Indonesian Propolis Inhibit Proinflammatory Cytokines, Apoptosis and Oxidative Stress in Anthrax Animal Model

Ratih Tri Kusuma Dewi, Dhani Redhono, Agung Susanto, Diding Heri Prasetyo, Evi Nurhayatun, Ida Nurwati, Bambang Purwanto

Abstract


BACKGROUND: Anthrax is a zoonotic disease caused by Bacillus anthracis, whose endospores stimulate the release of pro-inflammatory cytokines and promote oxidative stress. Propolis, a natural resource that can be found in Indonesia, has been proven to have anti-apoptotic and antioxidant role which might be a potential adjuvant therapy for anthrax treatment. Hence in this study we aimed to investigate effect of propolis as an anti-inflammatory, anti-apoptotic, and antioxidant in anthrax rats model by examining the level of tumor necrosis factor (TNF)-α, caspase-3, and malondialdehyde (MDA), respectively.

METHODS: This was an experimental post-test only study with 40 male rats weighed 180-200 g that were induced by anthrax spores injected subcutaneously. The rats were divided into one control positive group and four intervention groups that were administered with 200 mg/kgBW propolis extract for 7 to 14 days. The levels of serum TNF-α, caspase-3, and MDA were measured using enzyme-linked immunosorbent assay (ELISA) and analyzed with bivariate analysis.

RESULTS: TNF-α, caspase-3, and MDA level were found lower in anthrax rats model given ethanol extract of propolis than the control group. The lowest concentration of TNF-α value was found in group administered with propolis extract 200 mg/kgBW for 7 days before the anthrax induction (6.136±0.205 pg/mL). The results were similar to the MDA serum and caspase-3 which were the lowest when the propolis was administered 7 days earlier (1.893±0.188 nmol/mL and 2.040±0.067 ng/mL). There was significant difference in the TNF-α, caspase-3, and MDA serum levels (p≤0.001) compared to control group.

CONCLUSION: Propolis has anti-apoptotic and antioxidant effects which can be used as complementary therapy in anthrax infection.

KEYWORDS: propolis, anthrax, anti-apoptotic, antioxidants


Full Text:

PDF

References


Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Philadelphia: Elsevier; 2020, NLMID.

Olani A, Dawo, F, Lakew M. Laboratory diagnostic methods and reported outbreaks of anthrax in Ethiopia. Eur J Biol Res. 2020; 10(2): 81-95, article.

Islami R, Zahra SF, Yuniastuti P, Pranata PEA, Sefi M, Widianingrum DC. Pengetahuan, kebijakan, dan pengendalian penyakit antraks pada ternak di Indonesia. J Peternak Sriwij. 2021; 10(2): 1-8, article.

Savransky V, Ionin B, Reece J. Current status and trends in prophylaxis and management of anthrax disease. Pathogens. 2020; 9(5): 370, CrossRef.

Jeon JH, Kim YH, Choi MK, Kim KA, Lee HR, Jang J, et al. Bacillus anthracis genomic DNA enhances lethal toxin-induced cytotoxicity through TNF-αproduction. BMC Microbiol. 2014; 14: 300, CrossRef.

Cherian D, Peter T, Narayanan A, Madhavan S, Achammada S, Vynat G. Malondialdehyde as a marker of oxidative stress in periodontitis patients. J Pharm Bioallied Sci. 2019; 11(6): S297-300, CrossRef.

Febriza A, Ridwan, As’ad S, Kasim VN, Idrus HH. Adiponectin and its role in inflammatory process of obesity. Mol Cell Biomed Sci. 2019; 3(2): 60-6, CrossRef.

Xie T, Auth RD, Frucht DM. The effects of anthrax lethal toxin on host barrier function. Toxins (Basel). 2011; 3(6): 591-607, CrossRef.

Coggeshall KM, Lupu F, Ballard J, Metcalf JP, James JA, Farris D, et al. The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax. J Cell Mol Med. 2013; 17(7): 914-20, CrossRef.

Rossiter SE, Fletcher MH, Wuest WM. Natural products as platforms to overcome antibiotic resistance. Chem Rev. 2017; 117(19): 12415-74, CrossRef.

Bankova V, Popova M, Bogdanov S, Sabatini AG. Chemical composition of European propolis: expected and unexpected results. Zeitschrift für Naturforsch C. 2002; 57(5-6): 530-3, CrossRef.

Lotfy M. Biological activity of bee propolis in health and disease. Asian Pac J Cancer Prev. 2006; 7(1): 22-31, PMID.

Nurhayati B, Rahayu IG, Rinaldi SF, Zaini WS, Afifah E, Arumwardana S, et al. The antioxidant and cytotoxic effects of Cosmos caudatus ethanolic extract on cervical cancer. Indones Biomed J. 2018; 10(3): 243-9, CrossRef.

Kusumawardani A, Kariosentono H, Purwanto B, Redhono D, Arief RC, Wasita B, et al. The effect of ethanolic extract of propolis on skin manifestation and skin tissue necrosis in cutaneous anthrax animal model. Syst Rev Pharm. 2020; 11(11): 1539-44, article.

Diding HP, Martini, Ipop S, Sarsono. Identifikasi caffeic acid phenethyl ester dalam ekstrak etanol propolis isolat gunung lawu. J Bahan Alam Indones. 2012; 8(2): 132-6, article.

Parawansah P, Nuralifah N, Alam G, Natzir R. Inhibition of xanthine oxidase activity by ethanolic extract of Piperomia pellucida L., Acacypha indica L. and Momordica charantia L. Indones Biomed J. 2016; 8(3): 161-6, CrossRef.

Ketherin, Sandra F. Osteoclastogenesis in periodontitis: Signaling pathway, synthetic and natural inhibitors. Mol Cell Biomed Sci. 2018; 2(1): 11-8, CrossRef.

Scobie HM, Wigelsworth DJ, Marlett JM, Thomas D, Rainey GJA, Lacy DB, et al. Anthrax toxin receptor 2–dependent lethal toxin killing in vivo. PLoS Pathog. 2006; 2(10): e111, CrossRef.

Ecem Bayram N, Gercek YC. Appropriate maceration duration for the extraction of propolis. Fresenius Environ Bull. 2019; 28(1): 188-92, article.

Trusheva B, Trunkova D, Bankova V. Different extraction methods of biologically active components from propolis: a preliminary study. Chem Cent J. 2007;1(1): 13, CrossRef.

Triyono EA, Firdausa S, Prasetyo H, Susanto J, Hutagalung J, Masyfufah L, et al. The effects of propolis extract administration on HIV patients receiving ARV. Indones Biomed J. 2021; 13(1): 75-83, CrossRef.

Hasan AEZ, Sunarti DMTC, Suparno O, Setiyono A. Ekstraksi propolis menggunakan cara maserasi dengan pelarut etanol 70% dan pemanasan gelombang mikro serta karakterisasinya sebagai bahan antikanker payudara. J Teknol Ind Pertan. 2013; 23(1): 13-21, article.

Hastuti RD, Diding HP, Hartati S. Perbedaan kadar caffeic acid phenethyl ester antara propolis yang diekstraksi dengan etanol dan air. Nexus Biomedika. 2013; 2(2): 43-7, article.

Prasetyo DH, Suparyanti EL, Guntur AH. Ekstrak etanol propolis isolat menurunkan derajat inflamasi dan kadar malondialdehid pada serum tikus model sepsis. Maj Kedokt Bandung. 2013; 45(3): 161-6, CrossRef.

Chang H, Wang Y, Yin X, Liu X, Xuan H. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy. BMC Complement Altern Med. 2017 ;17(1): 471, CrossRef.

Ellenbroek B, Youn J. Rodent models in neuroscience research: is it a rat race? Dis Model Mech. 2016; 9(10): 1079-87, CrossRef.

Goossens PL. Animal models of human anthrax: the Quest for the Holy Grail. Mol Aspects Med. 2009; 30(6): 467-80, CrossRef.

Harioputro DR, Sanjaya W, Werdiningsih Y. Comparison of propolis effects on tumor necrosis factor alpha and malondialdehyde between inhalation and cutaneous anthrax animal models. African J Infect Dis. 2022; 16(1): 1-5, CrossRef.

Pickering AK, Merkel TJ. Macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular Bacillus anthracis spores. Infect Immun. 2004; 72(5): 3069-72, CrossRef.

Wu J, Omene C, Karkoszka J, Bosland M, Eckard J, Klein CB, et al. Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer. Cancer Lett. 2011; 308(1): 43-53, CrossRef.

Nani BD, Sardi J de CO, Lazarini JG, Silva DR, Massariolli AP, Cunha TM, et al. Anti-inflammatory and anti-Candida effects of Brazilian organic Propolis, a promising source of bioactive molecules and functional food. J Agric Food Chem. 2019; 68(10): 2861-71, CrossRef.

Korish AA, Arafa MM. Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock. Brazilian J Infect Dis. 2011; 15(4): 332-8, CrossRef.

Fatahinia M, Khosravi AR, Shokri H. Propolis efficacy on TNF-α, IFN-γ and IL2 cytokines production in old mice with and without systemic candidiasis. J Mycol Med. 2012; 22(3): 237-42, CrossRef.

Shang H, Bhagavathula AS, Aldhaleei WA, Rahmani J, Karam G, Rinaldi G, et al. Effect of propolis supplementation on C-reactive protein levels and other inflammatory factors: A systematic review and meta-analysis of randomized controlled trials. J King Saud Univ. 2020; 32(2): 1694-701, CrossRef.

Sameni HR, Ramhormozi P, Bandegi AR, Taherian AA, Mirmohammadkhani M, Safari M. Effects of ethanol extract of propolis on histopathological changes and anti‐oxidant defense of kidney in a rat model for type 1 diabetes mellitus. J Diabetes Investig. 2016; 7(4): 506-13, CrossRef.

Wiwekowati W, Maâ MT, Walianto S, Sabir A, Widyadharma IPE. Indonesian propolis reduces malondialdehyde level and increase osteoblast cell number in wistar rats with orthodontic tooth movement. Open Access Maced J Med Sci. 2020; 8(A): 100-4, CrossRef.

Soleimani D, Miryan M, Tutunchi H, Navashenaq JG, Sadeghi E, Ghayour‐Mobarhan M, et al. A systematic review of preclinical studies on the efficacy of propolis for the treatment of inflammatory bowel disease. Phyther Res. 2021; 35(2): 701-10, CrossRef.

Sudrajad H, Mudigdo A, Purwanto B, Setiamika M. Ethanol extract of propolis decreases the Interleukin-8 (IL-8) expression and blood Malondialdehyde (MDA) level in otitis media rat model induced by Pseudomonas aeruginosa. Bali Med J. 2020; 9(2): 504-10, CrossRef.

Trumbeckaite S, Pauziene N, Trumbeckas D, Jievaltas M, Baniene R. Caffeic acid phenethyl ester reduces ischemia-induced kidney mitochondrial injury in rats. Oxid Med Cell Longev. 2017; 2017: 1697018, CrossRef.

Lossi L, Castagna C, Merighi A. Caspase-3 mediated cell death in the normal development of the mammalian cerebellum. Int J Mol Sci. 2018; 19(12): 3999, CrossRef.




DOI: https://doi.org/10.18585/inabj.v14i3.1873

 

Indexed by:

                  

               

                 

 

 

The Prodia Education and Research Institute