Abstract
The goal of the current study was to investigate the antioxidant, anti-ulcer, and analgesic properties of a metal-curcumin complex (MCC) utilizing different mouse and rat models. The antioxidant component of the analysis was completed in vitro, whereas the other activities were completed in vivo. The 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation scavenging test, the ferric-reducing antioxidant power (FRAP) assay, and the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging assay were used to measure the antioxidant activity. MCC demonstrated potent radical scavenging abilities. In all three experiments, Trolox served as the reference substance. When curcumin’s radical scavenging abilities were compared, it became clear that MCC was a superior radical scavenger. Using the ethanol-induced technique on Sprague–Dawley rats, the anti-ulcerogenic effect was assessed. It shows that at an oral dosage of 100 mg/kg body weight, MCC might provide gastroprotection (b.w.). Additionally, we have examined MCC’s potential as an analgesic. Swiss albino mice were used to measure the analgesic activity of MCC using the hot plate technique. At an oral dosage of 50 mg/kg b.w., MCC displayed analgesic efficacy. As a result, MCC could be useful in the management of inflammatory diseases.
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References
Ahmed SA, Hasan MN, Bagchi D et al (2020) Combating essential metal toxicity: key information from optical spectroscopy. ACS Omega 5:15666–15672. https://doi.org/10.1021/acsomega.0c01898
Ak T, Gülçin I (2008) Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 174:27–37. https://doi.org/10.1016/j.cbi.2008.05.003
Al-Sayed E, Abdel-Daim MM (2018) Analgesic and anti-inflammatory activities of epicatechin gallate from Bauhinia hookeri. Drug Dev Res 79:157–164. https://doi.org/10.1002/ddr.21430
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. https://doi.org/10.1021/mp700113r
Araújo CC, Leon LL (2001) Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 96:723–728. https://doi.org/10.1590/s0074-02762001000500026
Aziz RS, Siddiqua A, Shahzad M et al (2019) Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6, TNF-α, NF-ĸB, and COX-2 levels, and upregulation of TFF-2 levels. Biomed Pharmacother 110:554–560. https://doi.org/10.1016/j.biopha.2018.12.002
Badr AM, EL- Orabi NF, Ali RA (2019) The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: potential protective effect is afforded by raspberry ketone. PLoS ONE 14:e0220548. https://doi.org/10.1371/journal.pone.0220548
Barik A, Mishra B, Kunwar A et al (2007) Comparative study of copper(II)-curcumin complexes as superoxide dismutase mimics and free radical scavengers. Eur J Med Chem 42:431–439. https://doi.org/10.1016/j.ejmech.2006.11.012
Bashkin A, Ghanim M, Abu-Farich B et al (2021) Forty-one plant extracts screened for dual antidiabetic and antioxidant functions: evaluating the types of correlation between α-amylase inhibition and free radical scavenging. Molecules 26. https://doi.org/10.3390/molecules26020317
Beneduci A, Corrente GA, Marino T et al (2019) Insight on the chelation of aluminum (III) and iron (III) by curcumin in aqueous solution. J Mol Liq 296:111805
Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/abio.1996.0292
Bicer N, Yildiz E, Yegani AA, Aksu F (2018) Synthesis of curcumin complexes with iron (III) and manganese (II), and effects of curcumin–iron (III) on Alzheimer’s disease. New J Chem 42:8098–8104
Calam J, Baron JH (2001) Pathophysiology of duodenal and gastric ulcer and gastric cancer. BMJ 323:980–982. https://doi.org/10.1136/bmj.323.7319.980
Cameron AM, Castoldi A, Sanin DE et al (2019) Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species–mediated DNA damage. Nat Immunol 20:420–432. https://doi.org/10.1038/s41590-019-0336-y
Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med 9:161–168
Chou C-C, Wang C-P, Chen J-H, Lin H-H (2019) Anti-atherosclerotic effect of hibiscus leaf polyphenols against tumor necrosis factor-alpha-induced abnormal vascular smooth muscle cell migration and proliferation. Antioxidants (Basel) 8. https://doi.org/10.3390/antiox8120620
Cook AD, Christensen AD, Tewari D et al (2018) Immune cytokines and their receptors in inflammatory pain. Trends Immunol 39:240–255. https://doi.org/10.1016/j.it.2017.12.003
Damon C (1966) Hawk’s physiological chemistry. 14th Ed. Edited by Bernard L. Oser. McGraw-Hill Book Co., 330 West 42nd strcet, New York, N. Y., 1965 xv + 1472 pp. 16.5 × 23.5 cm. price $19.50. J Pharm Sci 55:455–455. https://doi.org/10.1002/jps.2600550432
Dengiz GO, Odabasoglu F, Halici Z et al (2007) Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats. J Pharmacol Sci 105:94–102. https://doi.org/10.1254/jphs.fp0070122
Dogru M, Kojima T, Simsek C, Tsubota K (2018) Potential role of oxidative stress in ocular surface inflammation and dry eye disease. Invest Ophthalmol Vis Sci 59:DES163–DES168. https://doi.org/10.1167/iovs.17-23402
Domper Arnal M-J, Hijos-Mallada G, Lanas A (2022) Gastrointestinal and cardiovascular adverse events associated with NSAIDs. null 21:373–384. https://doi.org/10.1080/14740338.2021.1965988
Gnanasekar N, Perianayagam J (2004) Influence of sodium curcuminate on castor oil-induced diarrhea in rats. Indian J Pharmacol 36:177–178
Guo C-G, Leung WK (2020) Potential strategies in the prevention of nonsteroidal anti-inflammatory drugs-associated adverse effects in the lower gastrointestinal tract. Gut Liver 14:179–189. https://doi.org/10.5009/gnl19201
Ho H-H, Chang C-S, Ho W-C et al (2010) Anti-metastasis effects of gallic acid on gastric cancer cells involves inhibition of NF-κB activity and downregulation of PI3K/AKT/small GTPase signals. Food Chem Toxicol 48:2508–2516. https://doi.org/10.1016/j.fct.2010.06.024
Hseu Y-C, Chen X-Z, Vudhya Gowrisankar Y et al (2020) The skin-whitening effects of ectoine via the suppression of α-MSH-stimulated melanogenesis and the activation of antioxidant Nrf2 pathways in UVA-irradiated keratinocytes. Antioxidants (Basel) 9. https://doi.org/10.3390/antiox9010063
Ito N, Hirose M, Fukushima S et al (1986) Studies on antioxidants: their carcinogenic and modifying effects on chemical carcinogenesis. Food Chem Toxicol 24:1071–1082. https://doi.org/10.1016/0278-6915(86)90291-7
Kamada T, Satoh K, Itoh T et al (2021) Evidence-based clinical practice guidelines for peptic ulcer disease 2020. J Gastroenterol 56:303–322. https://doi.org/10.1007/s00535-021-01769-0
Khan MS, Ikram M, Park JS et al (2020) Gut microbiota, its role in induction of Alzheimer’s disease pathology, and possible therapeutic interventions: special focus on anthocyanins. Cells 9. https://doi.org/10.3390/cells9040853
Kuna L, Jakab J, Smolic R et al (2019) Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. J Clin Med 8. https://doi.org/10.3390/jcm8020179
Kunwar A, Narang H, Priyadarsini KI et al (2007) Delayed activation of PKCδ and NFκB and higher radioprotection in splenic lymphocytes by copper (II)–curcumin (1:1) complex as compared to curcumin. J Cell Biochem 102:1214–1224. https://doi.org/10.1002/jcb.21348
Lokman MS, Zaafar D, Althagafi HA, Abdel Daim MM, Theyab A, Hasan Mufti A, Algahtani M, Habotta OA, Alghamdi AAA, Alsharif KF, Albrakati A, Oyouni AAA, Bauomy AA, Baty RS, Zhery AS, Hassan KE, Abdel Moneim AE, Kassab RB (2022) Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries. J Food Biochem 46:e14070. https://doi.org/10.1111/jfbc.14070
Maity R, Mondal P, Giri MK et al (2021) Gastroprotective effect of hydromethanolic extract of Ayapana triplinervis leaves on indomethacin-induced gastric ulcer in male Wistar rats. J Food Biochem 45:e13859
Marrazzo P, Angeloni C, Hrelia S (2019) Combined treatment with three natural antioxidants enhances neuroprotection in a SH-SY5Y 3D culture model. Antioxidants (Basel) 8. https://doi.org/10.3390/antiox8100420
Mary CPV, Vijayakumar S, Shankar R (2018) Metal chelating ability and antioxidant properties of curcumin-metal complexes—a DFT approach. J Mol Graph Model 79:1–14
Mei X, Luo X, Xu S et al (2009) Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chem Biol Interact 181:316–321. https://doi.org/10.1016/j.cbi.2009.06.022
Mei X, Xu D, Xu S et al (2011) Gastroprotective and antidepressant effects of a new zinc(II)-curcumin complex in rodent models of gastric ulcer and depression induced by stresses. Pharmacol Biochem Behav 99:66–74. https://doi.org/10.1016/j.pbb.2011.04.002
Mei X, Xu D, Xu S et al (2012) Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers. Chem Biol Interact 197:31–39. https://doi.org/10.1016/j.cbi.2012.03.006
Michels da Silva D, Langer H, Graf T (2019) Inflammatory and molecular pathways in heart failure-ischemia, HFpEF and transthyretin cardiac amyloidosis. Int J Mol Sci 20. https://doi.org/10.3390/ijms20092322
Mukherjee S, Jana T, Pan J-J (2018) Adverse effects of proton pump inhibitors on platelet count: a case report and review of the literature. Case Rep Gastrointest Med 2018:4294805. https://doi.org/10.1155/2018/4294805
Musa A, Shady NH, Ahmed SR et al (2021) Antiulcer potential of olea europea l. Cv. arbequina leaf extract supported by metabolic profiling and molecular docking. Antioxidants 10:644
Narayanan M, Reddy KM, Marsicano E (2018) Peptic ulcer disease and Helicobacter pylori infection. Mo Med 115:219–224
Owoade O, Adetutu A, Olorunnisola O (2019) Free radicals as mediators of oxidative damage and disease. https://doi.org/10.9790/3008-1402025764
Peni P, Sasri R, Silalahi IH (2020) Synthesis of metal–curcumin complex compounds (M = Na+, Mg2+, Cu2+). Jurnal Kimia Sains dan Aplikasi 23:75–82. https://doi.org/10.14710/jksa.23.3.75-82
Pohl F, Kong Thoo Lin P (2018) The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: in vitro, in vivo and clinical trials. Molecules 23. https://doi.org/10.3390/molecules23123283
Prasad S, DuBourdieu D, Srivastava A et al (2021) Metal–curcumin complexes in therapeutics: an approach to enhance pharmacological effects of curcumin. Int J Mol Sci 22:7094
Ramprasad C, Sirsi M (1956) Observations on the pharmacology of Curcuma longa. Studies in Indian plants Curcuma longa Linn—effects of curcumin and essential oil of C longaon bile secretion J Sci Res Inst 15:212–216
Rao TS, Basu N, Siddiqui HH (1982) Anti-inflammatory activity of curcumin analogues. Indian J Med Res 75:574–578
Rao T, Basu N, Seth S, Siddiqui H (1984) Some aspects of pharmacological profile of sodium curcuminate. Indian J Physiol Pharmacol 28:211–215
Re R, Pellegrini N, Proteggente A et al (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237. https://doi.org/10.1016/S0891-5849(98)00315-3
Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000. https://doi.org/10.1161/ATVBAHA.110.207449
Robert A, Nezamis JE, Lancaster C, Hanchar AJ (1979) Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77:433–443
Sahraee S, Milani JM, Regenstein JM, Kafil HS (2019) Protection of foods against oxidative deterioration using edible films and coatings: a review. Food Biosci 32:100451. https://doi.org/10.1016/j.fbio.2019.100451
Sampath Kumar NS, Nazeer RA, Jaiganesh R (2012) Purification and identification of antioxidant peptides from the skin protein hydrolysate of two marine fishes, horse mackerel (Magalaspis cordyla) and croaker (Otolithes ruber). Amino Acids 42:1641–1649. https://doi.org/10.1007/s00726-011-0858-6
Sharma GN, Gupta G, Sharma P (2018) A comprehensive review of free radicals, antioxidants, and their relationship with human ailments. 28:139–154
Shen C-H, Liu C-T, Song X-J et al (2018) Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships. J Chromatogr B 1090:73–80. https://doi.org/10.1016/j.jchromb.2018.05.021
Shimamura T, Sumikura Y, Yamazaki T et al (2014) Applicability of the DPPH assay for evaluating the antioxidant capacity of food additives - inter-laboratory evaluation study -. Anal Sci 30:717–721. https://doi.org/10.2116/analsci.30.717
Singh A, Dutta PK (2020) Green synthesis, characterization and biological evaluation of chitin glucan based zinc oxide nanoparticles and its curcumin conjugation. Int J Biol Macromol 156:514–521. https://doi.org/10.1016/j.ijbiomac.2020.04.081
Singh G, Mohit D et al (2022) Functionalized organosilanes and their magnetic nanoparticles as receptor for Sn (II) ions detection and potent antioxidants. J Mol Struct 1247:131297. https://doi.org/10.1016/j.molstruc.2021.131297
Suresh K, Nangia A (2018) Curcumin: pharmaceutical solids as a platform to improve solubility and bioavailability. CrystEngComm 20:3277–3296. https://doi.org/10.1039/C8CE00469B
Tabanelli R, Brogi S, Calderone V (2021) Improving curcumin bioavailability: current strategies and future perspectives. Pharmaceutics 13. https://doi.org/10.3390/pharmaceutics13101715
Taverne YJ, Merkus D, Bogers AJ et al (2018) Reactive oxygen species: radical factors in the evolution of animal life. BioEssays 40:1700158. https://doi.org/10.1002/bies.201700158
Test No. 425: Acute oral toxicity: up-and-down procedure | OECD Guidelines for the Testing of Chemicals, Section 4 : Health Effects | OECD iLibrary (n.d.) https://www.oecd-ilibrary.org/environment/test-no-425-acute-oral-toxicity-up-and-down-procedure_9789264071049-en. Accessed 6 Jun 2022
Tian C, Chang Y, Zhang Z et al (2019) Extraction technology, component analysis, antioxidant, antibacterial, analgesic and anti-inflammatory activities of flavonoids fraction from Tribulus terrestris L. leaves. Heliyon 5:e02234. https://doi.org/10.1016/j.heliyon.2019.e02234
Tran QH, Doan TT (2020) A novel study on curcumin metal complexes: solubility improvement, bioactivity, and trial burn wound treatment in rats. New J Chem 44:13036–13045
Woolfe G (1944) The evaluation of the analgesic actions of pethidine hydrochlodide (Demerol). J Pharmacol Exp Ther 80:300–307
Zahran EM, Abdelmohsen UR, Hussein AS et al (2021) Antiulcer potential and molecular docking of flavonoids from Ocimum forskolei Benth., family Lamiaceae. Nat Prod Res 35:1933–1937
Zhao J, Maitituersun A, Li C et al (2018) Evaluation on analgesic and anti-inflammatory activities of total flavonoids from Juniperus sabina. Evid Based Complement Alternat Med 2018:7965306. https://doi.org/10.1155/2018/7965306
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AJ and SL designed research, and AJ and SL performed in vitro antioxidant assays. BL and DK conducted the analgesic activity. PP and SP conducted the anti-ulcer activity. AJ analyzed the data. AJ wrote the manuscript. All authors read and approved the manuscript. AJ and SL gave final approval to the manuscript submission. The authors declare that all data were generated in-house and that no paper mill was used.
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Joshi, A., Lehene, S., Lasnapure, B. et al. Investigation of antioxidant, anti-ulcer, and analgesic potential of a metal-curcumin complex. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1043–1052 (2023). https://doi.org/10.1007/s00210-022-02381-6
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DOI: https://doi.org/10.1007/s00210-022-02381-6