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The Natural Products Journal

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ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

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Research Article

Chemical Composition, Antioxidant, Antimicrobial, and Immunomodulatory Activity of Mandragora autumnalis Grown in Jordan

Author(s): Asma Ismail Mahmod and Wamidh H. Talib*

Volume 13, Issue 3, 2023

Published on: 07 October, 2022

Article ID: e020622205552 Pages: 12

DOI: 10.2174/2210315512666220602092915

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Abstract

Background: The activity of phytochemicals has a huge impact on pharmaceutical research and developing new drugs. Hence, numerous studies have been conducted to investigate the efficacy of different natural products and their potential to be used in different types of therapy.

Objective: This study was carried out to investigate the biological activity of M. autumnalis crude extract and fractions, and the assessment included antimicrobial activity, radical scavenging potential, and their effect on the immune system. The work also emphasizes determining the chemical constituents and the main bioactive compounds in M. autumnalis leaves.

Methods: Ethanol crude extract was prepared by maceration method, followed by solvents fractionation using n-hexane, aqueous/methanol, and water. Phytochemical analysis of ethanol extract using LC-MS and total phenolic and flavonoid content were conducted. The immunomodulatory activity was also evaluated by measuring the effect of M. autumnalis on splenocyte proliferation in the presence and absence of mitogens. Nitro blue tetrazolium assay and neutral red method have been used to determine the effect of M. autumnalis on the phagocytic activity of macrophages and the function of pinocytosis, respectively. Antibacterial assay was applied using the microtiter plate dilution method, and DPPH assay was used to determine the antioxidant activity.

Results: The phytochemical analysis has shown the presence of flavonoids, polyphenolic compounds, and other organic acids like quinic and chlorogenic acids. M. autumnalis aqueous fraction exhibited high antioxidant activity with an IC₅₀ value of 23.67±0.3 μg/ml. Ethanol extract and n-hexane fraction inhibited the bacterial growth of P. auriginosa with an MIC value of 25 mg/ml, while n-hexane fraction was more active against C. albicans with an MIC value of 12.5 mg/ml. On the other hand, the immune assay revealed a slight modulation of the lymphocyte and macrophage activity compared to the control results.

Conclusion: The results suggested that M. autumnalis leaves are rich in polyphenolic compounds and its crude extract and fractions exhibited antimicrobial and antioxidant potential. However, further research is needed to understand the effect of M. autumnalis on the immune parameters.

Keywords: Mandragora autumnalis, DPPH assay, LC-MS analysis, antibacterial, immunomodulation

Graphical Abstract

[1]
Pan, S.-Y.; Zhou, S.-F.; Gao, S.-H.; Yu, Z.-L.; Zhang, S.-F.; Tang, M.-K.; Sun, J.-N.; Ma, D.-L.; Han, Y.-F.; Fong, W.-F.; Ko, K.-M. New perspectives on how to discover drugs from herbal medicines: CAM’s outstanding contribution to modern therapeutics. Evid. Based Complement. Alternat. Med., 2013, 2013, 627375.
[http://dx.doi.org/10.1155/2013/627375] [PMID: 23634172]
[2]
Alamgir, M.; Uddin, S.J. Recent advances on the ethnomedicinal plants as immunomodulatory agents. Ethnomedicine: a source of complementary therapeutics, 2010, 37(661), 2.
[3]
Riaz, F. Antimicrobial potential and DNA barcoding of some Jordanian medicinal plants., 2013. PhD Thesis, AGRIS.
[4]
Al-Salt, J. Antimicrobial activity of crude extracts of some plant leaves. Res. J. Microbiol., 2012, 7, 59-67.
[http://dx.doi.org/10.3923/jm.2012.59.67]
[5]
Bagamboula, C.F.; Uyttendaele, M.; Debevere, J. Antimicrobial effect of spices and herbs on Shigella sonnei and Shigella flexneri. J. Food Prot., 2003, 66(4), 668-673.
[http://dx.doi.org/10.4315/0362-028X-66.4.668] [PMID: 12696694]
[6]
Savoia, D. Plant-derived antimicrobial compounds: alternatives to antibiotics. Future Microbiol., 2012, 7(8), 979-990.
[http://dx.doi.org/10.2217/fmb.12.68] [PMID: 22913356]
[7]
Zhang, Y-J.; Gan, R-Y.; Li, S.; Zhou, Y.; Li, A-N.; Xu, D-P.; Li, H-B. Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules, 2015, 20(12), 21138-21156.
[http://dx.doi.org/10.3390/molecules201219753] [PMID: 26633317]
[8]
Barraza-Garza, G.; Pérez-León, J.A.; Castillo-Michel, H.; de la Rosa, L.A.; Martinez-Martinez, A.; Cotte, M.; Alvarez-Parrilla, E. Antioxidant effect of phenolic compounds (PC) at different concentrations in IEC-6 cells: A spectroscopic analysis. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2020, 227, 117570.
[http://dx.doi.org/10.1016/j.saa.2019.117570] [PMID: 31669938]
[9]
Heinonen, M. Antioxidant activity and antimicrobial effect of berry phenolics- a Finnish perspective. Mol. Nutr. Food Res., 2007, 51(6), 684-691.
[http://dx.doi.org/10.1002/mnfr.200700006] [PMID: 17492800]
[10]
Grey-Wilson, C.; Blamey, M. Mediterranean Wild Flowers; HarperCollins, 1993.
[11]
Ungricht, S.; Knapp, S.; Press, J.R. A revision of the genus Mandragora (Solanaceae). Bull. Nat. Hist. Mus. Bot. Ser., 1998, 28(1), 17-40.
[12]
Carter, A.J. Myths and mandrakes. J. R. Soc. Med., 2003, 96(3), 144-147.
[http://dx.doi.org/10.1177/014107680309600312] [PMID: 12612119]
[13]
Al-Khalil, S.; Alkofahi, A. The chemical constituents of Mandragora autumnalis. Alex. J. Pharm. Sci., 1996, 10, 135-138.
[14]
Bekkouche, K.; Daali, Y.; Cherkaoui, S.; Veuthey, J-L.; Christen, P. Calystegine distribution in some solanaceous species. Phytochemistry, 2001, 58(3), 455-462.
[http://dx.doi.org/10.1016/S0031-9422(01)00283-7] [PMID: 11557078]
[15]
Fatur, K. “Hexing Herbs” in Ethnobotanical perspective: A historical review of the uses of anticholinergic solanaceae plants in Europe. Econ. Bot., 2020, 74(2), 140-158.
[http://dx.doi.org/10.1007/s12231-020-09498-w]
[16]
Aburjai, T.; Hudaib, M.; Tayyem, R.; Yousef, M.; Qishawi, M. Ethnopharmacological survey of medicinal herbs in Jordan, the Ajloun Heights region. J. Ethnopharmacol., 2007, 110(2), 294-304.
[http://dx.doi.org/10.1016/j.jep.2006.09.031] [PMID: 17097250]
[17]
Al-Qura’n, S. Ethnopharmacological survey of wild medicinal plants in Showbak, Jordan. J. Ethnopharmacol., 2009, 123(1), 45-50.
[http://dx.doi.org/10.1016/j.jep.2009.02.031] [PMID: 19429338]
[18]
Al-Ahmad, H. In vitro decoated seed germination and seedling development for propagation of wild mandrake (Mandragora autumnalis Bertol.). Plants, 2020, 9(10), 1339.
[http://dx.doi.org/10.3390/plants9101339] [PMID: 33050523]
[19]
Oran, S.; Al-Eisawi, D. Ethnobotanical survey of the medicinal plants in the central mountains (North-South) in Jordan. J. Biodivers. Environ. Sci., 2015, 6, 2220-6663. [JBES]
[20]
Jaradat, N.A.; Al-Ramahi, R.; Zaid, A.N.; Ayesh, O.I.; Eid, A.M. Ethnopharmacological survey of herbal remedies used for treatment of various types of cancer and their methods of preparations in the West Bank-Palestine. BMC Complement. Altern. Med., 2016, 16(1), 93.
[http://dx.doi.org/10.1186/s12906-016-1070-8] [PMID: 26955822]
[21]
Mahmod, A.I.; Talib, W.H. Anticancer activity of Mandragora autumnalis: An in vitro and in vivo study. Pharmacia, 2021, (4), 827-836.
[http://dx.doi.org/10.3897/pharmacia.68.e71695]
[22]
Liu, W.; Yin, D.; Li, N.; Hou, X.; Wang, D.; Li, D.; Liu, J. Influence of Environmental Factors on the Active Substance Production and Antioxidant Activity in Potentilla fruticosa L. and Its Quality Assessment. Sci. Rep., 2016, 6(1), 28591.
[http://dx.doi.org/10.1038/srep28591] [PMID: 27373366]
[23]
Talib, W.H.; Mahasneh, A.M. Antiproliferative activity of plant extracts used against cancer in traditional medicine. Sci. Pharm., 2010, 78(1), 33-45.
[http://dx.doi.org/10.3797/scipharm.0912-11] [PMID: 21179373]
[24]
Jing, L.; Ma, H.; Fan, P.; Gao, R.; Jia, Z. Antioxidant potential, total phenolic and total flavonoid contents of Rhododendron anthopogonoides and its protective effect on hypoxia-induced injury in PC12 cells. BMC Complement. Altern. Med., 2015, 15, 287.
[http://dx.doi.org/10.1186/s12906-015-0820-3] [PMID: 26283543]
[25]
Woisky, R.G.; Salatino, A. Analysis of propolis: Some parameters and procedures for chemical quality control. J. Apic. Res., 1998, 37(2), 99-105.
[http://dx.doi.org/10.1080/00218839.1998.11100961]
[26]
Brand-Williams, W.; Cuvelier, M-E.; Berset, C. Use of a free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol., 1995, 28(1), 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[27]
Al Obaydi, M.F.; Hamed, W.M.; Al Kury, L.T.; Talib, W.H. Terfezia boudieri: A desert truffle with anticancer and immunomodulatory activities. Front. Nutr., 2020, 7, 38.
[http://dx.doi.org/10.3389/fnut.2020.00038] [PMID: 32322585]
[28]
Chen, J-R.; Yang, Z-Q.; Hu, T-J.; Yan, Z-T.; Niu, T-X.; Wang, L.; Cui, D-A.; Wang, M. Immunomodulatory activity in vitro and in vivo of polysaccharide from Potentilla anserina. Fitoterapia, 2010, 81(8), 1117-1124.
[http://dx.doi.org/10.1016/j.fitote.2010.07.009] [PMID: 20624446]
[29]
Müller, J.; Alföldy, P.; Lemmel, E-M. Nitroblue-tetrazolium test for the functional evaluation of phagocytic cells: A critical analysis of the methodology. Agents Actions, 1981, 11(4), 384-390.
[http://dx.doi.org/10.1007/BF01982475] [PMID: 7282490]
[30]
Boothapandi, M.; Ramanibai, R. Immunomodulatory activity of Indigofera tinctoria leaf extract on in vitro macrophage responses and lymphocyte proliferation. Int. J. Pharm. Pharm. Sci., 2016, 8, 58-63.
[31]
Talib, W.H.; Zarga, M.H.A.; Mahasneh, A.M. Antiproliferative, antimicrobial and apoptosis inducing effects of compounds isolated from Inula viscosa. Molecules, 2012, 17(3), 3291-3303.
[http://dx.doi.org/10.3390/molecules17033291] [PMID: 22418930]
[32]
Zgoda, J.; Porter, J. A convenient microdilution method for screening natural products against bacteria and fungi. Pharm. Biol., 2001, 39(3), 221-225.
[http://dx.doi.org/10.1076/phbi.39.3.221.5934]
[33]
Blainski, A.; Lopes, G.C.; de Mello, J.C.P. Application and analysis of the folin ciocalteu method for the determination of the total phenolic content from Limonium brasiliense L. Molecules, 2013, 18(6), 6852-6865.
[http://dx.doi.org/10.3390/molecules18066852] [PMID: 23752469]
[34]
Popova, M.; Bankova, V.; Butovska, D.; Petkov, V.; Nikolova-Damyanova, B.; Sabatini, A.G.; Marcazzan, G.L.; Bogdanov, S. Validated methods for the quantification of biologically active constituents of poplar-type propolis. Phytochem. Anal., 2004, 15(4), 235-240.
[http://dx.doi.org/10.1002/pca.777] [PMID: 15311843]
[35]
Aazza, S.; Lyoussi, B.; Miguel, M.G. Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds. Molecules, 2011, 16(9), 7672-7690.
[http://dx.doi.org/10.3390/molecules16097672] [PMID: 21900869]
[36]
Kliebenstein, D.J. Secondary metabolites and plant/environment interactions: A view through Arabidopsis thaliana tinged glasses. Plant Cell Environ., 2004, 27(6), 675-684.
[http://dx.doi.org/10.1111/j.1365-3040.2004.01180.x]
[37]
Ji, H-F.; Li, X-J.; Zhang, H-Y. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep., 2009, 10(3), 194-200.
[http://dx.doi.org/10.1038/embor.2009.12] [PMID: 19229284]
[38]
Li, H.; Tsao, R.; Deng, Z. Factors affecting the antioxidant potential and health benefits of plant foods. Can. J. Plant Sci., 2012, 92(6), 1101-1111.
[http://dx.doi.org/10.4141/cjps2011-239]
[39]
Uysal, S.; Zengin, G.; Aktümsek, A. Antioxidant properties and enzyme inhibitory effects of extracts from Mandragora autumnalis and its fatty acid composition. Marmara Pharm. J., 2016, 20(2), 144-151.
[http://dx.doi.org/10.12991/mpj.201620206523]
[40]
Jodallah, N.B.E. Antioxidant and antimicrobial activity of Mandragora autumnalis Bertol extracts., 2013.
[41]
Rice-Evans, C.A.; Miller, N.J.; Paganga, G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic. Biol. Med., 1996, 20(7), 933-956.
[http://dx.doi.org/10.1016/0891-5849(95)02227-9] [PMID: 8743980]
[42]
Sato, Y.; Itagaki, S.; Kurokawa, T.; Ogura, J.; Kobayashi, M.; Hirano, T.; Sugawara, M.; Iseki, K. In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid. Int. J. Pharm., 2011, 403(1-2), 136-138.
[http://dx.doi.org/10.1016/j.ijpharm.2010.09.035] [PMID: 20933071]
[43]
Wu, L. Effect of chlorogenic acid on antioxidant activity of Flos Lonicerae extracts. J. Zhejiang Univ. Sci. B, 2007, 8(9), 673-679.
[http://dx.doi.org/10.1631/jzus.2007.B0673] [PMID: 17726749]
[44]
Heim, K.E.; Tagliaferro, A.R.; Bobilya, D.J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem., 2002, 13(10), 572-584.
[http://dx.doi.org/10.1016/S0955-2863(02)00208-5] [PMID: 12550068]
[45]
Kim, S-J.; Kim, G-H. Quantification of quercetin in different parts of onion and its DPPH radical scavenging and antibacterial activity. Food Sci. Biotechnol., 2006, 15(1), 39-43.
[http://dx.doi.org/10.1007/s10068-013-0006-z]
[46]
Azab, A. Solanaceae plants of israel and palestine. rich source of medicinally active natural products. Eur. Chem. Bull., 2020, 9(8), 199-261.
[http://dx.doi.org/10.17628/ecb.2020.9.199-261]
[47]
Bhatt, S.K.; Javagal, R.M.; Nanjarajurs, M.S.; Eligar, S.M. In vitro anti-inflammatory property of a Quercetin-3-O-diglucoside-7-O-glucoside characterized from fresh leaves of Trigonella foenum-graecum L. Int. J. Food Prop., 2021, 24(1), 1438-1452.
[http://dx.doi.org/10.1080/10942912.2021.1969946]
[48]
Coppo, E.; Marchese, A. Antibacterial activity of polyphenols. Curr. Pharm. Biotechnol., 2014, 15(4), 380-390.
[http://dx.doi.org/10.2174/138920101504140825121142] [PMID: 25312620]
[49]
Quecan, B.X.V.; Santos, J.T.C.; Rivera, M.L.C.; Hassimotto, N.M.A.; Almeida, F.A.; Pinto, U.M. Effect of quercetin rich onion extracts on bacterial quorum sensing. Front. Microbiol., 2019, 10, 867.
[http://dx.doi.org/10.3389/fmicb.2019.00867] [PMID: 31105665]
[50]
Cinkilic, N.; Cetintas, S.K.; Zorlu, T.; Vatan, O.; Yilmaz, D.; Cavas, T.; Tunc, S.; Ozkan, L.; Bilaloglu, R. Radioprotection by two phenolic compounds: chlorogenic and quinic acid, on X-ray induced DNA damage in human blood lymphocytes in vitro. Food Chem. Toxicol., 2013, 53, 359-363.
[http://dx.doi.org/10.1016/j.fct.2012.12.008] [PMID: 23266271]
[51]
Jang, S-A.; Park, D.W.; Kwon, J.E.; Song, H.S.; Park, B.; Jeon, H.; Sohn, E-H.; Koo, H.J.; Kang, S.C. Quinic acid inhibits vascular inflammation in TNF-α-stimulated vascular smooth muscle cells. Biomed. Pharmacother., 2017, 96, 563-571.
[http://dx.doi.org/10.1016/j.biopha.2017.10.021] [PMID: 29032340]
[52]
Bai, J.; Wu, Y.; Wang, X.; Liu, X.; Zhong, K.; Huang, Y.; Chen, Y.; Gao, H. In vitro and in vivo characterization of the antibacterial activity and membrane damage mechanism of quinic acid against Staphylococcus aureus. J. Food Saf., 2018, 38(1), e12416.
[http://dx.doi.org/10.1111/jfs.12416]
[53]
Bai, J.; Wu, Y.; Zhong, K.; Xiao, K.; Liu, L.; Huang, Y.; Wang, Z.; Gao, H. A comparative study on the effects of quinic acid and shikimic acid on cellular functions of Staphylococcus aureus. J. Food Prot., 2018, 81(7), 1187-1192.
[http://dx.doi.org/10.4315/0362-028X.JFP-18-014] [PMID: 29939792]
[54]
Adamczak, A. Ożarowski, M.; Karpiński, T.M. Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J. Clin. Med., 2019, 9(1), 109.
[http://dx.doi.org/10.3390/jcm9010109] [PMID: 31906141]
[55]
Kweon, M-H.; Hwang, H-J.; Sung, H-C. Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis). J. Agric. Food Chem., 2001, 49(10), 4646-4655.
[http://dx.doi.org/10.1021/jf010514x] [PMID: 11600002]
[56]
Ayaz, F.A. Hayırlıoglu-Ayaz, S.; Alpay-Karaoglu, S.; Grúz, J.; Valentová, K.; Ulrichová, J.; Strnad, M. Phenolic acid contents of kale (Brassica oleraceae L. var. acephala DC.) extracts and their antioxidant and antibacterial activities. Food Chem., 2008, 107(1), 19-25.
[http://dx.doi.org/10.1016/j.foodchem.2007.07.003]
[57]
Lou, Z.; Wang, H.; Zhu, S.; Ma, C.; Wang, Z. Antibacterial activity and mechanism of action of chlorogenic acid. J. Food Sci., 2011, 76(6), M398-M403.
[http://dx.doi.org/10.1111/j.1750-3841.2011.02213.x] [PMID: 22417510]
[58]
Sung, W.S.; Lee, D.G. Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. Pure Appl. Chem., 2010, 82(1), 219-226.
[http://dx.doi.org/10.1351/PAC-CON-09-01-08]
[59]
Karunanidhi, A.; Thomas, R.; Van Belkum, A.; Neela, V. In vitro antibacterial and antibiofilm activities of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia including the trimethoprim/sulfamethoxazole resistant strain. BioMed Res. Int., 2013, 2013, 392058.
[http://dx.doi.org/10.1155/2013/392058] [PMID: 23509719]
[60]
Kabir, F.; Katayama, S.; Tanji, N.; Nakamura, S. Antimicrobial effects of chlorogenic acid and related compounds. J. Korean Soc. Appl. Biol. Chem., 2014, 57(3), 359-365.
[http://dx.doi.org/10.1007/s13765-014-4056-6]
[61]
Sun, Z.; Zhang, X.; Wu, H.; Wang, H.; Bian, H.; Zhu, Y.; Xu, W.; Liu, F.; Wang, D.; Fu, L. Antibacterial activity and action mode of chlorogenic acid against Salmonella enteritidis, a foodborne pathogen in chilled fresh chicken. World J. Microbiol. Biotechnol., 2020, 36(2), 24.
[http://dx.doi.org/10.1007/s11274-020-2799-2] [PMID: 31965331]
[62]
Wang, Z.; Zhai, X.; Sun, Y.; Yin, C.; Yang, E.; Wang, W.; Sun, D. Antibacterial activity of chlorogenic acid-loaded SiO2 nanoparticles caused by accumulation of reactive oxygen species. Nanotechnology, 2020, 31(18), 185101.
[http://dx.doi.org/10.1088/1361-6528/ab70fb] [PMID: 31995525]
[63]
da Costa Cordeiro, B.M.P.; de Lima Santos, N.D.; Ferreira, M.R.A.; de Araújo, L.C.C.; Junior, A.R.C.; da Conceição Santos, A.D.; de Oliveira, A.P.; da Silva, A.G.; da Silva Falcão, E.P.; Dos Santos Correia, M.T.; da Silva Almeida, J.R.G.; da Silva, L.C.N.; Soares, L.A.L.; Napoleão, T.H.; da Silva, M.V.; Paiva, P.M.G. Hexane extract from Spondias tuberosa (Anacardiaceae) leaves has antioxidant activity and is an anti-Candida agent by causing mitochondrial and lysosomal damages. BMC Complement. Altern. Med., 2018, 18(1), 284.
[http://dx.doi.org/10.1186/s12906-018-2350-2] [PMID: 30340567]
[64]
Xu, H-S.; Wu, Y-W.; Xu, S-F.; Sun, H-X.; Chen, F-Y.; Yao, L. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha. J. Ethnopharmacol., 2009, 125(2), 310-317.
[http://dx.doi.org/10.1016/j.jep.2009.06.015] [PMID: 19559777]
[65]
Brindha, P. Role of phytochemicals as immunomodulatory agents: A review. Int. J. Green Pharm., 2016, 10(1) [IJGP]
[66]
John, C.M.; Sandrasaigaran, P.; Tong, C.K.; Adam, A.; Ramasamy, R. Immunomodulatory activity of polyphenols derived from Cassia auriculata flowers in aged rats. Cell. Immunol., 2011, 271(2), 474-479.
[http://dx.doi.org/10.1016/j.cellimm.2011.08.017] [PMID: 21924708]
[67]
Yi, D. X. U. M.-s. S. X.-c. Z. m.-y. Immunoregulation effect of chlorogenic acid on mouse peritoneal macrophages. Nat. Product Res. Develop., 2015, 27(12), 2128-2133.
[68]
Han, Y-M. Immunoadjuvant activity of chlorogenic acid. Yakhak Hoeji, 2010, 54(6), 494-499.
[69]
Ding, X.; Xiang, S. Endocytosis and human innate immunity. J. Immunol. Sci., 2018.
[http://dx.doi.org/10.29245/2578-3009/2018/1.1121]
[70]
Sridharan, R.; Cameron, A.R.; Kelly, D.J.; Kearney, C.J.; O’Brien, F.J. Biomaterial based modulation of macrophage polarization: A review and suggested design principles. Mater. Today, 2015, 18(6), 313-325.
[http://dx.doi.org/10.1016/j.mattod.2015.01.019]

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