Effects of Encapsulation of Caesalpinia sappan L. with Cyclodextrins for Bovine Mastitis.
Caesalpinia sappan L.
bovine mastitis
brazilein
brazilin
cyclodextrins-inclusion complexes
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
received:
09
08
2023
accepted:
24
10
2023
medline:
15
11
2023
pubmed:
15
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
The main components of Caesalpinia sappan L. (CS) are brazilin and brazilein, which show high potential in pharmacologic applications. However, these have been drastically limited by the poor water solubility and stability. The present study investigates the formation of inclusion complexes F1, F2, and F3 between CS and β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), and methyl-β-cyclodextrin (MβCD), respectively. These complexes were characterized by Fourier transform infrared spectroscopy (FT-IR). The results showed that the highest encapsulation efficiency and loading capacity of CS extract were 44.24% and 9.67%, respectively. The solubility and stability of CS extract were significantly increased through complexation in phase solubility and stability studies. The complexes F1-F3 showed mainly significant antibacterial activities on gram-positive bacteria pathogens causing mastitis. Moreover, the expression levels of COX-2 and iNOS were significantly decreased in LPS-induced inflammatory cells at concentrations of 50 and 100 µg/mL. In addition, treatment of complex F3 (CS/MβCD) in bovine endothelial cells remarkably increased the chemokine gene expression of CXCL3 and CXCL8, which were responsible for immune cell recruitment (9.92 to 11.17 and 8.23 to 9.51-fold relative to that of the LPS-treated group, respectively). This study provides a complete characterization of inclusion complexes between CS extract and βCD, HPβCD, and MβCD for the first time, highlighting the impact of complex formation on the pharmacologic activities of bovine mastitis.
Identifiants
pubmed: 37964017
doi: 10.1208/s12249-023-02687-5
pii: 10.1208/s12249-023-02687-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
230Informations de copyright
© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Références
Kibebew K. Bovine mastitis: a review of causes and epidemiological point of view. J Bio Agr Healthcare. 2017;7(2):1–14.
Thompson-Crispi K, Atalla H, Miglior F, Mallard BA. Bovine mastitis: frontiers in immunogenetics. Front Immunol. 2014;5(493):1–10.
Cheng WN, Han SG. Bovine mastitis: risk factors, therapeutic strategies, and alternative treatments-a review. Asian-Australas J Anim Sci. 2020;33(11):1699–713.
pubmed: 32777908
pmcid: 7649072
doi: 10.5713/ajas.20.0156
Boonyayatra S. Treatment of bovine mastitis during lactating period. Chiang Mai Veterinary J. 2012;10(2):89–109.
Rossiter SE, Fletcher MH, Wuest WM. Natural products as platforms to overcome antibiotic resistance. Chem Rev. 2017;117(19):12415–74.
pubmed: 28953368
pmcid: 5869711
doi: 10.1021/acs.chemrev.7b00283
Su T, Qiu Y, Hua X, Ye B, Luo H, Liu D, et al. Novel opportunity to reverse antibiotic resistance: to explore traditional Chinese medicine with potential activity against antibiotics-resistance bacteria. Front Microbiol. 2020;11:1–11.
doi: 10.3389/fmicb.2020.610070
Zhao H, Bai H, Wang Y, Li W, Koike K. A new homoisoflavan from Caesalpinia sappan. J Nat Med. 2008;62(3):325–7.
pubmed: 18404306
doi: 10.1007/s11418-008-0231-6
Toegel S, Wu SQ, Otero M, Goldring MB, Leelapornpisid P, Chiari C, et al. Caesalpinina sappan extract inhibits IL 1b-mediated overexpression of matrix metalloproteinases in human chondrocytes. Genes Nutri. 2012;7(2):312–8.
Sireeratawong S, Piyabhan P, Singhalak T, Wongkrajang Y, Temsiririrkkul R, Punsrirat J, et al. Toxicity evaluation of sappan wood extract in rats. J Med Assoc Thai. 2010;93(7):50–7.
Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: Medical Science and Technology Press; 2015.
China Pharmacopoeia Commission. The Chinese pharmacopoeia. Beijing: China Medical Science Press; 2010. p. 153.
Zhao HX, Bai H, Wang YS. The NMR characterization of Caesalpinia sappan phenolic compounds. Qilu Pharm Affairs. 2007;26(7):417–9.
Li Q, Wang RP, Zou X. Research progress on chemical constituents and antitumor Caesalpinia sappan. J Tradit Chin Med Univ Hunan. 2012;32(4):76–8.
Badami S, Moorkoth S, Suresh B. Caesalpinia sappan-a medicinal and dye yielding plant. Indian J Nat Prod Res. 2004;3(2):75–82.
Jin SK, Ha SR, Choi JS. Effect of Caesalpinia sappan L extract on physico-chemical properties of emulsion-type pork sausage during cold storage. Meat Sci. 2015;110:245–52.
pubmed: 26283171
doi: 10.1016/j.meatsci.2015.08.003
Washiyama M, Sasaki Y, Hosokawa T, Nagumo S. Anti-inflammatory constituents of Sappan lignum. Biol Pharma Bull. 2009;32(5):941–4.
doi: 10.1248/bpb.32.941
Handayani S, Susidarti RA, Jenie RI, Meiyanto E. Two active compounds from Caesalpinia sappan L. In combination with cisplatin synergistically induce apoptosis and cell cycle arrest on WiDr cells. Adv Pharm Bull. 2017;7(3):375–80.
pubmed: 29071219
pmcid: 5651058
doi: 10.15171/apb.2017.045
Cuong TD, Hung TM, Kim JC, Kim EH, Woo MH, Choi JH, et al. Phenolic compounds from Caesalpinia sappan heartwood and their anti-inflammatory activity. J Nat Prod. 2012;75:2069–75.
pubmed: 23234407
doi: 10.1021/np3003673
Sasaki Y, Hosokawa T, Nagai M, Nagumo S. In vitro study for inhibition of NO production about constituents of Sappan lignum. Biol Pharma Bull. 2007;30(1):193–6.
doi: 10.1248/bpb.30.193
Nirmal NP, Rajput MS, Prasad RGSV, Ahmad M. Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: a review. Asian Pac J Trop Med. 2015;8(6):421–30.
pubmed: 26194825
doi: 10.1016/j.apjtm.2015.05.014
Xu HX, Lee SF. The antibacterial principle of Caesalpinia sappan. Phytother Res. 2004;18(8):647–51.
pubmed: 15476302
doi: 10.1002/ptr.1524
Li CX, Si CP, Gao HJ, Ming JK, Fu J, Sun M. Experimental study Caesalpinia sappan aqueous extract to induce immune tolerance in allogeneic skin transplantation. Chin J Cell Mol Immunol. 2011;27(2):186–9.
Badami S, Moorkoth S, Rai SR, Kannan E, Bhojraj S. Antioxidant activity of Caesalpinia sappan heartwood. Biol Pharm Bull. 2003;26(11):1534–7.
pubmed: 14600396
doi: 10.1248/bpb.26.1534
Niu Y, Wang S, Li C, Wang J, Liu Z, Kang W. Effective compounds from Caesalpinia sappan L. on the tyrosinase in vitro and in vivo. Nat Prod Commun. 2020;15(4):1–8.
Xu JG, Guo ST, Qiao LJ. The effect of Caesalpinia sappan L. extract on tumor. Cancer Res Clin. 2006;18(11):726–8.
Khil LY, Han SS, Kim SG, Chang TS, Jeon SD, So DS, et al. Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes. Biochem Pharmacol. 1999;58(11):1705–12.
pubmed: 10571244
doi: 10.1016/S0006-2952(99)00275-0
Khil LY, Moon CK. Hydrogen peroxide mediates brazilin-induced glucose transport in adipocytes. J Appl Pharmacol. 2004;12(4):228–34.
Watkins R, Wu L, Zhang C, Davis RM, Xu B. Natural product-based nanomedicine: recent advances and issues. Int J Nanomed. 2015;10:6055–74.
Wüpper S, Lüersen K, Rimbach R. Cyclodextrins, natural compounds, and plant bioactives a nutritional perspective. Biomolecules. 2021;11:401–21.
pubmed: 33803150
pmcid: 7998733
doi: 10.3390/biom11030401
Singh M, Sharma R, Banerjee UC. Biotechnological applications of cyclodextrins. Biotechnol Adv. 2002;20(5–6):341–59.
pubmed: 14550020
doi: 10.1016/S0734-9750(02)00020-4
Loftsson T, Jarho P, Másson M, Järvinen T. Cyclodextrins in drug delivery. Expert Opin Drug Deliv. 2005;2(2):335–51.
pubmed: 16296758
doi: 10.1517/17425247.2.1.335
Poulson BG, Alsulami QA, Sharfalddin A, El Agammy EF, Mouffouk F, Emwas AH, et al. Cyclodextrins: structural, chemical, and physical properties, and applications. Polysaccharides. 2022;3:1–31.
doi: 10.3390/polysaccharides3010001
Szejtli J. Introduction and general overview of cyclodextrin chemistry. Chem Rev. 1998;98:1743–54.
pubmed: 11848947
doi: 10.1021/cr970022c
Connors KA. The Stability of cyclodextrin complexes in solution. Chem Rev. 1997;97:1325–58.
pubmed: 11851454
doi: 10.1021/cr960371r
Saenger W, Jacob J, Gessler K, Steiner T, Hoffmann D, Sanbe H, et al. Structures of the common cyclodextrins and their larger analogues beyond the doughnut. Chem Rev. 1998;98:1787–802.
pubmed: 11848949
doi: 10.1021/cr9700181
Gidwani B, Vyas A. A comprehensive review on cyclodextrin-based carriers for delivery of chemotherapeutic cytotoxic anticancer drugs. Bio Med Res Int. 2015;2015:198268.
Aloisioa C, Longhi M. Diloxanide furoate binary complexes with β-, methyl-β- and hydroxypropyl-β-cyclodextrins: inclusion mode, characterization in solution and in solid state and in-vitro dissolution studies. Pharm Dev Technol. 2017;23(7):723–31.
doi: 10.1080/10837450.2017.1362435
Sandilya AA, Natarajan U, Priya MH. Molecular view into the cyclodextrin cavity: structure and hydration. ACS Omega. 2020;40(5):25655–67.
doi: 10.1021/acsomega.0c02760
Jug M. Cyclodextrin-based drug delivery systems. nanomaterials for clinical applications. 2020;29–68.
Crini G, Fourmentin S, Fenyvesi E, Torri G, Fourmentin M, Morin-Crini N. Cyclodextrins, from molecules to applications. Environmental Chem Lett. 2018;16:1361–75.
doi: 10.1007/s10311-018-0763-2
Arsiningtyas IS. Antioxidant profile of heartwood and sapwood of Caesalpinia sappan L tree’s part grown in Imogiri Nature Preserve, Yogyakarta. IOP Conf Series Earth Environ Sci. 2021;810(1):012040.
doi: 10.1088/1755-1315/810/1/012040
Khamsita R, Hermawan A, Putri DDP, Meiyanto E. Ethanolic extract of Secang (Caesalpinia sappan L.) wood performs as chemosensitizing agent through apoptotic induction on breast cancer MCF-7 Cells. Ind J Cancer Chemo Prev. 2012;3(3):444–9.
Loescher CM, Morton DW, Razic S, Agatonovic-Kustrin S. High performance thin layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) for the qualitative and quantitative analysis of Calendula officinalis–advantages and limitations. J Pharm Biomed Anal. 2014;98:52–9.
pubmed: 24880991
doi: 10.1016/j.jpba.2014.04.023
Moricz AM, Lapat V, Morlock GE, Ott PG. High-performance thin-layer chromatography hyphenated to high-performance liquid chromatography-diode array detection-mass spectrometry for characterization of coeluting isomers. Talanta. 2020;219:121306–11.
pubmed: 32887047
doi: 10.1016/j.talanta.2020.121306
He J, Guo F, Lin L, Chen H, Chen J, Cheng Y, et al. Investigating the oxyresveratrol β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin complexes: the effects on oxyresveratrol solution, stability, and antibrowning ability on fresh grape juice. LWT-Food Sci Tech. 2018.
Das S, Gazdag Z, Szente L, Meggyes M, Horváth G, Lemli B, et al. Antioxidant and antimicrobial properties of randomly methylated β cyclodextrin-captured essential oils, Food Chem. 2018.
Chaisri W, Hennink WE, Ampasavate C, Okonogi S. Cephalexin microspheres for dairy mastitis: effect of preparation method and surfactant type on physicochemical properties of the microspheres. AAPS Pharm Sci Tech. 2010;11(2):945–51.
doi: 10.1208/s12249-010-9453-5
Najlah M, Parveen I, Alhnan MA, Ahmed W, Faheem A, Phoenix DA, et al. The effects of suspension particle size on the performance of air-jet, ultrasonic and vibrating-mesh nebulisers. Int J Pharm. 2014;461:234–41.
pubmed: 24275450
doi: 10.1016/j.ijpharm.2013.11.022
Higuchi T, Connors KA. Phase-solubility techniques. In Advances in Analytical Chemistry and Instrumentation. Reilly CN, editor. Wiley-Interscience; 1965. 4. p. 117−212.
Siva S, Li C, Cui H, Lin L. Encompassment of isoeugenol in 2-hydroxypropyl-β-cyclodextrin using ultrasonication: characterization, antioxidant and antibacterial activities. J Mol Liquids. 2019;296:111777.
doi: 10.1016/j.molliq.2019.111777
Siva S, Lib C, Cuia H, Meenatchic V, Lin L. Encapsulation of essential oil components with methyl-β-cyclodextrin using ultrasonication: solubility, characterization, DPPH and antibacterial assay. Ultrasonics - Sonochemistry. 2020;64:104997.
pubmed: 32058914
doi: 10.1016/j.ultsonch.2020.104997
Yang LJ, Chang Q, Zhou SY, Yang YH, Xia FT, Chen W, et al. Host–guest interaction between brazilin and hydroxypropyl-β-cyclodextrin: preparation, inclusion mode, molecular modelling and characterization. Dyes Pigments. 2018;150:193–201.
doi: 10.1016/j.dyepig.2017.12.010
Crupi V, Ficarra R, Guardo M, Majolino D, Stancanelli R, Venuti V. UV–vis and FTIR–ATR spectroscopic techniques to study the inclusion complexes of genistein with B-cyclodextrins. J Pharm Biomed Anal. 2007;44:110–7.
pubmed: 17379467
doi: 10.1016/j.jpba.2007.01.054
ICH harmonised tripartite guideline, stability testing of new drug substances and products Q1A(R2), Current Step 4 version, dated 6 February 2003.
ASEAN guidelines on stability study of drug product (R1), February 2005, Revision 9th ACCSQ-PPWG, Meeting; Philippines.
Clinical and Laboratory Standards Institue (CLSI). Performance standards for antimicobial susceptibility testing: twenty-fifth informational supplement; 2015;35(3): 1−236.
Bae IK, Min HY, Han AR, Seo EK, Lee SK. Suppression of lipopolysacchride-induced expression of inducible nitric oxide synthase by brazilin in RAW 264.7 macrophage cells. Eur J Pharmacol. 2005;513(3):237–42.
pubmed: 15862806
doi: 10.1016/j.ejphar.2005.03.011
Panya A, Pundith H, Thongyim S, Kaewkod T, Chitov T, Bovonsombut S, et al. Antibiotic-antiapoptotic dual function of clinacanthus nutans (Burm. F.) lindau leaf extracts against bovine mastitis. Antibiotics. 2020;9:429.
pubmed: 32708141
pmcid: 7400556
doi: 10.3390/antibiotics9070429
Thongyim S, Chiangchin S, Pandith H, Tragoolpua Y, Jangsutthivorawat S, Panya A. Anti-inflammatory activity of glyceryl 1,3-distearate identified from Clinacanthus nutans extract against bovine mastitis pathogens. Antibiotics. 2023;12:549.
pubmed: 36978416
pmcid: 10044565
doi: 10.3390/antibiotics12030549
Hemthanon T, Ungcharoenwiwat P. Antibacterial activity, stability, and hemolytic activity of heartwood extract from Caesalpinia sappan for application on nonwoven fabric. Elect J Biotechnol. 2022;55:9–17.
doi: 10.1016/j.ejbt.2021.10.002
Ngamwonglumlert L, Devahastin S, Chiewchan N, Raghavan GSV. Color and molecular structure alterations of brazilein extracted from Caesalpinia sappan L under different pH and heating conditions. Scientific Reports. 2020;10(1):12386–95.
pubmed: 32709964
pmcid: 7382456
doi: 10.1038/s41598-020-69189-3
Gomes LMM, Petito N, Costa VG, Falcão DQ, de Lima Araújo KG. Inclusion complexes of red bell pepper pigments with β-cyclodextrin: preparation, characterisation and application as natural colorant in yogurt. Food Chem. 2014;148:428–36.
pubmed: 24262579
doi: 10.1016/j.foodchem.2012.09.065
Trenkenschuh E, Friess W. Freeze-drying of nanoparticles: how to overcome colloidal instability by formulation and process optimization. Eur J Pharm Biopharm. 2021;165:345–60.
pubmed: 34052428
doi: 10.1016/j.ejpb.2021.05.024
Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified β-cyclodextrins. I: Preparation and in-vitro evaluation. Eur J Pharm Biopharm. 2008;70:819–27.
pubmed: 18655829
doi: 10.1016/j.ejpb.2008.06.024
Kalogeropoulos N, Konteles S, Mourtzinos I, Troullidou E, Chiou A, Karathanos VT. Encapsulation of complex extracts in β-cyclodextrin: an application to propolis ethanolic extract. J Microencapsulation. 2009;26(7):603–13.
pubmed: 19839796
doi: 10.3109/02652040802586373
Mourtzinos I, Salta F, Yannakopoulou K, Chiou A, Karathanos VT. Encapsulation of olive leaf extract in β-cyclodextrin. J Agric Food Chem. 2007;55:8088–94.
pubmed: 17764146
doi: 10.1021/jf0709698
Santos PS, Souza LM, Araujo TSL, Medeiros JVR, Nunes SCC, Carvalho RA, et al. Methyl-β-cyclodextrin inclusion complex with β-caryophyllene: preparation, characterization, and improvement of pharmacological activities. ACS Omega. 2017;2:9080–94.
pubmed: 30023600
pmcid: 6044968
doi: 10.1021/acsomega.7b01438
Fenyvesi F, Nguyen TLP, Haimhoffer A, Rusznyák A, Vasvári G, Bácskay I, et al. Cyclodextrin complexation improves the solubility and Caco-2 permeability of chrysin. Materials. 2020;13:3618–29.
pubmed: 32824341
pmcid: 7475839
doi: 10.3390/ma13163618
Arima H, Yunomae K, Miyake K, Irie T, Hirayama F, Uekama K. Comparative studies of the enhancing effects of cyclodextrins on the solubility and oral bioavailability of tacrolimus in rats. J Pharm Sci. 2001;90:690–701.
pubmed: 11357172
doi: 10.1002/jps.1025
Mura P. Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review. J Pharm Biomed Anal. 2014;101:238–50.
pubmed: 24680374
doi: 10.1016/j.jpba.2014.02.022
Liu B, Li W, Zhao J, Liu Y, Zhu X, Liang G. Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex. Food Chem. 2013;141:900–6.
pubmed: 23790865
doi: 10.1016/j.foodchem.2013.03.097
Pattananandecha T, Apichai S, Julsrigival J, Ogata F, Kawasaki N, Saenjum C. Antibacterial activity against foodborne pathogens and inhibitory effect on anti-inflammatory mediators’ production of brazilin-enriched extract from Caesalpinia sappan Linn. Plants (Basel). 2022;11(13):1698.
pubmed: 35807650
pmcid: 9269513
doi: 10.3390/plants11131698
Puttipan R, Chansakaow S, Khongkhunthian S, Okonogi S. Caesalpinia sappan: a promising natural source of antimicrobial agent for inhibition of cariogenic bacteria. Drug Dis Therapeutics. 2018;12(4):197–205.
doi: 10.5582/ddt.2018.01035
Nirmal NP, Panichayupakaranant P. Antioxidant, antibacterial, and anti-inflammatory activities of standardized brazilin-rich Caesalpinia sappan extract. Pharm Biol. 2015;53(9):1339–43.
pubmed: 25864864
doi: 10.3109/13880209.2014.982295
Xu HX, Lee SF. The antibacterial principle of Caesalpinia sappan. Phytother Res. 2004;18(8):647–51.
pubmed: 15476302
doi: 10.1002/ptr.1524
Liu Y, Chen W, Zheng F, Yu H, Wei K. Xanthatin alleviates LPS-induced inflammatory response in RAW264.7 macrophages by inhibiting NF-κB MAPK and STATs activation. Molecules. 2022;27:4603–17.
pubmed: 35889477
pmcid: 9322085
doi: 10.3390/molecules27144603
Xiong H, Cheng T, Zhang X, Zhang X. Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages. J Ethnopharmacol. 2014;155:753–7.
pubmed: 24945401
doi: 10.1016/j.jep.2014.06.023
Wu SQ, Otero M, Unger FM, Goldring MB, Phrutivorapongkul A, Chiari C, Toegel S. Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human chondrocytes and macrophages. J Ethnopharmacol. 2011;138(2):364–72.
pubmed: 21963554
pmcid: 3282169
doi: 10.1016/j.jep.2011.09.011
Tewtrakul S, Tungcharoen P, Sudsai T, Karalai C, Ponglimanont C, Yodsaoue O. Antiinflammatory and wound healing effects of Caesalpinia sappan L. Phytotherapy Res. 2015;29(6):850–6.
doi: 10.1002/ptr.5321
Min BS, Cuong TD. Phenolic compounds from Caesalpinia sappan and their inhibitory effects on LPS-induced NO production in RAW264.7 ells. Nat Prod Sci. 2013;19(3):201–5.
Hoskina RT, Xiong J, Esposito DA, Lila MA. Blueberry polyphenol-protein food ingredients: the impact of spray drying on the in vitro antioxidant activity, anti-inflammatory markers, glucose metabolism and fibroblast migration. Food Chem. 2019;280:187–94.
doi: 10.1016/j.foodchem.2018.12.046
Macías-Cortés E, Gallegos-Infante JA, Rocha-Guzmán NE, Moreno-Jiménez MR, Villanueva-Fierro I, Ochoa-Martínez LA, et al. Spray drying conditions of antioxidant and anti-inflammatory polyphenols in microcapsules of ultrasound assisted extract of salvilla (Buddleja scordioides Kunth). ACS Food Sci Technol. 2022;2:1574–85.
doi: 10.1021/acsfoodscitech.2c00212
Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes. J Pharm Pharmacol. 2011;63:1119–35.
pubmed: 21827484
doi: 10.1111/j.2042-7158.2011.01279.x
Stella VJ, He Q. Cyclodextrins. Toxicol Pathol. 2008;36:30–42.
pubmed: 18337219
doi: 10.1177/0192623307310945
Zhao Q, Temsamani J, Iadarola PL, Agrawal S. Modulation of oligonucleotide-induced immune stimulation by cyclodextrin analogs. Biochem Pharmacol. 1996;52(10):1537–44.
pubmed: 8937468
doi: 10.1016/S0006-2952(96)00555-2
Geisshüsler S, Schineis P, Langer L, Wäckerle-Men Y, Leroux JC, Halin C, et al. Amphiphilic cyclodextrin-based nanoparticulate vaccines can trigger T-Cell immune responses. Adv Nano Biomed Res. 2021;2(4):2100082–94.
doi: 10.1002/anbr.202100082
Islam MdA, Takagi M, Fukuyama K, Komatsu R, Albarracin L, Nochi T, et al. Transcriptome analysis of the inflammatory responses of bovine mammary epithelial cells: exploring immunomodulatory target genes for bovine mastitis. Pathogens. 2020;9(3):200.
pubmed: 32182886
pmcid: 7157600
doi: 10.3390/pathogens9030200
Ryman VE, Packiriswamy N, Sordillo LM. Role of endothelial cells in bovine mammary gland health and disease. Published online by Cambridge University Press: 25 August 2015.