Hepatoprotective and Antifibrotic Effects of Indonesian Propolis

Diding Heri Prasetyo, Sarsono Sarsono, Ida Nurwati, Prihandjojo Andri Putranto, Martini Martini, Nabila Aushaf Prasetyo

Abstract


Liver cirrhosis is the irreversible stage in liver damage process which occurs after liver fibrosis due to necro-inflammatory activities and liver fibrosis. Therefore, inhibition of liver inflammation and fibrosis is very important to prevent liver cirrhosis. This study aimed to analyze the effect of ethanol extract of propolis (EEP) from mount Lawu, Indonesia to prevent liver damage and fibrosis progression in mice with hepatic cirrhosis. This study was performed during the period of June 2018 to May 2019 on a sample of 32 male Balb/C mice divided into control group (P1), induction of carbon tetrachloride (CCl4 ) group (P2), induction of 50 mg/BW CCl4 + EEP group (P3), and (induction of 100 mg/KgBW CCl4 + EEP (P4) with each group consisted of eight mice. The CCl4 in olive oil was administered intraperitoneally three times a week for six weeks. Mean differences between group was determined using ANOVA test with a significance level of 0.05. The induction of CCl4 increased liver cell damage and serum alanin aminotransferase (ALT) level. However, the addition of EEP significantly (p<0.001) reduced liver cell damage as seen in P3 (54.38±4.17 per 100 liver cells) and P4 (37.13±4.36 per 100 liver cells) groups and serum alanin aminotransferase (ALT) as seen in P3 (291.19±113.92 U/L) and P4 (229.38±73.45 U/L) groups. The APRI scores were also reduced after EEP as seen in P3 (0.738±0.292) and P4 (0.513±0.253) groups. Thus, EEP isolates from Gunung Lawu can reduce liver cell damage and fibrosis in mice model of hepatic cirrhosis.

 

Efek Hepatoprotektif dan Antifibrotik Propolis Indonesia

Sirosis hati (SH) merupakan tahap ireversibel dalam proses kerusakan hati yang terjadi setelah fibrosis hati sebagai hasil aktivitas nekroinflamasi dan fibrosis hati. Oleh karena itu, penghambatan inflamasi hati dan fibrosis sangat penting untuk mencegah terjadi SH. Penelitian ini bertujuan menganalisis efek ekstrak etanol isolat propolis (EEP) gunung Lawu dalam mencegah progresifitas kerusakan dan fibrosis hati pada mencit model SH. Penelitian dilakukan di Laboratorium Histolgis Fakultas Kedokteran Universitas Sebelas Maret Surakarta dan Lembaga Penelitian dan Pengujian Terpadu (LPPT) Universitas Gajah Mada Yogyakarta . Penilitian ini dilakukan periode Juni 2018 sampai Mei 2019, dengan sampel 32 ekor mencit Balb/C jantan dibagi menjadi kelompok (P1) kontrol negatif, (P2) induksi karbon tetraklorida (CCl4 ), (P3) induksi CCl4 +EEP dosis 50 mg.kgBB-1, dan (P4) induksi CCl4 +EEP dosis 100 mg.kgBB-1, dengan tiap-tiap sampel terdiri dari delapan ekor mencit Balb/C jantan. CCl4 dalam minyak zaitun diberikan pada tikus Balb/C tiga kali seminggu selama enam minggu secara intraperitoneal. Uji ANOVA digunakan untuk menentukan perbedaan rata-rata antar kelompok dengan tingkat kemaknaan sebesar 0,05. Namun, penambahan EEP secara signifikan (p<0,001) menurunkan tingkat kerusakan sel hati seperti yang terlihat pada P3 (54,38±4,17 per 100 sel hati) dan kelompok P4 (37,13±4,36 per 100 sel hati) dan serum alanin aminotransferase (ALT) seperti yang terlihat dalam kelompok P3 (291,19±113,92 U / L) dan P4 (229,38±73,45 U / L). Hasil skor APRI menunjukkan kelompok P1(0,213±0,113) dan P2 (0,863±0,534), EEP dapat menurunkan skor APRI pada kelompok P3 (0,738±0,292) dan P4 (0,513±0,253). Simpulan, EEP isolat Gunung Lawu menurunkan tingkat kerusakan sel hati dan fibrosis pada mencit model SH.


Keywords


ALT; APRI score; liver cirrhosis; liver damage; propolis

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References


Kamath PS and Shah VH. Overview of Cirrhosis. In: Feldman M, Friedman LS and Brandt LJ, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease.10th ed. Philadelphia: Saunders Inc; 2016.p.1254-1260.

Islam A, Al Mamun A, Faruk, Ul Islam T, Rahman M, Alam MN, et al. Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon Tetrachloride-administered Rats. Pharmacognosy Res. 2017; 9(Suppl 1):S84-S91.

Aydin MM and Akcali KC. Liver fibrosis. Turk J Gastroenterol. 2018; 29(1):14-21.

Jain P, Tripathi BK, Gupta B, Bhandari B, Jalan D. Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis. J Clin Diagn Res. 2015; 9(11):OC22-4

Tolba MF, Omar HA, Azab SS, Khalifa AE, Abdel-Naim AB, Abdel-Rahman SZ.Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.Crit Rev Food Sci Nutr. 2016; 56(13):2183-90.

Bezerra RM, Veiga LF, Caetano AC, Rosalen PL, Amaral ME, Palanch AC, et al. Caffeic acid phenethyl ester reduces the activation of the nuclear factor κB pathway by high-fat diet-induced obesity in mice. Metabolism. 2012; 61(11):1606-14.

Bankova V, Popova M and Trusheva B. Propolis volatile compounds: chemical diversity and biological activity: a review. Chem Cent J. 2014; 8:28.

Sarsono, Syarifah I, Martini, Diding HP. Identifikasi caffeic acid phenethyl ester dalam ekstrak etanol propolis isolat gunung lawu. Jurnal Bahan Alam Indonesia. 2012; 8(2):132-6.

Indrayanto I, Diding HP, Sarsono. Ekstrak Etanol Propolis Menurunkan High-Mobility Group Box 1Mencit Model Infertilitas Jantan. Jurnal Bahan Alam Indonesia. 2013; 8(6):395-98.

Susanto A, Purwanto B, Mudigdo A, Suroto. Indonesian Propolis Extract attenuates Unilateral Ureteral Obstruction Induced Renal Damage by Reducing Oxidative Stress and Blood Pressure. IJPCR. 2017; 9(6): 430-434.

Susanto A, Purwanto B, Mudigdo A, Suroto. Antihypertensive and Superoxide Dismutase Effect of Indonesian Propolis extract in Kidney Damage. IJCAR. 2017; 6(10):6472-6475.

Elgawish RAR, Rahman HGA,Abdelrazek HMA. Green tea extract attenuates CCl4-induced hepatic injury in male hamsters via inhibition of lipid peroxidation and p53-mediated apoptosis.Toxicology Reports. 2015; 2:1149–1156.

Yanguas SC, Cogliati B, Willebrords J, Maes M, Colle I, Bossche B, et al. Experimental models of liver fibrosis. Arch Toxicol. 2016; 90(5):1025-1048.

Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011; 53(3):726-36.

El-Bini, Dhouib I, Lasram MM, Annabi A, Gharbi N, El-Fazaa S. A comparative study on toxicity induced by carbosulfan and malathion in Wistar rat liver and spleen. Pestic. Biochem. Pestic Biochem Physiol. 2015; 124:21-8.

Xuan J, Chen S, Ning B, Tolleson WH, Guo L. Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity. Chem Biol Interact. 2016; 255:63-73.

Liang B, Xiao-Ling G, Jin J, Yong-Chun M, Zheng-Quan F. Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury. World J Gastroenterol. 2015; 21(17):5271-80.

Khan RA, Khan MR, and Sahreen S. CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat. BMC Complement Altern Med. 2012; 12:178.

Li M, Xiu-Fang W, Juan-Juan S, Ya-Ping L, Yang N, Zhai S and Shuang-Suo D. Caffeic acid phenethyl ester inhibits liver fibrosis in rats. World J Gastroenterol. 2015; 21(13):3893-903.




DOI: https://doi.org/10.15395/mkb.v51n3.1768

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