Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Clinical Trial

The Effects of Nano-curcumin Supplementation on Leptin and Adiponectin in Migraine Patients: A Double-blind Clinical Trial Study from Gene Expression to Clinical Symptoms

Author(s): Mohsen Sedighiyan, Elham Jafari, Sara Sohrabi Athar, Mir-Saeed Yekaninejad, Ehsan Alvandi, Mina Abdolahi and Mahmoud Djalali*

Volume 23, Issue 5, 2023

Published on: 27 December, 2022

Page: [711 - 720] Pages: 10

DOI: 10.2174/1871530322666220701100817

Price: $65

Abstract

Background: Migraine is a disabling neurogenic disorder characterized by recurrent headache attacks. Adipokines act as inflammatory and pain mediators that contribute to migraine pathogenesis. Leptin and adiponectin levels change in migraine patients and are associated with headache attacks. Curcumin can exert modulatory and analgesic effects on adipokines through several mechanisms, from gene expression to suppressing pain. The aim of the present study was to evaluate the effects of nano-curcumin supplementation on leptin and adiponectin gene expression, their serum levels and migraine symptoms in patients with migraine.

Methods: Forty-four episodic migraine patients enrolled in this trial were divided into two groups as nano-curcumin (80 mg/day) and placebo group, over a two-month period. At the beginning and the end of the study, the mRNA expression of leptin and adiponectin from isolated PBMCs and their serum levels were measured using real-time PCR and ELISA method, respectively. The headache frequencies, severity and duration of pain were also recorded.

Results: The results of the present research showed that nano-curcumin can up-regulate adiponectin mRNA and increase its serum level significantly (P < 0.05). In the case of leptin, a reduction in gene expression and concentration was found in the nano-curcumin group but it was not statistically significant (P > 0.05). Nano-curcumin also significantly reduced the frequency, severity and duration of headaches (P < 0.05).

Conclusion: These findings indicate that nano-curcumin supplement can be considered as a promising approach to migraine management and clinical symptoms improvement.

Keywords: Migraine, Leptin, Adiponectin, Headache, Curcumin, Gene expression.

« Previous Next »
Graphical Abstract

[1]
Arnold, M. Headache classification committee of the International Headache Society (IHS) the international classification of headache disorders. Cephalalgia, 2018, 38(1), 1-211.
[http://dx.doi.org/10.1177/0333102417738202] [PMID: 29368949]
[2]
Yeh, W.Z.; Blizzard, L.; Taylor, B.V. What is the actual prevalence of migraine? Brain Behav., 2018, 8(6), e00950.
[http://dx.doi.org/10.1002/brb3.950] [PMID: 30106228]
[3]
Ebahimzadeh, K.; Gholipour, M.; Samadian, M.; Taheri, M.; Ghafouri-Fard, S. A comprehensive review on the role of genetic factors in the pathogenesis of migraine. J. Mol. Neurosci., 2021, 71(10), 1987-2006.
[http://dx.doi.org/10.1007/s12031-020-01788-1] [PMID: 33447900]
[4]
Bigal, M.E.; Lipton, R.B.; Holland, P.R.; Goadsby, P.J. Obesity, migraine, and chronic migraine: possible mechanisms of interaction. Neurology, 2007, 68(21), 1851-1861.
[http://dx.doi.org/10.1212/01.wnl.0000262045.11646.b1] [PMID: 17515549]
[5]
Farello, G.; Ferrara, P.; Antenucci, A.; Basti, C.; Verrotti, A. The link between obesity and migraine in childhood: A systematic review. Ital. J. Pediatr., 2017, 43(1), 27.
[http://dx.doi.org/10.1186/s13052-017-0344-1] [PMID: 28270183]
[6]
Kos, K.; Harte, A.L.; da Silva, N.F.; Tonchev, A.; Chaldakov, G.; James, S.; Snead, D.R.; Hoggart, B.; O’Hare, J.P.; McTernan, P.G.; Kumar, S. Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus. J. Clin. Endocrinol. Metab., 2007, 92(3), 1129-1136.
[http://dx.doi.org/10.1210/jc.2006-1841] [PMID: 17213280]
[7]
Abbasi, M.; Noori-Zadeh, A.; Seidkhani-Nahal, A.; Kaffashian, M.; Bakhtiyari, S.; Panahi, S. Leptin, adiponectin, and resistin blood adipokine levels in migraineurs: Systematic reviews and meta-analyses. Cephalalgia, 2019, 39(8), 1010-1021.
[http://dx.doi.org/10.1177/0333102418807182] [PMID: 30798617]
[8]
Goulart, A.C.; de Almeida-Pititto, B.; Lotufo, P.A.; Santos, I.S.; Ferreira, S.R.; Benseñor,, I.M. Adiponectin and leptin levels in migraineurs: Results from the Brazilian longitudinal study of adult health (ELSA-Brasil). Cephalalgia Reports.,, 2020, 3, 2515816320966965.
[http://dx.doi.org/10.1177/2515816320966965]
[9]
Sarchielli, P.; Alberti, A.; Baldi, A.; Coppola, F.; Rossi, C.; Pierguidi, L.; Floridi, A.; Calabresi, P. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache, 2006, 46(2), 200-207.
[http://dx.doi.org/10.1111/j.1526-4610.2006.00337.x] [PMID: 16492228]
[10]
Martins-Oliveira, M.; Akerman, S.; Holland, P.R.; Hoffmann, J.R.; Tavares, I.; Goadsby, P.J. Neuroendocrine signaling modulates specific neural networks relevant to migraine. Neurobiol. Dis., 2017, 101, 16-26.
[http://dx.doi.org/10.1016/j.nbd.2017.01.005] [PMID: 28108291]
[11]
Domínguez,, C.; Vieites-Prado,, A.; Pérez-Mato,, M.; Sobrino,, T.; Rodríguez-Osorio,, X.; López,, A.; Campos, , F.; Martínez,, F.; Castillo,, J.; Leira,, R. Role of adipocytokines in the pathophysiology of migraine: A cross-sectional study. Cephalalgia, 2018, 38(5), 904-911.
[http://dx.doi.org/10.1177/0333102417720213] [PMID: 28677995]
[12]
Chai, N.C.; Gelaye, B.; Tietjen, G.E.; Dash, P.D.; Gower, B.A.; White, L.W.; Ward, T.N.; Scher, A.I.; Peterlin, B.L. Ictal adipokines are associated with pain severity and treatment response in episodic migraine. Neurology, 2015, 84(14), 1409-1418.
[http://dx.doi.org/10.1212/WNL.0000000000001443] [PMID: 25746563]
[13]
Hajavi, J.; Momtazi, A.A.; Johnston, T.P.; Banach, M.; Majeed, M.; Sahebkar, A. Curcumin: A naturally occurring modulator of adipokines in diabetes. J. Cell. Biochem., 2017, 118(12), 4170-4182.
[http://dx.doi.org/10.1002/jcb.26121] [PMID: 28485496]
[14]
Shehzad, A.; Lee, Y. Curcumin: Multiple molecular targets mediate multiple pharmacological actions: A review. Drugs Future, 2010, 35(2), 113.
[http://dx.doi.org/10.1358/dof.2010.035.02.1426640]
[15]
Fisher, C.D.; Lickteig, A.J.; Augustine, L.M.; Oude Elferink, R.P.; Besselsen, D.G.; Erickson, R.P.; Cherrington, N.J. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats. Eur. J. Pharmacol., 2009, 613(1-3), 119-127.
[http://dx.doi.org/10.1016/j.ejphar.2009.04.002] [PMID: 19358839]
[16]
Sasaki, H.; Sunagawa, Y.; Takahashi, K.; Imaizumi, A.; Fukuda, H.; Hashimoto, T.; Wada, H.; Katanasaka, Y.; Kakeya, H.; Fujita, M.; Hasegawa, K.; Morimoto, T. Innovative preparation of curcumin for improved oral bioavailability. Biol. Pharm. Bull., 2011, 34(5), 660-665.
[http://dx.doi.org/10.1248/bpb.34.660] [PMID: 21532153]
[17]
Schütt, M.; Brinkhoff, J.; Drenckhan, M.; Lehnert, H.; Sommer, C. Weight reducing and metabolic effects of topiramate in patients with migraine-an observational study. Exp. Clin. Endocrinol. Diabetes, 2010, 118(7), 449-452.
[http://dx.doi.org/10.1055/s-0030-1248289] [PMID: 20200812]
[18]
Berilgen, M.S.; Bulut, S.; Gonen, M.; Tekatas, A.; Dag, E.; Mungen, B. Comparison of the effects of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels when used as migraine preventive treatment. Cephalalgia, 2005, 25(11), 1048-1053.
[http://dx.doi.org/10.1111/j.1468-2982.2005.00956.x] [PMID: 16232156]
[19]
Abdolahi, M.; Tafakhori, A.; Togha, M.; Okhovat, A.A.; Siassi, F.; Eshraghian, M.R.; Sedighiyan, M.; Djalali, M.; Mohammadzadeh Honarvar, N.; Djalali, M. The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients. Immunogenetics, 2017, 69(6), 371-378.
[http://dx.doi.org/10.1007/s00251-017-0992-8] [PMID: 28478481]
[20]
Soveyd, N.; Abdolahi, M.; Djalali, M.; Hatami, M.; Tafakhori, A.; Sarraf, P. The combined effects of ω-3 fatty acids and nano-curcumin supplementation on intercellular adhesion molecule-1 (ICAM-1) gene expression and serum levels in migraine patients. CNS Neurol. Disord. Drug Targets, 2017, 16(10), 1120-1126.
[21]
Abdolahi, M.; Karimi, E.; Sarraf, P.; Tafakhori, A.; Siri, G.; Sedighiyan, M.; Asanjarani, B.; Badeli, M.; Abdollahi, H.; Yoosefi, N.; Yousefi, A.; Rad, A.S. Djalali. The omega-3 and nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: A randomized clinical trial. BMC Res. Notes, 2021, 14, 283.
[22]
Ismail, N.A.; Abd El Dayem, S.M.; Salama, E.; Ragab, S.; Abd El Baky, A.N.; Ezzat, W.M. Impact of curcumin intake on gluco-insulin homeostasis, leptin and adiponectin in obese subjects. Res. J. Pharm. Biol. Chem. Sci., 2016, 7(1), 1891-1897.
[23]
Kanai, M.; Imaizumi, A.; Otsuka, Y.; Sasaki, H.; Hashiguchi, M.; Tsujiko, K.; Matsumoto, S.; Ishiguro, H.; Chiba, T. Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother. Pharmacol., 2012, 69(1), 65-70.
[http://dx.doi.org/10.1007/s00280-011-1673-1] [PMID: 21603867]
[24]
Abdolahi, M.; Sarraf, P.; Javanbakht, M.H.; Honarvar, N.M.; Hatami, M.; Soveyd, N. A novel combination of ω-3 fatty acids and nano-curcumin modulates interleukin-6 gene expression and high sensitivity C-reactive protein serum levels in patients with migraine: A randomized clinical trial study. CNS Neurol. Disord. Drug Targets, 2018, 17(6), 430-438.
[25]
Price, D.D.; McGrath, P.A.; Rafii, A.; Buckingham, B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain, 1983, 17(1), 45-56.
[http://dx.doi.org/10.1016/0304-3959(83)90126-4] [PMID: 6226917]
[26]
Fasshauer, M.; Blüher, M. Adipokines in health and disease. Trends Pharmacol. Sci., 2015, 36(7), 461-470.
[http://dx.doi.org/10.1016/j.tips.2015.04.014] [PMID: 26022934]
[27]
Rubino, E.; Vacca, A.; Govone, F.; Gai, A.; Boschi, S.; Zucca, M.; De Martino, P.; Gentile, S.; Pinessi, L.; Rainero, I. Investigating the role of adipokines in chronic migraine. Cephalalgia, 2017, 37(11), 1067-1073.
[http://dx.doi.org/10.1177/0333102416665871] [PMID: 27553954]
[28]
Peterlin, B.L.; Tietjen, G.E.; Gower, B.A.; Ward, T.N.; Tepper, S.J.; White, L.W.; Dash, P.D.; Hammond, E.R.; Haythornthwaite, J.A. Ictal adiponectin levels in episodic migraineurs: A randomized pilot trial. Headache, 2013, 53(3), 474-490.
[http://dx.doi.org/10.1111/head.12071] [PMID: 23489216]
[29]
Guldiken, B.; Guldiken, S.; Demir, M.; Turgut, N.; Tugrul, A. Low leptin levels in migraine: A case control study. Headache, 2008, 48(7), 1103-1107.
[http://dx.doi.org/10.1111/j.1526-4610.2008.01152.x] [PMID: 18547265]
[30]
Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Soflaei, S.S.; Majeed, M.; Sahebkar, A. Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial. Nutrition, 2016, 32(10), 1116-1122.
[http://dx.doi.org/10.1016/j.nut.2016.03.018] [PMID: 27297718]
[31]
Adibian, M.; Hodaei, H.; Nikpayam, O.; Sohrab, G.; Hekmatdoost, A.; Hedayati, M. The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Phytother. Res., 2019, 33(5), 1374-1383.
[http://dx.doi.org/10.1002/ptr.6328] [PMID: 30864188]
[32]
Clark, C.C.T.; Ghaedi, E.; Arab, A.; Pourmasoumi, M.; Hadi, A. The effect of curcumin supplementation on circulating adiponectin: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab. Syndr., 2019, 13(5), 2819-2825.
[http://dx.doi.org/10.1016/j.dsx.2019.07.045] [PMID: 31425942]
[33]
Ali, B.H.; Al-Salam, S.; Al Suleimani, Y.; Al Kalbani, J.; Al Bahlani, S.; Ashique, M.; Manoj, P.; Al Dhahli, B.; Al Abri, N.; Naser, H.T.; Yasin, J.; Nemmar, A.; Al Za’abi, M.; Hartmann, C.; Schupp, N. Curcumin ameliorates kidney function and oxidative stress in experimental chronic kidney disease. Basic Clin. Pharmacol. Toxicol., 2018, 122(1), 65-73.
[http://dx.doi.org/10.1111/bcpt.12817] [PMID: 28561324]
[34]
Nagai, T.; Tabara, Y.; Igase, M.; Miki, T.; Kohara, K.; Dearborn, J.L.; Gottesman, R.F.; Kurth, T.; Williams, M.A.; Peterlin, B.L. Adiponectin and leptin levels in migraineurs in the atherosclerosis risk in communities study. Neurology, 2015, 85(5), 482.
[http://dx.doi.org/10.1212/WNL.0000000000001797] [PMID: 26238820]
[35]
Ronti, T.; Lupattelli, G.; Mannarino, E. The endocrine function of adipose tissue: An update. Clin. Endocrinol. (Oxf.), 2006, 64(4), 355-365.
[http://dx.doi.org/10.1111/j.1365-2265.2006.02474.x] [PMID: 16584505]
[36]
Atkin, S.L.; Katsiki, N.; Derosa, G.; Maffioli, P.; Sahebkar, A. Curcuminoids lower plasma leptin concentrations: A meta-analysis. Phytother. Res., 2017, 31(12), 1836-1841.
[http://dx.doi.org/10.1002/ptr.5905] [PMID: 28880413]
[37]
Mirhafez, S.R.; Farimani, A.R.; Dehhabe, M.; Bidkhori, M.; Hariri, M.; Ghouchani, B.F.N.M.; Abdollahi, F. Effect of phytosomal curcumin on circulating levels of adiponectin and leptin in patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled clinical trial. J. Gastrointestin. Liver Dis., 2019, 28(2), 183-189.
[http://dx.doi.org/10.15403/jgld-179] [PMID: 31204416]
[38]
Tang, Y.; Zheng, S.; Chen, A. Curcumin eliminates leptin’s effects on hepatic stellate cell activation via interrupting leptin signaling. Endocrinology, 2009, 150(7), 3011-3020.
[http://dx.doi.org/10.1210/en.2008-1601] [PMID: 19299451]
[39]
Nejati-Koshki, K.; Akbarzadeh, A.; Pourhasan-Moghaddam, M.; Abhari, A.; Dariushnejad, H. Inhibition of leptin and leptin receptor gene expression by silibinin-curcumin combination. Asian Pac. J. Cancer Prev., 2014, 14(11), 6595-6599.
[http://dx.doi.org/10.7314/APJCP.2013.14.11.6595] [PMID: 24377502]
[40]
Deng, Z-H.; Liao, J.; Zhang, J-Y.; Hao, X-H.; Liang, C.; Wang, L-H.; Xue, H.; Zhang, K.; Yan, G.T. Localized leptin release may be an important mechanism of curcumin action after acute ischemic injuries. J. Trauma Acute Care Surg., 2013, 74(4), 1044-1051.
[http://dx.doi.org/10.1097/TA.0b013e3182826eba] [PMID: 23511143]
[41]
Peterlin, B.L.; Sacco, S.; Bernecker, C.; Scher, A.I. Adipokines and migraine: A systematic review. Headache, 2016, 56(4), 622-644.
[http://dx.doi.org/10.1111/head.12788] [PMID: 27012149]
[42]
Abdolahi, M.; Jafarieh, A.; Sarraf, P.; Sedighiyan, M.; Yousefi, A.; Tafakhori, A. The neuromodulatory effects of ω-3 fatty acids and nano-curcumin on the COX-2/iNOS network in migraines: A clinical trial study from gene expression to clinical symptoms. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(6), 874-884.
[43]
Sun, J.; Chen, F.; Braun, C.; Zhou, Y-Q.; Rittner, H.; Tian, Y-K.; Cai, X.Y.; Ye, D.W. Role of curcumin in the management of pathological pain. Phytomedicine, 2018, 48, 129-140.
[http://dx.doi.org/10.1016/j.phymed.2018.04.045] [PMID: 30195871]
[44]
Ganjali, S.; Sahebkar, A.; Mahdipour, E.; Jamialahmadi, K.; Torabi, S.; Akhlaghi, S. Investigation of the effects of curcumin on serum cytokines in obese individuals: A randomized controlled trial. ScientificWorldJournal, 2014, 2014, 898361.
[http://dx.doi.org/10.1155/2014/898361]
[45]
Lee, J.Y.; Shin, T.J.; Choi, J.M.; Seo, K.S.; Kim, H.J.; Yoon, T.G.; Lee, Y.S.; Han, H.; Chung, H.J.; Oh, Y.; Jung, S.J.; Shin, K.J. Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice. Br. J. Anaesth., 2013, 111(4), 667-672.
[http://dx.doi.org/10.1093/bja/aet176] [PMID: 23719767]
[46]
Singh, A.K.; Vinayak, M. Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6. Neurochem. Res., 2015, 40(3), 463-472.
[http://dx.doi.org/10.1007/s11064-014-1489-6] [PMID: 25479948]

Rights & Permissions Print Cite
Article Metrics
3
© 2024 Bentham Science Publishers | Privacy Policy