- •Potential beneficial effect of saffron on AD patients.
- •Trans-crocetin induces amyloid-β(1–42) degradation in monocytes from AD patients.
- •Trans-crocetin enhances cathepsin B levels on cultured monocytes from AD patients.
Herbal medicines have been recently employed in research and clinical studies for the potential treatment of behavioral and psychological symptoms associated with Alzheimer's Disease (AD) and other types of dementia. The present study investigates the effect of trans-crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability of AD patients' monocytes to degrade amyloid-β(1–42) (Aβ42). CD14+ monocytes from 22 sporadic AD patients with moderate cognitive impairment were isolated; then, the role of trans-crocetin, purified from saffron extracts, was evaluated in terms of Aβ42 degradation rate through flow cytometry, as well as expression of cathepsin B by Western blotting. We observed that low micromolar doses of trans-crocetin enhanced Aβ42 degradation in AD monocytes through the upregulation of the lysosomal protease cathepsin B. CA074Me, a potent and selective cathepsin B inhibitor, counteracted such trans-crocetin-induced effect. These data suggest that the carotenoid trans-crocetin improves in vitro the clearance of Aβ42 through the involvement of cathepsin B, and this could be of value in developing a new anti-amyloid strategy in AD.
Abbreviations:AD (Alzheimer's Disease), Aβ42 (amyloid-β (1–42)), CatB (cathepsin B), SAD (sporadic form of Alzheimer's Disease)
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of the Neurological Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.Science. 2002; 297: 353-356
- Decreased clearance of CNS β-amyloid in Alzheimer's disease.Science. 2010; 330: 1774
- Are circulating monocytes as microglia orthologues appropriate biomarker targets for neuronal diseases?.Cent. Nerv. Syst. Agents Med. Chem. 2009; 9: 307-330
- Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells.Proc. Natl. Acad. Sci. U. S. A. 2012; 109: 18150-18155
- Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease.Neuron. 2006; 49: 489-502
- miR128 up-regulation correlates with impaired amyloid-β42 degradation in monocytes from sporadic Alzheimer's disease patients.Neurobiol. Aging. 2014; 35: 345-356
- Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease.Neuron. 2006; 51: 703-714
- Cystatin C-cathepsin B axis regulates amyloid-β levels and associated neuronal deficits in an animal model of Alzheimer's disease.Neuron. 2008; 60: 247-257
- Mechanism mediating oligomeric Aβ clearance by naïve primary microglia.Neurobiol. Dis. 2011; 42: 221-230
- Higher cathepsin B levels in plasma in Alzheimer's disease compared to healthy controls.J. Alzheimers Dis. 2010; 22: 1223-1230
- Chronic inflammatory disorders and their redox control: from molecular mechanisms to therapeutic opportunities.Antioxid. Redox Signal. 2011; 15: 2605-2641
- Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection.Behav. Brain Res. 2011; 219: 197-204
- Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders.Phytother. Res. 2003; 17: 1-18
- Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers.Phytother. Res. 2014; 28: 539-543
- Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers.Iran. J. Basic Med. Sci. 2013; 16: 39-46
- Inhibitory activity on amyloid-β aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents.J. Agric. Food Chem. 2006; 54: 8762-8768
- Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.J. Clin. Pharm. Ther. 2010; 35: 581-588
- A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.Psychopharmacology. 2010; 207: 637-664
- Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment.Food Chem. Toxicol. 2013; 52: 163-170
- Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease.Neurology. 1984; 34: 939-944
- “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.J. Psychiatr. Res. 1975; 12: 189-198
- Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type.Int. Psychogeriatr. 1997; 9: 173-176
- Validity of the clinical dementia rating scale for the detection and staging of dementia in Brazilian patients.Alzheimer Dis. Assoc. Disord. 2007; 21: 210-217
- Effective isolation protocol for secondary metabolites from saffron: semi-preparative scale preparation of crocin-1 and trans-crocetin.Fitoterapia. 2014; 92: 290-295
- The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells.Int. Immunol. 2015; 3: 153-160
- CA-074Me, a cathepsin B inhibitor, decreases APP accumulation and protects primary rat cortical neurons treated with okadaic acid.Neurosci. Lett. 2013; 548: 222-227
- Lysosomal β-galactosidase and β-hexosaminidase activities correlate with clinical stages of dementia associated with Alzheimer's disease and type 2 diabetes mellitus.J. Alzheimers Dis. 2011; 24: 785-797
- The protective effects of crocetin on aβ1-42-induced toxicity in Ht22 cells.CNS Neurol. Disord. Drug Targets. 2014; 13: 1627-1632
- Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.Eur. J. Pharmacol. 2011; 650: 110-119
- Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro.Cancer Lett. 1996; 100: 23-30
- Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma.Hepatology. 2011; 54: 857-867
- Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells.Oncol. Lett. 2015; 9: 1254-1260
- Crocetin from saffron: an active component of an ancient spice.Crit. Rev. Food Sci. Nutr. 2004; 44: 155-172
- Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.Invest. Ophthalmol. Vis. Sci. 2010; 51: 6118-6124
- Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina.Mol. Vis. 2010; 16: 1801-1822
- Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.Eur. J. Pharmacol. 2010; 648: 110-116
- Inhibitors of cathepsin B improve memory and reduce β-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, β-secretase site of the amyloid precursor protein.J. Biol. Chem. 2008; 283: 7745-7753
- Cysteine cathepsins in the secretory vesicle produce active peptides: cathepsin L generates peptide neurotransmitters and cathepsin B produces β-amyloid of Alzheimer's disease.Biochim. Biophys. Acta. 2012; 1824: 89-104
Published online: November 06, 2016
Accepted: November 3, 2016
Received in revised form: October 18, 2016
Received: May 1, 2016
© 2016 Elsevier B.V. All rights reserved.