Abstract
Coliform mastitis is a worldwide serious disease of the mammary gland. Curcumin is a pleiotropic polyphenol obtained from turmeric, but it is hydrophobic and rapidly eliminated from the body. However, nanoformulation of curcumin significantly improves its pharmacological activity by enhancing its hydrophobicity and oral bioavailability. Our study aimed to investigate the possible antioxidant and anti-inflammatory effects of nanocurcumin as a prophylactic against LPS-induced coliform mastitis in rat model, where LPS was extracted from a field strain of Escherichia coli (bovine mastitis isolate). The study was conducted on twenty lactating Wistar female rats divided into four equal groups, and the mastitis model was initiated by injection of LPS through the duct of the mammary gland. The results showed that nanocurcumin significantly attenuated the lipid peroxidation (MDA), oxidized glutathione, the release of pro-inflammatory cytokines (TNF-α and IL-1β), and the gene expression of TLR4, NF-κB p65, and HMGB1. Meanwhile, it improved the reduced glutathione level and Nrf2 activity and preserved the normal alveolar architecture. These findings suggested that nanocurcumin supplementation can be a promising potential protective approach for coliform mastitis.
Similar content being viewed by others
Data availability
The data analyzed in this current study are incorporated in this published article.
References
Aggarwal BB, Gupta SC, Sung B (2013) Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol 169:1672–1692
AlBasher G, Abdel-Daim MM, Almeer A, Ibrahim KA, Hamza RZ, Bungau S, Aleya L (2020) Synergistic antioxidant effects of resveratrol and curcumin against fipronil-triggered oxidative damage in male albino rats. Environ Sci Pollut Res 27(6):6505–6514
Al-Kahtani M, Abdel-Daim MM, Sayed AA, El-Kott A, Morsy K (2020) Curcumin phytosome modulates aluminum-induced hepatotoxicity via regulation of antioxidant, Bcl-2, and caspase-3 in rats. Environ Sci Pollut Res 27(17):21977–21985
Andersson U, Yang H, Harris H (2018) Extracellular HMGB1 as a therapeutic target in inflammatory diseases. Expert Opin Ther Targets 22:263–277
Arozal W, Ramadanty WT, Louisa M, Satyana RPU, Hartono G, Fatrin S, Purbadi S, Estuningtyas A, Instiaty I (2019) pharmacokinetic profile of curcumin and nanocurcumin in plasma, ovary, and other tissues. Drug Res (Stuttg) 69:559–564
Bajic VP, Van Neste C, Obradovic M, Zafirovic S, Radak D, Bajic VB, Essack M, Isenovic ER (2019) Glutathione “redox homeostasis” and its relation to cardiovascular disease. Oxidative Med Cell Longev 2019:5028181–5028181
Bancroft JD, Gamble M (2008): Theory and practice of histological techniques. Elsevier health sciences
Barreto F, Jank L, Castilhos T, Rau RB, Tomaszewski CA, Ribeiro C, Hillesheim DR (2019) Chemical residues and mycotoxins in raw milk, Raw milk. Elsevier, pp:273–293
Bhattarai D, Worku T, Dad R, Rehman ZU, Gong X, Zhang S (2018) Mechanism of pattern recognition receptors (PRRs) and host pathogen interplay in bovine mastitis. Microb Pathog 120:64–70
Bisht A, Dickens M, Rutherfurd-Markwick K, Thota R, Mutukumira AN, Singh H (2020) Chlorogenic acid potentiates the anti-inflammatory activity of curcumin in LPS-stimulated THP-1 cells. Nutrients 12:2706
Boyanapalli SS, Paredes-Gonzalez X, Fuentes F, Zhang C, Guo Y, Pung D, Saw CL, Kong AN (2014) Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin. Chem Res Toxicol 27:2036–2043
Brouillette E, Malouin F (2005) The pathogenesis and control of Staphylococcus aureus-induced mastitis: study models in the mouse. Microbes Infect 7:560–568
Carvalho-Sombra TCF, Fernandes DD, Bezerra BMO, Nunes-Pinheiro DCS (2021) Systemic inflammatory biomarkers and somatic cell count in dairy cows with subclinical mastitis. Vet Anim Sci 11:100165
Catanzaro M, Corsini E, Rosini M, Racchi M, Lanni C (2018) Immunomodulators inspired by nature: a review on curcumin and echinacea. Molecules:23
Chen CY, Kao CL, Liu CM (2018) The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. Int J Mol Sci 19:2729
Cheng WN, Han SG (2020) Bovine mastitis: risk factors, therapeutic strategies, and alternative treatments - A review. Asian Australas J Anim Sci 33:1699–1713
Cobirka M, Tancin V, Slama P (2020) Epidemiology and classification of mastitis. Animals 10:2212
Colagar AH, Pouramir M, Marzony ET, Jorsaraei SGA (2009) Relationship between seminal malondialdehyde levels and sperm quality in fertile and infertile men. Braz Arch Biol Technol 52:1387–1392
Da W, Zhang J, Zhang R, Zhu J (2019) Curcumin inhibits the lymphangiogenesis of gastric cancer cells by inhibiton of HMGB1/VEGF-D signaling. Int J Immunopathol Pharmacol 33:2058738419861600
de Almeida Alvarenga L, de Oliveira LV, Borges NA, de Aguiar AS, Faxén-Irving G, Stenvinkel P, Lindholm B, Mafra D (2018) Curcumin-A promising nutritional strategy for chronic kidney disease patients. J Funct Foods 40:715–721
Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431
Edwards P, Ewing WJCMM (1972) Identification of Enterobacteriaceae. Burgess Publ:103–104
Elfeky M, Yoneshiro T, Okamatsu-Ogura Y, Kimura K (2018) Adiponectin suppression of late inflammatory mediator, HMGB1-induced cytokine expression in RAW264 macrophage cells. J Biochem 163:143–153
El-Sayed A, Kamel M (2020) Advanced applications of nanotechnology in veterinary medicine. Environ Sci Pollut Res 27:19073–19086
Eskiler GG, Özkan AD, Kaleli S, Bilir C (2019) Inhibition of TLR4/TRIF/IRF3 signaling pathway by curcumin in breast cancer cells. J Pharm Pharm Sci 22:281–291
Fahim KM, Ismael E, Khalefa HS, Farag HS, Hamza DA (2019) Isolation and characterization of E. coli strains causing intramammary infections from dairy animals and wild birds. Int J Vet Sci Med 7:61–70
Fallahi F, Borran S, Ashrafizadeh M, Zarrabi A, Pourhanifeh MH, Khaksary Mahabady M, Sahebkar A, Mirzaei H (2021) Curcumin and inflammatory bowel diseases: from in vitro studies to clinical trials. Mol Immunol 130:20–30
Fu Y, Zhou E, Liu Z, Li F, Liang D, Liu B, Song X, Zhao F, Fen X, Li D, Cao Y, Zhang X, Zhang N, Yang Z (2013) Staphylococcus aureus and Escherichia coli elicit different innate immune responses from bovine mammary epithelial cells. Vet Immunol Immunopathol 155:245–252
Fu Y, Zhou E, Wei Z, Liang D, Wang W, Wang T, Guo M, Zhang N, Yang Z (2014) Glycyrrhizin inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model. FEBS J 281:2543–2557
Fusco R, Cordaro M, Siracusa R, Peritore AF, D'Amico R, Licata P, Crupi R, Gugliandolo E (2020) Effects of hydroxytyrosol against lipopolysaccharide-induced inflammation and oxidative stress in bovine mammary epithelial cells: a natural therapeutic tool for bovine mastitis. Antioxidants 9:693
Ganugula R, Arora M, Jaisamut P, Wiwattanapatapee R, Jørgensen HG, Venkatpurwar VP, Zhou B, Rodrigues Hoffmann A, Basu R, Guo S, Majeti N (2017) Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus. Br J Pharmacol 174:2074–2084
Glynn DJ, Hutchinson MR, Ingman WV (2014) Toll-like receptor 4 regulates lipopolysaccharide-induced inflammation and lactation insufficiency in a mouse model of mastitis. Biol Reprod 90:91
Gomes F, Henriques M (2016) Control of bovine mastitis: old and recent therapeutic approaches. Curr Microbiol 72:377–382
Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106:207–212
Gupta SC, Patchva S, Koh W, Aggarwal BB (2012) Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 39:283–299
Gupta SC, Patchva S, Aggarwal BB (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15:195–218
Hassanzadeh S, Read MI, Bland AR, Majeed M, Jamialahmadi T, Sahebkar A (2020) Curcumin: an inflammasome silencer. Pharmacol Res 104921
He X, Wei Z, Zhou E, Chen L, Kou J, Wang J, Yang Z (2015) Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice. Int Immunopharmacol 28:470–476
Hosseinia A, Rasaieb D, Aslc SS, Ahmadabadid AN, Ranjbard A (2019) Evaluation of the protective effects of curcumin and nanocurcumin against lung injury induced by sub-acute exposure to paraquat in rats. Toxin Rev. https://doi.org/10.1080/15569543.2019.1675707
Ingman WV, Glynn DJ, Hutchinson MR (2014) Inflammatory mediators in mastitis and lactation insufficiency. Mammary Gland Biol Neoplasia 19:161–167
Jang J, Hur HG, Sadowsky MJ, Byappanahalli M, Yan T, Ishii S (2017) Environmental Escherichia coli: ecology and public health implications—a review. J Appl Microbiol 123:570–581
Ji L, Qu L, Wang C, Peng W, Li S, Yang H, Luo H, Yin F, Lu D, Liu X (2020) Identification and optimization of piperlongumine analogues as potential antioxidant and anti-inflammatory agents via activation of Nrf2. Eur J Med Chem 210:112965
Jiang A, Zhang Y, Zhang X, Wu D, Liu Z, Li S, Liu X, Han Z, Wang C, Wang J (2020) Morin alleviates LPS-induced mastitis by inhibiting the PI3K/AKT, MAPK, NF-κB and NLRP3 signaling pathway and protecting the integrity of blood-milk barrier. Int Immunopharmacol 78:105972
Kan X, Liu B, Guo W, Wei L, Lin Y, Guo Y, Gong Q, Li Y, Xu D, Cao Y (2019) Myricetin relieves LPS-induced mastitis by inhibiting inflammatory response and repairing the blood–milk barrier. J Cell Physiol 234:16252–16262
Khan MZ, Khan A, Xiao J, Ma J, Ma Y, Chen T, Shao D, Cao Z (2020) Overview of research development on the role of NF-κB signaling in mastitis. Animals 10:1625
Kim DC, Lee W, Bae JS (2011) Vascular anti-inflammatory effects of curcumin on HMGB1-mediated responses in vitro. Inflamm Res 60:1161–1168
Li X, Zhong CQ, Yin Z, Qi H, Xu F, He Q, Shuai J (2020) Data-driven modeling identifies TIRAP-independent MyD88 activation complex and myddosome assembly strategy in LPS/TLR4 signaling. Int J Mol Sci 21:3061
Mazgaeen L, Gurung P (2020) Recent advances in lipopolysaccharide recognition systems. Int J Mol Sci 21:379
Meng F-C, Zhou Y-Q, Ren D, Wang R, Wang C, Lin L-G, Zhang X-Q, Ye W-C, Zhang Q-W (2018) Turmeric: a review of its chemical composition, quality control, bioactivity, and pharmaceutical application. Natural artificial flavoring agents food dyes:299–350
Mirzaei A, Hedayati M, Re, Ashtiani A, Rahbar M, Rastegar H, Beheshti SJSR, Essays (2011) A simple method for non phenolic extraction of lipopolysaccharide from Salmonella typhimurium and Salmonella enteritidis with high purity and pyrogenicity in rat. 6, 1101-1105
Moghaddasi F, Housaindokht MR, Darroudi M, Bozorgmehr MR, Sadeghi A (2018) Synthesis of nano curcumin using black pepper oil by O/W nanoemulsion technique and investigation of their biological activities. Food Sci Technol 92:92–100
Panaro MA, Corrado A, Benameur T, Paolo CF, Cici D, Porro C (2020) The emerging role of curcumin in the modulation of TLR-4 signaling pathway: focus on neuroprotective and anti-rheumatic properties. Int J Mol Sci 21:2299
Panzarini E, Mariano S, Tacconi S, Carata E, Tata AM, Dini L (2020) Novel therapeutic delivery of nanocurcumin in central nervous system related disorders. Nanomaterials (Basel, Switzerland) 11
Prantner D, Nallar S, Vogel SN (2020) The role of RAGE in host pathology and crosstalk between RAGE and TLR4 in innate immune signal transduction pathways. FASEB J 34:15659–15674
Priyadarsini KI (2014) The chemistry of curcumin: from extraction to therapeutic agent. Molecules 19:20091–20112
Pu HL, Chiang WL, Maiti B, Liao ZX, Ho YC, Shim MS, Chuang EY, Xia Y, Sung HW (2014) Nanoparticles with dual responses to oxidative stress and reduced ph for drug release and anti-inflammatory applications. ACS Nano 8:1213–1221
Quesnell RR, Klaessig S, Watts JL, Schukken YH (2012) Bovine intramammary Escherichia coli challenge infections in late gestation demonstrate a dominant antiinflammatory immunological response. J Dairy Sci 95:117–126
Quinn PJ (1994) Clinical veterinary microbiology
Rahimi HR, Nedaeinia R, Sepehri Shamloo A, Nikdoust S, Kazemi Oskuee R (2016) Novel delivery system for natural products: nano-curcumin formulations. Avicenna J Phytomed 6:383–398
Rai M, Pandit R, Gaikwad S, Yadav A, Gade A (2015) Potential applications of curcumin and curcumin nanoparticles: from traditional therapeutics to modern nanomedicine. Nanotechnol Rev 4:161–172
Sampath V (2018) Bacterial endotoxin-lipopolysaccharide; structure, function and its role in immunity in vertebrates and invertebrates. Agric Nat Resour 52:115–120
Schalm OW, Noorlander DO (1957) Experiments and observations leading to development of the California mastitis test. J Am Vet Med Assoc 130:199–204
Seegers H, Fourichon C, Beaudeau F (2003) Production effects related to mastitis and mastitis economics in dairy cattle herds. Vet Res 34:475–491
Shi H, Guo Y, Liu Y, Shi B, Guo X, Jin L, Yan S (2016) The in vitro effect of lipopolysaccharide on proliferation, inflammatory factors and antioxidant enzyme activity in bovine mammary epithelial cells. Anim Nutr 2:99–104
Smulski S, Gehrke M, Libera K, Cieslak A, Huang H, Patra AK, Szumacher-Strabel M (2020) Effects of various mastitis treatments on the reproductive performance of cows. BMC Vet Res 16:99
Spitzer AJ, Tian Q, Choudhary RK, Zhao F-Q (2020) Bacterial endotoxin induces oxidative stress and reduces milk protein expression and hypoxia in the mouse mammary gland. Oxidative Med Cell Longev 2020:3894309–3894309
Sun X, Luo S, Jiang C, Tang Y, Cao Z, Jia H, Xu Q, Zhao C, Loor JJ, Xu C (2020) Sodium butyrate reduces bovine mammary epithelial cell inflammatory responses induced by exogenous lipopolysaccharide, by inactivating NF-κB signaling. J Dairy Sci 103:8388–8397
Suojala L, Kaartinen L, Pyörälä S (2013) Treatment for bovine Escherichia coli mastitis - an evidence-based approach. J Vet Pharmacol Ther 36:521–531
Suresh S, Sankar P, Telang AG, Kesavan M, Sarkar SN (2018) Nanocurcumin ameliorates Staphylococcus aureus-induced mastitis in mouse by suppressing NF-κB signaling and inflammation. Int Immunopharmacol 65:408–412
Trivedi MK, Mondal SC, Gangwar M, Jana S (2017) Immunomodulatory potential of nanocurcumin-based formulation. Inflammopharmacology 25:609–619
Villanueva-Flores F, Castro-Lugo A, Ramirez OT, Palomares LA (2020) Understanding cellular interactions with nanomaterials: towards a rational design of medical nanodevices. Nanotechnology 31:132002
Wang C, Nie H, Li K, Zhang YX, Yang F, Li CB, Wang CF, Gong Q (2012) Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice. Eur J Pharmacol 697:152–157
Wang F-C, Pei J-X, Zhu J, Zhou N-J, Liu D-S, Xiong H-F, Liu X-Q, Lin D-J, Xie YJW Jo GW (2015a) Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro. 21:7764
Wang FC, Pei JX, Zhu J, Zhou NJ, Liu DS, Xiong HF, Liu XQ, Lin DJ, Xie Y (2015b) Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro. World J Gastroenterol 21:7764–7776
Weiss J, Barker J (2018): Diverse pro-inflammatory endotoxin recognition systems of mammalian innate immunity. F1000Res 7
Yang Y, Han C, Guo L, Guan Q (2018) High expression of the HMGB1–TLR4 axis and its downstream signaling factors in patients with Parkinson’s disease and the relationship of pathological staging. Brain Behavior 8:e00948
Zambrano LMG, Brandao DA, Rocha FRG, Marsiglio RP, Longo IB, Primo FL, Tedesco AC, Guimaraes-Stabili MR, Rossa Junior C (2018) Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease. Sci Rep 8:6652
Zangui M, Atkin SL, Majeed M, Sahebkar A (2019) Current evidence and future perspectives for curcumin and its analogues as promising adjuncts to oxaliplatin: state-of-the-art. Pharmacol Res 141:343–356
Author information
Authors and Affiliations
Contributions
MAL and MSE designed the research; IHE, MAL, and MSE conducted the research; MAL, NMT, and MSE contributed to the interpretation of data; MAL, IHE, and MSE analyzed the data and wrote the manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
All authors carefully read and approved the study.
Consent to publish
All authors have read and approved the final version of the manuscript for publication.
Competing interests
The authors declare no competing interests.
Additional information
Responsible Editor: Mohamed M. Abdel-Daim
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
ESM 1
(DOCX 5791 kb)
Rights and permissions
About this article
Cite this article
Lebda, M.A., Elmassry, I.H., Taha, N.M. et al. Nanocurcumin alleviates inflammation and oxidative stress in LPS-induced mastitis via activation of Nrf2 and suppressing TLR4-mediated NF-κB and HMGB1 signaling pathways in rats. Environ Sci Pollut Res 29, 8294–8305 (2022). https://doi.org/10.1007/s11356-021-16309-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-021-16309-9