Saffron: The Age-Old Panacea in a New Light

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Saffron: The Age-Old Panacea in a New Light
Copyright
List of Contributors
Foreword
Preface
Acknowledgment
Part I: Introduction
1. Amelioration of Liver Ailments by Saffron (Crocus sativus) and Its Secondary Metabolites
	Introduction
		Cellular Structure of the Liver
		Physiology of the Liver
	Effect of Saffron on Liver
		Antioxidant Activity
			Saffron extract and crocin reduce MDA and glutathione S-transferase in STZ-induced diabetic rats
		Hepatoprotective Activity of Saffron
			Saffron protects susceptible aged liver
			Crocin alleviates hemorrhagic shock–induced organ damages
			Crocin protects the liver from ischemia-reperfusion (IR) injury
			Crocin protects the liver by preventing proteolysis and subcellular organelle damage and apoptosis
			Saffron reduces toxicity in the liver
			Crocin ameliorates biochemical alterations due to iron overload in the liver
			Crocin reduces 5-fluorouracil–induced liver toxicity and injury
			Crocin protects the liver from CCl4-induced liver injury
			Crocin removes acrylamide-induced liver damages
			Crocin provides partial protection from nicotine-induced toxicity
			Crocin reduces morphine-induced liver damage
			Saffron and honey provide protection to the liver from aluminum chloride–induced injury
			Crocin relieved cisplatin-induced hepatic damage
		Anticancer Activity of Saffron on the Liver
			Crocin averts early lesions in liver cancer
			Crocin inhibits STAT3 activation induced by IL-6
			Crocin inhibits telomerase activity and downregulates Human telomerase reverse transcriptase (hTERT)
			Aqueous extract of saffron reduces nitric oxide production and has antitumour effect on HepG2 and Hep2 cell lines
			Magnetite nanoparticles coated with crocin enhances liver cancer treatment
		Genoprotective Property of Saffron in the Liver
		Saffron's Activity on Fatty Liver
	Conclusion and Future Perspective
	References
2. Ethnomedicinal and Traditional Usage of Saffron (Crocus sativus L.) in Turkey
	Introduction
	Saffron in Turkish History
	Saffron in Anatolia
		Traditional Usage of Saffron in Turkey
			Saffron in traditional Turkish Cuisine
			Saffron in traditional Turkish sweets
			Saffron in traditional Turkish sherbet, beverages, and herbal tea
			Saffron in dyeing
			Usage of saffron in producing fragrance, cologne, perfumery, and cosmetic products
			Saffron in Turkish literature (text, poetry, and folk riddles)
		Ethnomedicinal Usage of Saffron in Turkey
	References
Part II: Cultivation
3. Saffron (Crocus sativus L.) Cultivation in Turkey
	Saffron Sowing
	Climate and Average Monthly Weather in Safranbolu (Black Sea Region Turkey)
	Storage
	Planting Depth and Spacing
	Saffron Cultivation in Other Areas of Turkey
	Weather and Climate
	Future Prospects
		Possible Solutions
	References
4. Ex Vitro Macropropagation of Saffron (Crocus sativus L.) Corms
	Introduction
	Methods of Saffron Multiplication
	Natural Conditions
	Hybridization and Seed Multiplications
	Cultivated Conditions
		In Vitro Conditions
		Ex vitro Conditions
	Conclusions
	References
5. Molecular Approaches to Determine Phylogeny in Saffron
	Introduction
	Origin of Saffron
	Autoploidy and Alloploidy Situation in Saffron
		Variation Level in Saffron
	Saffron Genetic Variation
	Conclusion
	References
Part III: Biosynthesis and Phytochemistry
6. Saffron (Crocus sativus L.): Its Aroma and Key Odorants
	Introduction
	Extraction Methods for Volatile Compounds of Saffron
	Representativeness of the Aromatic Extract for Olfactometric Analysis
	Key Odorants of Saffron
	Conclusions
	References
7. Biosynthesis and Derivatization of the Major Phytoconstituents of Saffron
	Introduction
	Phytochemical Constituents of Saffron
		Carotenoids
			Crocins
			Crocetin
		Monoterpene Glycoside
		Monoterpene Aldehyde
	Biosynthesis of Crocin, Picrocrocin, and Safranal
	Derivatives of Crocetin and Safranal
		Derivatives of Crocetin
		Derivative of Safranal
	Conclusion
	References
8. Saffron as a Neuroprotective Agent
	Introduction
	In Vitro Neuroprotective Functions of Saffron
		Saffron Extract Crocin Prevents Oxidative Stress and PC-12 Cell Apoptosis by Increasing Intracellular Antioxidant Glutathio ...
	Neuroprotective Activity of Crocin in In Vivo
		Crocin Reduces the Infarcted Areas Caused by Occultation of the Middle Cerebral Artery in Mice Brian
		Neuroprotective Effects of Saffron Extract on Neurodegenerative Disorders
		Saffron Extract Crocin Improves Learning and Memory Capacity
		Saffron Promotes Neurogenesis through Regulation of Sleep
	Conclusion
	References
Part IV: Role of Saffron on Diseases
Part IV-A: Nervous System
9. Saffron and Neurological Disorders
	Background
	Neuroprotective Impact
		Impact of Crocus sativus and Its Main Components on Oxidative Stress-Induced Neurotoxicity
		Impact of Crocus sativus and IIts Main Components on Apoptosis-Induced Neurotoxicity
		Impact of Crocus sativus and Its Main Components on Inflammation-nduced Neurotoxicity
		Impact of Crocus sativus and Its Main Components on Neurotransmitters
		Impact of Crocus sativus and Its Main Components on Opioids System
		Alzheimer's Disease
		Parkinson's Disease
		Anxiety and Depression
		Epilepsy
		Encephalomyelitis
		Schizophrenia
		Ischemia
		Traumatic Injury
			Brain injury
			Spinal injury
	References
	Further Reading
10. Therapeutic Benefits of Saffron in Brain Diseases: New Lights on Possible Pharmacological Mechanisms
	Introduction
	Role of Saffron in the Treatment of Brain Conditions
	Possible Mechanism of Action for Modulatory Effects of Saffron and its Actives
		Nuclear Factor-κB (NF-κB) Signalling
		B-Cell Lymphoma (Bax) and B-Cell Lymphoma–Associated X Protein (Bcl-2) Regulation
		C-Fos Protein Regulation
		p53 Signaling Pathway
		Kelch-like ECH-Associated Protein 1 (Keap1)–Nuclear Factor Erythroid-Derived two like 2 (Nrf2) Signaling
		CCA AT-Enhancer–Binding Protein Homologous Protein (CHOP)/Wnt/β-Catenin (Wnt) Pathway
		MAPK Pathway
		PI3K Signaling
		Notch Signaling Pathway
		GRK Pathway
		cAMP Response Element-Binding Protein (CREB)
		Brain-Derived Neurotrophic Factor
		VGF Nerve Growth Factor Inducible
		Glutamate Signaling
		GABAergic Benzodiazepine Receptor Regulation
		Serotonergic Signaling
		Dopaminergic Signaling
		Acetyl-Cholinergic Signaling
		Hypothalamo-Pituitary-Adrenocortical (HPA) Axis
		Amyloid-β
	Conclusion
	References
11. Assessment of Crocus sativus L., and Its Bioactive Constituents as Potential Anti-Anxiety Compounds. Basic and Clinical Evi ...
	Introduction
		Anxiety
		C. sativus
			The chemical profile of C. sativus
			Pharmacological profile of C. sativus and its constituents
				Effects of C. sativus and its constituents on nonneurological/neuropsychiatric pathologies
				Effects of C. sativus and its constituents on nonneurological/neuropsychiatric pathologies
				Effects of C. sativus and its constituents on pathologies of the central nervous system
				Effects of C. sativus and its constituents on pathologies of the central nervous system
				Safety studies
				Safety studies
	Effects of C. Sativus and its Constituents on anxiety
		Preclinical Evidence
		Clinical Evidence
		Potential mechanism(s) of Action of C. sativus and its Constituents in anxiety Disorders
	Conclusions and Future Plans
	References
Part IV-B: Cardiovascular System
12. Protecting Mechanisms of Saffron Extract Against Doxorubicin Toxicity in Ischemic Heart
	Introduction
	Materials and Methods
		Preparation of Saffron Extract
		HPLC Analysis
		Determination of Total Polyphenols
		Experimental Protocol for Cultured Cardiomyocytes
		Experimental Protocol for Chronic Administration of DOX and Saffron in Rabbits
	Results
		Effect of Saffron Extracts on DOX Toxicity in Hypoxic H9c2 Cells
		Saffron Extract Effects on Phosphorylation of AKT, 4EBP1, ERK, and P38 in H9c2 Cells
		Animal Observation
		Cardiodynamic Parameters
		Electrophysiological Parameters
		Biochemical Parameters
	Discussion
	References
	Further Reading
Part IV-C: Eye
13. Beneficial Effects of Saffron (Crocus sativus L.) in Ocular Diseases
	Introduction
	Chemical Profile of Saffron
		Carotenoids of Saffron
	Ocular Diseases
		Glaucoma
		Age-Related Macular Degeneration
		Treatment of AMD
	Saffron Carotenoids for the Treatment of Glaucoma and AMD
		Clinical Trials for Ocular Diseases with Saffron
	Conclusion
	References
14. Saffron Shifts the Degenerative and Inflammatory Phenotype in Photoreceptor Degeneration
	Saffron Chemistry
	Photoreceptors
		Oxidative Damage in Acquired and Inherited Photoreceptor Degenerations
		Saffron (Crocus sativus Extract) Neuroprotection
		Cell Cultures (Retinal Pigment Epithelial RPE)
	Muller Cells and Microglia in Degenerating Retina
		Saffron Fractions
	Behavioral Evaluation of Animal Distress
	Ratio Among Saffron Components Determines Neuroprotective Efficacy
	Clinical Trials: AMD and Stargardt
		Age-Related Macular Degeneration
		Stargardt
	Conclusions
	References
Part IV-D: Immune System
15. Saffron—Immunity System
	Introduction
	Phytochemistry
	Pharmacology
	Antiinflammatory and Antioxidative Properties
	Antioxidative Properties
		Superoxide Dismutase
		Catalase
		Glutathione Levels
		Ascorbate
		Glutathione Reductase
		Glutathione Peroxidase
	Modulation of Antioxidant Systems by Saffron Extracts
	Antimicrobial Activity
	Antinociceptive Activity
	Conclusion and Future Aspects
	References
16. The Effects of Saffron (Crocus sativus) and its Constituents on Immune System: Experimental and Clinical Evidence
	Introduction
	The Effect of Saffron (Crocus sativus) and its Constituents on Humoral and Cell-Mediated Immunity
		Humoral Immunity (Immunoglobulins/Antibody Titer)
			Experimental studies
			Clinical studies
		Cell-Mediated Immunity (Phagocytic Activity)
			Saffron extracts
			Crocin and crocetin
	The Effect of Saffron (Crocus sativus) and its Constituents on WBC and Platelets
		Saffron Extracts
		Crocin
	The Effect of Saffron (Crocus sativus) and its Constituents on Th1, Th2, and Th17 Responses
		Saffron Extracts
			In vivo studies
			In vitro studies
		Safranal
			In vivo studies
			In vitro studies
		Crocin
			In vivo studies
			In vitro studies
		Crocetin
			In vivo studies
			In vivo studies
	The Effect of Saffron (Crocus sativus) and its Constituents on Immunoregulatory Proteins
		Saffron Extracts
			In vivo studies
		Safranal
			In vivo studies
		Crocin
			In vivo studies
			In vitro studies
		Crocetin
			In vivo studies
	The Effect of Saffron (Crocus sativus) and its Constituents on Oxidative Stress
		Saffron Extracts
			In vivo studies
			In vitro studies
		Safranal
			In vivo studies
			In vitro studies
		Crocin
			In vivo studies
			In vitro studies
		Crocetin
			In vivo studies
			In vitro studies
	Clinical Applications of the Effect of Saffron (Crocus sativus) and its Constituents on Immune System
	Conclusion
	References
Part IV-E: Locomotor System
17. Crocus sativus L. (Saffron) and Its Components Relaxant Effect on Smooth Muscles and Clinical Applications of This Effect
	Introduction
	Method
	Saffron and Its Components Relaxant Effect on Smooth Muscles
		Saffron and Its Components Relaxant Effect on Tracheal Smooth Muscle
		Saffron and Its Components Relaxant Effect on Vascular Smooth Muscle
		Saffron and Its Components Relaxant Effect on GI and Urogenital Smooth Muscle
	Mechanisms Responsible for the Relaxant Effect of Saffron and Its Components on Smooth Muscles
		β2-Adrenoreceptors Stimulatory Effect of Saffron and Its Components
		Muscarinic Receptor Blocking Effects of Saffron and Its Components
		Histaminic Antagonistic Activity of Saffron and Its Components
		Calcium Channel Antagonist Activity of Saffron and Its Components
		EDR Effect of Saffron and Its Components
		Intracellular cAMP Effects of Saffron and Its Components
	Clinical Applications of Saffron and Its Components Relaxant Effect on Smooth Muscles
		Cardiovascular System
		Respiratory System
		GI Tract
		Urogenital Tracts
	Conclusion
	References
Part IV-F: Cancer
18. Medicinal Properties of Saffron With Special Reference to Cancer—A Review of Preclinical Studies
	Introduction
	Saffron and Metabolic Syndrome
	Saffron and Antidiabetic Agent
	Saffron and Antioxidant Property
	Saffron and Neuropharmacology Effect
		Cognitive Deficits
		Anticonvulsant Effects
		Antidepressant
		Learning Memory Effect
	Saffron and Antimicrobial Effect
	Saffron and Immunomodulatory Effect
	Saffron and Respiratory Disorder
	Saffron and Anticancer Properties
	Other Applications
	Perspective on Clinical Trial
	Conclusion
	References
19. The Remarkable Pharmacological Efficacy of Saffron Spice via Antioxidant, Immunomodulatory, and Antitumor Activities
	Introduction
	Chemoprevention
	Free Radicals and Antioxidants
		Antioxidant Activity
	Immunomodulation Activity
	Antitumor Activity
	Significance of Saffron (Crocus sativus L.) Spice
	PHYTOCHEMISTRY of Saffron (C. sativus L.)
		Carotenoids as Anti-Oxidative Damage Modifier
	PHARMACOLOGICAL and Biological Activities of Saffron (C. sativus L.)
		Potential of Dietary Crocin the Marker Compound in Saffron (C. sativus L.) Against Different Malignancies
	Hindering Impacts of Saffron
	Conclusion
	References
	Further Reading
20. Role of Crocus sativus L. in the Modern Green Anticancer Approach
	Introduction
	Chemical Composition of Saffron
	Chemoprevention
	Gastric Cancer
	Hepatic Cancer
	Breast Cancer
	Ovarian Cancer
	Skin Cancer
	Lung Cancer
	Biotechnological Approach to Saffron Production
	Conclusions
	References
	Further Reading
Index
	A
	B
	C
	D
	E
	F
	G
	H
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	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Y
	Z
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