The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density in optical coherence tomography angiography (OCTA) in patients with non-proliferative diabetic retinopathy: Study protocol for a randomized, double-blind controlled trial

Document Type : Original Research Article

Authors

1 Nutrition and Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Ophthalmology Ward, Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

4 Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

5 Sabinsa Corporation, East Windsor, NJ, United States

Abstract

Objective: Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. This study aims to investigate the efficacy of curcumin-piperine in non-proliferative diabetic retinopathy.
Materials and Methods: In this double-blind randomized trial, 60 diabetic retinopathy patients after meeting the inclusion criteria will be randomly assigned to two groups of curcumin-piperine supplementation (1000 mg per day for 12 weeks) or receiving placebo. The density of small blood vessels in the retina by optical coherence tomography angiography (OCTA), fasting blood glucose, triglyceride, renal indices (blood urea nitrogen and creatinine), high-sensitivity C-reactive protein, total antioxidant capacity, total oxidant status, body mass index, waist circumference, and weight will be measured.
Conclusion: If the beneficial effects of curcumin on diabetic retinopathy are observed, this safe, this natural and inexpensive herbal supplement can be considered a therapeutic solution in these patients.

Keywords


Adibian M, Hodaei H, Nikpayam O, Sohrab G,
Hekmatdoost A, Hedayati M. 2019. 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, 33: 1374-1383.
Altobelli E, Angeletti PM, Marziliano C,
Mastrodomenico M, Giuliani AR,
Petrocelli R. 2021. Potential therapeutic
effects of curcumin on glycemic and lipid
profile in uncomplicated type 2 diabetes-a
meta-analysis of randomized controlled
trial. Nutrients, 13: 404.
Anand P, Kunnumakkara AB, Newman RA,
Aggarwal BB. 2007. Bioavailability of
curcumin: problems and promises. Mol
Pharm, 4: 807-818.
Barzegar A, Moosavi-Movahedi A. 2011.
Intracellular ROS protection efficiency
and free radical-scavenging activity of
curcumin. PLoS One, 6: e26012.
Behl T, Kaur I, Kotwani A. 2016. Implication
of oxidative stress in progression of
diabetic retinopathy. Surv Ophthalmol, 61:
187-196.
Brownlee M. 2001. Biochemistry and
molecular cell biology of diabetic
complications. Nature, 414: 813-820.
Carlo TED, Romano A, Waheed NK, Duker JS.
2015. A review of optical coherence
tomography angiography (octa). Int J
Retina Vitreous, 1: 5.
Chaturvedi N, Sjoelie AK, Porta M, Aldington
SJ, Fuller JH, Songini M, Kohner EM,
EURODIAB Prospective Complications
Study Group. 2001. Markers of insulin
resistance are strong risk factors for
retinopathy incidence in type 1 diabetes:
the eurodiab prospective complications
study. Diabetes Care, 24: 284-289.
Chen FY, Zhou J, Guo N, Ma WG, Huang X,
Wang H, Yuan ZY. 2015. Curcumin
retunes cholesterol transport homeostasis
and inflammation response in m1
macrophage to prevent atherosclerosis.
Biochem Biophys Res Commun, 467: 872-
878.
Choi W, Mohler KJ, Potsaid B, Lu CD, Liu JJ,
Jayaraman V, Cable AE, Duker JS, Huber
R, Fujimoto JG. 2013. Choriocapillaris
and choroidal microvasculature imaging
with ultrahigh speed oct angiography.
PLoS One, 8: e81499.
Antonetti DA, Klein R, Gardner TW. 2012.
Diabetic retinopathy. N Engl J Med, 366,
1227-1239.
El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi
SFI, Ahmed AF. 2011. The
antihyperglycemic effect of curcumin in
Amini et al.
AJP, Vol. 13, No. 2, Mar-Apr 2023 162
high fat diet fed rats. Role of TNF-α and
free fatty acids. Food Chem Toxicol, 49,
1129-1140.
Farhood B, Mortezaee K, Hashemi-Goradel N,
Khanlarkhani N, Salehi E, ShabaniNashtaei M, Najafi M, Sahebkar A. 2019.
Curcumin as an anti‐ inflammatory agent:
implications to radiotherapy and
chemotherapy. J Cell Physiol, 234: 5728-
5740.
Fingler J, Schwartz D, Yang C, Fraser SE.
2007. Mobility and transverse flow
visualization using phase variance contrast
with spectral domain optical coherence
tomography. Opt Express, 15: 12636-
12653.
Gonzalez VH, Campbell J, Holekamp NM,
Kiss S, Loewenstein A, Augustin AJ, Ma
J, Ho AC, Patel V, Whitcup SM. 2016.
Early and long-term responses to anti–
vascular endothelial growth factor therapy
in diabetic macular edema: analysis of
protocol data. Am J Ophthalmol, 172: 72-
79.
Mahdavi- Gorabi A, Kiaie N, Hajighasemi S,
Jamialahmadi T, Majeed M, Sahebkar A.
2019. The effect of curcumin on the
differentiation of mesenchymal stem cells
into mesodermal lineage. Molecules, 24:
4029.
Guariguata L, Whiting DR, Hambleton I,
Beagley J, Linnenkamp U, Shaw JE. 2014.
Global estimates of diabetes prevalence
for 2013 and projections for 2035.
Diabetes Res Clin Pract, 103: 137-149.
Ip MS, Scott IU, Brown GC, Brown MM, Ho
AC, Huang SS, Recchia FM. 2008. Anti–
vascular endothelial growth factor
pharmacotherapy for age-related macular
degeneration: a report by the american
academy of ophthalmology. Ophthalmol,
115: 1837-1846.
Jacob A, Wu R, Zhou M, Wang P. 2007.
Mechanism of the anti-inflammatory
effect of curcumin: ppar-gamma
activation. PPAR Res, 2007: 89369.
Jeenger MK, Shrivastava S, Yerra VG, Naidu
VGM, Ramakrishna S, Kumar A. 2015.
Curcumin: A pleiotropic phytonutrient in
diabetic complications. Nutr J, 31: 276-
282.
Karam BS, Chavez-Moreno A, Koh W, Akar
JG, Akar FG. 2017. Oxidative stress and
inflammation as central mediators of atrial
fibrillation in obesity and diabetes.
Cardiovasc Diabetol, 16: 120.
Kaur G. 2012. Amelioration of obesity, glucose
intolerance, and oxidative stress in high-fat
diet and low-dose streptozotocin-induced
diabetic rats by combination consisting of
curcumin with piperine and quercetin.
ISRN Pharmacol, 2012: 957283.
Kim DY, Fingler J, Zawadzki RJ, Park SS,
Morse LS, Schwartz DM, Fraser SE,
Werner JS. 2013. Optical imaging of the
chorioretinal vasculature in the living
human eye. Proc Natl Acad Sci U S A,
110: 14354-14359.
Kondamudi PK, Kovelamudi H, Nayak V, Rao
MC, Shenoy RR. 2015. Curcumin half
analog modulates interleukin-6 and tumor
necrosis factor-alpha in inflammatory
bowel disease. Pharmacogn Mag, 11:
S296-302.
Li Y, Zhang Y, Liu DB, Liu HY, Hou WG,
Dong YS. 2013. Curcumin attenuates
diabetic neuropathic pain by
downregulating tnf-α in a rat model. Int J
Med Sci, 10: 377-381.
Lontchi-Yimagou E, Sobngwi E, Tandi EM,
Kengne AP. 2013. Diabetes mellitus and
inflammation. Curr Diab Rep, 13: 435-
444.
Mahdavi A, Moradi S, Askari G, Iraj B,
Sathyapalan T, Guest PC, Bagherniya M,
Sahebkar A. 2021. Effect of curcumin on
glycemic control in patients with type 2
diabetes: a systematic review of
randomized clinical trials. Adv Exp Med
Biol, 139-149.
Matsunaga D, Yi J, Puliafito CA, Kashani AH.
2014. OCT angiography in healthy human
subjects. Ophthalmic Surg Lasers Imaging
Retina, 45: 510-515.
Mirzaei H, Shakeri A, Rashidi B, Jalili A,
Banikazemi Z, Sahebkar A. 2017.
Phytosomal curcumin: a review of
pharmacokinetic, experimental and
clinical studies. Biomed Pharmacother, 85:
102-112.
Mohajeri M, Bianconi V, Ávila-Rodriguez MF,
Barreto GE, Jamialahmadi T, Pirro M,
Sahebkar A. 2020. Curcumin: a
phytochemical modulator of estrogens and
androgens in tumors of the reproductive
system. Pharmacol Res, 156: 104765.
Mohamed Q, Gillies MC, Wong TY. 2007.
Management of diabetic retinopathy: a
systematic review. JAMA, 298: 902-916.
Mokgalaboni K, Ntamo Y, Ziqubu K,
Curcumin-piperine and diabetic retinopathy
AJP, Vol. 13, No. 2, Mar-Apr 2023 163
Nyambuya TM, Nkambule BB,
Mazibuko-Mbeje SE, Gabuza KB, Chellan
N, Tiano L, Dludla PV. 2021. Curcumin
supplementation improves biomarkers of
oxidative stress and inflammation in
conditions of obesity, type 2 diabetes and
nafld: updating the status of clinical
evidence. Food Funct, 12: 12235-12249.
Mortezaee K, Salehi E, Mirtavoos-mahyari H,
Motevaseli E, Najafi M, Farhood B,
Rosengren RJ, Sahebkar A. 2019.
Mechanisms of apoptosis modulation by
curcumin: implications for cancer therapy.
J Cell Physiol, 234: 12537-12550.
Nabavi SM, Marchese A, Izadi M, Curti V,
Daglia M, Nabavi SF. 2015. Plants
belonging to the genus thymus as
antibacterial agents: from farm to
pharmacy. Food Chem, 173: 339-347.
Nanditha A, Ma RCW, Ramachandran A,
Snehalatha C, Chan JCN, Chia KS, Shaw
JE, Zimmet PZ. 2016. Diabetes in asia and
the pacific: implications for the global
epidemic. Diabetes Care, 39: 472-485.
Neerati P, Devde R, Gangi AK. 2014.
Evaluation of the effect of curcumin
capsules on glyburide therapy in patients
with type‐ 2 diabetes mellitus. Phytother
Res, 28: 1796-1800.
Nguyen QD, Brown DM, Marcus DM, Boyer
DS, Patel S, Feiner L, Gibson A, Sy J,
Rundle AC, Hopkins JJ. 2012.
Ranibizumab for diabetic macular edema:
results from 2 phase iii randomized trials:
rise and ride. Ophthalmol, 119: 789-801.
Nishiyama T, Mae T, Kishida H, Tsukagawa
M, Mimaki Y, Kuroda M, Sashida Y,
Takahashi K, Kawada T, Nakagawa K.
2005. Curcuminoids and sesquiterpenoids
in turmeric (curcuma longa l.) suppress an
increase in blood glucose level in type 2
diabetic kk-ay mice. Agric Food Chem 53:
959-963.
Panahi Y, Kianpour P, Mohtashami R, Jafari R,
Simental-Mendía LE, Sahebkar A. 2016.
Curcumin lowers serum lipids and uric
acid in subjects with nonalcoholic fatty
liver disease: a randomized controlled
trial. Cardiovasc Pharmacol, 68: 223-229.
Parsamanesh N, Moossavi M, Bahrami A,
Butler AE, Sahebkar A. 2018. Therapeutic
potential of curcumin in diabetic
complications. Pharmacol Res, 136: 181-
193.
Peddada KV, Brown A, Verma V, Nebbioso M.
2019. Therapeutic potential of curcumin in
major retinal pathologies. Int Ophthalmol,
39: 725-734.
Peeyush KT, Gireesh G, Jobin M, Paulose CS.
2009. Neuroprotective role of curcumin in
the cerebellum of streptozotocin-induced
diabetic rats. Life Sci, 85: 704-710.
Pivari F, Mingione A, Brasacchio C, Soldati L.
2019. Curcumin and type 2 diabetes
mellitus: prevention and treatment. Nutr J,
11: 1837.
Poolsup N, Suksomboon N, Kurnianta PDM,
Deawjaroen K. 2019. Effects of curcumin
on glycemic control and lipid profile in
prediabetes and type 2 diabetes mellitus: a
systematic review and meta-analysis.
PLoS One, 14: e0215840.
Schwartz DM, Fingler J, Kim DY, Zawadzki
RJ, Morse LS, Park SS, Fraser SE, Werner
JS. 2014. Phase-variance optical
coherence tomography: a technique for
noninvasive angiography. Ophthalmol,
121: 180-187.
Seyyedebrahimi S, Khodabandehloo H, NasliEsfahani E, Meshkani R. 2018. The effects
of resveratrol on markers of oxidative
stress in patients with type 2 diabetes: a
randomized, double-blind, placebocontrolled clinical trial. Acta Diabetol, 55:
341-353.
Shakeri A, Cicero AFG, Panahi Y, Mohajeri M,
Sahebkar A. 2019. Curcumin: a naturally
occurring autophagy modulator. Cell
Physiol, 234: 5643-5654.
Simó-Servat O, Hernández C, Simó R. 2019.
Diabetic retinopathy in the context of
patients with diabetes. Ophthalmic Res 62:
211-217.
Spaide RF, Jr JMK, Cooney MJ. 2015. Retinal
vascular layers imaged by fluorescein
angiography and optical coherence
tomography angiography. JAMA
Ophthalmol, 133: 45-50.
Srinivasan K. 2005. Plant foods in the
management of diabetes mellitus: spices as
beneficial antidiabetic food adjuncts. Int J
Food Sci Nutr, 56: 399-414.
Steigerwalt R, Nebbioso M, Appendino G,
Belcaro G, Ciammaichella G, Cornelli U,
Luzzi R, Togni S, Dugall M, Cesarone
MR, Ippolito E, Errichi BM, Ledda
A, Hosoi M, Corsi M. 2012. Meriva®, a
lecithinized curcumin delivery system, in
diabetic microangiopathy and retinopathy.
Panminerva Med, 54: 11-16.
Amini et al.
AJP, Vol. 13, No. 2, Mar-Apr 2023 164
Stitt AW, Curtis TM, Chen M, Medina RJ,
McKay GJ, Jenkins A, Gardiner TA,
Lyons TJ, Hammes TJ, Simó R, Lois N.
2016. The progress in understanding and
treatment of diabetic retinopathy. Prog
Retin Eye Res, 51: 156-186.
Tolentino M. 2011. Systemic and ocular safety
of intravitreal anti-vegf therapies for
ocular neovascular disease. Surv
Ophthalmol, 56: 95-113.
Watal G, Dhar P, Srivastava SK, Sharma B.
2014. Herbal medicine as an alternative
medicine for treating diabetes: the global
burden. eCAM, 2014: 596071.
Weisberg SP, Leibel R, Tortoriello DV. 2008.
Dietary curcumin significantly improves
obesity-associated inflammation and
diabetes in mouse models of diabesity.
Endocr J, 149: 3549-3558.
Yang F, Yu J, Ke F, Lan M, Li D, Tan K, Ling
J, Wang Y, Wu K, Li D. 2018. Curcumin
alleviates diabetic retinopathy in
experimental diabetic rats. Ophthalmic
Res, 60: 43-54.
Yang YS, Su YF, Yang HW, Lee YH, Chou JI,
Ueng KC. 2014. Lipid-lowering effects of
curcumin in patients with metabolic
syndrome: a randomized, double-blind,
placebo-controlled trial. Phytother
Res, 28: 1770-1777.
Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH,
Ko SH, Zimmet P, Son HY. 2006.
Epidemic obesity and type 2 diabetes in
asia. Lancet, 368: 1681-1688.
Zhang T, He Q, Liu Y, Chen Z, Hu H. 2021.
Efficacy and safety of curcumin
supplement on improvement of insulin
resistance in people with type 2 diabetes
mellitus: a systematic review and metaanalysis of randomized controlled trials.
eCAM, 2021: 4471944.