Abstract
Curcumin is a natural compound found in turmeric root (Curcuma longa L.), a plant widely used in traditional medicine and cooking. This substance has important chemical and pharmacological properties, being a potent antioxidant with anti-inflammatory and anticancer activities. Through its antioxidant effects, curcumin is able to neutralize free radicals, which are unstable molecules associated with aging and various diseases, such as cardiovascular and neurodegenerative diseases. In addition, curcumin shows the ability to modulate cell signaling pathways involved in inflammatory processes, making it a promising option in the treatment of chronic inflammatory diseases such as arthritis and inflammatory bowel disease. Many studies suggest that the anticancer effect may occur through inhibition of tumor cell growth, induction of apoptosis (programmed cell death), and inhibition of angiogenesis (formation of new blood vessels). It is worth noting that curcumin undergoes extensive first-pass metabolism and molecular instability. These properties may compromise the use of the molecule for therapeutic purposes. Thus, we can state that curcumin has potential in the treatment of several diseases. However, pharmaceutical formulations need to be developed to ensure effective blood and tissue concentrations.
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References
Abrahams S, Haylett WL, Johnson G, Carr JA, Bardien S (2019) Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: a review. Neuroscience 406:1–21. https://doi.org/10.1016/j.neuroscience.2019.02.020
Asai A, Miyazawa T (2000) Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci 67(23):2785–2793. https://doi.org/10.1016/S0024-3205(00)00868-7s
Babu KV, Rajasekharan KN (1994) A convenient synthesis of curcumin-I analogues. Org Prep Proced Int 26:674–677. https://doi.org/10.1080/00304949409458165
Baj T, Seth R (2018) Role of curcumin in regulation of TNF-α mediated brain inflammatory responses. Recent Patents Inflamm Allergy Drug Discov 12(1):69–77. https://doi.org/10.2174/1872213X12666180703163824
Balasubramanian K (2006) Molecular orbital basis for yellow curry spice curcumin’s prevention of Alzheimer’s disease. J Agric Food Chem 54(10):3512–3520. https://doi.org/10.1021/jf0603533
Banik U, Parasuraman S, Adhikary AK, Othman NH (2017) Curcumin: the spicy modulator of breast carcinogenesis. J Exp Clin Cancer Res 36(1):98. https://doi.org/10.1186/s13046-017-0566-5
Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD et al (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther 326(1):196–208. https://doi.org/10.1124/jpet.108.137455
Berginc K, Trontelj J, Basnet NS, Kristl A (2012) Physiological barriers to the oral delivery of curcumin. Die Pharmazie 67(6):518–524
Borsari M, Ferrari E, Grandi R, Saladini M (2002) Curcuminoids as potential new iron-chelating agents: spectroscopic, polarographic and potentiometric study on their Fe(III) complexing ability. Inorg Chim Acta 328:61–68. https://doi.org/10.1016/S0020-1693(01)00687-9
Burapan S, Kim M, Han J (2017) Curcuminoid demethylation as an alternative metabolism by human intestinal microbiota. J Agric Food Chem 65(16):3305–3310. https://doi.org/10.1021/acs.jafc.7b00943
Chai YS, Chen YQ, Lin SH, Xie K, Wang CJ, Yang YZ, Xu F (2020) Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Biomed Pharmacother 125:109946. https://doi.org/10.1016/j.biopha.2020.109946
Chen WT, Yang TS, Chen HC, Chen HH, Chiang HC, Lin TC, Yeh CH, Ke TW, Chen JS, Hsiao KH, Kuo ML (2014) Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer. Nutr Res 34(7):585–594. https://doi.org/10.1016/j.nutres.2014.06.010
Chen M, Du ZY, Zheng X, Li DL, Zhou RP, Zhang K (2018) Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease. Neural Regen Res 13(4):742–752. https://doi.org/10.4103/1673-5374.230303
Dei Cas M, Ghidoni R (2019) Dietary curcumin: correlation between bioavailability and health potential. Nutrients 11(9):2147. https://doi.org/10.3390/nu11092147
Derosa G, Maffioli P, Simental-Mendía LE, Bo S, Sahebkar A (2016) Effect of curcumin on circulating interleukin-6 concentrations: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 111:394–404. https://doi.org/10.1016/j.phrs.2016.07.004
El Nebrisi E, Javed H, Ojha SK, Oz M, Shehab S (2020) Neuroprotective effect of curcumin on the nigrostriatal pathway in a 6-hydroxydopmine-induced rat model of Parkinson’s disease is mediated by α7-nicotinic receptors. Int J Mol Sci 21(19):7329. https://doi.org/10.3390/ijms21197329
Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G (2012) Curcumin—from molecule to biological function. Angew Chem Int Ed Engl 51(22):5308–5332. https://doi.org/10.1002/anie.201107724
Fu YS, Chen TH, Weng L, Huang L, Lai D, Weng CF (2021) Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharmacother 141:111888. https://doi.org/10.1016/j.biopha.2021.111888
Ghosh S, Banerjee S, Sil PC (2015) The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update. Food Chem Toxicol 83:111–124. https://doi.org/10.1016/j.fct.2015.05.022
Ghosh SS, He H, Wang J, Gehr TW, Ghosh S (2018) Curcumin-mediated regulation of intestinal barrier function: the mechanism underlying its beneficial effects. Tissue Barriers 6(1):e1425085. https://doi.org/10.1080/21688370.2018.1425085
Girardon M, Parant S, Monari A, Dehez F, Chipot C, Rogalska E et al (2019) Triggering tautomerization of curcumin by confinement into liposomes. ChemPhotoChem 3(10):10341041. https://doi.org/10.1002/cptc.201900159
Gordon ON, Luis PB, Sintim HO, Schneider C (2015) Unraveling curcumin degradation: autoxidation proceeds through spiroepoxide and vinylether intermediates en route to the main bicyclopentadione. J Biol Chem 290(8):4817–4828. https://doi.org/10.1074/jbc.m114.618785
Graf E (1968) Curcumin from vanillin and acetyl acetone . Patent 1,280,849. German
Grynkiewicz G, Ślifirski P (2012) Curcumin and curcuminoids in quest for medicinal status. Acta Biochim Pol 59(2):201–212. https://doi.org/10.18388/abp.2012_2139
Hassaninasab A, Hashimoto Y, Tomita-Yokotani K, Kobayashi M (2011) Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism. Proc Natl Acad Sci 108(16):6615–6620. https://doi.org/10.1073/pnas.101621710
Heger M, van Golen RF, Broekgaarden M, Michel MC (2014) The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol Rev 66(1):222–307. https://doi.org/10.1124/pr.110.004044
Hidaka H, Ishiko T, Furuhashi T, Kamohara H, Suzuki S, Miyazaki M, Ikeda O, Mita S, Setoguchi T, Ogawa M (2002) Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface: impact on human pancreatic carcinoma cell growth by autocrine regulation. Cancer 95(6):1206–1214. https://doi.org/10.1002/cncr.10812
Hoehle SI, Pfeiffer E, Sólyom AM, Metzler M (2006) Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver. J Agric Food Chem 54(3):756–764. https://doi.org/10.1021/jf058146a
Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL et al (2001) Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res 61(3):1058–1064
Ji HF, Shen L (2014) Can improving bioavailability improve the bioactivity of curcumin? Trends Pharmacol Sci 35(6):265–266. https://doi.org/10.1016/j.tips.2014.04.001
Kawano SI, Inohana Y, Hashi Y, Lin JM (2013) Analysis of keto-enol tautomers of curcumin by liquid chromatography/mass spectrometry. Chin Chem Lett 24(8):685–687. https://doi.org/10.1016/j.cclet.2013.05.006
Kim SG, Veena MS, Basak SK, Han E, Tajima T, Gjertson DW, Starr J, Eidelman O, Pollard HB, Srivastava M, Srivatsan ES, Wang MB (2011) Curcumin treatment suppresses IKKβ kinase activity of salivary cells of patients with head and neck cancer: a pilot study. Clin Cancer Res 17(18):5953–5961. https://doi.org/10.1158/1078-0432.CCR-11-1272
Kolev TM, Velcheva EA, Stamboliyska BA, Spiteller M (2005) DFT and experimental studies of the structure and vibrational spectra of curcumin. Int J Quantum Chem 102(6):1069–1079. https://doi.org/10.1002/qua.20469
Kotha RR, Luthria DL (2019) Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules 24(16):2930. https://doi.org/10.3390/molecules24162930
Krackov MH, Bellis HE (1997) Process for the synthesis of curcumin-related compounds. U.S. Patent n. 5,679,864, 21 out
Lampe V, Milobedzka J (1913) Studien über Curcumin. Ber Dtsch Chem Ges 46(2):2235–2240. https://doi.org/10.1002/cber.191304602149
Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM et al (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6(1):1–4. https://doi.org/10.1186/1472-6882-6-10
Lin JK, Pan MH, Lin-Shiau SY (2000) Recent studies on the biofunctions and biotransformations of curcumin. Biofactors 13(1–4):153–158. https://doi.org/10.1002/biof.5520130125
Liu Z, Ying Y (2020) The inhibitory effect of curcumin on virus-induced cytokine storm and its potential use in the associated severe pneumonia. Front Cell Dev Biol 8:479. https://doi.org/10.3389/fcell.2020.00479
Liu Z, Smart JD, Pannala AS (2020) Recent developments in formulation design for improving oral bioavailability of curcumin: a review. J Drug Deliv Sci Technol 60:102082. https://doi.org/10.1517/17425247.2014.916686
Ma Z, Wang N, He H, Tang X (2019) Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. J Control Release 316:359–380. https://doi.org/10.1016/j.jconrel.2019.10.053
Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA (2017) The essential medicinal chemistry of curcumin: miniperspective. J Med Chem 60(5):1620–1637. https://doi.org/10.1021/acs.jmedchem.6b00975
Pan MH, Huang TM, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27(4):486–494
Pawar HA, Gavasane AJ, Choudhary PD (2018) A novel and simple approach for extraction and isolation of curcuminoids from turmeric rhizomes. Nat Prod Chem Res 6(1):300. https://doi.org/10.4172/2475-7675.1000300
Perkins S, Verschoyle RD, Hill K, Parveen I, Threadgill MD, Sharma RA et al (2002) Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol Biomark Prev 11(6):535–540
Prasad S, Gupta SC, Tyagi AK, Aggarwal BB (2014a) Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv 32(6):1053–1064. https://doi.org/10.1016/j.biotechadv.2014.04.004
Prasad S, Tyagi AK, Aggarwal BB (2014b) Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat 46(1):2–18. https://doi.org/10.4143/crt.2014.46.1.2
Priyadarsini KI (2014) The chemistry of curcumin: from extraction to therapeutic agent. Molecules 19(12):20091–20112. https://doi.org/10.3390/molecules191220091
Rao EV, Sudheer P (2011) Revisiting curcumin chemistry part I: a new strategy for the synthesis of curcuminoids. Indian J Pharm Sci 73(3):262–270. https://doi.org/10.4103/0250-474X.93508
Rathore S, Mukim M, Sharma P, Devi S, Nagar JC, Khalid M (2020) Curcumin: a review for health benefits. Int J Res Rev 7(1):273–290. https://www.ijrrjournal.com/IJRR_Vol.7_Issue.1_Jan2020/IJRR0039.pdf
Rege SA, Arya M, Momin SA (2019) Mini review on keto-enol ratio of curcuminoids. Ukr J Food Sci 7(1):27–32. https://doi.org/10.24263/2310-1008-2019-7-1-5
Roughley PJ, Whiting DA (1973) Experiments in the biosynthesis of curcumin. J Chem Soc Perkin Trans 1:2379–2388. https://doi.org/10.1039/P19730002379
Samarghandian S, Azimi-Nezhad M, Farkhondeh T, Samini F (2017) Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomed Pharmacother 87:223–229. https://doi.org/10.1016/j.biopha.2016.12.105
Scazzocchio B, Minghetti L, D’Archivio M (2020) Interaction between gut microbiota and curcumin: a new key of understanding for the health effects of curcumin. Nutrients 12(9):2499. https://doi.org/10.3390/nu12092499
Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J (2014) The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 58(3):516–527. https://doi.org/10.1002/mnfr.201300724
Serafim MSM, Kronenberger T, de Oliveira RB, Kroon EG, Abrahão JS, Mota BEF, Maltarollo VG (2023) Synthetic curcumin analogues present antiflavivirus activity in vitro with potential multiflavivirus activity from a thiazolylhydrazone moiety. Future Pharmacol 3(2):364–378. https://doi.org/10.3390/futurepharmacol3020022
Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Steward WP (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7(7):1894–1900
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Steward WP (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10(20):6847–6854. https://doi.org/10.1158/1078-0432.ccr-04-0744
Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: the story so far. Eur J Cancer 41(13):1955–1968. https://doi.org/10.1016/j.ejca.2005.05.009
Shehzad A, Qureshi M, Anwar MN, Lee YS (2017) Multifunctional curcumin mediate multitherapeutic effects. J Food Sci 82(9):2006–2015. https://doi.org/10.1111/1750-3841.13793
Siviero A, Gallo E, Maggini V, Gori L, Mugelli A, Firenzuoli F, Vannacci A (2015) Curcumin, a golden spice with a low bioavailability. J Herb Med 5(2):57–70. https://doi.org/10.1016/j.hermed.2015.03.001
Slika L, Patra D (2020) A short review on chemical properties, stability and nano-technological advances for curcumin delivery. Expert Opin Drug Deliv 17(1):61–75. https://doi.org/10.1080/17425247.2020.1702644
Stohs SJ, Chen CYO, Preuss HG, Ray SD, Bucci LR, Ji J, Ruff KJ (2019) The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study. BMC Complement Altern Med 19(1):1–8. https://doi.org/10.1186/s12906-019-2699-x
Tomeh MA, Hadianamrei R, Zhao X (2019) A review of curcumin and its derivatives as anticancer agents. Int J Mol Sci 20(5):1033. https://doi.org/10.3390/ijms20051033
Trist BG, Hare DJ, Double KL (2019) Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell 18(6):e13031. https://doi.org/10.1111/acel.13031
Urošević M, Nikolić L, Gajić I, Nikolić V, Dinić A, Miljković V (2022) Curcumin: biological activities and modern pharmaceutical forms. Antibiotics (Basel) 11(2):135. https://doi.org/10.3390/antibiotics11020135
Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z, Brenner DE (2008) Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomark Prev 17(6):1411–1417. https://doi.org/10.1158/1055-9965.epi-07-2693
Vogel HA, Pelletier J (1815) Curcumin-biological and medicinal properties. J Pharma 2(50):24–29. https://doi.org/10.3390/molecules24162930
Vollono L, Falconi M, Gaziano R, Iacovelli F, Dika E, Terracciano C, Bianchi L, Campione E (2019) Potential of curcumin in skin disorders. Nutrients 11(9):2169. https://doi.org/10.3390/nu11092169
Volpe DA, Faustino PJ, Ciavarella AB, Asafu-Adjaye EB, Ellison CD, Yu LX, Hussain AS (2007) Classification of drug permeability with a Caco-2 cell monolayer assay. Clin Res Regul Aff 24(1):39–47. https://doi.org/10.1080/10601330701273669
Wahlström B, Blennow G (1978) A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol 43(2):86–92. https://doi.org/10.1111/j.1600-0773.1978.tb02240.x
Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 15(12):1867–1876. https://doi.org/10.1016/s0731-7085(96)02024-9
Wang YL, Ju B, Zhang YZ, Yin HL, Liu YJ, Wang SS, Zeng ZL, Yang XP, Wang HT, Li JF (2017) Protective effect of curcumin against oxidative stress-induced injury in rats with Parkinson’s disease through the Wnt/β-catenin signaling pathway. Cell Physiol Biochem 43(6):2226–2241. https://doi.org/10.1159/000484302
Yang J, Song S, Li J, Liang T (2014) Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat. Pathol Res Pract 210(6):357–362. https://doi.org/10.1016/j.prp.2014.02.005
Yuan J, Liu R, Ma Y, Zhang Z, Xie Z (2018) Curcumin attenuates airway inflammation and airway remolding by inhibiting NF-κB signaling and COX-2 in cigarette smoke-induced COPD mice. Inflammation 41(5):1804–1814. https://doi.org/10.1007/s10753-018-0823-6
Zheng B, McClements DJ (2020) Formulation of more efficacious curcumin delivery systems using colloid science: enhanced solubility, stability, and bioavailability. Molecules 25(12):2791. https://doi.org/10.3390/molecules25122791
Zhu T, Chen Z, Chen G, Wang D, Tang S, Deng H, Wang J, Li S, Lan J, Tong J, Li H, Deng X, Zhang W, Sun J, Tu Y, Luo W, Li C (2019) Curcumin attenuates asthmatic airway inflammation and mucus hypersecretion involving a PPARγ-dependent NF-κB signaling pathway in vivo and in vitro. Mediat Inflamm 2019:4927430. https://doi.org/10.1155/2019/4927430
Zielińska A, Alves H, Marques V, Durazzo A, Lucarini M, Alves TF, Morsink M, Willemen N, Eder P, Chaud MV, Severino P, Santini A, Souto EB (2020) Properties, extraction methods, and delivery systems for curcumin as a natural source of beneficial health effects. Medicina (Kaunas) 56(7):336. https://doi.org/10.3390/medicina56070336
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da Silva Lopes, L., Pereira, S.K.S., Lima, L.K.F. (2023). Pharmacokinetics and Pharmacodynamics of Curcumin. In: Rai, M., Feitosa, C.M. (eds) Curcumin and Neurodegenerative Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-99-7731-4_1
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