Clinical and metabolic responses to crocin in patients under methadone maintenance treatment: A randomized clinical trial.
crocin
mental health
metabolic profiles
methadone maintenance treatment
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
06
05
2019
revised:
14
06
2019
accepted:
26
06
2019
pubmed:
31
7
2019
medline:
27
12
2019
entrez:
31
7
2019
Statut:
ppublish
Résumé
Patients under methadone maintenance treatment (MMT) programs are susceptible to several complications including metabolic and clinical disorders. This study was designed to determine the effect of crocin supplementation on mental health parameters and metabolic profiles in subjects under MMT. The current randomized, double-blind, placebo-controlled, clinical trial was conducted among 53 patients under MMT to receive either 15 mg/day of crocin (n = 26) or placebo (n = 27) twice a day for 8 weeks. Crocin administration significantly decreased Beck Depression Inventory score (P = 0.01) and Beck Anxiety Inventory score (P = 0.008) compared with the placebo. In addition, crocin administration resulted in a significant reduction in fasting glucose (P = 0.003), insulin levels (P = 0.01), insulin resistance (P = 0.008), triglycerides (P = 0.001), very low-density lipoprotein (P = 0.001), total cholesterol levels (P = 0.03), and a significant increase in insulin sensitivity (.003) compared with the placebo. Additionally, crocin intake was associated with a significant reduction in high-sensitivity C-reactive protein (p < .001) and malondialdehyde (P = 0.001) and a significant rise in total antioxidant capacity levels (P = 0.01) compared with the placebo. The findings of this clinical trial indicate that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health and improved their metabolic profiles.
Substances chimiques
Blood Glucose
0
Lipids
0
Carotenoids
36-88-4
crocin
877GWI46C2
Methadone
UC6VBE7V1Z
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2714-2725Subventions
Organisme : Research Deputy of Kashan University of Medical Sciences (KAUMS)
ID : IR.KAUMS.REC.1397.006
Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
Amin-Esmaeili, M., Rahimi-Movaghar, A., Sharifi, V., Hajebi, A., Radgoodarzi, R., Mojtabai, R., … Motevalian, A. (2016). Epidemiology of illicit drug use disorders in Iran: Prevalence, correlates, comorbidity and service utilization results from the Iranian Mental Health Survey. Addiction, 111(10), 1836-1847. https://doi.org/10.1111/add.13453
Ayatollahi, H., Javan, A. O., Khajedaluee, M., Shahroodian, M., & Hosseinzadeh, H. (2014). Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytotherapy Research, 28(4), 539-543. https://doi.org/10.1002/ptr.5021
Azimi, P., Ghiasvand, R., Feizi, A., Hariri, M., & Abbasi, B. (2014). Effects of cinnamon, cardamom, saffron, and ginger consumption on markers of glycemic control, lipid profile, oxidative stress, and inflammation in type 2 diabetes patients. The Review of Diabetic Studies, 11(3-4), 258-266. https://doi.org/10.1900/RDS.2014.11.258
Bakshi, H. A., Hakkim, F. L., & Sam, S. (2016). Molecular mechanism of crocin induced caspase mediated mcf-7 cell death: In vivo toxicity profiling and ex vivo macrophage activation. Asian Pacific Journal of Cancer Prevention, 17(3), 1499-1506. https://doi.org/10.7314/apjcp.2016.17.3.1499
Beck, A. T., Epstein, N., Brown, G., & Steer, R. A. (1988). An inventory for measuring clinical anxiety: Psychometric properties. Journal of Consulting and Clinical Psychology, 56(6), 893-897. https://doi.org/10.1037/0022-006X.56.6.893
Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561-571. https://doi.org/10.1001/archpsyc.1961.01710120031004
Benzie, I. F., & Strain, J. J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": The FRAP assay. Analytical Biochemistry, 239(1), 70-76. https://doi.org/10.1006/abio.1996.0292
Beutler, E., & Gelbart, T. (1985). Plasma glutathione in health and in patients with malignant disease. The Journal of Laboratory and Clinical Medicine, 105(5), 581-584.
Callaly, T., Trauer, T., Munro, L., & Whelan, G. (2001). Prevalence of psychiatric disorder in a methadone maintenance population. The Australian and New Zealand Journal of Psychiatry, 35(5), 601-605. https://doi.org/10.1080/0004867010060507
Chan, Y. Y., Yang, S. N., Lin, J. C., Chang, J. L., Lin, J. G., & Lo, W. Y. (2015). Inflammatory response in heroin addicts undergoing methadone maintenance treatment. Psychiatry Research, 226(1), 230-234. https://doi.org/10.1016/j.psychres.2014.12.053
Cousins, G., Teljeur, C., Motterlini, N., McCowan, C., Dimitrov, B. D., & Fahey, T. (2011). Risk of drug-related mortality during periods of transition in methadone maintenance treatment: a cohort study. Journal of Substance Abuse Treatment, 41(3), 252-260. https://doi.org/10.1016/j.jsat.2011.05.001
Danial, Z., Motamedi, M. H., Mirhashemi, S., Kazemi, A., & Mirhashemi, A. H. (2014). Ageing in iran. Lancet, 384(9958), 1927. https://doi.org/10.1016/s0140-6736(14)62278-9
Dolan, K. A., Shearer, J., MacDonald, M., Mattick, R. P., Hall, W., & Wodak, A. D. (2003). A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system. Drug and Alcohol Dependence, 72(1), 59-65. https://doi.org/10.1016/S0376-8716(03)00187-X
Dorri, S. A., Hosseinzadeh, H., Abnous, K., Hasani, F. V., Robati, R. Y., & Razavi, B. M. (2015). Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iranian Journal of Basic Medical Sciences, 18(10), 958-966.
Doumouchtsis, E. K., Tzani, A., Doulamis, I. P., Konstantopoulos, P., Laskarina-Maria, K., Agrogiannis, G., … Perrea, D. N. (2018). Effect of saffron on metabolic profile and retina in apolipoprotein E-Knockout mice fed a high-fat diet. Journal of Dietary Supplements, 15(4), 471-481. https://doi.org/10.1080/19390211.2017.1356417
Erfanparast, A., Tamaddonfard, E., Taati, M., & Dabbaghi, M. (2015). Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats. Avicenna Journal of Phytomedicine, 5(5), 392-402.
Fadai, F., Mousavi, B., Ashtari, Z., Ali Beigi, N., Farhang, S., Hashempour, S., … Bathaie, S. Z. (2014). Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: A randomized triple blind placebo controlled study. Pharmacopsychiatry, 47(4-5), 156-161. https://doi.org/10.1055/s-0034-1382001
Farkhondeh, T., & Samarghandian, S. (2014). The effect of saffron (Crocus sativus L.) and its ingredients on the management of diabetes mellitus and dislipidemia. African Journal of Pharmacy and Pharmacology, 8(20), 541-549.
Fonseca, F., Marti-Almor, J., Pastor, A., Cladellas, M., Farre, M., de la Torre, R., & Torrens, M. (2009). Prevalence of long QTc interval in methadone maintenance patients. Drug and Alcohol Dependence, 99(1-3), 327-332. https://doi.org/10.1016/j.drugalcdep.2008.06.018
Forrester, J. E., Tucker, K. L., & Gorbach, S. L. (2004). Dietary intake and body mass index in HIV-positive and HIV-negative drug abusers of Hispanic ethnicity. Public Health Nutrition, 7(7), 863-870. https://doi.org/10.1079/PHN2004617
Ghaderi, A., Banafshe, H. R., Mirhosseini, N., Motmaen, M., Mehrzad, F., Bahmani, F., … Karimi, M. A. (2019). The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment. Addiction Biology, 24(4), 754-764. https://doi.org/10.1111/adb.12650
Gmelig-Meyling, F., & Waldmann, T. A. (1980). Separation of human blood monocytes and lymphocytes on a continuous Percoll gradient. Journal of Immunological Methods, 33(1), 1-9. https://doi.org/10.1016/0022-1759(80)90077-0
Gohari, A. R., Saeidnia, S., & Mahmoodabadi, M. K. (2013). An overview on saffron, phytochemicals, and medicinal properties. Pharmacognosy Reviews, 7(13), 61-66. https://doi.org/10.4103/0973-7847.112850
Gowing, L. R., & Ali, R. L. (2006). The place of detoxification in treatment of opioid dependence. Current Opinion in Psychiatry, 19(3), 266-270. https://doi.org/10.1097/01.yco.0000218596.54054.a1
Gros, D. F., Milanak, M. E., Brady, K. T., & Back, S. E. (2013). Frequency and severity of comorbid mood and anxiety disorders in prescription opioid dependence. The American Journal on Addictions, 22(3), 261-265. https://doi.org/10.1111/j.1521-0391.2012.12008.x
Hausenblas, H. A., Saha, D., Dubyak, P. J., & Anton, S. D. (2013). Saffron (Crocus sativus L.) and major depressive disorder: A meta-analysis of randomized clinical trials. Journal of Integrative Medicine, 11(6), 377-383. https://doi.org/10.3736/jintegrmed2013056
Hosseini, A., Razavi, B. M., & Hosseinzadeh, H. (2018). Saffron (Crocus sativus) petal as a new pharmacological target: A review. Iranian Journal of Basic Medical Sciences, 21(11), 1091-1099. https://doi.org/10.22038/ijbms.2018.31243.7529
Hosseinzadeh, H., Abootorabi, A., & Sadeghnia, H. R. (2008). Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs. DNA and Cell Biology, 27(12), 657-664. https://doi.org/10.1089/dna.2008.0767
Hosseinzadeh, H., Motamedshariaty, V., & Hadizadeh, F. (2007). Antidepressant effect of kaempferol, a constituent of saffron (Crocus sativus) petal, in mice and rats. Pharmacology, 2, 367-370.
Hosseinzadeh, H., Sadeghnia, H. R., Ghaeni, F. A., Motamedshariaty, V. S., & Mohajeri, S. A. (2012). Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytotherapy Research, 26(3), 381-386. https://doi.org/10.1002/ptr.3566
Jam, I. N., Sahebkar, A. H., Eslami, S., Mokhber, N., Nosrati, M., Khademi, M., … Abbasi, M. (2017). The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Advances in Clinical and Experimental Medicine, 26(6), 925-930. https://doi.org/10.17219/acem/62891
Janero, D. R. (1990). Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radical Biology & Medicine, 9(6), 515-540. https://doi.org/10.1016/0891-5849(90)90131-2
Javandoost, A., Afshari, A., Nikbakht-Jam, I., Khademi, M., Eslami, S., Nosrati, M., … Mohajeri, A. (2017). Effect of crocin, a carotenoid from saffron, on plasma cholesteryl ester transfer protein and lipid profile in subjects with metabolic syndrome: A double blind randomized clinical trial. ARYA Atheroscler, 13(5), 245-252.
Kaviani, H., & Mousavi, A. (2008). Psychometric properties of the Persian version of Beck Anxiety Inventory (BAI). Tehran University Medical Journal, 66, 136-140.
Kermani, T., Kazemi, T., Molki, S., Ilkhani, K., Sharifzadeh, G., & Rajabi, O. (2017). The efficacy of crocin of saffron (Crocus sativus L.) on the components of metabolic syndrome: A randomized controlled clinical trial. Journal of Research in Pharmacy Practice, 6(4), 228-232. https://doi.org/10.4103/jrpp.JRPP_17_26
Kermani, T., Mousavi, S. H., Shemshian, M., Norouzy, A., Mazidi, M., Moezzi, A., … A Ferns, G. (2015). Saffron supplements modulate serum pro-oxidant-antioxidant balance in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial. Avicenna Journal of Phytomedicine, 5(5), 427-433.
Khalatbari-Mohseni, A., Banafshe, H. R., Mirhosseini, N., Asemi, Z., Ghaderi, A., & Omidi, A. (2019). The effects of crocin on psychological parameters in patients under methadone maintenance treatment: A randomized clinical trial. Substance Abuse Treatment, Prevention, and Policy, 14(1), 9. https://doi.org/10.1186/s13011-019-0198-1
Khanali, M., Shahvarooghi Farahani, S., Shojaei, H., & Elhami, B. (2017). Life cycle environmental impacts of saffron production in Iran. Environmental Science and Pollution Research International, 24(5), 4812-4821. https://doi.org/10.1007/s11356-016-8228-2
Koch, T., Widera, A., Bartzsch, K., Schulz, S., Brandenburg, L. O., Wundrack, N., … Hollt, V. (2005). Receptor endocytosis counteracts the development of opioid tolerance. Molecular Pharmacology, 67(1), 280-287. https://doi.org/10.1124/mol.104.004994
Li, S., Liu, X., Lei, J., Yang, J., Tian, P., & Gao, Y. (2017). Crocin protects podocytes against oxidative stress and inflammation induced by high glucose through inhibition of NF-kappaB. Cellular Physiology and Biochemistry, 42(4), 1481-1492. https://doi.org/10.1159/000479212
Li, X., Jiang, C., & Zhu, W. (2017). Crocin reduces the inflammation response in rheumatoid arthritis. Bioscience, Biotechnology, and Biochemistry, 81(5), 891-898. https://doi.org/10.1080/09168451.2016.1263145
Lim, S. Y., Kim, E. J., Kim, A., Lee, H. J., Choi, H. J., & Yang, S. J. (2016). Nutritional factors affecting mental health. Clinical Nutrition Research, 5(3), 143-152. https://doi.org/10.7762/cnr.2016.5.3.143
Lv, C. F., Luo, C. L., Ji, H. Y., & Zhao, P. (2008). Influence of crocin on gene expression profile of human bladder cancer cell lines T24. Zhongguo Zhong Yao Za Zhi, 33(13), 1612-1617.
Mannelli, P., Patkar, A., Rozen, S., Matson, W., Krishnan, R., & Kaddurah-Daouk, R. (2009). Opioid use affects antioxidant activity and purine metabolism: Preliminary results. Human Psychopharmacology, 24(8), 666-675. https://doi.org/10.1002/hup.1068
Maruyama, A., Macdonald, S., Borycki, E., & Zhao, J. (2013). Hypertension, chronic obstructive pulmonary disease, diabetes and depression among older methadone maintenance patients in B ritish C olumbia. Drug and Alcohol Review, 32(4), 412-418. https://doi.org/10.1111/dar.12031
Mohammadzadeh, L., Abnous, K., Razavi, B. M., & Hosseinzadeh, H. (2019). Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects. Nutritional Neuroscience, 1-16.
Mohammadzadeh, L., Hosseinzadeh, H., Abnous, K., & Razavi, B. M. (2018). Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats. Environmental Science and Pollution Research International, 25(5), 4904-4914. https://doi.org/10.1007/s11356-017-0842-0
Moravej Aleali, A., Amani, R., Shahbazian, H., Namjooyan, F., Latifi, S. M., & Cheraghian, B. (2019). The effect of hydroalcoholic saffron (Crocus sativus L.) extract on fasting plasma glucose, HbA1c, lipid profile, liver, and renal function tests in patients with type 2 diabetes mellitus: A randomized double-blind clinical trial. Phytotherapy Research. https://doi.org/10.1002/ptr.6351
Nazrul Islam, S. K., Jahangir Hossain, K., Ahmed, A., & Ahsan, M. (2002). Nutritional status of drug addicts undergoing detoxification: Prevalence of malnutrition and influence of illicit drugs and lifestyle. The British Journal of Nutrition, 88(5), 507-513. https://doi.org/10.1079/bjn2002702
Nosrati, M., Nikbakht-Jam, I., Eslami, S., Khademi, M. M., Foroutan-Tanha, M., Hadizadeh, F., … Ferns, G. A. A. (2017). Effect of crocin on antibody titers to heat-shock protein 27 in subjects with metabolic syndrome. Current Clinical Pharmacology, 12(2), 113-121. https://doi.org/10.2174/1574884712666170509162523
Ochiai, T., Soeda, S., Ohno, S., Tanaka, H., Shoyama, Y., & Shimeno, H. (2004). Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide signaling by increasing glutathione synthesis. Neurochemistry International, 44(5), 321-330. https://doi.org/10.1016/S0197-0186(03)00174-8
Pisprasert, V., Ingram, K. H., Lopez-Davila, M. F., Munoz, A. J., & Garvey, W. T. (2013). Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: Impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care, 36(4), 845-853. https://doi.org/10.2337/dc12-0840
Pourmasoumi, M., Hadi, A., Najafgholizadeh, A., Kafeshani, M., & Sahebkar, A. (2019). Clinical evidence on the effects of saffron (Crocus sativus L.) on cardiovascular risk factors: A systematic review meta-analysis. Pharmacological Research, 139, 348-359. https://doi.org/10.1016/j.phrs.2018.11.038
Rajagopalan, S., Meng, X. P., Ramasamy, S., Harrison, D. G., & Galis, Z. S. (1996). Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. The Journal of Clinical Investigation, 98(11), 2572-2579. https://doi.org/10.1172/jci119076
Razavi, B. M., & Hosseinzadeh, H. (2017). Saffron: a promising natural medicine in the treatment of metabolic syndrome. Journal of the Science of Food and Agriculture, 97(6), 1679-1685. https://doi.org/10.1002/jsfa.8134
Razavi, B. M., Hosseinzadeh, H., Abnous, K., Khoei, A., & Imenshahidi, M. (2016). Protective effect of crocin against apoptosis induced by subchronic exposure of the rat vascular system to diazinon. Toxicology and Industrial Health, 32(7), 1237-1245. https://doi.org/10.1177/0748233714554941
Razavi, B. M., Sadeghi, M., Abnous, K., Vahdati Hasani, F., & Hosseinzadeh, H. (2017). Study of the role of CREB, BDNF, and VGF neuropeptide in long term antidepressant activity of crocin in the rat cerebellum. Iranian Journal of Pharmaceutical Research, 16(4), 1452-1462.
Rios, J., Recio, M., Giner, R., & Manez, S. (1996). An update review of saffron and its active constituents. Phytotherapy Research, 10(3), 189-193. https://doi.org/10.1002/(SICI)1099-1573(199605)10:3<189::AID-PTR754>3.0.CO;2-C
Saeland, M., Haugen, M., Eriksen, F. L., Smehaugen, A., Wandel, M., Bohmer, T., & Oshaug, A. (2009). Living as a drug addict in Oslo, Norway-A study focusing on nutrition and health. Public Health Nutrition, 12(5), 630-636. https://doi.org/10.1017/s1368980008002553
Sahraian, A., Jelodar, S., Javid, Z., Mowla, A., & Ahmadzadeh, L. (2016). Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian Journal of Psychiatry, 22, 174-176. https://doi.org/10.1016/j.ajp.2015.10.012
Salarian, A., Kadkhodaee, M., Zahmatkesh, M., Seifi, B., Bakhshi, E., Akhondzadeh, S., … Arbabi, M. (2018). Opioid use disorder induces oxidative stress and inflammation: The attenuating effect of methadone maintenance treatment. Iranian Journal of Psychiatry, 13(1), 46-54.
Schmidt, M., Betti, G., & Hensel, A. (2007). Saffron in phytotherapy: Pharmacology and clinical uses. Wiener Medizinische Wochenschrift (1946), 157(13-14), 315-319. https://doi.org/10.1007/s10354-007-0428-4
Shafiee, M., Arekhi, S., Omranzadeh, A., & Sahebkar, A. (2018). Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. Journal of Affective Disorders, 227, 330-337. https://doi.org/10.1016/j.jad.2017.11.020
Shakibi, M. R. (2004). Prevalence of opium addiction in Iranian drivers 2001-2003. Journal of Medical Sciences, 4(3), 210-213.
Shirali, S., Zahra Bathaie, S., & Nakhjavani, M. (2013). Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytotherapy Research, 27(7), 1042-1047. https://doi.org/10.1002/ptr.4836
Tabeshpour, J., Sobhani, F., Sadjadi, S. A., Hosseinzadeh, H., Mohajeri, S. A., Rajabi, O., … Eslami, S. (2017). A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomedicine, 36, 145-152. https://doi.org/10.1016/j.phymed.2017.10.005
Talaei, A., Hassanpour Moghadam, M., Sajadi Tabassi, S. A., & Mohajeri, S. A. (2015). Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. Journal of Affective Disorders, 174, 51-56. https://doi.org/10.1016/j.jad.2014.11.035
Tatsch, E., Bochi, G. V., Pereira Rda, S., Kober, H., Agertt, V. A., de Campos, M. M., … Moresco, R. N. (2011). A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clinical Biochemistry, 44(4), 348-350. https://doi.org/10.1016/j.clinbiochem.2010.12.011
Thushara, R. M., Hemshekhar, M., Paul, M., Shanmuga Sundaram, M., Shankar, R. L., Kemparaju, K., & Girish, K. S. (2014). Crocin prevents sesamol-induced oxidative stress and apoptosis in human platelets. Journal of Thrombosis and Thrombolysis, 38(3), 321-330. https://doi.org/10.1007/s11239-014-1056-7
Tsai, M. C., & Huang, T. L. (2017). Brain-derived neurotrophic factor (BDNF) and oxidative stress in heroin-dependent male patients undergoing methadone maintenance treatment. Psychiatry Research, 249, 46-50. https://doi.org/10.1016/j.psychres.2016.12.042
Vahdati Hassani, F., Mehri, S., Abnous, K., Birner-Gruenberger, R., & Hosseinzadeh, H. (2017). Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression. Food and Chemical Toxicology, 107(Pt A), 395-405. https://doi.org/10.1016/j.fct.2017.07.007
Vakili, A., Einali, M. R., & Bandegi, A. R. (2014). Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke. Journal of Stroke and Cerebrovascular Diseases, 23(1), 106-113. https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.10.008
Vallecillo, G., Robles, M. J., Torrens, M., Samos, P., Roquer, A., Martires, P. K., … Pedro-Botet, J. (2018). Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors. Substance Abuse, 39(1), 46-51. https://doi.org/10.1080/08897077.2017.1363122
Wang, Y., Han, T., Zhu, Y., Zheng, C. J., Ming, Q. L., Rahman, K., & Qin, L. P. (2010). Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. Journal of Natural Medicines, 64(1), 24-30. https://doi.org/10.1007/s11418-009-0360-6
Yang, X., Huo, F., Liu, B., Liu, J., Chen, T., Li, J., … Lv, B. (2017). Crocin inhibits oxidative stress and pro-inflammatory response of microglial cells associated with diabetic retinopathy through the activation of PI3K/Akt signaling pathway. Journal of Molecular Neuroscience, 61(4), 581-589. https://doi.org/10.1007/s12031-017-0899-8
Yarijani, Z. M., Pourmotabbed, A., Pourmotabbed, T., & Najafi, H. (2017). Crocin has anti-inflammatory and protective effects in ischemia-reperfusion induced renal injuries. Iranian Journal of Basic Medical Sciences, 20(7), 753-759. https://doi.org/10.22038/ijbms.2017.9005
Yin, W., Pang, L., Cao, X., McGoogan, J. M., Liu, M., Zhang, C., … Rou, K. (2015). Factors associated with depression and anxiety among patients attending community-based methadone maintenance treatment in China. Addiction, 110(Suppl 1), 51-60. https://doi.org/10.1111/add.12780
Yosri, H., Elkashef, W. F., Said, E., & Gameil, N. M. (2017). Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. International Immunopharmacology, 50, 305-312. https://doi.org/10.1016/j.intimp.2017.07.012