Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-d-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.
Aim of the Research | Type of Study | No. of Patients | Treatment | Time of Treatment (Weeks) | Results | References |
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Comparison of saffron and imipramine | Double-blind, randomized trial | 30 | Stigma of saffron, 30 mg/day | 6 | The effect of stigma of saffron was similar to imipramine in the treatment of mild to moderate depression. | [86] |
Hydro-alcoholic extract of saffron versus fluoxetine | Double-blind, randomized pilot trial | 40 | Stigma of saffron, 30 mg/day | 6 | The effect of stigma of saffron was similar to fluoxetine in the treatment of mild to moderate depression. | [85] |
Saffron (petal) in the treatment of mild to moderate depression | Double-blind, randomized, and placebo-controlled trial | 40 | Petal of saffron, 30 mg/day | 6 | The outcome on the HAM-D showed that the petal of saffron could produce a significantly better effect than the placebo. | [109] |
Comparison of petal of saffron and fluoxetine | Double-blind, randomized trial | 40 | Petal of saffron, 15 mg/day (morning and evening) | 8 | Petal of saffron was found to be similarly effective to fluoxetine in the treatment of mild to moderate depression. | [87,110] |
40 and 80 mg HAE of saffron against fluoxetine | Double-blind, randomized, clinical trial | 60 | Saffron, 40 and 80 mg/day + fluoxetine (30 mg) | 6 | Effective in treatment of mild to moderate depressive disorders. | [88,111] |
Saffron with fluoxetine in PCI patients | Double-blind, randomized, clinical trial | 40 | Saffron (30mg/day) | 6 | Effective as fluoxetine (40 mg/day) in improving depressive symptoms of patients who were suffering from major depressive disorder (MDD). | [112] |
Saffron and crocin in improving mental and sexual health in CAD patients | Double-blind, placebo-controlled, randomized, clinical trial | 58 | Stigma of saffron, 30 mg/day OR | 8 | The outcome of BDI-II scores significantly decreased after 8 weeks of intervention. | [113] |
Saffron in the treatment of PMS | Double-blind, randomized, and placebo-controlled trial | 50 | 30 mg, saffron petal during pre-menstrual syndrome | 8 | The depression measured significantly decreased. | [114] |
Saffron versus citalopram in the major depressive disorder with anxious distress | Double-blind, controlled, clinical trial | 66 | 30 mg, saffron stigma | 6 | Effective against moderate to major depression. | [107] |
Saffron as an add-on therapy to sertraline in mild to moderate generalized anxiety disorder | Double-blind, randomized, controlled trial | 40 | 500-mg capsule containing 450 mg of saffron (type not recorded) | 6 | Decreased mild to moderate generalized anxiety disorder with saffron as well as with sertraline. | [108] |
Crocin on depression in subjects with metabolic syndrome | Randomized, double-blind, controlled, clinical trial | 33 | 30 mg, saffron (crocin) | 8 | Decreased depressive symptoms in patients with metabolic syndrome. | [115] |
Saffron improved depression and reduced homocysteine level in patients with major depression | Randomized, double-blind study | 40 | 30 mg, saffron (stigma) and 20 mg, fluoxetine | 4 | The BDI score decreased in patients with major depression. | [116] |
Comparison of saffron versus fluoxetine in treatment of mild to moderate post-partum depression | Double-blind, randomized, clinical trial | 60 | 30 mg, saffron (stigma) | 6 | Significantly decreased mild to moderate depression and post-menopausal hot flashes. | [110] |
Affron®, a standardized extract from saffron | Randomised, double-blind, placebo-controlled study | 80 | 14 mg, saffron (stigma) | 8 | Significant reduction in mild to moderate depression. | [117] |
Saffron in the treatment of anxiety and depression | Double-blind, randomized, and placebo- controlled trial | 60 | 100 mg, saffron (stigma) | 12 | Significant decrease in mild to moderate depression. | [118] |
Saffron (petal) in the treatment of mild to moderate depression | Double-blind, randomized, and placebo-controlled trial | 36 | 30 mg, saffron (stigma) and 40 mg, fluoxetine | 4 | No significant decrease. | [119] |
Effects of saffron on depression and lipid profile | Double-blind comparative study | 40 | 30 mg, saffron (petal) | 6 | Decrease in major depression of those who met DSM-IV criteria. | [109] |
Saffron stigma in mothers suffering from mild to moderate post-partum depression | Double-blind, randomized, placebo-controlled trial | 40 | 30 mg, saffron (type not recorded) and 20 mg, fluoxetine | 4 | Significant decrease in major depression. | [120] |
Crocin in major depressive disorder | Randomized, double-blind, placebo-controlled, pilot clinical trial | 78 | 30 mg, saffron (stigma) | 8 | Significant decrease in mild to moderate depression. | [111] |
Crocin on psychological parameters in patients under MMT | Randomized clinical trial | 46 | 30 mg, saffron (crocin) and 20 mg, fluoxetine | 4 | Significant decrease in major depression. | [121] |
Crocin on psychological parameters in patients under MMT | Randomized, double-blind, placebo-controlled trial | 50 | 30 mg per day, saffron (crocin) | 8 | Improved depression symptoms during methadone maintenance treatment (MMT). | [122] |
Double-blind, randomized, and placebo- controlled trial | 28 | 150 mg per day, saffron | 6 | Increased serotonin and happiness were further heightened in supplemented group. Anandamide, dopamine, and β-endorphin were significantly increased under suplementeation, whereas placebo remained unchanged. |
[123] |
Matrix | Results | Reference |
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Chitosan-alginate nanoparticles | Highest crocin loading achieved at pH 1.2 with a biphasic release in simulated gastric fluids. The loaded nanoparticles were equivalent in DPPH free radical scavenging and ferric-reducing ability of plasma as free crocin and exhibited an anti-cancer effect. | [128] |
Maltodextrin nanoencapsulates | Nanoencapsulated crocin was more stable at simulated gastrointestinal conditions. While encapsulation increased bioaccessibility (from 61% to 72%), the combination of caffeic acid with encapsulation increased the bioaccessibility to almost 80%. | [129] |
Maltodextrin/pectin/whey protein concentrate nanoencapsulates | Combinations of whey protein concentrate and pectin yielded the highest crocin encapsulation efficiencies, exceeding 95%. Thus, minimal amounts of crocins were exposed at the particles’ surfaces. Furthermore, an improved stability against stressors was suggested. | [130] |
Chitosan-gum arabic nanoencapsulates | Crocin was encapsulated with an efficiency of 29 to 52%. The release profiles showed an oscillatory relationship with time at pH 1 and 2. This oscillatory relation was suggested to be a result of rapid degradation of released crocin. | [131] |
Cholesterol-Tween 40 nanoniosomes | Encapsulation efficiency was 46%, and 61% of crocin was released after 6 h in mice. Intra-arterially injected crocin-laden niosomes decreased ischemic indicator molecules in rats and mitigated I/R tissue damages. | [132] |
Bacterial nanocellulose membrane | The nanocellulose membrane exhibited a stable and prolonged transdermal release through mice skin in a Franz diffusion cell. | [133] |
Chitosan-alginate | An encapsulation efficiency of 92% was attained. The resulting nanoparticles stabilized crocin degradation at pH 2, enhanced bioavailability, and showed a pH-mediated release. | [134] |
Solid lipid nanoparticles | Increased stability, high encapsulation efficiency. | [135] |
Selenium nanoparticles | Crocin release rate was pH dependant, with 91% released after 48 h at pH 5.3, whereas just a mere 35% was released at pH 7.4 during the same time. The administration of loaded nanoparticles resulted in enhanced cytotoxicity in lung cancer cells and inhibited tumor growth in a mice model. | [136] |
Poly(lactic-co-glycolic acid) nanoparticles | Entrapment efficiency reached 59%, and 78% of crocin was released after 24 h at pH 7.4, sustaining release throughout 48 h. Release was increased at pH 6.5 to 84% after 24 h. | [137] |
This entry is adapted from the peer-reviewed paper 10.3390/molecules27072076