Effect of Curcumin on Serum Cathepsin D in Patients with Metabolic Syndrome

Author(s): Leila Shirmohammadi, Majid Ghayour-Mobarhan*, Maryam Saberi-Karimian, Mehrdad Iranshahi, Shima Tavallaie, Marzieh Emamian, Amirhossein Sahebkar*

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
Formerly Current Drug Targets - Cardiovascular & Hematological Disorders

Volume 20 , Issue 2 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Inflammation has been shown to accompany Metabolic Syndrome (MetS) and its features. Cathepsin D is one of a proinflammatory mediator. In the current study, we aimed to investigate the effect of curcumin supplementation on serum cathepsin D levels in patients with MetS.

Methods: The current study was conducted on 18-65 years old individuals with MetS diagnosed according to the International Diabetes Federation guidelines. A total of 80 participants were randomly divided into treatment and control groups. The first group (n=40) was given 2 capsules containing 500 mg of phosphatidylcholine complex of curcumin, and the other group (n=40) was given two 500 mg placebo capsules for 6 weeks. Before (week 0) and after (week 6) the intervention, anthropometric indices and blood pressure were measured and blood samples were taken. Serum cathepsin D was measured using an ELISA kit.

Results: There was no significant difference between treatment and control groups in terms of weight, body mass index, waist circumference and serum cathepsin D levels before and after the intervention. In addition, there was no significant difference between pre- and post-trial values of serum cathepsin D.

Conclusion: The present results do not suggest any effect of curcumin on cathepsin D levels in patients with MetS.

Keywords: Curcumin, cathepsin D, metabolic syndrome, obesity, blood pressure, osteoarthritis.

Sharma, R.A.; Gescher, A.J.; Steward, W.P. Curcumin: the story so far. Eur. J. Cancer, 2005, 41(13), 1955-1968.
[http://dx.doi.org/10.1016/j.ejca.2005.05.009] [PMID: 16081279]
Brouet, I.; Ohshima, H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem. Biophys. Res. Commun., 1995, 206(2), 533-540.
[http://dx.doi.org/10.1006/bbrc.1995.1076] [PMID: 7530002]
Sahebkar, A. Curcuminoids for the management of hypertriglyceridaemia. Nat. Rev. Cardiol., 2014, 11(2), 123-123.
[http://dx.doi.org/10.1038/nrcardio.2013.140-c1] [PMID: 24395048]
Kelany, M.E.; Hakami, T.M.; Omar, A.H. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress. Can. J. Physiol. Pharmacol., 2017, 95(2), 140-150.
[http://dx.doi.org/10.1139/cjpp-2016-0152] [PMID: 27901349]
Gong, P.; Liu, M.; Hong, G.; Li, Y.; Xue, P.; Zheng, M.; Wu, M.; Shen, L.; Yang, M.; Diao, Z.; Hu, Y. Curcumin improves LPS-induced preeclampsia-like phenotype in rat by inhibiting the TLR4 signaling pathway. Placenta, 2016, 41, 45-52.
[http://dx.doi.org/10.1016/j.placenta.2016.03.002] [PMID: 27208407]
Kaur, H.; Patro, I.; Tikoo, K.; Sandhir, R. Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy. Neurochem. Int., 2015, 89, 40-50.
[http://dx.doi.org/10.1016/j.neuint.2015.07.009] [PMID: 26190183]
Panahi, Y.; Rahimnia, A.R.; Sharafi, M.; Alishiri, G.; Saburi, A.; Sahebkar, A. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother. Res., 2014, 28(11), 1625-1631.
[http://dx.doi.org/10.1002/ptr.5174] [PMID: 24853120]
Panahi, Y.; Ghanei, M.; Bashiri, S.; Hajihashemi, A.; Sahebkar, A. Short-term curcuminoid supplementation for chronic pulmonary complications due to sulfur mustard intoxication: Positive results of a randomized double-blind placebo-controlled trial. Drug Res. (Stuttg.), 2015, 65(11), 567-573.
[PMID: 25268878]
Ganjali, S.; Sahebkar, A.; Mahdipour, E.; Jamialahmadi, K.; Torabi, S.; Akhlaghi, S.; Ferns, G.; Parizadeh, S.M.; Ghayour-Mobarhan, M. 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] [PMID: 24678280]
Sahebkar, A.; Cicero, A.F.G.; Simental-Mendía, L.E.; Aggarwal, B.B.; Gupta, S.C. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol. Res., 2016, 107, 234-242.
[http://dx.doi.org/10.1016/j.phrs.2016.03.026] [PMID: 27025786]
Sahebkar, A.; Serban, M.C.; Ursoniu, S.; Banach, M. Effect of curcuminoids on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J. Funct. Foods, 2015, 18, 898-909.
Mohammadi, A.; Sahebkar, A.; Iranshahi, M.; Amini, M.; Khojasteh, R.; Ghayour-Mobarhan, M.; Ferns, G.A. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother. Res., 2013, 27(3), 374-379.
[http://dx.doi.org/10.1002/ptr.4715] [PMID: 22610853]
Panahi, Y.; Khalili, N.; Hosseini, M.S.; Abbasinazari, M.; Sahebkar, A. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement. Ther. Med., 2014, 22(5), 851-857.
[http://dx.doi.org/10.1016/j.ctim.2014.07.006] [PMID: 25440375]
Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Majeed, M.; Sahebkar, A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin. Nutr., 2015, 34(6), 1101-1108.
[http://dx.doi.org/10.1016/j.clnu.2014.12.019] [PMID: 25618800]
Lelli, D.; Sahebkar, A.; Johnston, T.P.; Pedone, C. Curcumin use in pulmonary diseases: State of the art and future perspectives. Pharmacol. Res., 2017, 115, 133-148.
[http://dx.doi.org/10.1016/j.phrs.2016.11.017] [PMID: 27888157]
Devaraj, S.; Leonard, S.; Traber, M.G.; Jialal, I. Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. Free Radic. Biol. Med., 2008, 44(6), 1203-1208.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.12.018] [PMID: 18191645]
Rutter, M.K.; Meigs, J.B.; Sullivan, L.M.; D’Agostino, R.B., Sr; Wilson, P.W. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation, 2004, 110(4), 380-385.
[http://dx.doi.org/10.1161/01.CIR.0000136581.59584.0E] [PMID: 15262834]
Freeman, D.J.; Norrie, J.; Sattar, N.; Neely, R.D.; Cobbe, S.M.; Ford, I.; Isles, C.; Lorimer, A.R.; Macfarlane, P.W.; McKillop, J.H.; Packard, C.J.; Shepherd, J.; Gaw, A. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation, 2001, 103(3), 357-362.
[http://dx.doi.org/10.1161/01.CIR.103.3.357] [PMID: 11157685]
Vivanco, F.; Martín-Ventura, J.L.; Duran, M.C.; Barderas, M.G.; Blanco-Colio, L.; Dardé, V.M.; Mas, S.; Meilhac, O.; Michel, J.B.; Tuñón, J.; Egido, J. Quest for novel cardiovascular biomarkers by proteomic analysis. J. Proteome Res., 2005, 4(4), 1181-1191.
[http://dx.doi.org/10.1021/pr0500197] [PMID: 16083268]
Moallem, S.A.; Nazemian, F.; Eliasi, S.; Alamdaran, S.A.; Shamsara, J.; Mohammadpour, A.H. Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients. Int. Urol. Nephrol., 2011, 43(3), 841-848.
[http://dx.doi.org/10.1007/s11255-010-9729-4] [PMID: 20387115]
Lutgens, S.P.; Cleutjens, K.B.; Daemen, M.J.; Heeneman, S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J., 2007, 21(12), 3029-3041.
[http://dx.doi.org/10.1096/fj.06-7924com] [PMID: 17522380]
Benes, P.; Vetvicka, V.; Fusek, M. Cathepsin D--many functions of one aspartic protease. Crit. Rev. Oncol. Hematol., 2008, 68(1), 12-28.
[http://dx.doi.org/10.1016/j.critrevonc.2008.02.008] [PMID: 18396408]
Filep, J.G.; El Kebir, D. Neutrophil apoptosis: a target for enhancing the resolution of inflammation. J. Cell. Biochem., 2009, 108(5), 1039-1046.
[http://dx.doi.org/10.1002/jcb.22351] [PMID: 19760640]
Masson, O.; Prébois, C.; Derocq, D.; Meulle, A.; Dray, C.; Daviaud, D. Cathepsin-D, a key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis. PLoS One, 2011, 26(2) e16452
Alamuddin, N.; Bakizada, Z.; Wadden, T.A. Management of Obesity. J. Clin. Oncol., 2016, 34(35), 4295-4305.
[http://dx.doi.org/10.1200/JCO.2016.66.8806] [PMID: 27903153]
Brunzell, J.D.; Davidson, M.; Furberg, C.D.; Goldberg, R.B.; Howard, B.V.; Stein, J.H.; Witztum, J.L. Lipoprotein management in patients with cardiometabolic risk: Consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J. Am. Coll. Cardiol., 2008, 15, 51(15), 1512-24.
Sahebkar, A. Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome? Biofactors, 2013, 39(2), 197-208.
[http://dx.doi.org/10.1002/biof.1062] [PMID: 23239418]
Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Muhammed, M.; Sahebkar, A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin. Nutr, 2015. S0261-561415, 00002-3
Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. The Essential Medicinal Chemistry of Curcumin. J. Med. Chem., 2017, 60(5), 1620-1637.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00975] [PMID: 28074653]
Houben, T.; Oligschlaeger, Y.; Hendrikx, T.; Bitorina, A.V.; Walenbergh, S.M.A.; van Gorp, P.J.; Gijbels, M.J.J.; Friedrichs, S.; Plat, J.; Schaap, F.G.; Lütjohann, D.; Hofker, M.H.; Shiri-Sverdlov, R. Cathepsin D regulates lipid metabolism in murine steatohepatitis. Sci. Rep., 2017, 7(1), 3494.
[http://dx.doi.org/10.1038/s41598-017-03796-5] [PMID: 28615690]
Liu, L.; Chen, B.; Zhang, X.; Tan, L.; Wang, D.W. increased cathepsin d correlates with clinical parameters in newly diagnosed type 2 diabetes. Dis. Markers, 2017, 2017 5286408
[http://dx.doi.org/10.1155/2017/5286408] [PMID: 29375176]
Nirmala, C.; Puvanakrishnan, R. Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats. Biochem. Pharmacol., 1996, 51(1), 47-51.
[http://dx.doi.org/10.1016/0006-2952(95)02118-3] [PMID: 8534267]
Sahebkar, A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother. Res., 2014, 28(5), 633-642.
[http://dx.doi.org/10.1002/ptr.5045] [PMID: 23922235]
Singh, S.; Aggarwal, B.B. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J. Biol. Chem., 1995, 270(42), 24995-25000.
[http://dx.doi.org/10.1074/jbc.270.42.24995] [PMID: 7559628]
Nduhirabandi, F.; du Toit, E.F.; Lochner, A. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities? Acta Physiol. (Oxf.), 2012, 205(2), 209-223.
[http://dx.doi.org/10.1111/j.1748-1716.2012.02410.x] [PMID: 22226301]
Kai-Yamamoto, M.; Kanaide, H.; Yamamoto, H.; Kurozumi, T.; Kato, K.; Nakamura, M. The production of small arterial lesions in nephrectomized rats by the administration of pure cathepsin D. Br. J. Exp. Pathol., 1982, 63(5), 501-505.
[PMID: 7171474]
Zhou, H.; Xiao, Y.; Li, R.; Hong, S.; Li, S.; Wang, L.; Zeng, R.; Liao, K. Quantitative analysis of secretome from adipocytes regulated by insulin. Acta Biochim. Biophys. Sin. (Shanghai), 2009, 41(11), 910-921.
[http://dx.doi.org/10.1093/abbs/gmp085] [PMID: 19902125]
Masson, O.; Chavey, C.; Dray, C.; Meulle, A.; Daviaud, D.; Quilliot, D.; Muller, C.; Valet, P.; Liaudet-Coopman, E. LRP1 receptor controls adipogenesis and is up-regulated in human and mouse obese adipose tissue. PLoS One, 2009, 4(10) e7422
[http://dx.doi.org/10.1371/journal.pone.0007422] [PMID: 19823686]
Masson, O.; Prébois, C.; Derocq, D.; Meulle, A.; Dray, C.; Daviaud, D. Cathepsin-D, a key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis. PLoS One, 2011, 6(2) e16452
Jormsjö, S.; Wuttge, D.M.; Sirsjö, A.; Whatling, C.; Hamsten, A.; Stemme, S.; Eriksson, P. Differential expression of cysteine and aspartic proteases during progression of atherosclerosis in apolipoprotein E-deficient mice. Am. J. Pathol., 2002, 161(3), 939-945.
[http://dx.doi.org/10.1016/S0002-9440(10)64254-X] [PMID: 12213722]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [116 - 121]
Pages: 6
DOI: 10.2174/1871529X19666190919110652
Price: $65

Article Metrics

PDF: 25