice, cardamom, and black seed) inhibited histamine release from stimulated rat peritoneal mast cells (136). The effect of saffron is unclear.
  • Leukocyte countsLeukocyte counts: Based on animal study, treatment with Crocus sativus extract prevented cisplatin-induced decreases in leukocyte counts (166) and effected leukocyte counts in other animal studies (63).
  • Liver and kidney statusLiver and kidney status: Based on animal study, a combination of intraperitoneal cysteine, vitamin E, Crocus sativus, and Nigella sativa extracts had a protective effect against cisplatin-induced toxicity in rats (167). Blood urea nitrogen (BUN), serum creatinine levels, and cisplatin-induced serum total lipid increases were reduced and changes in serum activities of alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutathione reductase, isocitrate dehydrogenase, and kidney enzymes (glucose-6-phosphate dehydrogenase, alkaline phosphatase, isocitrate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase, and gamma-glutamyl transferase) were partially prevented. Based on animal study, crocin reduced blood urea, creatinine, urinary glucose and protein (168).
  • Sperm valuesSperm values: Based on human study, saffron improved sperm morphology and motility (115).