The Combined Effects of Saffron (Crocus sativus L.) and Exercise on Body Health: A Review Study
Vida Hojati
1
(
Department of Biology, Damghan Branch, Islamic Azad Universty, Damghan, Iran
)
Keywords: Saffron, Crocin, Exercise, Food supplement, Body mass,
Abstract :
Researchers have always been looking for a suitable combination of nutrition and physical activities to prevent and treat diseases, increase well-being and improve physical performance. Saffron (Crocus sativus L.) is a valuable plant in traditional medicine. The properties of this plant are attributed to its effective and bioactive compounds such as crocins, crostin, picrocrocin, safranal, and glycosides. This study provides a review of the effects associated with saffron consumption and its effective compounds along with various sports exercises on body health. Scientifis database such as Scopus, PubMed, Sciencedirect and Scientific Information Database (SID) were used to search for articles, and finally 106 articles were selected based on relevance to the topic and novelty. Saffron has a positive effect on the secretion of male sex hormones and IGF-1, causes an increase in muscle contraction during stimulation and increases the number, mobility and ability of sperm. It also strengthens the female reproductive system, such as reducing the symptoms of dysmenorrhea, premenstrual syndrome, polycystic ovary syndrome, menopause, and sexual dysfunction by regulation of hormones, folliculogenesis, ovulation, and protection of the ovary and uterus. Saffron supplement and exercise are known as two effective factors in preventing complications of type 2 diabetes, reducing appetite, improving glycemic indices, fasting glucose control and lipid profile. Saffron has beneficial effects on oxidative stress, inflammatory reactions, apoptotic indices, muscle strength, body mass index, metabolism regulation, leptin serum levels, blood pressure, lung function, liver, cardiovascular, digestive, chronic renal, neurological diseases, metabolic syndrome and cancer have a preventive and therapeutic role.
References:
1. Jodeir S., Dehghan Nayeri F., 2016. Study of expression of the MADS-box transcription factors involved in flower formation in saffron (Crocus sativus L.). Cellular and Molecular Research (Iranian Journal of Biology). 28(4), 488-499. [In Persian]
2. Xing B., Li S., Yang J., Lin D., Feng Y., Lu J., Shao Q., 2021. Phytochemistry, pharmacology, and potential clinical applications of saffron: A review. J Ethnopharmacol. 281, 114555.
3. Hosseini A., Razavi B.M., Hosseinzadeh H., 2018. Pharmacokinetic properties of saffron and its active components. Eur J Drug Metab Pharmacokinet. 43(4), 383-390.
4. Hooshmand Moghadam B., Rashid Lamir A., Attarzade Hosseini S.R., Gaeini A.A., 2019. A review on the effects of saffron with physical activity. J Med Plants. 18(72), 14-29.
5. Farhadi L., Hojati V., Khaksari M., Vaezi G. 2022. The effect of crocin on cognition and necrosis cell death in the hippocampus area in the model of fetal alcohol spectrum disorders in male rats. J Anim Environ. 14(3), 103-110. [In Persian]
6. Heidary M., Nejadi J.R., Delfan B., Birjandi M., Kaviani H., Givrad S., 2008. Effect of saffron on semen parameters of infertile men. Sexual Dysfunction and Infertility. 5, 255-259.
7. Marrone G., Urciuoli S., Di Lauro M., Cornali K., Montalto G., Masci C., Vanni G., Tesauro M., Vignolini. P, Noce A., 2024. Saffron (Crocus sativus L.) and its by-products: Healthy effects in internal medicine. Nutrients. 16(14), 2319.
8. Alaei M., Hosseini S.A., Azarbaijani M.A., 2014. The effect of a period of resistance training with the consumption of saffron extract on testosterone, FSH and LH in rats. Research in Sports Biosciences. 3(12), 77-86. [In Persian]
9. Abbasi H., Azarbaijani M.A, Tarvardizadeh B., 2015. Simultaneous effect of crocin and resistance exercise on PG axis hormones in male rats after nanderlone induction. 9th International Conference on Physical Education and Sports. [In Persian]
10. Lalabadi H., Azarbaijani M.A., Tarvardizadeh B., 2015. Effect of combination of crocin and resistance exercise on liver injury markers in nanderlone poisoned rats. 9th International Conference on Physical Education and Sports. [In Persian]
11. Rostami A., Hodsseini S.A., Azarbayjani M.A., 2019. Resistance ttraining with and without crocin consumption on catalase and glutathione peroxidase of heart tissue of nandrolone poisoned rats. J Torbat Heydariyeh Univ Med Sci. 6(4), 22-32. [In Persian]
12. Hooshmand Moghadam B., Gaeini A.A., 2018. Effect of complementary saffron and resistance training on serum levels of growth hormone, insulin-like growth factor-1 and testosterone in young men. Iran J Endocrinol Metabol. 20(4), 177-184. [In Persian]
13. Hooshmand Moghadam B., Gaeini A.A., 2018. Effect of saffron supplementation with resistance training on serum leptin levels, body composition and muscle strength in non-athletic young men. J Birjand Univ Med Sci (JBUMS). 25(4), 263-275. [In Persian]
14. Gaeini A.A., Pournemati P., Hooshmand Moghaddam B., 2018. Interactive effect of saffron supplementation and resistance training on serum levels of sex hormones in young men. Razi J Med Scie. 25(171), 20-30. [In Persian]
15. Ghanbari-Niaki A., Saeidi A., Ardeshiri S., Aliakbari Baydokhty M., 2019. Effects of circuit resistance training with different parts of saffron supplementation on testosterone and cortisol hormones. J Tabriz Uni Med Sci. 40(6), 56-63. [In Persian]
16. Heydari E., Hosseini A., Azarnayjani M.A., 2019. The effect of eight-weeks resistance training with two doses of crocin consumption on catalase and glutathione peroxidase in kidney tissue of nandrolone poisoned rats. J Adv Biomed Sci. 9(2), 1487-1497. [In Persian]
17. Aghajani V., Nazari M., Shabani R., 2019. Impact of aerobic and resistance training supplemented with the consumption of saffron on glutathione peroxidase and malondialdehyde in men with type 2 iabetes. J Gorgan Univ Med Sci. 21(3), 24-33. [In Persian]
18. Hooshmand-Moghadam B., Eskandari M., Shabkhiz F., Mojtahedi S., Mahmoudi N., 2021. Saffron (Crocus sativus L.) in combination with resistance training reduced blood pressure in the elderly hypertensive men: A randomized controlled trial. Br J Clin Pharmacol. 87(8), 3255-3267.
19. Hooshmand-Moghadam B., Bagheri R, Roozbeh B., Ashtary-Larky D., Gaeini A.A., Dutheil F, Wong A., 2021. Impact of saffron (Crocus sativus Linn) supplementation and resistance training on markers implicated in depression and happiness levels in untrained young males. Physiol Behav. 233, 113352.
20. Piri M., Moslim Haghigi M., Azarbaijani M.A., Khajelou A., 2012. The effect of saffron aqueous extract and aerobic exercise on the concentration of hepatic non-enzymatic antioxidants in streptotocin-treated diabetic rats. Res Sport Biosci. 2(7), 5-16. [In Persian]
21. Fazel Kalkhoran J., Shibak A., 2013. Effect of four weeks HIT on the levels of GH, IGFBP-3, IGF-1 and serum cortisol and some performance indicators in Iran women national basketball team. J Sport Biosci. 5(4), 1-19. [In Persian]
22. Varmazyar M., Azarbayjani M., 2014. The effect of saffron supplementation of antioxidant enzymes activities during a session eccentric exercise in active males. J. Med. Plants. 13(50), 54-63. [In Persian]
23. Akbarnejad A., Rajabi A., Yari M., Mamshali E., 2017. The effect of saffron consumption and intermittent aerobic exercise on spirometryand physiological parametersand blood pressure in non-athletic boys. Sport Physiology and Management Investigations. 9(2), 21-33. [In Persian]
24. Akbari M., Shahidi F., Rajabi H., Kashef M., Mazaheri Z., 2018. The simultaneous effect of six weeks forced swimming and crocin supplementation on the expression of 3-cardiomyocyte genesase 3 in male rats infected with hydrogen peroxide. Razi J Med Sci. 25(9), 26-37. [In Persian]
25. Rajabi A., Siahkouhian M., Akbarnejad A., 2018. The adaptability of serum irisin, lipid profile, and insulin resistance to an aerobic exercise and the consumption of saffron and its sustainability in type 2 diabetic women. Daneshvar Medicine. 26(1), 9-26. [In Persian]
26. Rajabi A., Akbarnejad A., Siahkouhian M., Yari M., 2019. Effect of saffron supplementation and exercise training on blood pressure, pulmonary function and spirometery indicators in obese and overweight women affected by type 2 diabetes. J Gorgan Univ Med Sci. 21(2), 59-69. [In Persian]
27. Akbari M., Shahidi F., Rajabi H., Kashef M., Mazaheri Z., 2019. The interactive effect of forced swimming and crocin supplementation on the expression of BAX and BCL-2 cardiomyocyte genes in male rats infected with hydrogen peroxide. J Isfahan Med Sci. 37(525), 443-453. [In Persian]
28. Khosravi A., 2020. The combined effect of aerobic exercise with saffron extract on some indices of soleus muscle apoptosis regulatory factors of male rats following an aerobic exercise until exhaustion. Journal of Applied Health Studies in Sport Physiology. 6(2), 86-95. [In Persian]
29. Rajabi A., Siahkouhian M., Akbarnejad A., 2019. Comparison of the effect of a therapeutic exercise program and oral administration of saffron on the levels of IL-6, TNF-α and glycemic control in type 2 diabetic women. Razi Journal of Medical Sciences. 25(166), 20-33. [In Persian]
30. Helalizadeh M., Labbafi Hoseinabadi M., Rohani H., Hajiaghaee R., Hatami E., 2020. Meta-analysis of the effectiveness of saffron supplementation on enzymatic antioxidant defense biomarkers in exercise. Sport Physiol. 12(45), 129-152. [In Persian]
31. Shekarriz H., Galedari M., Khorsandi L., Nikbakht M., 2020. Protective effects of aerobic training and crocin on doxorubicin induced heart tissue oxidative stress in male rats. Iranian J Nutr Sci Food Technol. 15(2), 11-20. [In Persian]
32. Davoodi M., Zilaei Bouri S., Dehghan Ghahfarokhi S., 2021. Antioxidant effects of aerobic training and crocin consumption on doxorubicin-induced testicular toxicity in rats. J Family Reprod Health. 15(1), 28-37. [In Persian]
33. Khosravi A., Khosravi P., Daneshyar S., Valipour Dehnou V., 2022. Effect of aerobic exercise combined with saffron extract supplementation on serum levels of tumor necrosis factor-α and C-reactive protein in rats following an aerobic exercise until exhaustion. Complement Med J. 11(4), 358-371. [In Persian]
34. Hosseini S.E., Akbarnejad A., Shabkhiz F., Soori R., 2021. The effect of aerobic exercise and oral consumption of Iranian saffron flower on nesfatin-1 and omentin-1 in obese women with type 2 diabetes. J Anim Biol. 13(4), 47-56. [In Persian]
35. Asvadi R., Akbarnejad A., Soori R., 2022. Evaluation of the effects of 9 weeks of aerobic exercise with and without saffron supplementation on liver enzyme AST and HOMA-IR in obese female patients with type 2 diabetes. Sport Physiology and Management Investigations (SPMI). 14(2), 121-135. [In Persian]
36. Bazyar F., Shabani R., Elmiyeh A., 2023. The effects of endurance training and saffron extract on the expression of Bax, Bcl-2, and Caspase-3 genes in the hippocampal tissue of Alzheimer's male rats. J Jiroft Univ Med Sci. 9(4), 1151-1159. [In Persian]
37. Maskanati F., Ghasemian S.O., Khanmohammadi R., Salehi O., 2022. Interactive effects of aerobic training and Crocin supplementation on some apoptosis markers in kidney tissue of rats exposed to doxorubicin. Feyz Med Sci J. 26(6), 683-690. [In Persian]
38. Poursadeghi S., Kashef M., Shahidi F., Vosadi E., 2022. Combined effect of aerobic exercise and crocin supplementation on the prevention of myocardial tissue cell death in male wistar rats. J. Ilam Uni. Med. Sci. 30(5), 101-111. [In Persian]
39. Rajabi A, Khajehlandi M, Siahkuhian M, Akbarnejad A, Khoramipour K, Suzuki K., 2022. Effect of 8 weeks aerobic training and saffron supplementation on inflammation and metabolism in middle-aged obese women with type 2 diabetes mellitus. Sports. 10(11), 167.
40. Pourmousavi L., Hashemkandi Asadi R., Zehsaz F., Jadidi R.P., 2023. Effect of crocin and treadmill exercise on oxidative stress and heart damage in diabetic rats. PLoS One. 18(12), e0281692.
41. Rajabi A., Akbar Nezhad Gharehlo A., Madadizadeh E., Basereh A., Khoramipoor K., Pirani H., Khoramipour K., Moser O., Khoramipour K., 2024. The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes-specific markers and inflammation in women with type 2 diabetes: A randomized double-blind placebo-controlled trial. Eur J Sport Sci. 24(7), 899-906.
42. Moghadasi M., Akbari F., Najafi P., 2024. Interaction of aerobic exercise and crocin improves memory, learning and hypocampic tau and neurotrophins gene expression in rats treated with trimethytin as a model of Alzheimer's disease. Mol Biol Rep. 51(1), 111.
43. Emamghoreishi M., Ghasemi F., 2012. The effect of subchronic administration of the aqueous and hydro-alcoholic extracts of Crocus sativus from Estahbanat, Fars Province, on mice. Armaghan-e-Danesh. 16(6), 527-536. [In Persian]
44. Asishirazi I., Hosseini S.A., Keikhosravi F., 2017. Hypoglycemic interactional effects of saffron (Crocus sativus) aqueous extract and swimming training in streptozotocin induced diabetic rats. J Sabzevar Univ Med Sci. 24(4), 273-279. [In Persian]
45. Khosravi A., Omidali O.A., Rasoulian B., Choobineh S., 2017. The effects of short-term aqueous saffron extracts consumption on malondialdehyde and anti-oxidant system content of liver of young male rats following an acute bout of exhaustive exercise. Yafteh. 19(1), 20-30. [In Persian]
46. Khosravi A., Omid Ali F., 2018. The effect of saffron stigmas aqueous extracts on serum cardiac troponin T and creatine kinase MB isoenzyme of male rats following an exhaustive exercise. J Arak Uni Med Sci. 21(2), 43-54. [In Persian]
47. Akbari F., Moghadasi M., Farsi S., Edalatmanesh M.A., 2019. The effect of eight weeks moderate-intensity endurance training with saffron intake on memory and learning in rats with trimethytin model of Alzheimer’s Disease. J Appl Exerc Physiol. 15(30), 115-128.
48. Akbari-Fakhrabadi M., Najafi M., Mortazavian S., Rasouli M., Memari A.H., Shidfar F., 2019. Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats. J Food Biochem. 43(8), e12946.
49. Shahidani S., Rajaei Z., Alaei H., 2019. Pretreatment with crocin along with treadmill exercise ameliorates motor and memory deficits in hemiparkinsonian rats by anti-inflammatory and antioxidant mechanisms. Metab Brain Dis. 34(2), 459-468.
50. Peyravi A., Yazdanpanahi N., Nayeri H., Hosseini S.A., 2020. The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats. J Food Biochem. 44(2), e13125.
51. Dastgerdi H.H., Radahmadi M., Reisi P., 2020. Comparative study of the protective effects of crocin and exercise on long-term potentiation of CA1 in rats under chronic unpredictable stress. Life Sci. 256, 118018.
52. Nezamdoost Z., Saghebjoo M., Hoshyar R., Hedayati M., Keska A., 2020. High-intensity training and saffron: Effects on breast cancer-related gene expression. Med Sci Sports Exerc. 52(7), 1470-1476.
53. Akbari-Fakhrabadi M., Najafi M., Mortazavian S., Memari A.H., Shidfar F., Shahbazi A., Heshmati J., 2021. Saffron (Crocus sSativus L.), combined with endurance exercise, synergistically enhances BDNF, serotonin, and NT-3 in wistar rats. Rep Biochem Mol Biol. 9(4), 426-434.
54. Akbari F., Moghadasi M., 2023. Effect of eight-week moderate intensity endurance training with crocin consumption on MAP-Tau and NFG gene expression in rats with hippocampal degeneration model. Sport Physiology and Management Investigations. 15(1), 169-180.
55. Khanmohammadi R., Azarbayjani M.A., Piri M., Khorsandi L.S., 2019. The effect of severe periodic training and crocin on oxidative stress in male rats subjected to doxorubicin induction. Armaghan-e-Danesh. 23(6), 694-708.
56. Darash K., Ghanbarzadeh M., Masoud M., 2020. Effect of eight-week exercise and crocin on the apoptotic indices of male rats’ testicles subjected to the apoptosis by Doxorubicin. Razi J Med Sci (RJMS). 26(11), 134-144.
57. Sadr Arhami H., Nourshahi M., Ebrahim K., Mousavi Mozafar M., Hedayati M., 2019. The effect of 8-week sprint interval training with consuming saffron extract on the factors affecting longevity in male rats. Iran J Nutr Sci Food Technol. 14(1), 19-26.
58. Razavi S.H., Hosseini S.A., Nikbakht M., 2019. The effect of continued and interval training with crocin consumption on BDNF and NGF gene expression in heart tissue of diabetic rats. Feyz Med Sci J. 23(1), 10-19.
59. Moradi M., Shakerian S., Nikbakht M., 2019. The effect of eight weeks high intensity interval training and crocin consumption on oxidative stress of liver tissue in male rats subjected to chronic doxorubicin injection. Feyz Med Sci J. 23(5), 485-494.
60. Moradi M., Shakerian S., Nikbakht M., 2020. Effect of eight weeks of high intensity interval training and crocin consumption on the apoptotic genes expression in the liver tissue of male rats under chronic doxorubicin induction. J Birjand Univ Med Sci. 27(4), 323-335.
61. Alaie M., Gaeini A.A., Nouri R., Chobineh S., 2020. Interaction effect of high interval and low intensity continuous trainings with crocin on the expressions of PGC-1a and UCP1 in heart tissue of male diabetic rats. Res Med. 44(3), 423-429.
62. Hasanvand B., Mehrialvar Y., Heydarianpour A., Erfaniadab F., 2020. Comparison of the effect of different intensities of exercise training with saffron supplementation on the metabolic balance in overweight and obese women. Yafteh. 22(2), 160-176.
63. Ahmadabadi F., Saghebjoo M., Hedayati M., Hoshyar R., Huang C.J., 2021. Treatment-induced tumor cell apoptosis following high-intensity interval training and saffron aqueous extract in mice with breast cancer. Physiol Int. 2021,19-26.
64. Davari F., Alimanesh Z., Alimanesh Z., Salehi O., Hosseini S.A., 2022. Effect of training and crocin supplementation on mitochondrial biogenesis and redox-sensitive transcription factors in liver tissue of type 2 diabetic rats. Arch Physiol Biochem. 128(5), 1215-1220.
65. Ahmadi Qaracheh R., Fathi M., Rahmati M., 2022. Effect of eight weeks of high intensity interval training and crocin consumption on serum markers of dox-induced cardiotoxicity in male wistar rats. Complement Med J. 12(2), 136-147.
66. Bahrami F., Pour F.J., Hassanpour M., Saki M., Ebrahimzadeh F., Jafaripour L., 2023. The effect of saffron and corrective exercises on depression and quality of life in women with multiple sclerosis: A randomized controlled clinical trial. Mult Scler Relat Disord. 79, 105038.
67. Hooshmand Moghadam B., Rashidlamir A., Attarzadeh Hosseini S.R., Gaeini A.A., Kaviani M., 2022. The effects of saffron (Crocus sativus L.) in conjunction with concurrent training on body composition, glycaemic status, and inflammatory markers in obese men with type 2 diabetes mellitus: A randomized double-blind clinical trial. Br J Clin Pharmacol. 88(7), 3256-3271.
68. Lopresti A.L., Smith S.J., 2022. An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study. J Int Soc Sports Nutr. 19(1), 219-238.
69. Khosravi A., 2019. The effect of aqueous saffron extract on maximum aerobic capacity, lipid peroxidation and total antioxidant capacity of serum of young male athletes following a sauna session leading to a 4% reduction in body weight. J Tabriz Univ Med Sci. 41(5), 44-55.
70. Ghalandari-Shamami M., Nourizade S., Yousefi B., Vafaei A.A., Pakdel R., Rashidy-Pour A., 2019. Beneficial effects of physical activity and crocin against adolescent stress induced anxiety or depressive-like symptoms and dendritic morphology remodeling in prefrontal cortex in adult male rats. Neurochem Res. 44(4), 917-929.
71. Ghalandari-Shamami M., Nourizade S., Barati M., Yousefi B., Pashayi M., Ali Vafaei A., Kokhaei P., Rashidy-Pour A., 2021. Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats. Brain Res. 1754, 147274.
72. Ghaffari S., Roshanravan N., 2019. Saffron; An updated review on biological properties with special focus on cardiovascular effects. Biomed Pharmacother. 109, 21-27.
73. Lu C., Ke L., Li J., Zhao H., Lu T., Mentis A.F.A., Wang Y., Wang Z., Polissiou M.G., Tang L., Tang H., Yang K., 2021. Saffron (Crocus sativus L.) and health outcomes: a meta-research review of meta-analyses and an evidence mapping study. Phytomedicine. 91, 153699.
74. Rashid M., Rashid R., Saroya S., Deverapalli M., Brim H., Ashktorab H., 2024. Saffron as a promising therapy for inflammatory bowel disease. Nutrients. 16(14), 2353.
75. Sadigi B., Yarani R., Mirghafourvand M., Travica N., Yousefi Z., Shakouri S.K., Ostadrahimi A., Mobasseri M., Pociot F., Sanaie S., Araj-Khodaei M., 2022. The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews. Phytother Res. 36(9), 3444-3458.
76. Han S., Cao Y., Wu X., Xu J., Nie Z., Qiu Y., 2024. New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms. Phytother Res. 38(5), 2276-2302.
77. Pourmousavi L., Asadi R.H., Zehsaz F., Jadidi R.P., 2024. Potential therapeutic effects of crocin. Naunyn Schmiedebergs Arch Pharmacol. https://doi.org/10.1007/s00210-024-03131-6
78. Hasheminasab F.S., Azimi M., Raeiszadeh M., 2024. Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review. Phytother Res. 38(6), 2832-2846.
79. Goyal A., Raza F.A., Sulaiman S.A., Shahzad A., Aaqil S.I., Iqbal M., Javed B., Pokhrel P., 2024. Saffron extract as an emerging novel therapeutic option in reproduction and sexual health: recent advances and future prospectives. Ann Med Surg (Lond). 86(5), 2856-2865.
80. Amatto P.P.G., Chaves L., Braga G.G., Carmona F., Pereira A.M.S., 2024. Effect of Crocus sativus L. (saffron) and crocin in the treatment of patients with type-2 diabetes mellitus: A systematic review and meta-analysis. J Ethnopharmacol. 319(Pt 2), 117255.
81. Seyedi-Sahebari S., Farhang S., Araj-Khodaei M., Akhondzadeh S., Naseri A., Sanaie S., Frounchi N., 2024. The effects of Crocus sativus (Saffron) on ADHD: A systematic review. J Atten Disord. 28(1), 14-24.
82. Poursamimi J., Shariati-Sarabi Z., Tavakkol-Afshari J., Mohajeri S.A., Mohammadi M. 2020. Crocus sativus (Saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iran J Allergy Asthma Immunol. 19(S1), 27-42.
83. Broadhead G.K., Grigg J., McCluskey P.J., Hong T., Schlub T.E., Chu E., Chang A.A., 2024. Saffron therapy for the ongoing treatment of age-related macular degeneration. BMJ Open Ophthalmol. 9(1), e001399.
84. Farhadi L., Hojati V., Khaksari M., Vaezi G., 2022. Neuroprotective effects of crocin against ethanol neurotoxicity in the animal model of fetal alcohol spectrum disorders. Neurochem Res. 47, 1001-1011.
85. Avgerinos K.I., Vrysis C., Chaitidis N., Kolotsiou K., Myserlis P.G., Kapogiannis D., 2020. Effects of saffron (Crocus sativus L.) on cognitive function. A systematic review of RCTs. Neurol Sci. 41(10), 2747-2754.
86. Aslani M.R., Abdollahi N., Matin S., Zakeri A., Ghobadi H., 2023. Effect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 130(3), 446-453.
87. Dariushnejad H., Mohammadi M., Ghorbanzadeh V., 2018. Crocin and voluntary exercise promote heart angiogenesis through Akt and ERK1/2 signalling in type 2 diabetic rats. Bratisl Lek Listy. 119(12), 757-761.
88. Ghorbanzadeh V., Mohammadi M., Dariushnejad H., Abhari A., Chodari L., Mohaddes G., 2017. Cardioprotective effect of crocin combined with voluntary exercise in rat: Role of Mir-126 and Mir-210 in heart angiogenesis. Arq Bras Cardiol. 109(1), 54-62.
89. Ghobadi H., Abdollahi N., Madani H., Aslani M.R., 2022. Effect of crocin from saffron (Crocus sativus L.) supplementation on oxidant/antioxidant markers, exercise capacity, and pulmonary function tests in COPD patients: A randomized, double-blind, placebo-controlled trial. Front Pharmacol. 13, 884710.
90. Hamedani S.G., Pourmasoumi M., Zarifi S.H., Askari G., Jamialahmadi T., Bagherniya M., Sahebkar A., 2024. Therapeutic effects of saffron and its components on neurodegenerative diseases. Heliyon. 10(2), e24334.
91. Bej E., Volpe A.R., Cesare P., Cimini A., d'Angelo M., Castelli V., 2024. Therapeutic potential of saffron in brain disorders: From bench to bedside. Phytother Res. 38(5), 2482-2495.
92. Ebrahimzadeh A., Moghadam S.Y., Rahimi H., Motaghinejad M., Motevalian M., Safari S., Mesrabadi M.A., 2019. Crocin acts as a neuroprotective mediator against methylphenidate induced neurobehavioral and neurochemical sequelae: Possible role of the CREB-BDNF signaling pathway. Acta Neurobiol Exp. 79(4), 352-366.
93. Shahbaz K., Chang D., Zhou X., Low M., Seto S.W., Li C.G., 2022. Crocins for Ischemic Stroke: A Review of Current Evidence. Front Pharmacol. 13, 825842.
94. Abdullaev F.I., Espinosa-Aguirre J.J., 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev. 28(6), 426-432.
95. Mokhtarian R., Rajabi S., Zahedian S., Jafarinejad-Farsangi S., Hadizadeh M., Sadeghinejad M., 2024. The effect of saffron and its extracts on the treatment of breast cancer: A narrative review. Ann Pharm Fr. 82(4), 629-640.
96. Colapietro A., Mancini A., D'Alessandro A.M., Festuccia C., 2019. Crocetin and crocin from saffron in cancer chemotherapy and chemoprevention. Anticancer Agents Med Chem. 19(1), 38-47.
97. Rashid M., Brim H., Ashktorab H., 2022. Saffron, its active components, and their association with DNA and histone modification: A narrative review of current knowledge. Nutrients. 14(16), 3317.
98. Wang Y., Han T., Zhu Y., Zheng C.H., Ming Q., Rahman K.H., Qin L., 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med. 64, 24-30.
99. El Midaoui A., Ghzaiel I., Vervandier-Fasseur D., Ksila M., Zarrouk A., Nury T., Khallouki F., El Hessni A., Ibrahimi S.O., Latruffe N., Couture R., Kharoubi O., Brahmi F., Hammami S., Masmoudi-Kouki O., Hammami M., Ghrairi T., Vejux A., Lizard G., 2022. Saffron (Crocus sativus L.): A source of nutrients for health and for the treatment of neuropsychiatric and age-related diseases. Nutrients. 14(3), 597.
100. Musazadeh V., Zarezadeh M., Faghfouri A.H., Keramati M., Ghoreishi Z., Farnam A., 2022. Saffron, as an adjunct therapy, contributes to relieve depression symptoms: An umbrella meta-analysis. Pharmacol Res. 175, 105963.
101. Cerdá-Bernad D., Valero-Cases E., Pastor J.J., Frutos M.J., 2022. Saffron bioactives crocin, crocetin and safranal: effect on oxidative stress and mechanisms of action. Crit Rev Food Sci Nutr. 62(12), 3232-3249.
102. Tavakkol-Afshari J., Brook A., Mousavi S.H., 2008. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxicol. 46(11), 3443-3447.
103. Amin A., Hamza A.A., Bajbouj K., Ashraf S.S., Daoud S., 2011. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology. 54(3), 857-867.
104. Mir R.A., Tyagi A., Hussain S.J., Almalki M.A., Zeyad M.T., Deshmukh R., Ali S., 2024. Saffron, a potential bridge between nutrition and disease therapeutics: Global health challenges and therapeutic opportunities. Plants (Basel). 13(11), 1467.
105. Hojati V., Jalali E. 2024. A review on the combined effects of saffron plant extract and sports activity on the male reproductive system. 7th National Conference of Saffron, 13-14 November, 2024, Univeristy of Birjand, Birjand, Iran.
106. Hojati V., 2024. A review of the effects of saffron plant (Crocus sativus L.) extract on the female reproductive system. 7th National Conference of Saffron, 13-14 November, 2024, Univeristy of Birjand, Birjand, Iran.
1. Jodeir S., Dehghan Nayeri F., 2016. Study of expression of the MADS-box transcription factors involved in flower formation in saffron (Crocus sativus L.). Cellular and Molecular Research (Iranian Journal of Biology). 28(4), 488-499. [In Persian]
2. Xing B., Li S., Yang J., Lin D., Feng Y., Lu J., Shao Q., 2021. Phytochemistry, pharmacology, and potential clinical applications of saffron: A review. J Ethnopharmacol. 281, 114555.
3. Hosseini A., Razavi B.M., Hosseinzadeh H., 2018. Pharmacokinetic properties of saffron and its active components. Eur J Drug Metab Pharmacokinet. 43(4), 383-390.
4. Hooshmand Moghadam B., Rashid Lamir A., Attarzade Hosseini S.R., Gaeini A.A., 2019. A review on the effects of saffron with physical activity. J Med Plants. 18(72), 14-29.
5. Farhadi L., Hojati V., Khaksari M., Vaezi G. 2022. The effect of crocin on cognition and necrosis cell death in the hippocampus area in the model of fetal alcohol spectrum disorders in male rats. J Anim Environ. 14(3), 103-110. [In Persian]
6. Heidary M., Nejadi J.R., Delfan B., Birjandi M., Kaviani H., Givrad S., 2008. Effect of saffron on semen parameters of infertile men. Sexual Dysfunction and Infertility. 5, 255-259.
7. Marrone G., Urciuoli S., Di Lauro M., Cornali K., Montalto G., Masci C., Vanni G., Tesauro M., Vignolini. P, Noce A., 2024. Saffron (Crocus sativus L.) and its by-products: Healthy effects in internal medicine. Nutrients. 16(14), 2319.
8. Alaei M., Hosseini S.A., Azarbaijani M.A., 2014. The effect of a period of resistance training with the consumption of saffron extract on testosterone, FSH and LH in rats. Research in Sports Biosciences. 3(12), 77-86. [In Persian]
9. Abbasi H., Azarbaijani M.A, Tarvardizadeh B., 2015. Simultaneous effect of crocin and resistance exercise on PG axis hormones in male rats after nanderlone induction. 9th International Conference on Physical Education and Sports. [In Persian]
10. Lalabadi H., Azarbaijani M.A., Tarvardizadeh B., 2015. Effect of combination of crocin and resistance exercise on liver injury markers in nanderlone poisoned rats. 9th International Conference on Physical Education and Sports. [In Persian]
11. Rostami A., Hodsseini S.A., Azarbayjani M.A., 2019. Resistance ttraining with and without crocin consumption on catalase and glutathione peroxidase of heart tissue of nandrolone poisoned rats. J Torbat Heydariyeh Univ Med Sci. 6(4), 22-32. [In Persian]
12. Hooshmand Moghadam B., Gaeini A.A., 2018. Effect of complementary saffron and resistance training on serum levels of growth hormone, insulin-like growth factor-1 and testosterone in young men. Iran J Endocrinol Metabol. 20(4), 177-184. [In Persian]
13. Hooshmand Moghadam B., Gaeini A.A., 2018. Effect of saffron supplementation with resistance training on serum leptin levels, body composition and muscle strength in non-athletic young men. J Birjand Univ Med Sci (JBUMS). 25(4), 263-275. [In Persian]
14. Gaeini A.A., Pournemati P., Hooshmand Moghaddam B., 2018. Interactive effect of saffron supplementation and resistance training on serum levels of sex hormones in young men. Razi J Med Scie. 25(171), 20-30. [In Persian]
15. Ghanbari-Niaki A., Saeidi A., Ardeshiri S., Aliakbari Baydokhty M., 2019. Effects of circuit resistance training with different parts of saffron supplementation on testosterone and cortisol hormones. J Tabriz Uni Med Sci. 40(6), 56-63. [In Persian]
16. Heydari E., Hosseini A., Azarnayjani M.A., 2019. The effect of eight-weeks resistance training with two doses of crocin consumption on catalase and glutathione peroxidase in kidney tissue of nandrolone poisoned rats. J Adv Biomed Sci. 9(2), 1487-1497. [In Persian]
17. Aghajani V., Nazari M., Shabani R., 2019. Impact of aerobic and resistance training supplemented with the consumption of saffron on glutathione peroxidase and malondialdehyde in men with type 2 iabetes. J Gorgan Univ Med Sci. 21(3), 24-33. [In Persian]
18. Hooshmand-Moghadam B., Eskandari M., Shabkhiz F., Mojtahedi S., Mahmoudi N., 2021. Saffron (Crocus sativus L.) in combination with resistance training reduced blood pressure in the elderly hypertensive men: A randomized controlled trial. Br J Clin Pharmacol. 87(8), 3255-3267.
19. Hooshmand-Moghadam B., Bagheri R, Roozbeh B., Ashtary-Larky D., Gaeini A.A., Dutheil F, Wong A., 2021. Impact of saffron (Crocus sativus Linn) supplementation and resistance training on markers implicated in depression and happiness levels in untrained young males. Physiol Behav. 233, 113352.
20. Piri M., Moslim Haghigi M., Azarbaijani M.A., Khajelou A., 2012. The effect of saffron aqueous extract and aerobic exercise on the concentration of hepatic non-enzymatic antioxidants in streptotocin-treated diabetic rats. Res Sport Biosci. 2(7), 5-16. [In Persian]
21. Fazel Kalkhoran J., Shibak A., 2013. Effect of four weeks HIT on the levels of GH, IGFBP-3, IGF-1 and serum cortisol and some performance indicators in Iran women national basketball team. J Sport Biosci. 5(4), 1-19. [In Persian]
22. Varmazyar M., Azarbayjani M., 2014. The effect of saffron supplementation of antioxidant enzymes activities during a session eccentric exercise in active males. J. Med. Plants. 13(50), 54-63. [In Persian]
23. Akbarnejad A., Rajabi A., Yari M., Mamshali E., 2017. The effect of saffron consumption and intermittent aerobic exercise on spirometryand physiological parametersand blood pressure in non-athletic boys. Sport Physiology and Management Investigations. 9(2), 21-33. [In Persian]
24. Akbari M., Shahidi F., Rajabi H., Kashef M., Mazaheri Z., 2018. The simultaneous effect of six weeks forced swimming and crocin supplementation on the expression of 3-cardiomyocyte genesase 3 in male rats infected with hydrogen peroxide. Razi J Med Sci. 25(9), 26-37. [In Persian]
25. Rajabi A., Siahkouhian M., Akbarnejad A., 2018. The adaptability of serum irisin, lipid profile, and insulin resistance to an aerobic exercise and the consumption of saffron and its sustainability in type 2 diabetic women. Daneshvar Medicine. 26(1), 9-26. [In Persian]
26. Rajabi A., Akbarnejad A., Siahkouhian M., Yari M., 2019. Effect of saffron supplementation and exercise training on blood pressure, pulmonary function and spirometery indicators in obese and overweight women affected by type 2 diabetes. J Gorgan Univ Med Sci. 21(2), 59-69. [In Persian]
27. Akbari M., Shahidi F., Rajabi H., Kashef M., Mazaheri Z., 2019. The interactive effect of forced swimming and crocin supplementation on the expression of BAX and BCL-2 cardiomyocyte genes in male rats infected with hydrogen peroxide. J Isfahan Med Sci. 37(525), 443-453. [In Persian]
28. Khosravi A., 2020. The combined effect of aerobic exercise with saffron extract on some indices of soleus muscle apoptosis regulatory factors of male rats following an aerobic exercise until exhaustion. Journal of Applied Health Studies in Sport Physiology. 6(2), 86-95. [In Persian]
29. Rajabi A., Siahkouhian M., Akbarnejad A., 2019. Comparison of the effect of a therapeutic exercise program and oral administration of saffron on the levels of IL-6, TNF-α and glycemic control in type 2 diabetic women. Razi Journal of Medical Sciences. 25(166), 20-33. [In Persian]
30. Helalizadeh M., Labbafi Hoseinabadi M., Rohani H., Hajiaghaee R., Hatami E., 2020. Meta-analysis of the effectiveness of saffron supplementation on enzymatic antioxidant defense biomarkers in exercise. Sport Physiol. 12(45), 129-152. [In Persian]
31. Shekarriz H., Galedari M., Khorsandi L., Nikbakht M., 2020. Protective effects of aerobic training and crocin on doxorubicin induced heart tissue oxidative stress in male rats. Iranian J Nutr Sci Food Technol. 15(2), 11-20. [In Persian]
32. Davoodi M., Zilaei Bouri S., Dehghan Ghahfarokhi S., 2021. Antioxidant effects of aerobic training and crocin consumption on doxorubicin-induced testicular toxicity in rats. J Family Reprod Health. 15(1), 28-37. [In Persian]
33. Khosravi A., Khosravi P., Daneshyar S., Valipour Dehnou V., 2022. Effect of aerobic exercise combined with saffron extract supplementation on serum levels of tumor necrosis factor-α and C-reactive protein in rats following an aerobic exercise until exhaustion. Complement Med J. 11(4), 358-371. [In Persian]
34. Hosseini S.E., Akbarnejad A., Shabkhiz F., Soori R., 2021. The effect of aerobic exercise and oral consumption of Iranian saffron flower on nesfatin-1 and omentin-1 in obese women with type 2 diabetes. J Anim Biol. 13(4), 47-56. [In Persian]
35. Asvadi R., Akbarnejad A., Soori R., 2022. Evaluation of the effects of 9 weeks of aerobic exercise with and without saffron supplementation on liver enzyme AST and HOMA-IR in obese female patients with type 2 diabetes. Sport Physiology and Management Investigations (SPMI). 14(2), 121-135. [In Persian]
36. Bazyar F., Shabani R., Elmiyeh A., 2023. The effects of endurance training and saffron extract on the expression of Bax, Bcl-2, and Caspase-3 genes in the hippocampal tissue of Alzheimer's male rats. J Jiroft Univ Med Sci. 9(4), 1151-1159. [In Persian]
37. Maskanati F., Ghasemian S.O., Khanmohammadi R., Salehi O., 2022. Interactive effects of aerobic training and Crocin supplementation on some apoptosis markers in kidney tissue of rats exposed to doxorubicin. Feyz Med Sci J. 26(6), 683-690. [In Persian]
38. Poursadeghi S., Kashef M., Shahidi F., Vosadi E., 2022. Combined effect of aerobic exercise and crocin supplementation on the prevention of myocardial tissue cell death in male wistar rats. J. Ilam Uni. Med. Sci. 30(5), 101-111. [In Persian]
39. Rajabi A, Khajehlandi M, Siahkuhian M, Akbarnejad A, Khoramipour K, Suzuki K., 2022. Effect of 8 weeks aerobic training and saffron supplementation on inflammation and metabolism in middle-aged obese women with type 2 diabetes mellitus. Sports. 10(11), 167.
40. Pourmousavi L., Hashemkandi Asadi R., Zehsaz F., Jadidi R.P., 2023. Effect of crocin and treadmill exercise on oxidative stress and heart damage in diabetic rats. PLoS One. 18(12), e0281692.
41. Rajabi A., Akbar Nezhad Gharehlo A., Madadizadeh E., Basereh A., Khoramipoor K., Pirani H., Khoramipour K., Moser O., Khoramipour K., 2024. The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes-specific markers and inflammation in women with type 2 diabetes: A randomized double-blind placebo-controlled trial. Eur J Sport Sci. 24(7), 899-906.
42. Moghadasi M., Akbari F., Najafi P., 2024. Interaction of aerobic exercise and crocin improves memory, learning and hypocampic tau and neurotrophins gene expression in rats treated with trimethytin as a model of Alzheimer's disease. Mol Biol Rep. 51(1), 111.
43. Emamghoreishi M., Ghasemi F., 2012. The effect of subchronic administration of the aqueous and hydro-alcoholic extracts of Crocus sativus from Estahbanat, Fars Province, on mice. Armaghan-e-Danesh. 16(6), 527-536. [In Persian]
44. Asishirazi I., Hosseini S.A., Keikhosravi F., 2017. Hypoglycemic interactional effects of saffron (Crocus sativus) aqueous extract and swimming training in streptozotocin induced diabetic rats. J Sabzevar Univ Med Sci. 24(4), 273-279. [In Persian]
45. Khosravi A., Omidali O.A., Rasoulian B., Choobineh S., 2017. The effects of short-term aqueous saffron extracts consumption on malondialdehyde and anti-oxidant system content of liver of young male rats following an acute bout of exhaustive exercise. Yafteh. 19(1), 20-30. [In Persian]
46. Khosravi A., Omid Ali F., 2018. The effect of saffron stigmas aqueous extracts on serum cardiac troponin T and creatine kinase MB isoenzyme of male rats following an exhaustive exercise. J Arak Uni Med Sci. 21(2), 43-54. [In Persian]
47. Akbari F., Moghadasi M., Farsi S., Edalatmanesh M.A., 2019. The effect of eight weeks moderate-intensity endurance training with saffron intake on memory and learning in rats with trimethytin model of Alzheimer’s Disease. J Appl Exerc Physiol. 15(30), 115-128.
48. Akbari-Fakhrabadi M., Najafi M., Mortazavian S., Rasouli M., Memari A.H., Shidfar F., 2019. Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats. J Food Biochem. 43(8), e12946.
49. Shahidani S., Rajaei Z., Alaei H., 2019. Pretreatment with crocin along with treadmill exercise ameliorates motor and memory deficits in hemiparkinsonian rats by anti-inflammatory and antioxidant mechanisms. Metab Brain Dis. 34(2), 459-468.
50. Peyravi A., Yazdanpanahi N., Nayeri H., Hosseini S.A., 2020. The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats. J Food Biochem. 44(2), e13125.
51. Dastgerdi H.H., Radahmadi M., Reisi P., 2020. Comparative study of the protective effects of crocin and exercise on long-term potentiation of CA1 in rats under chronic unpredictable stress. Life Sci. 256, 118018.
52. Nezamdoost Z., Saghebjoo M., Hoshyar R., Hedayati M., Keska A., 2020. High-intensity training and saffron: Effects on breast cancer-related gene expression. Med Sci Sports Exerc. 52(7), 1470-1476.
53. Akbari-Fakhrabadi M., Najafi M., Mortazavian S., Memari A.H., Shidfar F., Shahbazi A., Heshmati J., 2021. Saffron (Crocus sSativus L.), combined with endurance exercise, synergistically enhances BDNF, serotonin, and NT-3 in wistar rats. Rep Biochem Mol Biol. 9(4), 426-434.
54. Akbari F., Moghadasi M., 2023. Effect of eight-week moderate intensity endurance training with crocin consumption on MAP-Tau and NFG gene expression in rats with hippocampal degeneration model. Sport Physiology and Management Investigations. 15(1), 169-180.
55. Khanmohammadi R., Azarbayjani M.A., Piri M., Khorsandi L.S., 2019. The effect of severe periodic training and crocin on oxidative stress in male rats subjected to doxorubicin induction. Armaghan-e-Danesh. 23(6), 694-708.
56. Darash K., Ghanbarzadeh M., Masoud M., 2020. Effect of eight-week exercise and crocin on the apoptotic indices of male rats’ testicles subjected to the apoptosis by Doxorubicin. Razi J Med Sci (RJMS). 26(11), 134-144.
57. Sadr Arhami H., Nourshahi M., Ebrahim K., Mousavi Mozafar M., Hedayati M., 2019. The effect of 8-week sprint interval training with consuming saffron extract on the factors affecting longevity in male rats. Iran J Nutr Sci Food Technol. 14(1), 19-26.
58. Razavi S.H., Hosseini S.A., Nikbakht M., 2019. The effect of continued and interval training with crocin consumption on BDNF and NGF gene expression in heart tissue of diabetic rats. Feyz Med Sci J. 23(1), 10-19.
59. Moradi M., Shakerian S., Nikbakht M., 2019. The effect of eight weeks high intensity interval training and crocin consumption on oxidative stress of liver tissue in male rats subjected to chronic doxorubicin injection. Feyz Med Sci J. 23(5), 485-494.
60. Moradi M., Shakerian S., Nikbakht M., 2020. Effect of eight weeks of high intensity interval training and crocin consumption on the apoptotic genes expression in the liver tissue of male rats under chronic doxorubicin induction. J Birjand Univ Med Sci. 27(4), 323-335.
61. Alaie M., Gaeini A.A., Nouri R., Chobineh S., 2020. Interaction effect of high interval and low intensity continuous trainings with crocin on the expressions of PGC-1a and UCP1 in heart tissue of male diabetic rats. Res Med. 44(3), 423-429.
62. Hasanvand B., Mehrialvar Y., Heydarianpour A., Erfaniadab F., 2020. Comparison of the effect of different intensities of exercise training with saffron supplementation on the metabolic balance in overweight and obese women. Yafteh. 22(2), 160-176.
63. Ahmadabadi F., Saghebjoo M., Hedayati M., Hoshyar R., Huang C.J., 2021. Treatment-induced tumor cell apoptosis following high-intensity interval training and saffron aqueous extract in mice with breast cancer. Physiol Int. 2021,19-26.
64. Davari F., Alimanesh Z., Alimanesh Z., Salehi O., Hosseini S.A., 2022. Effect of training and crocin supplementation on mitochondrial biogenesis and redox-sensitive transcription factors in liver tissue of type 2 diabetic rats. Arch Physiol Biochem. 128(5), 1215-1220.
65. Ahmadi Qaracheh R., Fathi M., Rahmati M., 2022. Effect of eight weeks of high intensity interval training and crocin consumption on serum markers of dox-induced cardiotoxicity in male wistar rats. Complement Med J. 12(2), 136-147.
66. Bahrami F., Pour F.J., Hassanpour M., Saki M., Ebrahimzadeh F., Jafaripour L., 2023. The effect of saffron and corrective exercises on depression and quality of life in women with multiple sclerosis: A randomized controlled clinical trial. Mult Scler Relat Disord. 79, 105038.
67. Hooshmand Moghadam B., Rashidlamir A., Attarzadeh Hosseini S.R., Gaeini A.A., Kaviani M., 2022. The effects of saffron (Crocus sativus L.) in conjunction with concurrent training on body composition, glycaemic status, and inflammatory markers in obese men with type 2 diabetes mellitus: A randomized double-blind clinical trial. Br J Clin Pharmacol. 88(7), 3256-3271.
68. Lopresti A.L., Smith S.J., 2022. An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study. J Int Soc Sports Nutr. 19(1), 219-238.
69. Khosravi A., 2019. The effect of aqueous saffron extract on maximum aerobic capacity, lipid peroxidation and total antioxidant capacity of serum of young male athletes following a sauna session leading to a 4% reduction in body weight. J Tabriz Univ Med Sci. 41(5), 44-55.
70. Ghalandari-Shamami M., Nourizade S., Yousefi B., Vafaei A.A., Pakdel R., Rashidy-Pour A., 2019. Beneficial effects of physical activity and crocin against adolescent stress induced anxiety or depressive-like symptoms and dendritic morphology remodeling in prefrontal cortex in adult male rats. Neurochem Res. 44(4), 917-929.
71. Ghalandari-Shamami M., Nourizade S., Barati M., Yousefi B., Pashayi M., Ali Vafaei A., Kokhaei P., Rashidy-Pour A., 2021. Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats. Brain Res. 1754, 147274.
72. Ghaffari S., Roshanravan N., 2019. Saffron; An updated review on biological properties with special focus on cardiovascular effects. Biomed Pharmacother. 109, 21-27.
73. Lu C., Ke L., Li J., Zhao H., Lu T., Mentis A.F.A., Wang Y., Wang Z., Polissiou M.G., Tang L., Tang H., Yang K., 2021. Saffron (Crocus sativus L.) and health outcomes: a meta-research review of meta-analyses and an evidence mapping study. Phytomedicine. 91, 153699.
74. Rashid M., Rashid R., Saroya S., Deverapalli M., Brim H., Ashktorab H., 2024. Saffron as a promising therapy for inflammatory bowel disease. Nutrients. 16(14), 2353.
75. Sadigi B., Yarani R., Mirghafourvand M., Travica N., Yousefi Z., Shakouri S.K., Ostadrahimi A., Mobasseri M., Pociot F., Sanaie S., Araj-Khodaei M., 2022. The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews. Phytother Res. 36(9), 3444-3458.
76. Han S., Cao Y., Wu X., Xu J., Nie Z., Qiu Y., 2024. New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms. Phytother Res. 38(5), 2276-2302.
77. Pourmousavi L., Asadi R.H., Zehsaz F., Jadidi R.P., 2024. Potential therapeutic effects of crocin. Naunyn Schmiedebergs Arch Pharmacol. https://doi.org/10.1007/s00210-024-03131-6
78. Hasheminasab F.S., Azimi M., Raeiszadeh M., 2024. Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review. Phytother Res. 38(6), 2832-2846.
79. Goyal A., Raza F.A., Sulaiman S.A., Shahzad A., Aaqil S.I., Iqbal M., Javed B., Pokhrel P., 2024. Saffron extract as an emerging novel therapeutic option in reproduction and sexual health: recent advances and future prospectives. Ann Med Surg (Lond). 86(5), 2856-2865.
80. Amatto P.P.G., Chaves L., Braga G.G., Carmona F., Pereira A.M.S., 2024. Effect of Crocus sativus L. (saffron) and crocin in the treatment of patients with type-2 diabetes mellitus: A systematic review and meta-analysis. J Ethnopharmacol. 319(Pt 2), 117255.
81. Seyedi-Sahebari S., Farhang S., Araj-Khodaei M., Akhondzadeh S., Naseri A., Sanaie S., Frounchi N., 2024. The effects of Crocus sativus (Saffron) on ADHD: A systematic review. J Atten Disord. 28(1), 14-24.
82. Poursamimi J., Shariati-Sarabi Z., Tavakkol-Afshari J., Mohajeri S.A., Mohammadi M. 2020. Crocus sativus (Saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iran J Allergy Asthma Immunol. 19(S1), 27-42.
83. Broadhead G.K., Grigg J., McCluskey P.J., Hong T., Schlub T.E., Chu E., Chang A.A., 2024. Saffron therapy for the ongoing treatment of age-related macular degeneration. BMJ Open Ophthalmol. 9(1), e001399.
84. Farhadi L., Hojati V., Khaksari M., Vaezi G., 2022. Neuroprotective effects of crocin against ethanol neurotoxicity in the animal model of fetal alcohol spectrum disorders. Neurochem Res. 47, 1001-1011.
85. Avgerinos K.I., Vrysis C., Chaitidis N., Kolotsiou K., Myserlis P.G., Kapogiannis D., 2020. Effects of saffron (Crocus sativus L.) on cognitive function. A systematic review of RCTs. Neurol Sci. 41(10), 2747-2754.
86. Aslani M.R., Abdollahi N., Matin S., Zakeri A., Ghobadi H., 2023. Effect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 130(3), 446-453.
87. Dariushnejad H., Mohammadi M., Ghorbanzadeh V., 2018. Crocin and voluntary exercise promote heart angiogenesis through Akt and ERK1/2 signalling in type 2 diabetic rats. Bratisl Lek Listy. 119(12), 757-761.
88. Ghorbanzadeh V., Mohammadi M., Dariushnejad H., Abhari A., Chodari L., Mohaddes G., 2017. Cardioprotective effect of crocin combined with voluntary exercise in rat: Role of Mir-126 and Mir-210 in heart angiogenesis. Arq Bras Cardiol. 109(1), 54-62.
89. Ghobadi H., Abdollahi N., Madani H., Aslani M.R., 2022. Effect of crocin from saffron (Crocus sativus L.) supplementation on oxidant/antioxidant markers, exercise capacity, and pulmonary function tests in COPD patients: A randomized, double-blind, placebo-controlled trial. Front Pharmacol. 13, 884710.
90. Hamedani S.G., Pourmasoumi M., Zarifi S.H., Askari G., Jamialahmadi T., Bagherniya M., Sahebkar A., 2024. Therapeutic effects of saffron and its components on neurodegenerative diseases. Heliyon. 10(2), e24334.
91. Bej E., Volpe A.R., Cesare P., Cimini A., d'Angelo M., Castelli V., 2024. Therapeutic potential of saffron in brain disorders: From bench to bedside. Phytother Res. 38(5), 2482-2495.
92. Ebrahimzadeh A., Moghadam S.Y., Rahimi H., Motaghinejad M., Motevalian M., Safari S., Mesrabadi M.A., 2019. Crocin acts as a neuroprotective mediator against methylphenidate induced neurobehavioral and neurochemical sequelae: Possible role of the CREB-BDNF signaling pathway. Acta Neurobiol Exp. 79(4), 352-366.
93. Shahbaz K., Chang D., Zhou X., Low M., Seto S.W., Li C.G., 2022. Crocins for Ischemic Stroke: A Review of Current Evidence. Front Pharmacol. 13, 825842.
94. Abdullaev F.I., Espinosa-Aguirre J.J., 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev. 28(6), 426-432.
95. Mokhtarian R., Rajabi S., Zahedian S., Jafarinejad-Farsangi S., Hadizadeh M., Sadeghinejad M., 2024. The effect of saffron and its extracts on the treatment of breast cancer: A narrative review. Ann Pharm Fr. 82(4), 629-640.
96. Colapietro A., Mancini A., D'Alessandro A.M., Festuccia C., 2019. Crocetin and crocin from saffron in cancer chemotherapy and chemoprevention. Anticancer Agents Med Chem. 19(1), 38-47.
97. Rashid M., Brim H., Ashktorab H., 2022. Saffron, its active components, and their association with DNA and histone modification: A narrative review of current knowledge. Nutrients. 14(16), 3317.
98. Wang Y., Han T., Zhu Y., Zheng C.H., Ming Q., Rahman K.H., Qin L., 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med. 64, 24-30.
99. El Midaoui A., Ghzaiel I., Vervandier-Fasseur D., Ksila M., Zarrouk A., Nury T., Khallouki F., El Hessni A., Ibrahimi S.O., Latruffe N., Couture R., Kharoubi O., Brahmi F., Hammami S., Masmoudi-Kouki O., Hammami M., Ghrairi T., Vejux A., Lizard G., 2022. Saffron (Crocus sativus L.): A source of nutrients for health and for the treatment of neuropsychiatric and age-related diseases. Nutrients. 14(3), 597.
100. Musazadeh V., Zarezadeh M., Faghfouri A.H., Keramati M., Ghoreishi Z., Farnam A., 2022. Saffron, as an adjunct therapy, contributes to relieve depression symptoms: An umbrella meta-analysis. Pharmacol Res. 175, 105963.
101. Cerdá-Bernad D., Valero-Cases E., Pastor J.J., Frutos M.J., 2022. Saffron bioactives crocin, crocetin and safranal: effect on oxidative stress and mechanisms of action. Crit Rev Food Sci Nutr. 62(12), 3232-3249.
102. Tavakkol-Afshari J., Brook A., Mousavi S.H., 2008. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxicol. 46(11), 3443-3447.
103. Amin A., Hamza A.A., Bajbouj K., Ashraf S.S., Daoud S., 2011. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology. 54(3), 857-867.
104. Mir R.A., Tyagi A., Hussain S.J., Almalki M.A., Zeyad M.T., Deshmukh R., Ali S., 2024. Saffron, a potential bridge between nutrition and disease therapeutics: Global health challenges and therapeutic opportunities. Plants (Basel). 13(11), 1467.
105. Hojati V., Jalali E. 2024. A review on the combined effects of saffron plant extract and sports activity on the male reproductive system. 7th National Conference of Saffron, 13-14 November, 2024, Univeristy of Birjand, Birjand, Iran.
106. Hojati V., 2024. A review of the effects of saffron plant (Crocus sativus L.) extract on the female reproductive system. 7th National Conference of Saffron, 13-14 November, 2024, Univeristy of Birjand, Birjand, Iran.