Saffron (Crocus sativus) petal as a new pharmacological target: a review

Document Type: Review Article

Authors

1 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad Iran

2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Saffron petal is the main by-product of saffron processing which produced at high level but it is not applied and thrown out. Saffron petal is containing of several compounds such as mineral agents, anthocyanins, flavonoids, glycosides, alkaloids and kaempferol. As saffron petal is cheaper and produces in large amounts compared to saffron stigma, so, it can be considered as an appropriate source for different purposes. In this review different pharmacological properties of saffron petal such as antibacterial, antispasmodic, immunomodulatory, antitussive, antidepressant, antinociceptive, hepatoprotective, renoprotective, antihypertensive, antidiabetic and antioxidant activity have been introduced. According to these properties, saffron petal can be used as an alternative or supplementary medicine in some diseases.

Keywords

Main Subjects


1. Fernández JA. Biology, biotechnology and biomedicine of saffron. Recent Res Dev Plant Sci 2004; 2: 127-159.
2. Rios J, Recio M, Giner R, Manez S. An update review of saffron and its active constituents. Phytother Res 1996;10:189-193.
3. Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 2007;157:315-319.
4. Hosseinzadeh H, Nassiri‐Asl M. Avicenna’s (Ibn Sina) the canon of medicine and saffron (Crocus sativus): a review. Phytother Res 2013;27:475-83.
5. Mollazadeh H, Emami SA, Hosseinzadeh H. Razi’s Al-Hawi and saffron (Crocus sativus): a review. Iran J Basic Med Sci 2015;18:1153-1166.
6. Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, Tsatsakis AM. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed 2015;5:376-391.
7. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia 2006;77:446-448.
8. Asdaq SMB, Inamdar MN. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl Biochem Biotechnol 2010;162:358-372.
9. Hosseinzadeh H, Khosravan V. Anti-convulsant effects of aqueous and ethanolic extracts of Crocus sativus L stigma in mice. Arch Iran Med 2002; 5:44-47.
10. Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002; 15: 2-7.
11. Hosseinzadeh H, Karimi G, Niapoor M, editors. Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice.J Med Plants 2004; 3:48-58
12. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res 2009;23:768-774.
13. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res 2010;24:990-994.
14. Abdullaev F, Espinosa-Aguirre J. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 2004;28:426-432.
15. Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci 2005;8:387-393.
16. Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacogn Mag 2009;5:419-424.
17. Fahim NK, Janati SF, Feizy J. Chemical composition of agriproduct saffron (Crocus sativus L.) petals and its considerations as animal feed. GIAD J Food 2012;37:197-201.
18. Hadizadeh F, Khalili N, Hosseinzadeh H, Khair-Aldine R. Kaempferol from saffron petals. Iran J Pharm Res 2003; 2: 251-252.
19. eka K, Ruparelia KC, Continenza MA, Stagos D, Vegliò F, Arroo RR. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol. Fitoterapia 2015;107:128-134.
20. Khazaei KM, Jafari S, Ghorbani M, Kakhki AH, Sarfarazi M. Optimization of anthocyanin extraction from saffron petals with response surface methodology. Food Anal Methods 2016;9:1993-2001.
21. Goli SAH, Mokhtari F, Rahimmalek M. Phenolic compounds and antioxidant activity from saffron (Crocus sativus L.) petal. J Agric Sci 2012;4:175-181.
22. Termentzi A, Kokkalou E. LC-DAD-MS (ESI+) analysis and antioxidant capacity of crocus sativus petal extracts. Planta Med 2008;74:573-581.
23. Righi V, Parenti F, Tugnoli V, Schenetti L, Mucci A. Crocus sativus petals: waste or valuable resource? The answer of high-resolution and High-resolution magic angle spinning nuclear magnetic resonance. J Agric Food Chem 2015;63:8439-8444.
24. Li C-Y, Lee E-J, Wu T-S. Antityrosinase Principles and Constituents of the Petals of Crocus
 sativus. J Nat Prod 2004;67:437-440.
25. Hosseini D, Shariatmadar S. Identification of anthocyanins of Crocus sativus petals. Iran Inst Sci Technol Rep, Khorasan Center 1994.
26. Astarei AR, Eskandari-Torbaghan M, Abbasi-Ali Kamar R, editors. Effect of saffron (crocus sativus L.) petals on germination and primary growth of cotton (gossypium hirsutum L.). II Int Symp Saffron Biol Technol 2006; 739: 87-91.
27. Mortazavi S, Kamali MM, Safi S, Salehi R. Saffron petals, a by-product for dyeing of wool fibers. Prog Color Colorants Coat 201; 5: 75-84.
28. Johler S, Tichaczek-Dischinger PS, Rau J, Sihto HM, Lehner A, Adam M. Outbreak of Staphylococcal food poisoning due to SEA-producing Staphylococcus aureus. Food Pathog Dis 2013;10:777-781.
29. Madhumitha G, Saral AM. Preliminary phytochemical analysis, antibacterial, antifungal and anticandidal activities of successive extracts of Crossandra infundibuliformis. Asian Pac J Trop Med 2011;4:192-195.
30. Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects. Iran J Basic Med Sci 2014;17:929-938.
31. Asgarpanah J, Darabi-Mahboub E, Mahboubi A, Mehrab R, Hakemivala M. In-Vitro Evaluation of Crocus Sativus L. Petals and Stamens as Natural Antibacterial Agents Against Food-Borne Bacterial Strains. Iran J Pharm Sci 2013;9:69-82.
32. Fatehi M, Rashidabady T, Fatehi-Hassanabad Z. Effects of Crocus sativus petals’ extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J Ethnopharmacol 2003;84:199-203.
33. Patwardhan B, Gautam M. Botanical immunodrugs: scope and opportunities. Drug Discov Today 2005;10:495-502.
34. Plaeger SF. Clinical immunology and traditional herbal medicines. Clin Diagn Lab Immunol 2003;10:337-338.
35. Zeinali M, Rezaee SA, Hosseinzadeh H. An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed Pharmacother 2017;92:998-1009.
36. Babaei A, Arshami J, Haghparast A, Mesgaran MD. Effects of saffron (Crocus sativus) petal ethanolic extract on hematology, antibody response, and spleen histology in rats. Avicenna J  Phytomed 2014;4:103-109.
37. Agha‐Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara A, et al. Crocus sativus L.(saffron) in the treatment of premenstrual syndrome: a double‐blind, randomised and placebo‐controlled trial. BJOG: An Int J Obst Gynaecol 2008;115:515-519.
38. Bikomo E, Ebuehi O, Magbagbeola O. Antidepressant Activity of Ethanol Leaf Extract of Annona muricata L., in Sprague-Dawley Rats. Am J Biochem 2017;7:1-5.
39. Karimi GR, Hosseinzadeh H, Khaleghpanah P. Study of antidepressant effect of aqueous and ethanolic extract of Crocus sativus in mice. Irn J Basic Med Sci 2001; 4: 11-15.
40. Tabeshpour J, Sobhani F, Sadjadi SA, Hosseinzadeh H, Mohajeri SA, Rajabi O, et al. A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomed 2017;36:145-152.
41. Hassani FV, Naseri V, Razavi BM, Mehri S, Abnous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru J Pharm Sci 2014;22:16.
42. Ghasemi T, Abnous K, Vahdati F, Mehri S, Razavi B, Hosseinzadeh H. Antidepressant effect of Crocus sativus aqueous extract and its effect on CREB, BDNF, and VGF transcript and protein levels in rat hippocampus. Drug Res 2015;65:337-343.
43. Moshiri E, Basti AA, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Crocus sativus L.(petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomed 2006;13:607-611.
44. Basti AA, Moshiri E, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuro-Psychopharmacol Biol Psychiatry 2007;31:439-442.
45. Hosseinzadeh H, Motamedshariaty V, Hadizadeh F. Antidepressant effect of kaempferol, a constituent of saffron (Crocus sativus) petal, in mice and rats. Pharmacologyonline 2007;2:367-370.
46. Gholamnezhad Z, Koushyar H, Byrami G, Boskabady MH. The extract of Crocus sativus and its constituent safranal, affect serum levels of endothelin and total protein in sensitized guinea pigs. Iran J Basic Med Sci 2013;16:1022-1026.
47. Boskabady MH, Farkhondeh T. Antiinflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents. Phytother Res 2016;30:1072-1094.
48. Boskabady MH, Rahbardar MG, Jafari Z. The effect of safranal on histamine (H1) receptors of guinea pig tracheal chains. Fitoterapia 2011;82:162-167.
49. Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: a review. J Environ Sci Health Part C 2007;25:185-209.
50. Kamalakkannan N, Rukkumani R, Varma PS, Viswanathan P, Rajasekharan KN, Menon VP.  Comparative Effects of Curcumin and an Analogue of Curcumin in Carbon Tetrachloride‐Induced Hepatotoxicity in Rats. Basic Clin Pharmacol Toxicol 2005;97:15-21.
51. Iranshahi M, Khoshangosht M, Mohammadkhani Z, Karimi G. Protective effects of aqueous and ethanolic extracts of saffron stigma and petal on liver toxicity induced by carbon tetrachloride in mice. Pharmacologyonline 2011;1:203-212.
52. Bunchorntavakul C, Reddy KR. Acetaminophen-related hepatotoxicity. Clin Liver Dis 2013;17:587-607.
53. Tan SC, New LS, Chan EC. Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine. Toxicol Let 2008;180:174-181.
54. Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis.  Handb Exp Pharmacol 2010; 196: 369-405.
55. Omidi A, Riahinia N, Torbati MBM, Behdani M-A. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytomed 2014;4:330-336.
56. Nakanuma Y. Non‐neoplastic nodular lesions in the liver. Pathol Int 1995;45:703-714.
57. Omidi A, Torabi Z, Hassanpoorfard M, Zardast M. Evaluation of protective effect of hydroalcoholic extract of Crocus sativus petals on preventing of gentamicin induced peliosis hepatis and hepatic telangiectasis in rats. J Birjand Univ Med Sci 2013;19:455-462.
58. Cersosimo RJ. Hepatotoxicity associated with cisplatin chemotherapy. Ann Pharmacother 1993;27:438-4341.
59. Robbins ME, Zhao W, Davis CS, Toyokuni S, Bonsib SM. Radiation-induced kidney injury: a role for chronic oxidative stress? Micron 2002;33:133-141.
60. Mohajeri Dariush DY. Protective effects of Crocus sativus petal against cisplatin-induced hepatotoxicity in rats. Med Sci J Islamic Azad Univ 2011;21:251-261.
61. Omidi A, Riahinia N, Torbati MBM, Behdani MA. Evaluation of protective effect of hydroalcoholic extract of saffron petals in prevention of acetaminophen-induced renal damages in rats. Vet Sci Dev 2015;5: 68-71.
62. Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med. 2011;9:48-60.
63. Tousian HS, Razavi BM, Hosseinzadeh H. Review of Garcinia mangostana and its xanthones in metabolic syndrome and related complications. Phytother Res 2017; 31: 1173-1182.
64. Tabeshpour J, Imenshahidi M, Hosseinzadeh H. A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci 2017;20:557-568.
65. Razavi BM, Lookian F, Hosseinzadeh H. Protective effects of green tea on olanzapine-induced-metabolic syndrome in rats. Biomed Pharmacother 2017;92:726-731.
66. Tabeshpour J, Razavi BM, Hosseinzadeh H. Effects of Avocado (Persea americana) on metabolic syndrome: a comprehensive systematic review. Phytother Res 2017; 31: 819-837.
67. Mollazadeh H, Hosseinzadeh H. Cinnamon effects on metabolic syndrome: a review based on its mechanisms. Iran J Basic Med Sci 2016;19:1258-1270.
68. Hassani FV, Shirani K, Hosseinzadeh H. Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: a review. Naunyn-Schmiedeberg’s Arch Pharmacol 2016;389:931-49.
69. Akaberi M, Hosseinzadeh H. Grapes (Vitis vinifera) as a potential candidate for the therapy of the metabolic syndrome. Phytother Res 2016;30:540-556.
70. Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrin Invest 2015;38:1147-1157.
71. Razavi B, Hosseinzadeh H. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 2014;37:1031-1040.
72. Razavi BM, Hosseinzadeh H. Saffron: a promising natural medicine in the treatment of metabolic syndrome. J Sci Food Agric 2017;97:1679-1685.
73. Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2004;89:2595-2600.
74. Hoshyar R, Hosseinian M, Naghandar MR, Hemmati M, Zarban A, Amini Z, et al. Anti-dyslipidemic properties of Saffron: Reduction in the associated risks of atherosclerosis and insulin resistance. Iran Red Cres Med J 2016;18: e36266.
75. Lenzen S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetol 2008;51:216-226.
76. Zarez et al adeh M, Vazifeshenas-Darmiyan K, Afshar M, Valavi M, Serki E, Hosseini M. Effects of Extract of Crocus sativus Petal on Renal Function in Diabetic Rats. J Mazandaran Univ Med Sci 2017;27:11-24.
77. Halliwell B. Establishing the significance and optimal intake of dietary antioxidants: the biomarker concept. Nutr Rev 1999;57:104-113.
78. Ardalan T, Ardalan P, Heravi M. Kinetic study of free radicals scavenging by saffron petal extracts. J Chem Health Risks. 2012;2: 29-36.
79. Hosseinzadeh H, Behravan J, Ramezani M, Ajgan K. Anti-tumor and cytotoxic evaluation of Crocus sativus L. stigma and petal extracts using brine shrimp and potato disc assays. J Med Plants 2005;3:59-65.
80. Karimi G, Tabibi N, Hosseinzadeh H, Shirzad F. Sub-acute toxicity of saffron (Crocus sativus L.) stigma and petal in rats. J Med Plants 2004;12:32-39.