
<p>Saffron or<em> ;Crocus sativus</em> ;L. (<em>C.
sativus</em>) has been widely
used as a medicinal plant to promote human health, especially in Asia. The main
components of saffron are crocin, picrocrocin and safranal. Saffron has
been suggested to be effective in the treatment of a wide range of disorders
including coronary artery diseases, hypertension, stomach disorders,
dysmenorrhea and learning and memory impairments. In addition, different
studies have indicated that saffron has anti-inflammatory,
anti-atherosclerotic, antigenotoxic and cytotoxic activities. </p>



<p>Antitussive effects of stigmas and petals of ;<em>C.
sativus</em> ;and its
components, safranal and crocin have also been demonstrated. The anticonvulsant
and anti-Alzheimer properties of saffron extract were shown in human and animal
studies. The efficacy of ;<em>C. sativus</em>in the treatment of
mild to moderate depression was also reported in clinical trial. Administration
of<em> ;C.
sativus</em> ;and its
constituents increased glutamate and dopamine levels in the brain in a
dose-dependent manner. It also interacts with the opioid system to reduce
withdrawal syndrome.</p>
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<p><em>Crocus sativus</em> ;L (<em>C. sativus</em>), commonly known as saffron, is a small perennial plant belonging to the family of Iridaceas. This plant is cultivated in many countries including Iran, Afghanistan, Turkey and Spain (Abdullaev, 1993<a rel="noreferrer noopener" aria-label=" (opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B1" target="_blank"> ;â¶</a>). The stigmas of ;<em>C. sativus</em> ;are known to contain carotenoids, α-crocetin and glycoside crocin (responsible for saffron yellow color) and picrocrocin, the aglyconesafranal (responsible for saffron aroma) (Fernández and Pandalai, 2004<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B33" target="_blank" rel="noreferrer noopener" aria-label=" (opens in a new tab)"> ;â¶</a>; Champalab et al., 2011), the antioxidant carotenoids lycopene and zeaxanthin and vitamin B2(Vijaya Bhargava, 2011).</p>



<h2 class="wp-block-heading"><em><strong>C. sativus</strong></em><strong> ;constituents</strong></h2>



<p>More than 150 compounds have been identified in saffron stigma including colored carotenoids (e.g. crocetin and crocins as glycosidic derivatives), colorless monoterpene aldehydes, volatile agents (e.g. safranal and picrocrocin which are the bitter components), etc. (Bathaie and Mousavi, 2010<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B16" target="_blank" rel="noreferrer noopener" aria-label=" (opens in a new tab)"> ;â¶</a>).</p>



<h2 class="wp-block-heading"><strong>Anticonvulsant
effects</strong></h2>



<p>In Iranian folk medicine, ;<em>C. sativus</em> ;had been used as an anticonvulsant herb (Khosravan, 2002<a rel="noreferrer noopener" aria-label=" (opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B57" target="_blank"> ;â¶</a>). Experimental studies also confirmed saffron anticonvulsant effects in rats and mice (Sunanda et al., 2014<a rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B96" target="_blank">â¶</a>; Khosravan, 2002<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B57"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B57" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>). Saffron at the doses of 400 and 800 mg/kg showed a significant antiepileptic activity in pentylenetetrazole (PTZ)-induced seizure model in a dose-dependent manner. ;</p>



<h2 class="wp-block-heading"><strong>Anti-Alzheimer effects</strong></h2>



<p><em><strong>Clinical studies</strong></em></p>



<p>Administration of saffron 30 mg/day (15 mg twice daily) was found to be as effective as donepezil for treatment of mild-to-moderate AD in the subjects of 55 years and older (Akhondzadeh et al., 2010a<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B8"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B8" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a> ;).</p>



<h2 class="wp-block-heading"><strong>Antidepressant and anti-</strong> ;<strong>schizophrenia</strong> ;<strong>effects</strong></h2>



<p><em><strong>Clinical studies</strong></em></p>



<p>In a randomized and double-blind clinical trial study, saffron supplementation statistically improved the mood of subjects compared to the placebo group. For six weeks, 30 mg/day of saffron was given and subjects were evaluated based on the Hamilton Depression Rating Scale (HAM-D) (Akhondzadeh et al., 2005<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B10"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B10" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<p>Short-term administration of saffron (30 mg/day) capsules for six weeks was also shown to be as effective as fluoxetine (40 mg/day) in improving depression symptoms in patients who were suffering from major depressive disorder (MDD) after undergoing a percutaneous coronary intervention (Shahmansouri et al., 2014<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B92"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B92" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><strong>Anti-Parkinson effects</strong></h2>



<p>Saffron and its components (mainly crocin, crocetin, and safranal) have been used in animal models with neurodegenerative diseases (Ochiai et al., 2007<a rel="noreferrer noopener" aria-label=" (opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B79" target="_blank"> ;â¶</a>; Purushothuman et al., 2013<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B85"> ;</a><a rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B85" target="_blank">â¶</a>). Crocin and safranal have inhibitory effect on fibrillation of apo alpha-lactalbumin (a-alpha-LA), under amyloidogenic conditions which crocin was found to be more effective than safranal. Formation of toxic amyloid structures is related with various neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases (Ebrahim-Habibi et al. 2010<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B28"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B28" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><strong>Effects of ;</strong><em>C. sativus</em> ;<strong>on oxidative damages and
neurotoxicity</strong></h2>



<p>Treatment with saffron extract (5 and 25 mg/ml) and crocin (10 and 50 μM) could decrease the neurotoxic effect of glucose in PC12 cells. The results showed that glucose (13.5 and 27 mg/ml) reduced PC12 cells viability while cell death was reduced by saffron and crocin pretreatment (Mousavi et al., 2010<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B72" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>). ;</p>
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<p>In addition, crocin increased the activity of SOD and glutathione peroxidase (GPx) and remarkably reduced malondialdehyde (MDA) content in the ischemic cortex in rat model of ischemic stroke (Vakili et al., 2013<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B99" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><strong>Effects of ;</strong><em>C. sativus</em> ;<strong>on neuronal injury and
apoptosis</strong></h2>



<p>Crocin (30, 60 and 120 mg/kg) showed protective effect against ischemia/reperfusion injury and cerebral edema in a rat model of stroke and decreased infarct volume. Administration of crocin (60 mg/kg), one hour before, or one hour after the induction of ischemia, reduced brain edema (Vakili et al., 2013<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B99"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B99" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<p>The neuroprotective effects of crocetin in the brain injury in animal studies have been suggested to be related to its ability to inhibit apoptosis at early stages of the injury and its ability to promote angiogenesis at the subacute stage as directed by higher expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and serum response factor (SRF) (Bie et al., 2011<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B20"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B20" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><strong>Effects of ;</strong><em>C. sativus</em> ;<strong>on neuroinflammation</strong></h2>



<p>Crocin inhibited syncytin-1 and nitric oxide (NO)-induced astrocyte and oligodendrocyte cytotoxicity (Christensen, 2005<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B24"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B24" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>) and reduced neuropathology in experimental autoimmune encephalomyelitis (EAE) with significantly less neurological impairments.</p>



<p>Administration of crocin on day 7 post-EAE induction, suppressed ER stress and inflammatory gene expression in the spinal cord and also reduced the expression of ER stress genes ;<em>XBP-1/s</em> ;(Deslauriers et al., 2011<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B26"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B26" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><em><strong>C. sativus</strong></em><strong> ;and the brain neurotransmitters</strong></h2>



<p>Ettehadi et al. (2013)<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B29"> ;</a><a rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B29" target="_blank">â¶</a> ;showed that the aqueous extract of saffron (50, 100, 150 and 250 mg/kg, i.p.) increased brain dopamine concentration in a dose-dependent manner. Moreover, the extract had no effect on brain serotonin or norepinephrine concentration. In addition, the results showed that the aqueous extract of saffron especially at the dose of 250 mg/kg triggered and increased the production of important neurotransmitters including dopamine and glutamate in rat brain (Ettehadi et al., 2013<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B29"> ;</a><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/#B29" target="_blank" rel="noreferrer noopener" aria-label="ⶠ(opens in a new tab)">â¶</a>).</p>



<h2 class="wp-block-heading"><em><strong>C. sativus</strong></em><strong> ;and opioids system</strong></h2>



<p><strong>The effects of ;<em>C. sativus</em> ;on opioid
system</strong></p>



<figure class="wp-block-table"><table><thead><tr><td>
 <strong><em>C.
 Sativus</em></strong><strong>or its constituents</strong>
 </td><td>
 <strong>Dose</strong>
 </td><td>
 <strong>Results</strong>
 </td><td>
 <strong>References</strong>
 </td></tr></thead><tbody><tr><td>
 <strong>Sa</strong> ;<strong>ff</strong> ;<strong>ron</strong>
 </td><td>
 150 and
 450 mg/kg
 </td><td>
 Improved learning and memory impairment induced by morphine
 </td><td>
 Naghibi et
 al., 2012
 </td></tr><tr><td>
 <strong>Sa</strong> ;<strong>ff</strong> ;<strong>ron</strong>
 </td><td>
 Aqueous (80, 160, 320 mg/kg) and ethanolic (400 and 800 mg/kg) extract
 </td><td>
 Reduced
 naloxone precipitated jumping
 </td><td>
 Ghoshooni et al., 2011; shams et al., 2009
 </td></tr><tr><td>
 <strong>Crocin</strong>
 </td><td>
 200 and
 600 mg/kg
 </td><td>
 Reduced withdrawal sign without reducing locomotor activity
 </td><td>
 Amin and
 hosseinzadeh 2012
 </td></tr><tr><td>
 <strong><em>C. sativus</em></strong><strong>stigma</strong>
 </td><td>
 Alcohol extract (5 and 10 µg/rat)
 </td><td>
 Decrease in the time spent in drug paired side
 </td><td>
 Ghoshooni
 et al., 2011
 </td></tr><tr><td>
 <strong>Crocin</strong>
 </td><td>
 400 and
 600 mg/kg
 </td><td>
 Decreased the acquisition and reinstatement of morphine-induced cpp
 </td></tr><tr><td>
 <strong>Saffron</strong>
 </td><td>
 10, 50 and
 100 mg/kg
 </td><td>
 Reduced the acquisition and expression of morphine cpp
 </td></tr><tr><td>
 <strong>Safranal</strong>
 </td><td>
 1, 5 and
 10 mg/kg
 </td><td>
 Reduced the acquisition and expression of morphine cpp
 </td></tr><tr><td>
 <strong>Saffron</strong>
 </td><td>
 50, 100,
 150 and 250mg/kg
 </td><td>
 Increased the release of dopamine in rat brains and increased the release
 of glutamate only in dose 250
 </td><td>
 Ettehadi
 et al., 2013
 </td></tr></tbody></table></figure>



<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/table/T3/" target="_blank" rel="noreferrer noopener" aria-label=" (opens in a new tab)">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/table/T3/</a></p>



<h2 class="wp-block-heading"><strong>Conclusion</strong></h2>



<p>Anti-oxidant and anti-inflammatory effects of the
extracts of ;<em>C. sativus</em> ;and its constituents (crocetin,
crocins, safranal) implies saffron therapeutic potential for various nervous
system disorders.</p>



<p>Based on the literature, beneficial effects of the
plant and its components on neurodegenerative disorders such as Alzheimer and
Parkinson&#8217;s disease are mainly due to their interactions with cholinergic,
dopaminergic and glutamatergic systems. It is assumed that saffron
anticonvulsant and analgesic properties and its effects on morphine withdrawal
and rewarding properties of morphine might be due to an interaction between
saffron, GABA and opioid system.</p>



<p>According to human and animal
studies, saffron and its constituents have been shown to be effective in the treatment
of mild to moderate depression which may be because of an interaction with the
serotonin and noradrenaline system. However, to have a detailed perspective of
saffron effects on nervous system, more mechanistic investigations are highly
advised.
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<p>Research Source: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/">http</a><a rel="noreferrer noopener" aria-label="s://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/ (opens in a new tab)" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599112/" target="_blank">s://www.ncbi.nlm.nih.gov/</a>
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