Majra Honey Abrogated the Normal and Cancer Cells Proliferation Inhibition by Juniperus procera Extract and Extract/Honey Generated AgNPs

Hamed    A.    Ghramh; Essam    H.    Ibrahim; Mona       Kilnay

Abstract

Background: Juniperus procera and Majra honey are well-known as a folk medicine in many countries.

Objectives: This work aimed to study the immunomodulatory effects after mixing Majra honey, J. procera water leaves extract and silver Nanoparticles (AgNPs) on immune or cancer cells.

Methods: Juniperus procera water leaves extract and 20% Majra honey were prepared. Both the extract and honey were used separately to synthesize AgNPs. AgNPs were characterized using UV/Vis spectrophotometry and electron microscopy. Bioactive molecules in honey and the extract were explored using Fourier Transform Infrared (FT-IR) spectroscopy. Protein profile of honey was explored using Sodium Dodecyl Sulfate- Polyacrylamide Gel Electrophoresis (SDS-PAGE) and honey sugar content was determined using High- Performance Liquid Chromatography (HPLC). Biological activities of honey and the extract were tested.

Results: The results demonstrated the ability of the extract/honey to produce AgNPs in a spherical shape. The extract/honey contained many functional groups. SDS-PAGE of Majra honey showed many protein bands. HPLC revealed honey is of good quality and no external additives are added to it. The extract and extract+ AgNPs inhibited the growth of normal rat splenic cells while honey stimulated it. The extract+honey turned stimulatory to the splenic cells’ growth and significantly diminished the inhibitory potential of the extract containing AgNPs. Both the extract and honey have antimicrobial activities, this potential increased in the presence of AgNPs. Honey and Honey+AgNPs inhibited HepG2 cancer cell proliferation while Hela cell growth inhibited only with honey+AgNPs.

Conclusion: Both honey and the extract have antibacterial and immunomodulatory potentials as well as the power to produce AgNPs. Majra honey alone showed anticancer activity against HepGe2 cells, but not against Hela cells, and when contained AgNPs had anticancer activity on both cell lines. Mixing of Majra honey with J. procera extract showed characterized immunomodulatory potentials that can be described as immunostimulant.

Keywords: Juniperus procera, AgNPs, splenic cell proliferation, majra honey, antibacterial, antifungal, plant extract.

Graphical Abstract

[1] 
Yogalakshmi, B.; Viswanathan, P.; Anuradha, C.V. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology,  2010, 268(3), 204-212.
[http://dx.doi.org/10.1016/j.tox.2009.12.018] [PMID: 20036707] 
[2] 
Burits, M.; Asres, K.; Bucar, F. The antioxidant activity of the essential oils of Artemisia afra, Artemisia abyssinica and Juniperus procera. Phytother. Res.,  2001, 15(2), 103-108.
[http://dx.doi.org/10.1002/ptr.691] [PMID: 11268106] 
[3] 
Loizzo, M.; Tundis, R.; Confroti, F. Comparative chemical composition, antioxidant and hypoglycaemic activities of Juniperus oxycedrus ssp. oxycedrus L. berry and wood oils from Lebanon. Food Chem.,  2007, 105, 572-578.
[http://dx.doi.org/10.1016/j.foodchem.2007.04.015] 
[4] 
Oztürk, M.; Tümen, İ.; Uğur, A.; Aydoğmuş-Öztürk, F.; Topçu, G. Evaluation of fruit extracts of six Turkish Juniperus species for their antioxidant, anticholinesterase and antimicrobial activities. J. Sci. Food Agric.,  2011, 91(5), 867-876.
[http://dx.doi.org/10.1002/jsfa.4258] [PMID: 21384354] 
[5] 
Sarić-Kundalić, B.; Dobeš, C.; Klatte-Asselmeyer, V.; Saukel, J. Ethnobotanical survey of traditionally used plants in human therapy of east, north and north-east Bosnia and Herzegovina. J. Ethnopharmacol.,  2011, 133(3), 1051-1076.
[http://dx.doi.org/10.1016/j.jep.2010.11.033] [PMID: 21094241] 
[6] 
Alqasoumi, S.I.; Abdel-Kader, M.S. Terpenoids from Juniperus procera with hepatoprotective activity. Pak. J. Pharm. Sci.,  2012, 25(2), 315-322.
[7] 
Gil, M.I.; Ferreres, F.; Ortiz, A. Plant phenolic metabolites and floral origin of rosemary honey. J. Agric. Food Chem.,  1995, 43, 2833-2838.
[http://dx.doi.org/10.1021/jf00059a012] 
[8] 
Hermosín, I.; Chicón, R.M.; Cabezudo, M.D. Free amino acid composition and botanical origin of honey. Food Chem.,  2003, 83, 263-268.
[http://dx.doi.org/10.1016/S0308-8146(03)00089-X] 
[9] 
Gheldof, N.; Wang, X.H.; Engeseth, N.J. Identification and quantification of antioxidant components of honeys from various floral sources. J. Agric. Food Chem.,  2002, 50(21), 5870-5877.
[http://dx.doi.org/10.1021/jf0256135] [PMID: 12358452] 
[10] 
Beretta, G.; Granata, P.; Ferrero, M. Standardization of antioxidant properties of honey by a combination of spectrophotometric/fluorimetric assays and chemometrics. Anal. Chim. Acta,  2005, 533, 185-191.
[http://dx.doi.org/10.1016/j.aca.2004.11.010] 
[11] 
Almehdar, H.; Abdallah, H.M.; Osman, A.M.M.; Abdel-Sattar, E.A. In vitro cytotoxic screening of selected Saudi medicinal plants. J. Nat. Med.,  2012, 66(2), 406-412.
[http://dx.doi.org/10.1007/s11418-011-0589-8] [PMID: 21953271] 
[12] 
Shen, C.C.; Ni, C.L.; Huang, Y.L.; Huang, R.L.; Chen, C.C. Furanolabdane diterpenes from Hypoestes purpurea. J. Nat. Prod.,  2004, 67(11), 1947-1949.
[http://dx.doi.org/10.1021/np0497402] [PMID: 15568798] 
[13] 
Balkwill, K.; Norris, F.G. Taxonomic studies in the Acanthaceae; the genus Hypoestes in southern Africa. S. Afr. J. Bot.,  1985, 51(2), 133-144.
[http://dx.doi.org/10.1016/S0254-6299(16)31685-4] 
[14] 
Yokoyama, K.; Welchons, D.R. The conjugation of amyloid beta protein on the gold colloidal nanoparticles’ surfaces. Nanotechnology,  2007, 18(10)105101
[http://dx.doi.org/10.1088/0957-4484/18/10/105101] 
[15] 
Mohanta, Y.K.; Panda, S.K.; Jayabalan, R.; Sharma, N.; Bastia, A.K.; Mohanta, T.K. Antimicrobial, antioxidant and cytotoxic activity of silver nanoparticles synthesized by leaf extract of Erythrina suberosa (Roxb.). Front. Mol. Biosci.,  2017, 4, 14.
[http://dx.doi.org/10.3389/fmolb.2017.00014] [PMID: 28367437] 
[16] 
Majeed, A.; Ullah, W.; Anwar, A.W. Cost-effective biosynthesis of silver nanoparticles using different organs of plants and their antimicrobial applications: A review. Mater. Technol.,  2016, 33(5), 1-8.
[17] 
Marimuthu, S.; Rahuman, A.A.; Rajakumar, G.; Santhoshkumar, T.; Kirthi, A.V.; Jayaseelan, C.; Bagavan, A.; Zahir, A.A.; Elango, G.; Kamaraj, C. Evaluation of green synthesized silver nanoparticles against parasites. Parasitol. Res.,  2011, 108(6), 1541-1549.
[http://dx.doi.org/10.1007/s00436-010-2212-4] [PMID: 21181192] 
[18] 
Nayak, D.; Minz, A.P.; Ashe, S.; Rauta, P.R.; Kumari, M.; Chopra, P.; Nayak, B. Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines. J. Colloid Interface Sci.,  2016, 470, 142-152.
[http://dx.doi.org/10.1016/j.jcis.2016.02.043] [PMID: 26939078] 
[19] 
Okitsu, K.; Yue, A.; Tanabe, S. Formation of colloidal gold nanoparticles in an ultrasonic field: Control of rate of gold(III) reduction and size of formed gold particles. Langmuir,  2001, 17, 7717-7720.
[http://dx.doi.org/10.1021/la010414l] 
[20] 
Hanžić, N.; Jurkin, T.; Maksimović, A. The synthesis of gold nanoparticles by a citrate-radiolytical method. Radiat. Phys. Chem.,  2015, 106, 77-82.
[http://dx.doi.org/10.1016/j.radphyschem.2014.07.006] 
[21] 
Maleki, H.; Simchi, A.; Imani, M. Size-controlled synthesis of superparamagnetic iron oxide nanoparticles and their surface coating by gold for biomedical applications. J. Magn. Magn. Mater.,  2012, 324(23), 3997-4005.
[http://dx.doi.org/10.1016/j.jmmm.2012.06.045] 
[22] 
Makarov, V.V.; Love, A.J.; Sinitsyna, O.V. “Green” nanotechnologies: synthesis of metal nanoparticles using plants. Acta Nat.,  2014, 6(1), 35-44.
[23] 
Kumar, V.; Yadav, S.K. Plant-mediated synthesis of silver and gold nanoparticles and their applications. J. Chem. Technol. Biotechnol.,  2009, 84(2), 151-157.
[http://dx.doi.org/10.1002/jctb.2023] 
[24] 
El-Desouky, T.A.; Ammar, H.A.M. Honey mediated silver nanoparticles and their inhibitory effect on aflatoxins and ochratoxin A. J. Appl. Pharm. Sci.,  2016, 6(6), 83-90.
[http://dx.doi.org/10.7324/JAPS.2016.60615] 
[25] 
Singh, P.; Kim, Y.J.; Zhang, D.; Yang, D.C. Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol.,  2016, 34(7), 588-599.
[http://dx.doi.org/10.1016/j.tibtech.2016.02.006] [PMID: 26944794] 
[26] 
Ibrahim, E.H.; Kilany, M.; Ghramh, H.A.; Khan, K.A.; Ul Islam, S. Cellular proliferation/cytotoxicity and antimicrobial potentials of green synthesized silver nanoparticles (AgNPs) using Juniperus procera. Saudi J. Biol. Sci.,  2019, 26(7), 1689-1694.
[http://dx.doi.org/10.1016/j.sjbs.2018.08.014] [PMID: 31762645] 
[27] 
Ibrahim, E.H.; Asiri, R.; Al Syaad, K. Genetic fusion of tetanus toxin fragment C (Hc) gene to cholera toxin subunit B (CTB) gene as a preparatory step for double vaccine production. Gene Rep.,  2018, 10, 90-96.
[http://dx.doi.org/10.1016/j.genrep.2017.11.008] 
[28] 
Laemmli, U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature,  1970, 227(5259), 680-685.
[http://dx.doi.org/10.1038/227680a0] [PMID: 5432063] 
[29] 
Green, M.R.; Sambrook, J. Molecular Cloning: A Laboratory Manual; Cold Spring Harbor Laboratory Press: New York, 2012. 
[30] 
Ghramh, H.A.; Al-Ghamdi, K.M.; Mahyoub, J.A. Chrysanthemum extract and extract prepared silver nanoparticles as biocides to control Aedes aegypti (L.), the vector of dengue fever. J. Asia Pac. Entomol.,  2018, 21, 205-210.
[http://dx.doi.org/10.1016/j.aspen.2017.12.001] 
[31] 
Kilany, M. Isolation, screening and molecular identification of novel bacterial strain removing methylene blue from water solutions. Appl. Water Sci.,  2017, 7, 4091-4098.
[http://dx.doi.org/10.1007/s13201-017-0565-x] 
[32] 
Algarni, H.; AlShahrani, I.; Ibrahim, E.H. Nano and microstructure of bioglasses: In vitro and in vivo bioactivity properties. J. Non-Cryst. Solids,  2019, 512, 72-80.
[http://dx.doi.org/10.1016/j.jnoncrysol.2019.02.018] 
[33] 
Ghramh, H.A.; Khan, K.A.; Ibrahim, E.H. Biological activities of Euphorbia peplus leaves ethanolic extract and the extract fabricated gold nanoparticles (AuNPs). Molecules,  2019, 24(7), 1431.
[http://dx.doi.org/10.3390/molecules24071431] [PMID: 30978998] 
[34] 
Ranganathan, R.; Madanmohan, S.; Kesavan, A.; Baskar, G.; Krishnamoorthy, Y.R.; Santosham, R.; Ponraju, D.; Rayala, S.K.; Venkatraman, G. Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications. Int. J. Nanomedicine,  2012, 7, 1043-1060.
[PMID: 22403487] 
[35] 
Philip, D. Honey mediated green synthesis of gold nanoparticles. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2009, 73(4), 650-653.
[http://dx.doi.org/10.1016/j.saa.2009.03.007] [PMID: 19376740] 
[36] 
Balasooriya, E.R.; Jayasinghe, C.D.; Jayawardena, U.A. Honey mediated green synthesis of nanoparticles: New era of safe nanotechnology. J. Nanomater.,  2017, 2017 Article ID 5919836
[http://dx.doi.org/10.1155/2017/5919836] 
[37] 
Mock, J.J.; Barbic, M.; Smith, D.R. Shape effects in plasmon resonance of individual colloidal silver nanoparticles. J. Chem. Phys.,  2002, 116, 6755.
[http://dx.doi.org/10.1063/1.1462610] 
[38] 
Liu, Z.; Woo, S.I.; Lee, W.S. In situ FT-IR studies on the mechanism of selective catalytic reduction of NOx by propene over SnO2/Al2O3 catalyst. J. Phys. Chem. B,  2006, 110(51), 26019-26023.
[http://dx.doi.org/10.1021/jp0637274] [PMID: 17181252] 
[39] 
Li, H.; Mahyoub, S.A.A.; Liao, W.; Xia, S.; Zhao, H.; Guo, M.; Ma, P. Effect of pyrolysis temperature on characteristics and aromatic contaminants adsorption behavior of magnetic biochar derived from pyrolysis oil distillation residue. Bioresour. Technol.,  2017, 223, 20-26.
[http://dx.doi.org/10.1016/j.biortech.2016.10.033] [PMID: 27771526] 
[40] 
Prathna, T.C.; Chandrasekaran, N.; Raichur, A.M.; Mukherjee, A. Biomimetic synthesis of silver nanoparticles by Citrus limon (lemon) aqueous extract and theoretical prediction of particle size. Colloids Surf. B Biointerfaces,  2011, 82(1), 152-159.
[http://dx.doi.org/10.1016/j.colsurfb.2010.08.036] [PMID: 20833002] 
[41] 
Tavares, W.R.; Seca, A.M.L. The current status of the pharmaceutical potential of Juniperus L. metabolites. Medicines (Basel),  2018, 5(3)E81
[http://dx.doi.org/10.3390/medicines5030081] [PMID: 30065158] 
[42] 
González, M.A. Aromatic abietane diterpenoids: their biological activity and synthesis. Nat. Prod. Rep.,  2015, 32(5), 684-704.
[http://dx.doi.org/10.1039/C4NP00110A] [PMID: 25643290] 
[43] 
Agudelo-Gómez, L.S.; Betancur-Galvis, L.A.; González, M.A. Anti HHV-1 and HHV-2 activity in vitro of abietic and dehydroabietic acid derivatives. Pharmacologyonline,  2012, 1(1), 36.
[44] 
Seca, A.M.L.; Pinto, D.C.; Silva, A.M.S. The current status of bioactive metabolites from the genus Juniperus. InBioactive Phytochemicals: Perspectives for Modern Medicine; Gupta, V.K., Ed.; M/S Daya Publishing House: New Delhi, India, 2015, pp. 365-407.
[45] 
Yu, S.; Yan, H.; Zhang, L.; Shan, M.; Chen, P.; Ding, A.; Li, S.F. A review on the phytochemistry, pharmacology, and pharmacokinetics of amentoflavone, a naturally-occurring biflavonoid. Molecules,  2017, 22(2)E299
[http://dx.doi.org/10.3390/molecules22020299] [PMID: 28212342] 
[46] 
Seca, A.; Silva, A. The chemical composition of the Juniperus Genus (1970-2004). In Recent Progress in Medicinal Plants; Govil, J.N.; Singh, V.K.; Bhardwaj, R., Eds.; Studium Press LLC: Houston, TX, USA, 2005, pp. 401-522.
[47] 
Bardy, J.; Molassiotis, A.; Ryder, W.D.; Mais, K.; Sykes, A.; Yap, B.; Lee, L.; Kaczmarski, E.; Slevin, N. A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis. Br. J. Oral Maxillofac. Surg.,  2012, 50(3), 221-226.
[http://dx.doi.org/10.1016/j.bjoms.2011.03.005] [PMID: 21636188] 
[48] 
Tsiapara, A.V.; Jaakkola, M.; Chinou, I. Bioactivity of Greek honey extracts on breast cancer (MCF-7), prostate cancer (PC-3) and endometrial cancer (Ishikawa) cells: Profile analysis of extracts. Food Chem.,  2009, 116, 702-708.
[http://dx.doi.org/10.1016/j.foodchem.2009.03.024] 
[49] 
Gomes, S.; Dias, L.G.; Moreira, L.L.; Rodrigues, P.; Estevinho, L. Physicochemical, microbiological and antimicrobial properties of commercial honeys from Portugal. Food Chem. Toxicol.,  2010, 48(2), 544-548.
[http://dx.doi.org/10.1016/j.fct.2009.11.029] [PMID: 19909782] 
[50] 
Taormina, P.J.; Niemira, B.A.; Beuchat, L.R. Inhibitory activity of honey against foodborne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power. Int. J. Food Microbiol.,  2001, 69(3), 217-225.
[http://dx.doi.org/10.1016/S0168-1605(01)00505-0] [PMID: 11603859] 
[51] 
Tonks, A.J.; Dudley, E.; Porter, N.G.; Parton, J.; Brazier, J.; Smith, E.L.; Tonks, A. A 5.8-kDa component of manuka honey stimulates immune cells via TLR4. J. Leukoc. Biol.,  2007, 82(5), 1147-1155.
[http://dx.doi.org/10.1189/jlb.1106683] [PMID: 17675558] 
[52] 
Chua, L.S.; Lee, J.Y.; Chan, G.F. Characterization of the proteins in honey. Anal. Lett.,  2015, 48, 697-709.
[http://dx.doi.org/10.1080/00032719.2014.952374] 
[53] 
Tewari, J.; Irudayaraj, J. Quantification of saccharides in multiple floral honeys using fourier transform infrared microattenuated total reflectance spectroscopy. J. Agric. Food Chem.,  2004, 52(11), 3237-3243.
[http://dx.doi.org/10.1021/jf035176+] [PMID: 15161176] 
[54] 
Lee, D.C.; Lee, S.Y.; Cha, S.H. Discrimination of native bee-honey and foreign bee-honey by SDS-PAGE. Korean J. Food Sci.,  1998, 30, 1-5.
[55] 
Marshall, T.; Williams, K.M. Electrophoresis of honey: characterization of trace proteins from a complex biological matrix by silver staining. Anal. Biochem.,  1987, 167(2), 301-303.
[http://dx.doi.org/10.1016/0003-2697(87)90168-0] [PMID: 2450485] 
[56] 
Vit, P.; Pulcini, P. Diastase and invertase activities in Meliponini and Trigonini honeys from Venezuela. J. Apic. Res.,  1996, 35(2), 57-62.
[http://dx.doi.org/10.1080/00218839.1996.11100913] 
[57] 
Simuth, J. Some properties of the main protein of honeybee (Apis mellifera) royal jellyal jelly. Apidologie (Celle),  2001, 32, 69-80.
[http://dx.doi.org/10.1051/apido:2001112] 
[58] 
Mohammed, S.E.A.R.; Sajid, M.; Azim, M.K. Isolation of 62 kDa protein with antioxidant properties from natural honey. J. Chem. Soc. Pak.,  2014, 36, 453-456.
[59] 
Kamal, M.A.; Klein, P. Determination of sugars in honey by liquid chromatography. Saudi J. Biol. Sci.,  2011, 18(1), 17-21.
[http://dx.doi.org/10.1016/j.sjbs.2010.09.003] [PMID: 23961099] 
[60] 
White, J.W. Composition of honey.In Honey. A comprehensive survey; Crane, E., Ed.; London, 1975, pp. 157-206.
[61] 
Goodall, I.; Dennis, M.J.; Parker, I. Contribution of high-performance liquid chromatographic analysis of carbohydrates to authenticity testing of honey. J. Chromatogr. A,  1995, 706(1-2), 353-359.
[http://dx.doi.org/10.1016/0021-9673(94)01074-O] 
[62] 
Mora, M.I.; Marioli, J.M. Honey carbohydrate analysis by HPLC, with electrochemical detection, using a ni-cr alloy electrode. J. Liq. Chromatogr. Relat. Technol.,  2001, 24(5), 711-720.
[http://dx.doi.org/10.1081/JLC-100103405] 
[63] 
Muhammad, I.; Mossa, J.S.; Al‐Yahya, M.A. Further antibacterial diterpenes from the bark and leaves of Juniperus procera hochst. ex Endl. Phytother. Res.,  1995, 9, 584-588.
[http://dx.doi.org/10.1002/ptr.2650090810] 
[64] 
Muhammad, I.; Mossa, J.S.; El-Feraly, F.S. Additional antibacterial diterpenes from the bark of Juniperus procera. Phytother. Res., 1996, 10, 604-607.
[http://dx.doi.org/10.1002/(SICI)1099-1573(199611) 10:7 604::AID-PTR922>3.0.CO;2-C] 
[65] 
Bitew, D. Assessment of the inhibitory activity of resin from Juniperus procera against the Mycilium of Pyrofomes demidoffi. J. Plant Pathol. Microbiol.,  2015, 6, 1-8.
[66] 
Mungole, A.; Day, S.; Kamble, R. Active phytochemical and antibacterial potentiality of in vitro regenerated plantlets of Canscora decurrens (Dalzell). Indian J. Sci. Technol.,  2010, 3(6)
[http://dx.doi.org/10.17485/ijst/2010/v3i6/29782] 
[67] 
Sodipo, O.; Akanji, M.; Kolawole, F. Saponin is the active antifungal principle in Garcinia kola, heckle seed. Biosci. Res. Commun.,  1991, 3, 171.
[68] 
Guimarães, A.C.; Meireles, L.M.; Lemos, M.F.; Guimarães, M.C.C.; Endringer, D.C.; Fronza, M.; Scherer, R. Antibacterial activity of terpenes and terpenoids present in essential oils. Molecules,  2019, 24(13)E2471
[http://dx.doi.org/10.3390/molecules24132471] [PMID: 31284397] 
[69] 
Xie, Y.; Yang, W.; Tang, F.; Chen, X.; Ren, L. Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr. Med. Chem.,  2015, 22(1), 132-149.
[http://dx.doi.org/10.2174/0929867321666140916113443] [PMID: 25245513] 
[70] 
Favela-Hernández, J.M.J.; García, A.; Garza-González, E. Antibacterial and antimycobacterial lignans and flavonoids from Larrea tridentata. Phytother. Res.,  2012, 26(12), 1957-1960.
[http://dx.doi.org/10.1002/ptr.4660] 
[71] 
Kyselka, J.; Rabiej, D.; Dragoun, M. Antioxidant and antimicrobial activity of linseed lignans and phenolic acids. Eur. Food Res. Technol.,  2017, 243, 1633-1644.
[http://dx.doi.org/10.1007/s00217-017-2871-9] 
[72] 
Kwakman, P.H.S.; te Velde, A.A.; de Boer, L.; Speijer, D.; Vandenbroucke-Grauls, C.M.; Zaat, S.A. How honey kills bacteria. FASEB J.,  2010, 24(7), 2576-2582.
[http://dx.doi.org/10.1096/fj.09-150789] [PMID: 20228250] 
[73] 
Kwakman, P.H.S.; Zaat, S.A.J. Antibacterial components of honey. IUBMB Life,  2012, 64(1), 48-55.
[http://dx.doi.org/10.1002/iub.578] [PMID: 22095907] 
[74] 
Voidarou, C.; Alexopoulos, A.; Plessas, S.; Karapanou, A.; Mantzourani, I.; Stavropoulou, E.; Fotou, K.; Tzora, A.; Skoufos, I.; Bezirtzoglou, E. Antibacterial activity of different honeys against pathogenic bacteria. Anaerobe,  2011, 17(6), 375-379.
[http://dx.doi.org/10.1016/j.anaerobe.2011.03.012] [PMID: 21524711] 
[75] 
Nassar, H.M.; Li, M.; Gregory, R.L. Effect of honey on Streptococcus mutans growth and biofilm formation. Appl. Environ. Microbiol.,  2012, 78(2), 536-540.
[http://dx.doi.org/10.1128/AEM.05538-11] [PMID: 22038612] 
[76] 
Mandal, M.D.; Mandal, S. Honey: its medicinal property and antibacterial activity. Asian Pac. J. Trop. Biomed.,  2011, 1(2), 154-160.
[http://dx.doi.org/10.1016/S2221-1691(11)60016-6] [PMID: 23569748] 
[77] 
Olaitan, P.B.; Adeleke, O.E.; Ola, I.O. Honey: a reservoir for microorganisms and an inhibitory agent for microbes. Afr. Health Sci.,  2007, 7(3), 159-165.
[http://dx.doi.org/10.5555/afhs.2007.7.3.159] [PMID: 18052870] 
[78] 
Boateng, J.; Diunase, K.N. Comparing the antibacterial and functional properties of cameroonian and manuka honeys for potential wound healing-have we come full cycle in dealing with antibiotic resistance? Molecules,  2015, 20(9), 16068-16084.
[http://dx.doi.org/10.3390/molecules200916068] [PMID: 26364634] 
[79] 
Jeddar, A.; Kharsany, A.; Ramsaroop, U.G.; Bhamjee, A.; Haffejee, I.E.; Moosa, A. The antibacterial action of honey. An in vitro study. S. Afr. Med. J.,  1985, 67(7), 257-258.
[PMID: 3983773] 
[80] 
Durán, N.; Marcato, P.D.; De Conti, R. Potential use of silver nanoparticles on pathogenic bacteria, their toxicity and possible mechanisms of action. J. Braz. Chem. Soc.,  2010, 21, 949-959.
[http://dx.doi.org/10.1590/S0103-50532010000600002] 
[81] 
Wang, L.; Hu, C.; Shao, L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int. J. Nanomedicine,  2017, 12, 1227-1249.
[http://dx.doi.org/10.2147/IJN.S121956] [PMID: 28243086] 
[82] 
Adams, R.P.; Demeke, T.; Abulfatih, H.A. RAPD DNA fingerprints and terpenoids: clues to past migrations of Juniperus in Arabia and east Africa. Theor. Appl. Genet.,  1993, 87(1-2), 22-26.
[http://dx.doi.org/10.1007/BF00223738] [PMID: 24190186] 
[83] 
Mujwah, A.A.; Mohammed, M.A.; Ahmed, M.H. First isolation of a flavonoid from Juniperus procera using ethyl acetate extract. Arab. J. Chem.,  2010, 3, 85-88.
[http://dx.doi.org/10.1016/j.arabjc.2010.02.003] 
[84] 
Ali, A.A.; Elgimabi, M.E.N. Extraction and determination of antioxidants, polyphenols, flavonoids and antioxidant activity in some plants. Int. J. Chem. Sci.,  2015, 13, 1883-1892.
[85] 
Fujisawa, S.; Kadoma, Y. Relationship between phenol-induced cytotoxicity and experimental inhibition rate constant or a theoretical parameter. Mini Rev. Med. Chem.,  2012, 12(6), 477-490.
[http://dx.doi.org/10.2174/138955712800493816] [PMID: 22356159] 
[86] 
Langhoff, E.; Ladefoged, J.; Dickmeiss, E. The immunosuppressive potency of various steroids on peripheral blood lymphocytes, T cells, NK and K cells. Int. J. Immunopharmacol.,  1985, 7(4), 483-489.
[http://dx.doi.org/10.1016/0192-0561(85)90067-0] [PMID: 3876294] 
[87] 
Duddukuri, G.R.; Rao, D.N.; Athota, R.R. Suppressive effect of honey on antigen/mitogen stimulated murine T cell proliferation. Pharm. Biol.,  2002, 40(1), 39-44.http://dx.doi.org/101076/phbi401395851
[88] 
Zhang, X-F.; Liu, Z-G.; Shen, W. Silver nanoparticles: Synthesis, characterization, properties, applications, and therapeutic approaches. Int. J. Mol. Sci.,  2016, 17(9), 1534.
[http://dx.doi.org/10.3390/ijms17091534] 
[89] 
Barcińska, E.; Wierzbicka, J.; Zauszkiewicz-Pawlak, A.; Jacewicz, D.; Dabrowska, A.; Inkielewicz-Stepniak, I. Role of oxidative and nitro-oxidative damage in silver nanoparticles cytotoxic effect against human pancreatic ductal adenocarcinoma cells. Oxid. Med. Cell. Longev.,  2018, 2018 8251961
[http://dx.doi.org/10.1155/2018/8251961] [PMID: 30186549] 
[90] 
Nik Man, N.M.K.; Hassan, R.; Ang, C.Y.; Abdullah, A.D.; Mohd Radzi, M.A.; Sulaiman, S.A. Antileukemic effect of Tualang honey on acute and chronic leukemia cell lines. BioMed Res. Int.,  2015, 2015307094
[http://dx.doi.org/10.1155/2015/307094] [PMID: 26613081] 
[91] 
Hassan, M.I.; Mabrouk, G.M.; Shehata, H.H.; Aboelhussein, M.M. Antineoplastic effects of bee honey and Nigella sativa on hepatocellular carcinoma cells. Integr. Cancer Ther.,  2012, 11(4), 354-363.
[http://dx.doi.org/10.1177/1534735410387422] [PMID: 21147814] 
[92] 
Jaganathan, S.K.; Balaji, A.; Vellayappan, M.V.; Asokan, M.K.; Subramanian, A.P.; John, A.A.; Supriyanto, E.; Razak, S.I.; Marvibaigi, M. A review on antiproliferative and apoptotic activities of natural honey. Anticancer. Agents Med. Chem.,  2015, 15(1), 48-56.
[http://dx.doi.org/10.2174/1871520614666140722084747] [PMID: 25052987] 
[93] 
Liou, G-Y.; Storz, P. Reactive oxygen species in cancer. Free Radic. Res.,  2010, 44(5), 479-496.
[http://dx.doi.org/10.3109/10715761003667554] [PMID: 20370557] 
[94] 
Coussens, L.M.; Werb, Z. Inflammation and cancer. Nature,  2002, 420(6917), 860-867.
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959] 
[95] 
Porcza, L.M.; Simms, C.; Chopra, M. Honey and cancer: Current status and future directions. Diseases,  2016, 4(4)E30
[http://dx.doi.org/10.3390/diseases4040030] [PMID: 28933410] 
[96] 
Ren, W.; Qiao, Z.; Wang, H.; Zhu, L.; Zhang, L. Flavonoids: promising anticancer agents. Med. Res. Rev.,  2003, 23(4), 519-534.
[http://dx.doi.org/10.1002/med.10033] [PMID: 12710022] 
[97] 
Waheed, M.; Hussain, M.B.; Javed, A.; Mushtaq, Z.; Hassan, S.; Shariati, M.A.; Khan, M.U.; Majeed, M.; Nigam, M.; Mishra, A.P.; Heydari, M. Honey and cancer: A mechanistic review. Clin. Nutr.,  2019, 38(6), 2499-2503.
[http://dx.doi.org/10.1016/j.clnu.2018.12.019] [PMID: 30639116] 

Cite As

Anti-Cancer Agents in Medicinal Chemistry

Majra Honey Abrogated the Normal and Cancer Cells Proliferation Inhibition by Juniperus procera Extract and Extract/Honey Generated AgNPs

Abstract

Graphical Abstract