Effectiveness of Soursop Leaf Extract (Annona muricata l.) on IL-6 Levels in Mammary Sprague dawley Female Rats Induced by Staphylococcus aureus
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Abstract
Staphylococcus aureus is a Gram-positive bacterium that causes inflammation such as mastitis in the breast. Breast mastitis can occur in nursing mothers and requires first aid or initial treatment. Herbal ingredients can be utilized because they are easily obtained and can be prepared by the community themselves. The study aimed to analyze the effectiveness of soursop leaf extract on IL-6 levels in mammae of female rats Sprague dawley induced by S. aureus. The study was divided into four groups consisting of five rats that were induced by S. aureus 2 x 107 CFU/ml. Group I was given 0.5% Na.CMC, Group II gave 45 mg/kgBW cefadroxil antibiotics, group III administered 100 mg / kgBW soursop leaf extract, and group IV administered soursop leaf extract combined with cefadroxil. Each group was given treatment twice a day for 5 days. IL-6 levels were measured on days 3 and 6. The results of this study showed IL-6 levels in group III were 7.50 ± 1.74 pg/ml on the 3rd day, and 4.51 ± 1.47 pg/ml on the 6th day. The results showed there were differences in IL-6 levels in group III (p = 0.037). Soursop leaf extract can be used as a therapy for mastitis caused by S. aureus.
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How to Cite
Purnamasari, F., Yulianty, R., & Latief, S. (2020). Effectiveness of Soursop Leaf Extract (Annona muricata l.) on IL-6 Levels in Mammary Sprague dawley Female Rats Induced by Staphylococcus aureus. Unnes Journal of Public Health, 9(1), 56-63. https://doi.org/10.15294/ujph.v9i1.30904
References
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Alasiry, E. 2012. Buku Indonesia Menyusui. Retrieved from www.idai.or.id.
Amir L. 2014. ABM Clinical Protocol #4: Mastitis. Breastfeeding Medicine, 9(5): 239–243.
Anasari T., & Sumarni. 2014. Faktor-Faktor Yang Mempengaruhi Kejadian Mastitis di RSUD Prof. Dr. Margano Soekarjo Purwokerto. Jurnal Involusi Kebidanan, 4(7): 40-52.
Arican O., Aral M., Sasmaz S., & Ciragil P. 2005. Serum Levels of TNF-α, IFNµ, IL-6, IL-8, IL-12, IL-17, and IL-18 in Patients with Active Psoriasis and Correlation with Disease Severity. Mediators of Inflammation, 2005(5): 201561. DOI: https://doi.org/10.1155/MI.2005.273
Bauer, I., Gunther, I., Wheeler, T.T., Engelman, S., & Seyfert, H.M. 2015. Extracellular Milieu Grossly Alters Pathogenspecific Immune Response of Mammary Epithelial Cells. BMC Veterinary Research, 11: 172.
Chen. 2013. Alpinetin attenuates inflammatory responses by interfering toll-like receptor 4/ nuclear factor kappa B signaling pathway in lipopolysaccharide-induced mastitis in mice. International Immunipharmacology, 17(1): 26–32.
Choi, E.J., Kim, H.I., Kim, J.A., Kang, S.H., Park, D.J., Son, S.J., et al. 2015. The Herbal-Derived Honokiol and Magnolol Enhances Immune Response to Infection with Methicillin-Sensitive Staphylococcus Aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA). Applied Microbial and Cell Physiology, 99: 4387–4396.
Cushnie, T.P.T., & Lamb, A.J. 2005, Antimicrobial activity of avonoids. Int. J. Antimicrob. Agents, 26: 343–356.
Cowan, M.M. 1999. Plant products as antimicrobial agents. Clin. Micobiol. Rev., 12(4): 564 – 582.
Diacci, C., Laura, M. D., Bianchini, R., & Pinti, M. 2017. Label-Free Detection of Interleukin-6 Using Electrolyte Gated Organic Field Effect Transistors. Biointerphases, 12(5): 05F401
Dewi, Z.Y., Nur, A., & Hertriani, T. 2015. Efek antibakteri dan penghambatan bioï€ lm ekstrak sereh (Cymbopogon nardus l.) terhadap bakteri Streptococcus mutans. Majalah Kedokteran Gigi Indonesia, 1(2): 136–141.
Estela, K.M., Prameshinta, H.F., Dharmana, E., & Kridjamiatun, R.A. 2016. Efektifitas Ekstrak Daun Sirsak (Annona muricata) dalam Menurunkan Kadar TNF α dan Meningkatkan Kadar NO Uji Coba pada Mencit Swiss yang Diinokulasi Plasmodium berghei ANKA. Jurnal Kedokteran Brawijaya, 29(01): 39-42.
Fadel & Anwar. 2014. Antibacterial Efficacy of Variety Plants Against the Resistant Streptococcus which Cause Clinical Mastitis in Cows, AJPRHC, 5(1): 32-41.
Friska, Tetlana, & Trianna. 2017. Skrining Fitokimia dan Aktivitas Antibakteri Ekstrak Etanol Daun Sirsak (Annona muricata L.) pada Streptococcus mutans ATCC 35668. Majalah Kedokteran Gigi Indonesia, 3(1).
Fursova, K.K., Schchamikova, M.D., Loskutova, I.V., Shepelyakovskaya, A.O., Laman, A.G., Boutanaev, A.M., Sokolov, S.L., Artem’eva, O.A., Nikanova, D.A., Zinovieva, N.A., Brovko, F.A., Kim, Y., & Shin, O.S. 2018. Exotoxin Diversity of Staphylococcus Aureus Isolated from Milk of Cows with Subclinical Mastitis in Central Russia. Journal of Dairy Science, 101(5): 4325–4331. DOI: https://doi.org/ 10.3168/jds.2017-14074.
Goyal, R., Faiz, A., & Singhai, M. 2012. Evaluation of TNF-α and IL-6 levels in obese and non-obese diabetics: Pre- and postinsulin effects. North American Journal of Medical Sciences, 4(4): 180-184.
Han, Y., Ripley, B., Jerada, S., Naka, T., & Fujimoto, M. 2016. Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation. PLoS ONE, 11(4).
Hassan, SM. 2008. Antimicrobial activities of saponinrich guar meal extract poultry science. Doctoral Thesis. Texas: A & M University.
Ishartadiati, K. 2009. Peranan Tnf, Il-1, dan Il-6 pada Respon Imun Terhadap Protozoa. Surabaya: FK Universitas Wijaya Kusuma.
Jahanfar, S., Ng, C.J., & Teng, C.L. 2013. Antibiotics for mastitis in breastfeeding women. Cochrane Database of Systematic Reviews, 28(2): CD005458.
Kruspe, S., Meyer, C., & Ulrich. H. 2014. Chlorin E6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation. Molecular Therapy Nucleic Acids, 3(1): e143.
Lai, J.L., & Perg, Y.C. 2017. Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Ephithelial Cells. Mediators of Immflamation. 2017: 3082805.
Latifah, W. 2013. Uji Aktivitas Antioksidan Ekstrak Etanol Daun Sirsak (Annona Muricata L) Gugur. Master Thesis. Yogyakarta: Universitas Gadjah Mada.
Londok, J.J.M.R., & Mandey, J.S. 2014. Potensi Fitokimia dan Aktivitas Antimikroba Daun Sirsak (Annona muricata Linn.) Sebagai Kandidat Bahan Pakan Ayam Pedaging. Jurnal LPPM Bidang Sains dan Teknologi, 1(1).
Lutchmedial, M., Ramlal, R., Bridre, N., & Yen, I.C. 2014. Nutritional and Sensory Quality of Stirred Soursop (Annona Muricata L.) Yoghurt. International Journal of Food Sciences and Nutrition, 55(5): 407– 414.
Mardiana, L., & Ratnasari, J. 2011. Ramuan dan Khasiat Sirsak. Jakarta: Penebar Swadaya.
Maramis, R., Kaseke, M., & Tanudjadja, G.N. 2014. Gambaran Histologi Aorta Tikus Wistar dengan Diet Lemak Babi Setelah Pemberian Ekstrak Daun Sirsak (Annona muricata L.). Jurnal E-Biomedik (eBM), 2: 430–435.
Mulia, K., Krisanti, E., Maulana, T., & Dianursanti. 2015. Selective Polarity-Guided Extraction and Purification of Acetogenins in Annona Muricata L. Leaves. International Journal of Technology, 7: 1221–1227.
Oloyede, C. T., Akande F.B., & Oniya O.O. 2015. Moisture Dependent Physical properties of Sour-Sop (Annona Muricatal.) Seeds. CIGR Journal, 17(2): 185.
Putri, R.A., Sari, N.I, Supartono, & Mursiti, S. 2017. Lotion Ekstrak Daun Sirsak (Annona muricata L.) sebagai Antibakteri. Indonesian Journal of Chemical Science, 6(3).
Rahman, S., & Mustari. 2012. Uji efek antiinflamasi ekstrak etanol daun sirsak (Annona muricata Linn.) terhadap mencit (Mus musculus) jantan yang diinduksi dengan karagen. As-Syifaa Jurnal Farmasi. 4(1): 7-15.
Rajeswari, V., Gajalakshmi, S., & Vijayalakshmi, S. 2012. Phytochemical and Pharmacological Properties of Annona Muricata: A review. International Journal of Pharmacy and Pharmaceutical Science, 4(2): 3-6.
Rosmayanti, K. 2014. Uji Efektivitas Ekstrak Biji Sirsak (Annona Muricata L) Sebagai Larvasida pada Larva Aedes Aegypti Instar III/IV. Undergraduate Thesis. Jakarta: Universitas Islam Negeri Jakarta.
Samantha, K.W., Wennitz, O., Bruckmaier, R.M., & Schwartz, D. 2018. Differential Somatic Cell Count in Milk Before, During, and After Lipopolysaccharide and Lipoteichoic-Acid-Induced Mastitis in Dairy Cows. Journal of Dairy Science, 101(6).
Sardi, D. 2009. Herbal Indonesia Berkhasiat. Depok: Trubus Swadaya.
Silva, E.M. 2017. High Systemic Il-6 Is Associated with Worse Prognosis in Patients with Non-Small Cell Lung Cancer. PLoS ONE, 12 (7).
Soekaryo, E., Setyahadi S., Simanjuntak P. 2017. Identifikasi Senyawa Aktif Fraksi Etanol Daun Sirsak (Annona Muricata Linn.) Sebagai Penghambat Siklooksigenase-2. The 5th Urecol Proceeding, 862-867
Soetan KO, Oyekunle MA, Aiyelaagbe OO, & Fafunso MA., 2006, Evaluation of the antimicrobial activity of saponins extract of sorghum bicolor l. moench. African J of Biotechnology, 5(23): 2405–2407.
Solomon-Wisdom, G., Ugoh, S., & Mohammed, B. 2014. Phytochemical screening and antimicrobial activities of Annona muricata (L) leaf extract. American Journal Biology Chemistry Pharmaceutical Sciences, 2(1): 1-7.
Sudira, I. W., Merdana, I., & Wibawa, I. 2011. Uji daya hambat ekstrak daun kedondong (Lannea Grandis Engl) terhadap pertumbuhan bakteri Erwinia carotovora. Buletin Veteriner Udayana, 3(1), 45-50.
Sugimoto, Y, 2015, Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers : A cross-sectional study., Gene, 557(2): 158–162.
Sugianto, I.S. 2012. Uji Fitokimia Ekstrak Pegagan (Centella asiatica) dan Buah Sirsak (Annona muricata L.) Serta Potensinya Sebagai Inhibitor Enzim Xantin Oksidase. Undergraduate Thesis. Malang: Universitas Negeri Malang
Swarnakar, A. 2014. Literary approach to Annona muticata and its role in cancer- A review. Int. Journal if Reasearch in Pharmacology & Pharmacotherapeutics, 3 (4).
Stauth, D. 2007. Studies Force New View on Biology of Flavonoids. Oregon: Oregon State University.
Taleb-Contini, S.H., Salvador, M.J., Watanabe, E., Ito, I.Y., & Oliveira, D.C.R. 2003. Antimicrobial activity of avonoids and steroids isolated from two chromolaena species. Braz J Pharm Sci, 39(4): 403–408.
Telez, A.V.C., Gonzalez, E.M., Yahia, E.M., Vazquez, E.N.O. 2016. Annona muricata: A Comprehensive Review on Its Traditional Medicinal Uses, Phytochemicals, Pharmacological Activities, Mechanisms of Action and toxicity. Arabian Journal of Chemistry,11(5): 662-691.
Wendy, V. I. 2014. Inflammatory Mediators in Mastitis and Lactation Insufficiency. J Mammary Gland Biol Neoplasia, 19: 161–167.
Zuhud, A.M. 2011. Bukti Kedahsyatan Sirsak Menumpas Kanker. Jakarta: Agro Media Pustaka.
Zou, W., Feng, R., & Yong, Y. 2018. Changes in The Serum Levels of Inflammatory Cytokines in Antidepressant Drug-Naïve Patients with Major Depression. PLoS ONE, 13(6): e0197267.
Alasiry, E. 2012. Buku Indonesia Menyusui. Retrieved from www.idai.or.id.
Amir L. 2014. ABM Clinical Protocol #4: Mastitis. Breastfeeding Medicine, 9(5): 239–243.
Anasari T., & Sumarni. 2014. Faktor-Faktor Yang Mempengaruhi Kejadian Mastitis di RSUD Prof. Dr. Margano Soekarjo Purwokerto. Jurnal Involusi Kebidanan, 4(7): 40-52.
Arican O., Aral M., Sasmaz S., & Ciragil P. 2005. Serum Levels of TNF-α, IFNµ, IL-6, IL-8, IL-12, IL-17, and IL-18 in Patients with Active Psoriasis and Correlation with Disease Severity. Mediators of Inflammation, 2005(5): 201561. DOI: https://doi.org/10.1155/MI.2005.273
Bauer, I., Gunther, I., Wheeler, T.T., Engelman, S., & Seyfert, H.M. 2015. Extracellular Milieu Grossly Alters Pathogenspecific Immune Response of Mammary Epithelial Cells. BMC Veterinary Research, 11: 172.
Chen. 2013. Alpinetin attenuates inflammatory responses by interfering toll-like receptor 4/ nuclear factor kappa B signaling pathway in lipopolysaccharide-induced mastitis in mice. International Immunipharmacology, 17(1): 26–32.
Choi, E.J., Kim, H.I., Kim, J.A., Kang, S.H., Park, D.J., Son, S.J., et al. 2015. The Herbal-Derived Honokiol and Magnolol Enhances Immune Response to Infection with Methicillin-Sensitive Staphylococcus Aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA). Applied Microbial and Cell Physiology, 99: 4387–4396.
Cushnie, T.P.T., & Lamb, A.J. 2005, Antimicrobial activity of avonoids. Int. J. Antimicrob. Agents, 26: 343–356.
Cowan, M.M. 1999. Plant products as antimicrobial agents. Clin. Micobiol. Rev., 12(4): 564 – 582.
Diacci, C., Laura, M. D., Bianchini, R., & Pinti, M. 2017. Label-Free Detection of Interleukin-6 Using Electrolyte Gated Organic Field Effect Transistors. Biointerphases, 12(5): 05F401
Dewi, Z.Y., Nur, A., & Hertriani, T. 2015. Efek antibakteri dan penghambatan bioï€ lm ekstrak sereh (Cymbopogon nardus l.) terhadap bakteri Streptococcus mutans. Majalah Kedokteran Gigi Indonesia, 1(2): 136–141.
Estela, K.M., Prameshinta, H.F., Dharmana, E., & Kridjamiatun, R.A. 2016. Efektifitas Ekstrak Daun Sirsak (Annona muricata) dalam Menurunkan Kadar TNF α dan Meningkatkan Kadar NO Uji Coba pada Mencit Swiss yang Diinokulasi Plasmodium berghei ANKA. Jurnal Kedokteran Brawijaya, 29(01): 39-42.
Fadel & Anwar. 2014. Antibacterial Efficacy of Variety Plants Against the Resistant Streptococcus which Cause Clinical Mastitis in Cows, AJPRHC, 5(1): 32-41.
Friska, Tetlana, & Trianna. 2017. Skrining Fitokimia dan Aktivitas Antibakteri Ekstrak Etanol Daun Sirsak (Annona muricata L.) pada Streptococcus mutans ATCC 35668. Majalah Kedokteran Gigi Indonesia, 3(1).
Fursova, K.K., Schchamikova, M.D., Loskutova, I.V., Shepelyakovskaya, A.O., Laman, A.G., Boutanaev, A.M., Sokolov, S.L., Artem’eva, O.A., Nikanova, D.A., Zinovieva, N.A., Brovko, F.A., Kim, Y., & Shin, O.S. 2018. Exotoxin Diversity of Staphylococcus Aureus Isolated from Milk of Cows with Subclinical Mastitis in Central Russia. Journal of Dairy Science, 101(5): 4325–4331. DOI: https://doi.org/ 10.3168/jds.2017-14074.
Goyal, R., Faiz, A., & Singhai, M. 2012. Evaluation of TNF-α and IL-6 levels in obese and non-obese diabetics: Pre- and postinsulin effects. North American Journal of Medical Sciences, 4(4): 180-184.
Han, Y., Ripley, B., Jerada, S., Naka, T., & Fujimoto, M. 2016. Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation. PLoS ONE, 11(4).
Hassan, SM. 2008. Antimicrobial activities of saponinrich guar meal extract poultry science. Doctoral Thesis. Texas: A & M University.
Ishartadiati, K. 2009. Peranan Tnf, Il-1, dan Il-6 pada Respon Imun Terhadap Protozoa. Surabaya: FK Universitas Wijaya Kusuma.
Jahanfar, S., Ng, C.J., & Teng, C.L. 2013. Antibiotics for mastitis in breastfeeding women. Cochrane Database of Systematic Reviews, 28(2): CD005458.
Kruspe, S., Meyer, C., & Ulrich. H. 2014. Chlorin E6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation. Molecular Therapy Nucleic Acids, 3(1): e143.
Lai, J.L., & Perg, Y.C. 2017. Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Ephithelial Cells. Mediators of Immflamation. 2017: 3082805.
Latifah, W. 2013. Uji Aktivitas Antioksidan Ekstrak Etanol Daun Sirsak (Annona Muricata L) Gugur. Master Thesis. Yogyakarta: Universitas Gadjah Mada.
Londok, J.J.M.R., & Mandey, J.S. 2014. Potensi Fitokimia dan Aktivitas Antimikroba Daun Sirsak (Annona muricata Linn.) Sebagai Kandidat Bahan Pakan Ayam Pedaging. Jurnal LPPM Bidang Sains dan Teknologi, 1(1).
Lutchmedial, M., Ramlal, R., Bridre, N., & Yen, I.C. 2014. Nutritional and Sensory Quality of Stirred Soursop (Annona Muricata L.) Yoghurt. International Journal of Food Sciences and Nutrition, 55(5): 407– 414.
Mardiana, L., & Ratnasari, J. 2011. Ramuan dan Khasiat Sirsak. Jakarta: Penebar Swadaya.
Maramis, R., Kaseke, M., & Tanudjadja, G.N. 2014. Gambaran Histologi Aorta Tikus Wistar dengan Diet Lemak Babi Setelah Pemberian Ekstrak Daun Sirsak (Annona muricata L.). Jurnal E-Biomedik (eBM), 2: 430–435.
Mulia, K., Krisanti, E., Maulana, T., & Dianursanti. 2015. Selective Polarity-Guided Extraction and Purification of Acetogenins in Annona Muricata L. Leaves. International Journal of Technology, 7: 1221–1227.
Oloyede, C. T., Akande F.B., & Oniya O.O. 2015. Moisture Dependent Physical properties of Sour-Sop (Annona Muricatal.) Seeds. CIGR Journal, 17(2): 185.
Putri, R.A., Sari, N.I, Supartono, & Mursiti, S. 2017. Lotion Ekstrak Daun Sirsak (Annona muricata L.) sebagai Antibakteri. Indonesian Journal of Chemical Science, 6(3).
Rahman, S., & Mustari. 2012. Uji efek antiinflamasi ekstrak etanol daun sirsak (Annona muricata Linn.) terhadap mencit (Mus musculus) jantan yang diinduksi dengan karagen. As-Syifaa Jurnal Farmasi. 4(1): 7-15.
Rajeswari, V., Gajalakshmi, S., & Vijayalakshmi, S. 2012. Phytochemical and Pharmacological Properties of Annona Muricata: A review. International Journal of Pharmacy and Pharmaceutical Science, 4(2): 3-6.
Rosmayanti, K. 2014. Uji Efektivitas Ekstrak Biji Sirsak (Annona Muricata L) Sebagai Larvasida pada Larva Aedes Aegypti Instar III/IV. Undergraduate Thesis. Jakarta: Universitas Islam Negeri Jakarta.
Samantha, K.W., Wennitz, O., Bruckmaier, R.M., & Schwartz, D. 2018. Differential Somatic Cell Count in Milk Before, During, and After Lipopolysaccharide and Lipoteichoic-Acid-Induced Mastitis in Dairy Cows. Journal of Dairy Science, 101(6).
Sardi, D. 2009. Herbal Indonesia Berkhasiat. Depok: Trubus Swadaya.
Silva, E.M. 2017. High Systemic Il-6 Is Associated with Worse Prognosis in Patients with Non-Small Cell Lung Cancer. PLoS ONE, 12 (7).
Soekaryo, E., Setyahadi S., Simanjuntak P. 2017. Identifikasi Senyawa Aktif Fraksi Etanol Daun Sirsak (Annona Muricata Linn.) Sebagai Penghambat Siklooksigenase-2. The 5th Urecol Proceeding, 862-867
Soetan KO, Oyekunle MA, Aiyelaagbe OO, & Fafunso MA., 2006, Evaluation of the antimicrobial activity of saponins extract of sorghum bicolor l. moench. African J of Biotechnology, 5(23): 2405–2407.
Solomon-Wisdom, G., Ugoh, S., & Mohammed, B. 2014. Phytochemical screening and antimicrobial activities of Annona muricata (L) leaf extract. American Journal Biology Chemistry Pharmaceutical Sciences, 2(1): 1-7.
Sudira, I. W., Merdana, I., & Wibawa, I. 2011. Uji daya hambat ekstrak daun kedondong (Lannea Grandis Engl) terhadap pertumbuhan bakteri Erwinia carotovora. Buletin Veteriner Udayana, 3(1), 45-50.
Sugimoto, Y, 2015, Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers : A cross-sectional study., Gene, 557(2): 158–162.
Sugianto, I.S. 2012. Uji Fitokimia Ekstrak Pegagan (Centella asiatica) dan Buah Sirsak (Annona muricata L.) Serta Potensinya Sebagai Inhibitor Enzim Xantin Oksidase. Undergraduate Thesis. Malang: Universitas Negeri Malang
Swarnakar, A. 2014. Literary approach to Annona muticata and its role in cancer- A review. Int. Journal if Reasearch in Pharmacology & Pharmacotherapeutics, 3 (4).
Stauth, D. 2007. Studies Force New View on Biology of Flavonoids. Oregon: Oregon State University.
Taleb-Contini, S.H., Salvador, M.J., Watanabe, E., Ito, I.Y., & Oliveira, D.C.R. 2003. Antimicrobial activity of avonoids and steroids isolated from two chromolaena species. Braz J Pharm Sci, 39(4): 403–408.
Telez, A.V.C., Gonzalez, E.M., Yahia, E.M., Vazquez, E.N.O. 2016. Annona muricata: A Comprehensive Review on Its Traditional Medicinal Uses, Phytochemicals, Pharmacological Activities, Mechanisms of Action and toxicity. Arabian Journal of Chemistry,11(5): 662-691.
Wendy, V. I. 2014. Inflammatory Mediators in Mastitis and Lactation Insufficiency. J Mammary Gland Biol Neoplasia, 19: 161–167.
Zuhud, A.M. 2011. Bukti Kedahsyatan Sirsak Menumpas Kanker. Jakarta: Agro Media Pustaka.
Zou, W., Feng, R., & Yong, Y. 2018. Changes in The Serum Levels of Inflammatory Cytokines in Antidepressant Drug-Naïve Patients with Major Depression. PLoS ONE, 13(6): e0197267.