Crocin as a Neuroprotective Agent Against Stroke

Stroke is the fourth leading cause of death in the United States and the most common cause of disability for humans. Both blocked arteries (ischemic stroke) and bursting blood vessels (hemorrhagic stroke) can cause injury and death of brain cells. Prevention and immediate treatments can help mitigate brain injuries and recovery from stroke.

The neuroprotective effects of crocin against stroke is the focus of this blog article. Crocin, the only water-soluble carotenoid in nature and main active constituent of saffron (Crocus sativus L.), has potent antioxidant and anti-inflammation properties, and it has shown promising preventive and therapeutic effects on patients with stroke.

Highlights:

  • A recent clinical study demonstrated the short and long-term neuroprotective effects of aqueous extract of saffron containing 20% of crocin on ischemic stroke patients.
  • A number of studies have demonstrated that crocin provides neuroprotective, antioxidative, anti-inflammatory, edema suppressive, and brain injury protective effects in animal ischemia-reperfusion and hemorrhage models.

Recently, a clinical study using an aqueous extract of saffron with 20% of crocin for treatment of patients with acute ischemic stroke was reported in the Journal of Ethnopharmacology (2019, 238: 111833.)1. Patients who have had acute ischemic stroke were recruited at a hospital emergency unit and randomly allocated to receive either routine stroke care or routine care plus aqueous extract of saffron capsules. Both groups were treated and monitored during their four-day hospital stay and a three-month follow-up period. The saffron-treated group received eight aqueous extract of saffron capsules (total 80mg crocin) per day during the four days of hospitalization and four capsules (40mg crocin) per day after discharge until three months after the stroke. The short- and long-term effects of saffron (crocin) capsules were compared in the two groups using two clinical assessments (the National Institute of Health Stoke Scale (NIHSS) and Barthel Scale) and three biomarker analysis (serum neuron specific enolase (NSE), brain-derived neurotrophic factor (BDNF), S100 protein). NSE and S100 serve as markers of neuronal damage and glial injuries and are used for predicting the severity and prognosis of ischemic stroke. BDNF supports neuronal regeneration, development, survival, and neuroplasticity. BDNF is particularly formed in certain brain regions that are implicated in the control of memory, cognition, emotion and behaviors. BDNF measurements serve as good benchmark for diagnosis, prognosis and monitoring of the treatment of various diseases of the nervous system. Study results shown:

  • Short term: NIHSS assessment of severity of stroke and functional impairments during the first four days was significantly lower in the saffron-treated group than in the control group (P < 0.05).
  • Long term: At the end of the three-month follow-up period, the assessment of one's ability to perform activities of daily living by Barthel index was significantly higher in the saffron-treated group than in the control group (P < 0.001).
  • Higher BDNF and lower NSE and S100 levels in saffron treated than non-treated stroke patients in the acute period confirmed better neurological recovery and neuroprotection.

Ischemic and hemorrhagic strokes as well as traumatic brain injury lead to brain damages by similar mechanisms including, among others, increased cortical infarct volume and striatal infarct volume, inflammation, overproduction of oxidative radicals and toxins, disruption of microvessels and blood brain barrier, and brain cell death. The neuroprotective effects of crocin against both cerebral Ischemic and hemorrhagic injuries were also demonstrated in over a dozen of animal studies2-12. Findings from these studies indicate that crocin has multiple effects including improving memory and cognition, anti-inflammation properties, suppressing edema, inhibiting production of oxidative radicals and toxins, maintaining integrity of microvessels and blood brain barrier, and protecting brain cells.

In conclusion, crocin as a natural neuroprotective agent could help reduce risk of stroke and improve recovery.

 

Reference

  1. Asadollahi M, et al. (2019) Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial. J Ethnopharmacol. 2019 Jun 28; 238:111833. doi: 10.1016/j.jep.2019.111833. Epub 2019 Mar 23.
  2. Duan Z, et al. (2019) Crocin attenuation of neurological deficits in a mouse model of intracerebral hemorrhage. Brain Research Bulletin. 2019, 150: 186-195.
  3. Zheng YQ et al. (2007) Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 2007; 1138: 86−94.
  4. Hosseinzadeh H, et al. (2012) Effects of Saffron (Crocus sativus L.) and its Active Constituent, Crocin, on Recognition and Spatial Memory after Chronic Cerebral Hypoperfusion in Rats. Phytotherap Res. 2012, 26(3): 381-386.
  5. Sarshoori JR, et al. (2014) Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat. J. Basic Med. Sci. 2014; 17: 895−902.
  6. Vakili A, et al. (2014) Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke. Stroke Cerebrovasc. 2014; 23: 106-113.
  7. Oruc S, et al. (2016) The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats. Life Sci. 2016; 154: 79-86.
  8. Zhang X, et al. (2017) Crocin protects against cerebral-ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier. Restorative Neurology and Neuroscience, 2017, 35(1): 65-75.
  9. Zhang Y, et al. (2019) Orally Administered Crocin Protects Against Cerebral Ischemia/Reperfusion Injury Through the Metabolic Transformation of Crocetin by Gut Microbiota. Pharmacol., 30 April 2019 | https://doi.org/10.3389/fphar.2019.00440.
  10. Huang Z, et al (2019) Crocin induces anti-ischemia in middle cerebral artery occlusion rats and inhibits autophagy by regulating the mammalian target of rapamycin. Euro J of Pharm, 2019, 857, 172424.
  11. Huang A & Jia L. (2019) Crocin enhances hypothermia therapy in hypoxic ischemia-induced brain injury in mice. Acta Neurol Belg. 2019, doi:10.1007/s13760-019-01198-0
  12. Wang K, et al. (2015) Neuroprotective effects of crocin against traumatic brain injury in mice: involvement of notch signaling pathway. Lett. 2015; 591: 53−58.

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