Sains Malaysiana 49(2)(2020): 389-397

http://dx.doi.org/10.17576/jsm-2020-4902-17

 

Ameliorative Effect of Etlingera calophrys (K.Schum.) Rhizome Ethanolic Extract on High Fat Diet-Induced Obese Zebrafish

(Kesan Memperbaikkan Ekstrak Etanol Rizom Etlingera calophrys (K.Schum.) pada Diet Teraruh Tinggi Lemak Ikan Belang Obes)

 

LOLY SUBHIATY IDRUS1, FAJAR FAKRI1, RIKA HARTATI2, VIENNA SARASWATY3 & I KETUT ADNYANA1*

 

1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institute of Technology Bandung, Bandung, Indonesia

 

2Department of Pharmaceutical Biology, School of Pharmacy, Institute of Technology Bandung, Bandung, Indonesia

 

3Research Unit for Clean Technology, Indonesian Institute of Sciences, Bandung, Indonesia

 

Diserahkan: 19 Ogos 2019/Diterima: 30 Oktober 2019

 

Abstract

Obesity is a major factor associated with inflammatory and various metabolic syndromes. Etlingera caloprhys, an Indonesia plant native from Southeast Sulawesi, is traditionally used years as daily food ingredient by local communities. The present paper presents an in vitro and in vivo study related to the anti-obesity effects of Etlingera caloprhys ethanol extract (ECEE). An experiment was conducted to evaluate in vitro pancreatic lipase enzyme (PLE) inhibition and in vivo anti-obesity activity in high fat diet (HFD) induced obese zebrafish fed with 10% w/w and 20% w/w ECEE-HFD were evaluated. To confirm anti-obesity activity, a set of obesity and biochemistry parameters i.e. body weight, body mass index (BMI), triglyceride and blood glucose levels, were monitored. Additionally, gene expression levels related to obesity i.e. adiponectin and PPARγ in visceral adipose tissue (VAT) were also evaluated. The results showed that ECEE significantly (p <0.05) inhibited PLE activity with an inhibition concentration (IC)50 of below 100 µg/mL. The HFD induced obese zebrafish fed with 10% w/w and 20% w/w ECEE-HFD showed decreasing body weight and BMI. The biochemistry parameters of the HFD-induced obese zebrafish fed with 10% w/w ECEE-HFD obviously displayed optimum reduction of triglycerides and blood glucose levels. More importantly, the gene expression confirmed that ECEE suppressed adipogenesis in VAT. Hence, ECEE is suggested as a potent alternative medicine for prevention of metabolic syndromes related to obesity.

 

Keywords: Anti-obesity; Etlingera calophrys; pancreatic lipase; zebrafish

 

Abstrak

Keobesan adalah faktor utama yang dikaitkan dengan radang dan pelbagai sindrom metabolisme. Etlingera calophrys, tumbuhan asli Indonesia dari Sulawesi Tenggara, secara tradisinya digunakan selama bertahun-tahun sebagai bahan makanan harian oleh masyarakat tempatan. Kertas ini membentangkan kajian secara in vitro dan in vivo yang berkaitan dengan kesan anti-keobesan daripada ekstrak etanol Etlingera calophrys (ECEE). Satu uji kaji telah dijalankan untuk menilai perencatan enzim lipase pankreas (PLE) dan aktiviti anti-keobesan secara in vivo dalam diet teraruh lemak tinggi (HFD) daripada ikan zebra obes yang diberi makan 10% w/w dan 20% w/w ECEE -HFD telah dinilai. Untuk mengesahkan aktiviti anti-keobesan, satu set keobesan dan parameter biokimia iaitu berat badan, indeks jisim badan (BMI), trigliserida dan paras glukosa darah telah dipantau. Selain itu, tahap ekspresi gen yang berkaitan dengan keobesan iaitu adiponektin dan PPARγ dalam tisu adipos visera (VAT) juga dinilai. Hasil kajian menunjukkan bahawa ECEE dengan ketara (p < 0.05) merencat aktiviti PLE dengan kepekatan perencatan (IC)50 di bawah 100 μg/mL. HFD teraruh ikan zebra obes diberi makan 10% w/w dan 20% w/w ECEE-HFD menunjukkan penurunan berat badan dan BMI. Parameter biokimia daripada HFD teraruh ikan zebra obes yang diberi makan 10% w/w ECEE-HFD jelas menunjukkan pengurangan optimum trigliserida dan paras glukosa darah. Lebih penting lagi, pengekspresan gen mengesahkan bahawa ECEE menghalang adipogenesis dalam VAT. Oleh itu, ECEE dicadangkan sebagai ubat alternatif yang mujarab untuk mencegah sindrom metabolik yang berkaitan dengan keobesan.

 

Kata kunci: Anti-keobesan; Etlingera calophrys; ikan zebra; lipase pancreas

 

RUJUKAN

Afshin, A., Forouzanfar, M.H. & Reitsma, M.B. 2017. Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine 377(1): 13-27.

Balaji, M., Ganjayi, M.S., Hanuma, G.E., Parim, B.N., Mopuri, R. & Dasari, S. 2016. A review on possible therapeutic targets to contain obesity: The role of phytochemicals. Obesity Research & Clinical Practice 10(4): 363-380.

Balsan, G.A., Vieira, J.L., Oliveira, A.M. & Portal, V.L. 2015. Relationship between adiponectin, obesity and insulin resistance. Revista da Associacao Medica Brasileira 61(1): 72-80.

Baqai, N. & Wilding, J.P.H. 2015. Pathophysiology and aetiology of obesity. Medicine 43(2): 73-76.

Buchholz, T. & Melzig, M.F. 2015. Polyphenolic compounds as pancreatic lipase inhibitors. Planta Medica 81(10): 771-783.

Cabezas, M.C., Klop, B. & Elte, J.W.F. 2013. Dyslipidemia in obesity: Mechanisms and potential targets. Nutrients 5(4): 1218-1240.

Caesar, L.K. & Cech, N.B. 2019. Synergy and antagonism in natural product extracts: When 1+1 does not equal 2. Natural Product Reports 36: 869-888.

Choi, B.K., Park, S.B., Lee, D.R., Lee, H.J., Jin, Y.Y., Yang, S.H. & Suh, J.W. 2016. Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice. Asian Pacific Journal of Tropical Medicine 9(7): 635-643.

Czech, M.P. 2017. Insulin action and resistance in obese and type 2 diabetes. Nature Medicine 23(7): 804-814.

Den Broeder, M.J., Kopylova, V.A., Kamminga, L.M. & Legler, J. 2015. Zebrafish as a model to study the role of peroxisome proliferating-activated receptors in adipogenesis and obesity. PPAR Research 358029: 1-11.

Grygiel-Gorniak, B. 2014. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications-A review. Nutrition Journal 13: 1-10.

Harper, C. & Lawrence, Z. 2011. The Laboratory Zebrafish. New York: Taylor and Francis Group.

Hossin, F.L.A. 2009. Effect of pomegranate (Punica gratum) peels and its extract on hypercholesterolemic rats. Pakistan Journal of Nutrition 8(8): 1251-1257.

Inoue, M., Ohtake, T., Motomura, W., Takahashi, N., Hosoki, Y., Miyoshi, S., Suzuki, Y., Saito, H., Kohgo, Y. & Okumura, T. 2005. Increased expression of PPAR-gamma in high fat diet-induced liver steatosis in mice. Biochemical and Biophysical Research Communications 336(1): 215-222.

Kalueff, A.V., Stewart, A.M. & Gerlai, R. 2014. Zebrafish as an emerging model for studying complex brain disorders. Trends in Pharmacological Sciences 35(2): 63-75.

Kersten, S. 2001. Mechanism of nutritional and hormonal regulation of lipogenesis. EMBO Reports 2(4): 282-286.

Klein, S. & Romijn, J.A. 2017. Williams Textbook of Endocrinology. 13th edition. California: Elsevier.

Kumar, S. & Alagawadi, K.R. 2013. Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats. Pharmaceutical Biology 51(5): 607-613.

Landgraf, K., Schuster, S., Meusel, A., Garten, A., Riemer, T., Schleinitz, D., Kies, W. & Korner, A. 2017.  Short-term overfeeding of zebrafish with normal or high-fat diet as a model for the development of metabolically healthy versus unhealthy obesity. BMC Physiology 17(4): 1-10.

Lei, F., Zhang, X.N., Wang, W., Xing, D.M., Xie, W.D., Su, H. & Du, L.J. 2007. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. International Journal of Obesity 31(6): 1023-1029.

Leibold, S. & Hammerschmidt, M. 2015. Long-term hyperphagia and caloric restriction caused by low- or high-density husbandry have differential effects on zebrafish postembryonic development, somatic growth, fat accumulation and reproduction. PLoS ONE 10(3): e0120776.

Lin, R.J., Yen, C.M., Chou, T.H., Chiang, F.Y., Wang, G.H., Tseng, Y.P., Wang, L., Huang, T.W., Wang, H.C., Chan, L.P., Ding, H.Y. & Liang, C.H. 2013. Antioxidant, anti-adipocyte differentiation, antitumor activity, and anthelmintic activities against Anisakis simplex and Hymenolepis nana of yakuchinone A from Alpinia oxyphylla. BMC Complementary Alternative Medicine 13: 237.

Meguro, S. & Takahiro, H. 2018. Fish oil suppresses body fat accumulation in zebrafish. Zebrafish 15(1): 27-32

Moreira, D.L., Teixeira, S.S., Monteiro, M.H.D., De-Oliveira, A.C.A.X. & Paumgartten, F.J.R. 2014. Traditional use and safety of herbal medicines. The Brazilian Journal of Pharmacognosy 24(2): 248-257.

Nakayama, H., Shimada, Y., Zang, L., Terasawa, M., Nishiura, K., Matsuda, K., Toombs, C., Langdon, C. & Nishimura, N. 2018. Novel anti-obesity properties of Palmaria mollis in zebrafish and mouse models. Nutrients 10(10): 1-16.

Neia, V.B.M.J.C., Albuquerque, E.P.A., Figueiredo, I.L., Silva, T.C., Lewandowski, V., Almeida, F.L.A., Ribeiro, R.P., Visentainer, J.E.L. & Visentainer, J.V. 2018. Effect of peanut addition to the cafeteria diet on adiposity and inflammation in zebrafish (Danio rerio). Food and Agricultural Immunology 29(1): 762-775.

Oka, T., Nishimura, Y., Zang, L., Hirano, M., Shimada, Y., Wang, Z., Umemoto, N., Kuronayagi, J., Nishimura, N. & Tanaka, T. 2010. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity. BMC Physiology 10(21): 1-13.

Park, K.S., Ciaraldi, T.P., Abrams-Carter, L., Mudaliar, S., Nikoulina, S.E. & Henry, R.R. 1997. PPAR-gamma gene expression is elevated in skeletal muscle of obese and type II diabetic subjects. Diabetes 46(7): 1230-1234.

Pucci, A. & Finer, N. 2015. New medications for treatment of obesity: Metabolic and cardiovascular effects. Canadian Journal of Cardiology 31(2): 142-152.

Redinger, R.N. 2007. The pathophysiology of obesity and its clinical manifestations. Gastroenterology & Hepatology 3(11): 856-863.

Ruslin & Sahidin, I. 2008. Identification and determination of traditional medicinal plants of Southeast Sulawesi People at Arboretum Prof. Mahmud Hamundu Haluoleo University (In Indonesian). Indonesian Journal of Pharmacy 19(2): 101-107.

Sahidin, Wahyuni, Muhammad Hajrul Malaka, Jabbar A., Imran. & Marianti A. Mangaau. 2018. Evaluation of antiradical scavenger activity of extract and compounds from Etlingera calophrys stems.  Asian Journal Pharmaceutical Clinical Research 11(2): 238-241.

Schlegel, A. 2016. Zebrafish models for dyslipidemia and atherosclerosis research. Frontiers in Endocrinology 7: 1-8.

Sikder, K., Shukla, S.K., Patel, N., Singh, H. & Rafiq, K. 2018. High fat diet upregulates fatty acid oxidation and ketogenesis via intervention of PPAR-γ. Cellular Physiology and Biochemistry 48(3): 1317-1331.

Storlien, L.H., James, D.E., Burleigh, K.M., Chisholm, D.J. & Kraegen, E.W. 1986. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. American Journal of Physiology 251(5): 576-583.

Tian, C., Ye, X., Zhang, R., Long, J., Ren, W., Ding, S., Liao, D., Jin, X., Wu, H., Xu, S. & Ying, C. 2013. Green tea polyphenols reduced fat deposits in high fat-fed rats via erk1/2-PPARc-adiponectin pathway. PLoS ONE 8(1): e53796.

Vroegrijk, I.O., van Diepen, J.A., van den Berg, S., Westbroek, I., Keizer, H., Gambelli, L., Hontecillas, R., Bassaganya-Riera, J., Zondag, G.C., Romijn, J.A., Havekes, L.M. & Voshol, P.J. 2011. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. Food and Chemical Toxicology 49(6): 1426-1430.

World Health Organization. 2014. Obesity and Overweight. Fact sheet No. 311. Geneva, Switzerland.

Yang, M.H., Chin, Y.W., Yoon, K.D. & Kim, J.W. 2014. Phenolic compounds with pancreatic lipase inhibitory activity from Korean yam (Dioscorea opposita). Journal of Enzyme Inhibition Medicinal Chemistry 29(1): 1-6.

Yuniarto, A., Sukandar, E.Y., Fidrianny, I., Setiawan, F. & Adnyana, I.K. 2018. Antiobesity, antidiabetic, and antioxidant activities of Senna (Senna alexandrina Mill) and pomegranate (Punica gratum L.) leaves extracts and its fractions. International Journal of Pharmaceutical and Phytopharmacological Research 8(3): 18-24.

Zang, L., Maddison, L.A. & Chen, W. 2018. Zebrafish as a model for obesity and diabetes. Frontiers in Cell and Developmental Biology 6: 1-13.

Zang, L., Shimada, Y., Kawajiri, J., Tanaka, T. & Nishimura, N. 2014. Effects of yuzu (Citrus junos Siebold ex Tanaka) peel on the diet-induced obesity in a zebrafish model. Journal of Functional Foods 10: 499-510.

Zhou, J., Xu, Y.Q., Guo, S.Y. & Li, C.Q. 2015. Rapid analysis of hypolipidemic drugs in a live zebrafish assay. Journal of Pharmacological and Toxicological Methods 72: 47-52.

 

*Pengarang untuk surat-menyurat; email: ketut@fa.itb.ac.id

 

 

 

 

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