Planta Med
DOI: 10.1055/a-2157-8913

Review: The Chemistry, Toxicity and Antibacterial Activity of Curcumin and Its Analogues

Hannah J. Denison
1   Syngenta, Jealottʼs Hill International Research Centre, Bracknell, Berkshire, UK
Sianne L. Schwikkard
2   Department of Chemical and Pharmaceutical Science, Kingston University, London, UK
Mouhamad Khoder
3   Department of Pharmacy, Kingston University, London, UK
4   Department of Applied and Human Sciences, Kingston University, London, UK
› Author Affiliations


Antimicrobial resistance is a global challenge that is already exacting a heavy price both in terms of human health and financial cost. Novel ways of approaching this crisis include the investigation of natural products. Curcumin is the major constituent in turmeric, and it is commonly used in the preparation of Asian cuisine. In addition, it possesses a wide range of pharmacological properties. This review provides a detailed account of curcumin and its analoguesʼ antibacterial activity against both gram-positive and gram-negative isolates, including its potential mechanism(s) of action and the safety and toxicity in human and animal models. We also highlight the key challenges in terms of solubility/bioavailability associated with the use of curcumin and include research on how these challenges have been overcome.

Publication History

Received: 18 April 2023

Accepted after revision: 19 August 2023

Accepted Manuscript online:
21 August 2023

Article published online:
28 September 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 World Health Organization. Antimicrobial resistance. 2021. Accessed December 05, 2021 at:
  • 2 World Health Organization. Antibiotic resistance fact sheet. 2016. Accessed July 17, 2023 at:
  • 3 Antimicrobial Resistance Collaborators. Global burden if bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022; 399: 629-655
  • 4 AMR Industry Declaration. Declaration by the pharmaceutical, biotechnology and diagnosis industries on combating antimicrobial resistance. 2016. Accessed March 17, 2023 at:
  • 5 Boyd NK, Teng C, Frei CR. Brief overview of approaches and challenges in new antibiotic development: A focus on drug repurposing. Front Cell Infect Microbiol 2021; 11: 684515
  • 6 Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med 2003; 9: 161-168
  • 7 Vogel A, Pelletier J. Examen chimique de la racine de Curcuma. J Pharm 1815; 1: 289-300
  • 8 Milobedzka J, Kostanecki V, Lampe V. Structure. Chem Ber 1910; 43: 2163
  • 9 Roughley PJ, Whiting DA. Experiments in the biosynthesis of curcumin. J Chem Soc Perkin Trans 1973; 20: 2379-2388
  • 10 Sharma RA, Gescher AJ, Steward WP. Curcumin: The story so far. Eur J Cancer 2005; 41: 1955-1968
  • 11 Priyadarsini KI. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014; 19: 20091-20112
  • 12 Kew Science. Plants of the world online: Curcuma longa . Accessed April 21, 2020 at:
  • 13 Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 2008; 65: 1631-1652
  • 14 Schraufstatter E, Bernt H. Antibacterial action of curcumin and related compounds. Nature 1949; 164: 456
  • 15 Tyagi P, Singh M, Kumari H, Kumari A, Mukhopadhyay K. Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS One 2015; 10: 0121313
  • 16 De R, Kundu P, Swarnakar S, Ramamurthy T, Chowdhury A, Nair GB, Mukhopadhyay AK. Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrob Agents Chemother 2009; 53: 1592-1597
  • 17 Mandroli PS, Bhat K. An in vivo evaluation of antibacterial activity of curcumin against common endodontic bacteria. J App Pharma Sci 2013; 3: 106-108
  • 18 Mohammed NA, Habil NY. Evaluation of antimicrobial activity of curcumin against two oral bacteria. Autom Control Intell Syst 2015; 3: 18-21
  • 19 Gunes H, Gulen D, Mutlu R, Gumus A, Tas T, Topkaya AE. Antibacterial effects of curcumin: An in vitro minimum inhibitory concentration study. Toxicol Ind Health 2016; 32: 246-250
  • 20 Izui S, Sekine S, Maeda K, Kuboniwa M, Takada A, Amano A, Nagata H. Antibacterial Activity of Curcumin Against Periodontopathic Bacteria. J Peridontol 2016; 87: 83-90
  • 21 Bomdyal RS, Shah MU, Doshi YS, Shah VA, Khirade SP. Antibacterial activity of curcumin (turmeric) against periopathogens – An in vitro evaluation. J Ad Clin Res In 2017; 4: 175-180
  • 22 Adamczak A, Ozarowski M, Karpinski TM. Curcumin, a natural antimicrobial agent with strain-specific activity. Pharmaceuticals (Basel) 2020; 13: 153
  • 23 World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. 2017. Accessed February 06, 2020 at:
  • 24 Patridge E, Gareiss P, Kinch MS, Hoyer D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discov Today 2015; 21: 204-207
  • 25 Savoia D. Plant-derived antimicrobial compounds: Alternatives to antibiotics. Future Microbiol 2012; 7: 979-990
  • 26 Quave CL. Antibiotics from nature: traditional medicine as a source of new solutions for combating antimicrobial resistance. 2016. Accessed January 05, 2020 at:
  • 27 Mathur S, Hoskins C. Drug development: Lessons from nature. Biomed Rep 2017; 6: 612-614
  • 28 Kim MK, Park JC, Chong Y. Aromatic hydroxyl group plays a critical role in antibacterial activity of the curcumin analogues. Nat Prod Commun 2012; 7: 57-58
  • 29 Hamed OA, Mehdawi N, Taha AA, Hamed EM, Al-Nuri MA, Hussein AS. Synthesis and antibacterial activity of novel curcumin derivatives containing heterocyclic moiety. Iran J Pharm Res 2013; 12: 47-56
  • 30 Emam DR, Alhajoj AM, Elattar KM, Kheder NA, Fadda AA. Synthesis and evaluation of curcuminoid analogues as antioxidant and antibacterial agents. Molecules 2017; 22: 971
  • 31 Oglah MH, Mustafa YF. Curcumin analogs: Synthesis and biological activities. Med Chem Res 2020; 29: 479-486
  • 32 Singh A, Singh JV, Rana A, Bhagat K, Gulati HK, Kumar R, Salwan R, Bhagat K, Kaur G, Singh N, Kumar R, Singh H, Sharma S, Bedi PMS. Monocarbonyl curcumin-based molecular hybrids as potent antibacterial agents. ACS Omega 2019; 4: 11673-11684
  • 33 Kumar P, Kandi SK, Manohar S, Mukhopadhyay K, Rawat DS. Monocarbonyl curcuminoids with improved stability as antibacterial agents against Staphylococcus aureus and their mechanistic studies. ACS Omega 2019; 4: 675-687
  • 34 Polaquini CR, Marques BC, Ayusso GM, Morao LG, Sardi JCO, Campos DL, Cavalca LB, Scheffers DJ, Rosalen PL, Pavan FR, Ferreira H, Regasini LO. Antibacterial activity of a new monocarbonyl analog of curcumin MAC 4 is associated with divisome disruption. Bioorg Chem 2021; 109: 104668
  • 35 Ritmaleni R, Sardjiman AY, Purwantini P. Antimicrobial activity of curcumin analog PGV-6, HGV-6 and GVT-6. Res J Pharm Tech 2021; 14: 599-604
  • 36 Trotsko N, Kosikowska U, Paneth A, Plech T, Malm A, Wujec A. Synthesis and antibacterial activity of new thiazolidine-2,4-dione-based chlorophenylthiosemicarbazone hybrids. Molecules 2018; 23: 1023
  • 37 Santos AF, Brotto DF, Favarin LRV, Cabeza NA, Andrade GR, Batistote M, Cavalheiro AA, Neves A, Rodriques DCM, dos Anjos A. Study of the antimicrobial activity of metal complexes and their ligands through bioassays applied to plant extracts. Braz J Pharma 2014; 24: 309-315
  • 38 Rocha DP, Ferreira G, Ruggiero R, de Oliveira CA, War W, Sources APS, Tavares T, Marzano IM, Pereira-Maia EC. Coordination of metals to antibiotics as a strategy to combat bacterial resistance. Quim Nova 2011; 34: 111-118
  • 39 Riswan Ahamed MA, Azarudeen RS, Kani NM. Antimicrobial applications of transition metal complexes of benzothiazole based terpolymer: synthesis, characterization, and effect on bacterial and fungal strains. Bioinorg Chem Appl 2014; 2014: 764085
  • 40 Tajbakhsh S, Mohammadi K, Deilami I, Zandi K, Fouladvand M, Ramedani E, Asayesh G. Antibacterial activity of indium curcumin and indium diacetylcurcumin. Afr J Biotechnol 2008; 7: 3832-3835
  • 41 Hatamie S, Nouri M, Karandikar SK, Kulkarni A, Dhole SD, Phase DM, Kale SN. Complexes of cobalt nanoparticles and polyfunctional curcumin as antimicrobial agents. Mater Sci Eng C 2012; 32: 92-97
  • 42 Pallikkavil R, Ummathur Muhammed B, Sreedharan S, Krishnankutty K. Synthesis, characterization and antimicrobial studies of Cd(II), Hg(II), Pb(II), Sn(II) and Ca(II) complexes of curcumin. Main Group Met Chem 2013; 36: 123-127
  • 43 Refat MS. Synthesis and characterization of ligational behaviour of curcumin drug towards some transition metal ions: chelation effect on their thermal stability and biological activity. Spectrochim. Acta A Mol Biomol Spectrosc 2013; 105: 326-337
  • 44 Liao Y, Yao Y, Yu Y, Zeng Y. Enhanced antibacterial activity of curcumin by combination with metal ions. Colloid Interface Sci Commun 2018; 25: 1-6
  • 45 Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014; 2014: 186864
  • 46 Moghaddam KM, Iranshahi M, Yazdi MC, Shahverdi AR. The combination effect of curcumin with different antibiotics against Staphylococcus aureus . Int J Green Pharm 2009; 3: 141-143
  • 47 Kali A, Bhuvaneshwar D, Charles PMV, Seetha KS. Antibacterial synergy of curcumin with antibiotics against biofilm producing clinical bacterial isolates. J Basic Clin Pharm 2016; 7: 93-96
  • 48 Teow SY, Ali SA. Synergistic antibacterial activity of curcumin with antibiotics against Staphylococcus aureus . Pak J Pharm Sci 2015; 28: 2109-2114
  • 49 Sukandar EY, Kurniati NF, Puspatriani K, Adityas HP. Antibacterial activity of curcumin in combination with tetracycline against Staphylococcus aureus by disruption of cell wall. Res J Med Plants 2018; 12: 1-8
  • 50 De Kievit TR, Gillis R, Marx S, Brown C, Iglewski BH. Quorum-sensing genes in Pseudomonas aeruginosa biofilms: Their role and expression patterns. Appl Environ Microbiol 2001; 67: 1865-1873
  • 51 Morohoshi T, Shiono T, Takidouchi K, Kato M, Kato N, Kato J, Ikeda T. Inhibition of quorum sensing in Serratia marcescens AS-1 by synthetic analogs of N-acylhomoserine lactone. Appl Environ Microbiol 2007; 73: 6339-6344
  • 52 Liu GY, Nizet V. Color me bad: microbial pigments as virulence factors. Trends Microbiol 2009; 17: 406-413
  • 53 Packiavathy SV, Priya S, Pandian SK, Ravi AV. Inhibition of biofilm development of uropathogens by curcumin – an anti-quorum sensing agent from Curcuma longa . Food Chem 2014; 148: 453-460
  • 54 Sharma G, Raturi K, Dang S, Gupta S, Gabrani R. Combinatorial antimicrobial effect of curcumin with selected phytochemicals on Staphylococcus epidermidis . J Asian Nat Prod Res 2014; 16: 535-541
  • 55 Gordon ON, Luis PB, Sintim HO, Schneider C. Unraveling curcumin degradation: Autoxidation proceeds through spiroepoxide and vinylether intermediates en route to the main bicyclopentadione. J Biol Chem 2015; 290: 4817-4828
  • 56 Krausz AE, Adler BL, Cabral V, Navati M, Doerner J, Charafeddine RA, Chandra D, Liang H, Gunther L, Clendaniel A, Harper S, Friedman JM, Nosanchuk JD, Friedman AJ. Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine 2015; 11: 195-206
  • 57 Izui S, Sekine S, Maeda K, Kuboniwa M, Takada A, Amano A, Nagata H. Antibacterial activity of curcumin against periodontopathic bacteria. J Periodontol 2016; 87: 83-90
  • 58 Wu Y, Seyedsayamdost MR. Synergy and target promiscuity drive structural divergence in bacterial alkylquinolone biosynthesis. Cell Chem Biol 2017; 24: 1437
  • 59 Fulaz S, Vitale S, Quinn L, Casey E. Nanoparticle-biofilm interactions: The role of the EPS matrix. Trends Microbiol 2019; 27: 915-926
  • 60 Gayani B, Dilhari A, Wijesinghe GK, Kumarage S, Abayaweera G, Samarakoon SR, Perera IC, Kottegoda N, Weerasekera MM. Effect of natural curcumin oidsintercalated layered double hydroxide nanohybrid against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis: A bactericidal, antibiofilm, and mechanistic study. Microbiologyopen 2019; 8: e00723
  • 61 Selvam C, Prabu SL, Jordan BC, Purushothaman Y, Umamaheswari A, Hosseini Zare MS, Thilagavathi R. Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment. Life Sci 2019; 239: 117032-117043
  • 62 Zhang C, Zhu X, Li F, Gao F, Tu J, Zhang D. Enhanced eradication of Pseudomonas aeruginosa bio-films by using ultrasound combined with neutrophil and antibiotics. Appl Acoust 2019; 152: 101-109
  • 63 Yu Q, Deng T, Lin FC, Zhang B, Zink JI. Supramolecular assemblies of heterogeneous mesoporous silica nanoparticles to co-deliver antimicrobial peptides and antibiotics for synergistic eradication of pathogenic biofilms. ACS Nano 2020; 14: 5926-5937
  • 64 Oda Y. Inhibitory effect of curcumin on SOS functions induced by UV irradiation. Mutat Res 1995; 348: 67-73
  • 65 Gomez-Gomez JM, Manfredi C, Alonso JC, Blazquez J. A novel role for RecA under non-stress: Promotion of swarming motility in Escherichia coli K-12. BMC Biol 2007; 5: 14-28
  • 66 Rudrappa T, Bais HP. Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 2008; 56: 1955-1962
  • 67 Baharoglu Z, Mazel D. SOS, the formidable strategy of bacteria against aggressions. FEMS Microbiol Rev 2014; 38: 1126-1145
  • 68 Costa SB, Campos ACC, Pereira ACM, de Mattos-Guaraldi AL, Júnior RH, Rosa ACP, Asad LMBO. Adherence to abiotic surface induces SOS response in Escherichia coli K-12 strains under aerobic and anaerobic conditions. Microbiology 2014; 160: 1964-1973
  • 69 Jenkins HE, Tolman AW, Yuen CM, Parr JB, Keshavjee S, Perez-Velez CM, Pagano M, Becerra MC, Cohen T. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet 2014; 383: 1572-1579
  • 70 Strugeon E, Tilloy V, Ploy MC, Da Re S. The stringent response promotes antibiotic resistance dissemination by regulating integron integrase expression in biofilms. MBio 2016; 7: e00868-e00916
  • 71 Recacha E, Machuca J, Diaz-Diaz S, Garcia-Duque A, Ramos-Guelfo M, Docobo-Perez F, Blazquez J, Pascual A, Rodriguez-Martinez JM. Suppression of the SOS response modifies spatiotemporal evolution, post-antibiotic effect, bacterial fitness and biofilm formation in quinoloneresistant Escherichia coli . J Antimicrob Chemother 2019; 74: 66-73
  • 72 van der Heide T, Poolman B. ABC transporters: one, two or four extracytoplasmic substrate-binding sites?. EMBO Rep 2002; 3: 938-943
  • 73 Jun JH, Seu YB, Lee DG. Candicidal action of resveratrol isolated from grapes on human pathogenic yeast C. albicans . J Microbiol Biotechnol 2007; 17: 1324-1329
  • 74 Rai D, Singh JK, Roy N, Panda D. Curcumin inhibits FtsZ assembly: An attractive mechanism for its antibacterial activity. Biochem J 2008; 410: 147-155
  • 75 Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets. Trends Pharmacol Sci 2009; 30: 85-94
  • 76 Coleman KJ, Ngor E, Reynolds K, Quinn VP, Koebnick C, Young DR, Sternfeld B, Sallis RE. Initial validation of an exercise “vital sign” in electronic medical records. Med Sci Sports Exerc 2012; 44: 2071-2076
  • 77 Mun SH, Kim SB, Kong R, Choi JG, Kim YC, Shin DW, Kang OH, Kwon DY. Curcumin reverse methicillin resistance in Staphylococcus aureus . Molecules 2014; 19: 18283-18295
  • 78 Li LM, Li J, Zhang XY. Antimicrobial and molecular interaction studies on derivatives of curcumin against Streptococcus pneumoniae which caused pneumonia. Electron J Biotechnol 2016; 19: 8-14
  • 79 Barry J, Fritz M, Brender JR, Smith PES, Lee DK, Ramamoorthy A. Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: the case of the antioxidant curcumin. J Am Chem Soc 2009; 131: 4490-4498
  • 80 Tonon CC, Paschoal MA, Correia M, Spolidorio DMP, Bagnato VS, Giusti JSM, Santos-Pinto L. Comparative effects of photodynamic therapy mediated by curcumin on standard and clinical isolate of Streptococcus mutans . J Contemp Dent Pract 2015; 16: 1-6
  • 81 Wang H, Hao L, Wang P, Chen M, Jiang S, Jiang S. Release kinetics and antibacterial activity of curcumin loaded zein fibers. Food Hydrocoll 2017; 63: 437-446
  • 82 Duracka M, Lukac N, Kacaniova M, Kantor A, Hleba L, Ondruska L, Tvrda E. Antibiotics versus natural biomolecules: The case of in vitro induced bacteriospermia by Enterococcus Faecalis in Rabbit Semen. Molecules 2019; 24: 4329-4348
  • 83 Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. Int J Pharma Sci Rev Res 2010; 5: 41-51
  • 84 Tonnesen HH, Masson M, Loftsson T. Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int J Pharm 2002; 244: 127-135
  • 85 Ansari MJ, Ahmed MM, Fatima F, Anwer MK, Jamil S, Al-Shdefat R, Ali BE. Solubility and stability enhancement of curcumin through cyclodextrin complexation. IJBPAS 2014; 3: 266-267
  • 86 Ansari MJ, Parveen R. Solubility and stability enhancement of curcumin: Improving drug properties of natural pigment. Drug Dev Ther 2016; 7: 113-116
  • 87 Hassan AS, El-Mahdy MM, El-Badry M, El-Gindy GEDA. Different approaches for enhancement of curcumin aqueous solubility and dissolution rate. J Adv Biomed Pharm Sci 2019; 2: 152-163
  • 88 Celebioglu A, Uyar T. Fast-dissolving antioxidant curcumin/cyclodextrin inclusion complex electrospun nanofibrous webs. Food Chem 2020; 317: 126397
  • 89 Panda S, Das SK. Inclusion complexation of curcumin with beta cyclodextrin to improve solubility. Der Pharm Lett 2021; 13: 11-18
  • 90 Park H, Rho S, Kim Y. Solubility, stability, and bioaccessibility improvement of curcumin encapsulated using 4-α-glucanotransferase-modified rice starch with reversible pH-induced aggregation property. Food Hydrocoll 2019; 95: 19-32
  • 91 Kannamangalam Vijayan U, Shah NN, Muley AB, Singhal RS. Complexation of curcumin using proteins to enhance aqueous solubility and bioaccessibility: Pea protein vis-à-vis whey protein. J Food Eng 2020; 292: 110258
  • 92 Wang Y, Lu Z, Wu H, Lv F. Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens. Int J Food Microbiol 2009; 136: 71-74
  • 93 Taghavi Kevij H, Mohammadian M, Salami M. Complexation of curcumin with whey protein isolate for enhancing its aqueous solubility through a solvent-free pH-driven approach. J Food Process Presev 2019; 43: 14227
  • 94 Madhavi BB, Kusum B, Chatanya CK, Madhu MN, Harsha VS, Banji D. Dissolution enhancement of efavirenz by solid dispersion and PEGylation techniques. Int J Pharm Investig 2011; 1: 29-34
  • 95 Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 2002; 231: 131-144
  • 96 da Salva Júnior WF, Pinheiro JGO, de Menezes DLB, Silva NESE, de Almeida PDO, Lima ES, da Veiga Júnior VF, de Azevedo EP, de Lima ÁAN. Development, physicochemical characterization and in vitro anti-inflammatory activity of solid dispersions of α,β amyrin isolated from protium oilresin. Molecules 2017; 22: 1512
  • 97 Modasiya MK, Patel VM. Studies of solubility of curcumin. Int J Pharm Life Sci 2012; 3: 1490-1497
  • 98 Gangurde AB, Kundaikar HS, Javeer SD, Jaiswar DR, Degani MS, Amin PD. Enhanced solubility and dissolution of curcumin by a hydrophilic polymer solid dispersion and its insilico molecular modeling studies. J Drug Deliv Sci Technol 2015; 29: 226-237
  • 99 Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit E PO solid dispersion: A simple and potent method to solve the problems of curcumin. Eur J Pharm Biopharm 2015; 94: 322-332
  • 100 Alves T, Chaud M, Grotto D, Jozala AF, Pandit R, Rai M, Dos Santos CA. Association of silver nanoparticles and curcumin solid dispersion: Antimicrobial and antioxidant properties. AAPS PharmSciTech 2017; 19: 225-231
  • 101 Hernandez-Patlan D, Solis-Cruz B, Pontin KP, Latorre JD, Baxter MFA, Hernandez-Velasco X, Merino-Guzman R, Mendez-Albores A, Hargis BM, Lopez-Arellano R, Tellez G. Evaluation of a solid dispersion of curcumin with polyvinylpyrrolidone and boric acid against Salmonella Enteritidis infection and intestinal permeability in broiler chickens: A pilot study. Front Microbiol 2018; 9: 1289
  • 102 Muthu MJ, Kavitha K, Chitra KS, Nandhineeswari S. Soluble curcumin prepared by solid dispersion using four different carriers: Phase solubility, molecular modelling and physicochemical characterization. Trop J Pharm Res 2019; 18: 1581-1588
  • 103 Yu JY, Kim JA, Joung HJ, Ko JA, Park HJ. Preparation and characterization of curcumin solid dispersion using HPMC. J Food Sci 2020; 85: 3866-3873
  • 104 Shin GH, Li J, Cho JH, Kim JT, Park HJ. Enhancement of curcumin solubility be phase change from crystalline to amorphous in Cur-TPGS nanosuspension. J Food Sci 2016; 81: 494-501
  • 105 Flora G, Gupta D, Tiwari A. Nanocurcumin: A promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst 2013; 30: 331-368
  • 106 Elzoghby A, Samy W, Elgindy N. Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 2012; 157: 168-182
  • 107 Bhawana. Basniwal RK, Buttar HS, Jain VK, Jain N. Curcumin nanoparticles: Preparation, characterization, and antimicrobial study. J Agric Food Chem 2011; 59: 2056-2061
  • 108 Xie M, Fan D, Zhao Z, Li Z, Li G, Chen Y, He X, Chen A, Li J, Lin X, Zhi M, Li Y, Lan P. Nano-curcumin prepared via supercritical: Improved anti-bacterial, anti-oxidant and anti-cancer efficacy. Int J Pharm 2015; 496: 732-740
  • 109 No DS, Algburi A, Huynh P, Moret A, Ringard M, Comito N, Drider D, Takhistov P, Chikindas ML. Antimicrobial efficacy of curcumin nanoparticles against Listeria monocytogenes is mediated by surface charge. J Food Saf 2017; 37: 12353
  • 110 Adahoun MA, Al-Akhras MAH, Jaafar MS, Bououdina M. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artif Cells Nanomed Biotechnol 2017; 45: 98-107
  • 111 Jaiswal S, Mishra P. Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells. Med Microbiol Immunol 2018; 207: 39-53
  • 112 Kumar SSD, Houreld NN, Abrahamse H. Therapeutic potential and recent advances of curcumin in the treatment of aging-associated diseases. Molecules 2018; 23: 835
  • 113 Prado-Audelo D, María L, Caballero-Florán IH, Meza-Toledo JA, Mendoza-Muñoz N, González-Torres M, Florán B, Cortés H, Leyva-Gómez G. Formulations of curcumin nanoparticles for brain diseases. Biomolecules 2019; 9: 56
  • 114 Kumari M, Sharma N, Manchanda R, Gupta N, Syed A, Bahkali AH, Nimesh S. PGMD/curcumin nanoparticles for the treatment of breast cancer. Sci Rep 2021; 11: 1-7
  • 115 Salehi B, Prado-Audelo D, María L, Cortés H, Leyva-Gómez G, Stojanović-Radić Z, Singh YD, Patra JK, Das G, Martins N, Martorell M. Therapeutic applications of curcumin nanomedicine formulations in cardiovascular diseases. J Clin Med 2020; 9: 746
  • 116 Yavarpour-Bali H, Ghasemi-Kasman M, Pirzadeh M. Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders. Int J Nanomed 2019; 14: 4449
  • 117 Boarescu PM, Chirilă I, Bulboacă AE, Bocșan IC, Pop RM, Gheban D, Bolboacă SD. Effects of curcumin nanoparticles in isoproterenol-induced myocardial infarction. Oxid Med Cell Longev 2019; 2019: 7847142
  • 118 Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumour cells. Biochim Biophys Acta 2008; 1780: 673-679
  • 119 Chang R, Sun L, Webster TJ. Short communication: selective cytotoxicity of curcumin on osteosarcoma cells compared to healthy osteoblasts. Int J Nanomedicine 2014; 9: 461-465
  • 120 Ebrahimifar M, Hasanzadegan Roudsari M, Kazemi SM, Shahmabadi HE, Kanaani L, Alavi SA, Vasfi MI. Enhancing effects of curcumin on cytotoxicity of paclitaxel, methotrexate and vincristine in gastric cancer cells. Asian Pac J Cancer Prev 2017; 18: 65-68
  • 121 Li W, Zhou Y, Yang J, Li H, Zhang H, Zheng P. Curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells. Oncol Rep 2017; 37: 3459-3466
  • 122 Koohpar ZK, Entezari M, Movafagh A, Hashemi M. Anticancer activity of curcumin on human breast adenocarcinoma: Role of Mcl-1 gene. Iran J Cancer Prev 2015; 8: 2331
  • 123 Khan AQ, Siveen KS, Prabhu KS, Kuttikrishnan S, Akhtar S, Shaar A, Raza A, Mraiche F, Dermime S, Uddin S. Curcumin-mediated degradation of s-phase kinase protein 2 induces cytotoxic effects in human papillmavirus-positive and negative squamous carcinoma cells. Front Oncol 2018; 8: 399
  • 124 Wang C, Song X, Shang M, Zou W, Zhang M, Wei H, Shao H. Curcumin exerts cytotoxicity dependent on reactive oxygen species accumulation in non-small-cell lung cancer cells. Future Oncol 2019; 15: 1243-1253
  • 125 Walters DK, Muff R, Langsam B, Born W, Fuchs B. Cytotoxic effects of curcumin on osteosarcoma cell lines. Invest New Drugs 2008; 26: 289-297
  • 126 OʼSullivan-Coyne G, OʼSullivan GC, OʼDonovan TR, Piwocka K, McKenna SL. Curcumin induces apoptosis-independent death in oesophageal cancer cells. Br J Cancer 2009; 101: 1585-1595
  • 127 Agrawal S, Goel RK. Curcumin and its protective and therapeutic uses. Nat J Physiol Pharm Pharmacol 2016; 6: 1-8
  • 128 Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, Kamani DR, Chauhan BN. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. ScientificWorldJournal 2012; 2012: 338-345
  • 129 Aggarwal ML, Chacko KM, Kuruvilla BT. Investigation of the toxicity of curcuminoid-essential oil complex: A bioavailable turmeric formulation. Mol Med Rep 2016; 13: 592-604
  • 130 Liju V, Jeena K, Kuttan R. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L.). Food Chem Toxicol 2013; 53: 52-61
  • 131 Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, She TS, Ko JY, Lin JT, Lin BR, Wu MS, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001; 21: 2895-2900
  • 132 Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006; 6: 10
  • 133 Soni KB, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol 1992; 36: 273-275
  • 134 Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol 2015; 29: 642-651
  • 135 Oliver JM, Stoner L, Rowlands DS, Caldwell AR, Sanders E, Kreutzer A, Mitchell JB, Purpura M, Jäger R. Novel form of curcumin improves endothelial function in young, healthy individuals: A double-blind placebo controlled study. J Nutr Metab 2016; 2016: 1089653
  • 136 Sugawara J, Akazawa N, Miyaki A, Choi Y, Tanabe Y, Imai T, Maeda S. Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study. Am J Hypertens 2012; 25: 651
  • 137 Fanaei H, Khayat S, Kasaeian A, Javadimehr M. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial. Neuropeptides 2016; 56: 25-31
  • 138 Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, Lam L, Leung V, Hui E, Ng C, Woo J, Chiu HFK, Goggins WB, Zee BCY, Cheng KF, Fong CYS, Wong A, Mok H, Chow MSS, Ho PC, Ip SP, Ho CS, Yu XW, Lai CYL, Chan MH, Szeto S, Chan HIS, Mok V. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008; 28: 110-113
  • 139 Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM. Oral curcumin for Alzheimerʼs disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 2012; 4: 43
  • 140 Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR. Curcumin for radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 2013; 180: 34-43
  • 141 Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP. Pharmacodynamic and pharmacokinetic study of oral curcuma extract in patients with colorectal cancer. Clin Cancer Res 2001; 7: 1894-1900
  • 142 Bergman J, Miodownik C, Bersudsky Y, Sokolik S, Lerner PP, Kreinin A, Polakiewicz J, Lerner V. Curcumin as an add-on to antidepressive treatment: A randomized, double-blind, placebo-controlled, pilot clinical study. Clin Neuropharmacol 2013; 36: 73-77
  • 143 Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD. Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study. J Affect Disord 2014; 167: 368-375
  • 144 Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012; 35: 2121-2127
  • 145 Chuengsamarn S, Rattanamongkolgul S, Phonrat B, Tungtrongchitr R, Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial. J Nutr Biochem 2014; 25: 144-150
  • 146 Kuriakose MA, Ramdas K, Dey B, Iyer S, Rajan G, Elango KK, Suresh A, Ravindran D, Kumar RR, Prathiba R, Ramachandran S, Kumar NA, Thomas G, Somanathan T, Ravindran HK, Ranganathan K, Katakam SB, Parashuram S, Jayaprakash V, Pillai MR. A randomized double-blind placebo-controlled phase IIB trial of curcumin in oral leukoplakia. Cancer Prev Res (Phila) 2016; 9: 683-691
  • 147 Agarwal KA, Tripathi CD, Agarwal BB, Saluja S. Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: A double-blind, randomized placebo-controlled study. Surg Endosc 2011; 25: 3805-3810
  • 148 Yang YS, Su YF, Yang HW, Lee YH, Chou JI, Ueng KC. Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial. Phytother Res 2014; 28: 1770-1777
  • 149 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: 567-573
  • 150 Nakagawa Y, Mukai S, Yamada S, Matsuoka M, Tarumi E, Hashimoto T, Tamura C, Imaizumi A, Nishihira J, Nakamura T. Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: A randomized, double-blind, placebo-controlled prospective study. J Orthop Sci 2014; 19: 933-939
  • 151 Pinsornsak P, Niempoog S. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: A randomized control trial. J Med Assoc Thail 2012; 1: 51-58
  • 152 Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, Tsujikawa T, Fujiyama Y, Mitsuyama K, Sata M, Yamada M, Iwaoka Y, Kanke K, Hiraishi H, Hirayama K, Araji H, Yoshii S, Uchijima M, Nagata T, Koide Y. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006; 4: 1502-1506
  • 153 Pandaran Sudheeran S, Jacob D, Natinga Mulakal J, Gopinathan Nair G, Maliakel A, Maliakel B, Kuttan R, Im K. Safety, tolerance, and enhanced efficacy of a bioavailable formulation of curcumin with fenugreek dietary fiber on occupational stress: A randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 2016; 36: 236-243
  • 154 Hashemzadeh K, Davoudian N, Jaafari MR, Mirfeizi Z. The effect of nanocurcumin in improvement of knee osteoarthritis: A randomized clinical trial. Curr Rheumatol Rev 2020; 16: 158-164
  • 155 Abbasian S, Soltani-Zangbar MS, Khabbazi A, Farzaneh R, Mahdavi AM, Motavalli R, Hajialilo M, Yousefi M. Nanocurcumin supplementation ameliorates Behcetʼs disease by modulating regulatory T cells: A randomized, double-blind, placebo-controlled trial. Int Immunopharmacol 2021; 101: 108237
  • 156 Ahmadi R, Salari S, Sharifi MD, Reihani H, Rostamiani MB, Behmadi M, Taherzadeh Z, Eslami S, Rezayat SM, Jaafari MR, Elyasi S. Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial. Food Sci Nut 2021; 9: 4068-4075
  • 157 Hosseininasab M, Zarghami M, Mazhari S, Salehifar E, Moosazadeh M, Fariborzifar A, Babaeirad S, Hendouei N. Nanocurcumin as an add-on to antipsychotic drugs for treatment of negative symptoms in patients with chronic schizophrenia: A randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2021; 41: 25-30