Sains Malaysiana 52(9)(2023): 2559-2569

http://doi.org/10.17576/jsm-2023-5209-07

 

Antihyperlipidemic and Hepatoprotective Effect of Zingiber cassumunar Rhizome Extract in High-Fat Diet-Induced Hyperlipidemic Rats: The Role of Antioxidant Activity

(Kesan Antihiperlipidemik dan Hepatopelindung Ekstrak Rizom Zingiber cassumunar pada Tikus Hiperlipidemik Disebabkan Diet Tinggi Lemak: Peranan Aktiviti Antioksidan)

 

NURKHASANAH  MAHFUDH1,*,  NANIK SULISTYANI1,  NOVITA SARI1, INDAH PUSPITA SARI1, DEDI ADRIAN1, FEZAH OTHMAN2 & ZAINUL AMIRUDDIN ZAKARIA3

 

1Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia

2Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

3Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia

 

Diserahkan: 12 November 2022/Diterima: 16 Ogos 2023

 

Abstract

Hyperlipidemia and oxidative stress are major risk factors for the onset of cardiovascular diseases, and the oxidative stress caused by high level of lipids can cause liver damage. Zingiber cassumunar has been reported to contain a high antioxidant content that may provide therapeutic advantages. The present study was to evaluate the antihyperlipidemic and hepatoprotective effects of Z. cassumunar rhizome extract (ZCRE) in high-fat diet (HFD)-induced hyperlipidemicrats model and investigate the mechanism through its effect on the endogenous antioxidant enzymes. In this study, the rhizomes of Z. cassumunar was extracted using ethanol 96% (v/v) and evaporated to get the concentrated Z. cassumunar rhizome extract (ZCRE). Thin layer chromatography (TLC)-densitometry was performed to determine the curcumin content in the extract. High fat diet-induced hyperlipidemia model was used to evaluate the anti-hyperlipidemic and hepatoprotectiveactivities of ZCRE in rats. Male Wistar rats were randomly divided into five groups: normal control; High fat diet-induced hyperlipidemic rats (HFD); High Fat Diet and 100 mg/kgBW of ZCRE (HFD + 100 mg/kgBW); High Fat Diet and 200 mg/kgBW of ZCRE (HFD + 200 mg/kgBW); and High Fat Diet and 400 mg/kgBW of ZCRE (HFD + 400 mg/kgBW). The antihyperlipidemic and hepatoprotective potential of ZCRE were assessed through a series of analyses of body weight, blood biochemical parameters, which include total cholesterol (TC), triglycerides (TG), the serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The antioxidant activity of catalase (CAT) and glutation peroxidase (GSH-Px) were assessed on the liver homogenate. Data of the study were presented as mean ± SD and analyzed by using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test for multiple comparisons. The TLC analysis showed that ZCRE contained a significant amount of Curcumin. In addition, the study has also shown that ZRCE was able to significantly lower the levels of total cholesterol, triglyceride, SGPT, and SGOT as compared to hyperlipidemic rats (p <0.05). Concomitantly, the activity of CAT and GSH-Px was found significantly increased (p <0.05) when compared to hyperlipidemic control, with the dose of 400 mg/kg BW being the most effective. This study showed the significant antihyperlipidemic and hepatoprotective effects of ZCRE in HFD-induced hyperlipidemic rats, which mechanism might possibly connect to the increased antioxidant enzyme activities.

 

Keywords: Antihyperlipidemic; antioxidant enzymes; catalase (CAT); glutathione peroxidase (GSH-Px); hepatoprotective; Zingiber cassumunar

 

Abstrak

Hiperlipidemia dan tekanan oksidatif adalah faktor risiko utama untuk permulaan penyakit kardiovaskular dan tekanan oksidatif yang disebabkan oleh tahap lipid yang tinggi boleh menyebabkan kerosakan hati. Zingiber cassumunar telah dilaporkan mengandungi kandungan antioksidan yang tinggi yang mungkin memberikan kelebihan terapeutik. Kajian ini adalah untuk menilai kesan antihiperlipidemik dan hepatopelindung ekstrak rizom Z. cassumunar (ZCRE) pada model tikus hiperlipidemik akibat diet tinggi lemak (HFD) dan mengkaji mekanisme melalui kesannya ke atas enzim antioksidan endogen. Dalam kajian ini, rizom Z. cassumunar diekstrak menggunakan etanol 96% (v/v) dan disejat untuk mendapatkan ekstrak rizom Z. cassumunar pekat (ZCRE). Kromatografi lapisan nipis (TLC)-densitometri telah dijalankan untuk menentukan kandungan kurkumin dalam ekstrak. Model hiperlipidemia yang disebabkan oleh diet lemak tinggi digunakan untuk menilai aktiviti anti-hiperlipidemik dan hepatopelindung ZCRE pada tikus. Tikus Wistar jantan dibahagikan secara rawak kepada lima kumpulan: kawalan normal; Tikus hiperlipidemik (HFD) akibat diet tinggi lemak; Diet Tinggi Lemak dan 100 mg/kgBW ZCRE (HFD + 100 mg/kgBW); Diet Tinggi Lemak dan 200 mg/kgBW ZCRE (HFD + 200 mg/kgBW); dan Diet Tinggi Lemak dan 400 mg/kgBW ZCRE (HFD + 400 mg/kgBW). Potensi antihiperlipidemik dan hepatopelindung ZCRE dinilai melalui satu siri analisis berat badan, parameter biokimia darah yang termasuk jumlah kolesterol (TC), trigliserida (TG), serum glutamik-oksaloasetik transaminase (SGOT) dan serum glutamik-piruvik transaminase (SGPT). Aktiviti antioksidan katalase (CAT) dan glutation peroksidase (GSH-Px) dinilai pada homogenat hati. Data kajian dibentangkan sebagai min ± SD dan dianalisis dengan menggunakan analisis varians sehala (ANOVA) diikuti dengan ujian Perbezaan Ketara (LSD) untuk pelbagai perbandingan. Analisis TLC menunjukkan bahawa ZCRE mengandungi sejumlah besar Curcumin. Di samping itu, kajian juga telah mendedahkan bahawa ZRCE mampu menurunkan paras jumlah kolesterol, trigliserida, SGPT dan SGOT dengan ketara berbanding tikus hiperlipidemik (p <0.05). Pada masa yang sama, aktiviti CAT dan GSH-Px didapati meningkat dengan ketara (p <0.05) jika dibandingkan dengan kawalan hiperlipidemik dan dos 400 mg/kg BW adalah yang paling berkesan. Kajian ini menunjukkan kesan antihiperlipidemik dan hepatopelindung ZCRE yang ketara pada tikus hiperlipidemik yang disebabkan oleh HFD, yang mekanismenya mungkin bersambung dengan peningkatan aktiviti enzim antioksidan.

 

Kata kunci: Antihiperlipidemik; enzim antioksidan; katalase (CAT); glutation peroksidase (GSH-Px); hepatopelindung; Zingiber cassumunar

 

RUJUKAN

Adhila, G., Nurkhasanah, N. & Sulistyani, N. 2019. In vitro immunomodulatory activity test of Bengle rhizoma extract (Zingiber cassumunar Roxb.): Phagocytic activity of macrophages and lymphocyte proliferation in mice. Pharmaciana 9(2): 211-218. https://doi.org/10.12928/pharmaciana.v9i2.12881

Amiya, E. 2016. Interaction of hyperlipidemia and reactive oxygen species: Insights from the lipid-raft platform. World J. Cardiol. 8: 689. https://doi.org/10.4330/wjc.v8.i12.689

Barkas, F., Nomikos, T., Liberopoulos, E. & Panagiotakos, D. 2020. Diet and cardiovascular disease risk among individuals with familial hypercholesterolemia: Systematic review and meta-analysis. Nutrients 12: 1-22. https://doi.org/10.3390/nu12082436

Bhuiyan, M.N.I., Chowdhury, J.U. & Begum, J. 2008. Volatile constituents of essential oils isolated from leaf and rhizome of Zingiber cassumunar Roxb. Bangladesh Journal of Pharmacology 3(2): 69-73. https://doi.org/10.3329/bjp.v3i2.844

Borza, C., Borza, C., Muntean, D., Dehelean, C., Săvoiu, G., Şerban, C., Simu, G., Andoni, M., Butur, M. & Drăgan, S. 2013. Oxidative stress and lipid peroxidation - A lipid metabolism dysfunction. Lipid Metabolism. IntechOpen. pp: 23-38 https://doi.org/10.5772/51627

Cuomo, J., Appendino, G., Dern, A.S., Schneider, E., McKinnon, T.P., Brown, M.J., Togni, S. & Dixon, B.M. 2011. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J. Nat. Prod. 74: 664-669. https://doi.org/10.1021/np1007262

Dei Cas, M. & Ghidoni, R. 2019. Dietary curcumin: Correlation between bioavailability and health potential. Nutrients 11: 2147. https://doi.org/10.3390/nu11092147

Gadde, K.M., Martin, C.K., Berthoud, H.R. & Heymsfield, S.B. 2018. Obesity: Pathophysiology and management. J. Am. Coll. Cardiol. 71: 69-84. https://doi.org/10.1016/j.jacc.2017.11.011

Gusti, A.M.T., Qusti, S.Y., Alshammari, E.M., Toraih, E.A. & Fawzy, M.S. 2021. Antioxidants-related superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-s-transferase (GST), and nitric oxide synthase (NOS) gene variants analysis in an obese population: A preliminary case-control study. Antioxidants 10(4): 595. https://doi.org/10.3390/antiox10040595

Halliwell, B. 2015. Antioxidant and Anti-Inflammatory Components of Foods. Belgium: ILSI Europe. https://ilsi.eu/publication/antioxidant-and-anti-inflammatory-components-of-foods/

Han, A.R., Kim, H., Piao, D., Jung, C.H. & Seo, E.K. 2021. Phytochemicals and bioactivities of Zingiber cassumunar roxb. Molecules 26: 1-18. https://doi.org/10.3390/molecules26082377

Harikumar, K., Althaf, A.S. & Kumar, K.B. 2013. Review of hyperlipidemic. Int. J. Nov. Trends Pharm. Sci. 3(4): 59-71.

Hariri, N. & Thibault, L. 2010. High-fat diet-induced obesity in animal models. Nutr. Res. Rev. 23: 270-299. https://doi.org/10.1017/S0954422410000168

Hegde, M., Girisa, S., BharathwajChetty, B., Vishwa, R. & Kunnumakkara, A.B. 2023. Curcumin formulations for better bioavailability: What we learned from clinical trials thus far? ACS Omega 8: 10713-10746. https://doi.org/10.1021/acsomega.2c07326

Ibrahim, J., Kabiru, A.Y., Abdulrasheed-Adeleke, T., Lawal, B. & Adewuyi, A.H. 2020. Antioxidant and hepatoprotective potentials of curcuminoid isolates from turmeric (Curcuma longa) rhizome on CCl4-induced hepatic damage in Wistar rats. J. Taibah Univ. Sci. 14: 908-915. https://doi.org/10.1080/16583655.2020.1790928

Ihwah, A., Deoranto, P., Wijana, S. & Dewi, I. 2018. Comparative study between Federer and Gomez method for number of replication in complete randomized design using simulation: study of Areca Palm (Areca catechu) as organic waste for producing handicraft paper. IOP Conf. Ser. Earth Environ. Sci. 131: 012049. https://doi.org/doi :10.1088/1755-1315/131/1/012049

Joram, A., Das, A.K. & Mahanta, D. 2018. Evaluation of antioxidant and phenolic contents of Zingiber montanum (J. Koenig) Link ex Dietr.: A potential ethomedicinal plant of Arunachal Pradesh, India. Pleione 12: 255-264. https://doi.org/10.26679/Pleione.12.2.2018

Karam, I., Yang, Y.J. & Li, J.Y. 2017. Hyperlipidemia background and progress. SM Atheroscler. J. 1(1): 1003.

Kim, M. & Kim, Y. 2010. Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr. Res. Pract. 4(3): 191-195. https://doi.org/10.4162/nrp.2010.4.3.191

Kumar, D., Dwivedi, D.K., Lahkar, M. & Jangra, A. 2019. Hepatoprotective potential of 7,8-Dihydroxyflavone against alcohol and high-fat diet induced liver toxicity via attenuation of oxido-nitrosative stress and NF-κB activation. Pharmacol. Reports 71: 1235-1243. https://doi.org/10.1016/j.pharep.2019.07.002

Kumar, V., Khan, A.A., Tripathi, A., Dixit, P.K. & Bajaj, U.K. 2015. Role of oxidative stress in various diseases: Relevance of dietary antioxidants. J. Phytopharm. 4: 126-132.

Landmesser, U.L.F., Hornig, B. & Drexler, H. 2000. Endothelial dysfunction in hypercholesterolemia: Mechanisms, pathophysiological importance, and therapeutic interventions. Semin Thromb Hemost 26(5): 529-537.

Lasker, S., Rahman, M., Parvez, F., Zamila, M. & Miah, P. 2019. High-fat diet-induced metabolic syndrome and oxidative stress in obese rats are ameliorated by yogurt supplementation. Sci. Rep. 9: 1-15. https://doi.org/10.1038/s41598-019-56538-0

Lin, X., Bai, D., Wei, Z., Zhang, Y., Huang, Y., Deng, H. & Huang, X. 2019. Curcumin attenuates oxidative stress in RAW264. 7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2- Keap1 pathway. PLoS ONE 14: 1-13. https://doi.org/10.1371/journal.pone.0216711

Mahfudh, N., Sulistyani, N., Syakbani, M. & Dewi, A.C. 2021. The antihyperlipidaemic and hepatoprotective effect of Ipomoea batatas L. leaves extract in high-fat diet rats. Int. J. Public Heal. Sci. 10: 558-564. https://doi.org/10.11591/ijphs.v10i3.20777

Md Abdullah Al Mamun, Md Faruk, Md Mizanur Rahman, Kamrun Nahar, Fariha Kabir, Md Ashraful Alam & Nusrat Subhan 2019. High carbohydrate high fat diet induced hepatic steatosis and dyslipidemia were ameliorated by Psidium guajava leaf powder supplementation in rats. Evidence-based Complement. Altern. Med. 2019: 1897237. https://doi.org/10.1155/2019/1897237

Marliani, L., Rahmawati, W. & Sinurat, A. 2014. Antioxidant activity and total phenolic content of bangle (Zingiber cassumunar Roxb.) rhizome. J. Indones. Med. Plant 7: 22-27.

Nakamura, S., Iwami, J., Pongpiriyadacha, Y., Nakashima, S., Matsuda, H. & Yoshikawa, M. 2022. Chemical structures of phenylbutanoids from rhizomes of Zingiber cassumunar. Nat. Prod. Commun. 17(2): 1-6. https://doi.org/10.1177/1934578X221077823

Nita, M. & Grzybowski, A. 2016. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev. 2016: 3164734. https://doi.org/10.1155/2016/3164734

Paramita, S., Aminyoto, M., Ismail, S. & Arung, E.T. 2018. Effect of Zingiber montanum extract [version 2; peer review: 1 approved with reservations]. F1000Research 7: 1798. https://doi.org/10.12688/f1000research.16417.2

Rafi, M., Rohaeti, E., Miftahudin, A. & Darusman, L.K. 2011. Differentiation of Curcuma longa, Curcuma xanthorrhiza and Zingiber cassumunar by thin layer chromatography fingerprint analysis. Indones. J. Chem. 11: 71-74. https://doi.org/10.22146/ijc.21423

Ramadhan, M.F., Mahfudh, N. & Sulistyani, N. 2020. Isolation and identification of active coumpound from bengle rhizome (Zingiber cassumunar roxb) as a stimulant in phagocytosis by macrophages. Potravin. Slovak J. Food Sci. 14: 328-335. https://doi.org/10.5219/1238

Rindler, P.M., Plafker, S.M., Szweda, L.I. & Kinter, M. 2013. High dietary fat selectively increases catalase expression within cardiac mitochondria. J. Biol. Chem. 288: 1979-1990. https://doi.org/10.1074/jbc.M112.412890

Rini, S. 2012. Pengaruh pemberian diet lemak tinggi terhadap kadar trigliserida pada tikus. Thesis. Univ. Muhammadiyah Surakarta (Unpublished).

Rivera-Mancia, S., Angélica Saraí, J.O., Medina-Campos, O.N., Colín-Ramírez, E., Vallejo, M., Alcántara-Gaspar, A., Cartas-Rosado, R., Vargas-Barrón, J. & Pedraza-Chaverri, J. 2018. Activity of antioxidant enzymes and their association with lipid profile in Mexican people without cardiovascular disease: An analysis of interactions. Int. J. Environ. Res. Public Health 15(12): 2687. https://doi.org/10.3390/ijerph15122687

Sari, N., Nurkhasanah, N. & Sulistyani, N. 2020. The antioxidant effect of bangle (Zingiber cassumunar) rhizome extract on superoxide dismutase (SOD) activity in hyperlipidemic rats. Res. J. Chem. Environ. 24: 78-81.

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. cell. Physiol. Biochem. 48: 1317-1331. https://doi.org/10.1159/000492091

Skowron, M., Zalejska-fiolka, J., Błaszczyk, U., Chwalińska, E., Owczarek, A. & Birkner, E. 2018. Antioxidant enzyme activities in rabbits under oxidative stress induced by high fat diet. J. Vet. Res. 62: 199-205. https://doi.org/10.2478/jvetres-2018-0019

Sukatta, U., Rugthaworn, P., Punjee, P., Chidchenchey, S. & Keeratijnijakal, V. 2009. Chemical composition and physical properties of oil from Plai (Zingiber cassumunar Roxb.) obtained by hydro distillation and hexane extraction. Kasetsart J. (Nat. Sci.) 43: 212-217.

Tung, B.T., Hai, N.T. & Son, P.K. 2017. Hepatoprotective effect of phytosome curcumin against paracetamol-induced liver toxicity in mice. Brazilian J. Pharm. Sci. 53(1): e16136.

Valko, M., Rhodes, C.J., Moncol, J., Izakovic, M. & Mazur, M. 2006. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160: 1-40. https://doi.org/10.1016/j.cbi.2005.12.009

Widarti, W. & Nurqaidah, N. 2019. Analisis kadar serum glutamic pyruvic transaminase (SGPT) dan serum glutamic oxaloacetic transaminase (SGOT) pada petani yang menggunakan pestisida. J. Media Anal. Kesehat. 10(1): 35-43. https://doi.org/10.32382/mak.v10i1.984

Yang, R., Shi, Y., Hao, G., Li, W. & Le, G. 2008. Increasing oxidative stress with progressive hyperlipidemia in human: Relation between malondialdehyde and atherogenic index. J. Clin. Biochem. Nutr. 43: 154-158.

Yusuf, F.M. & Nurkhasanah. 2015. Evaluasi kadar kurkumin dalam jamu tradisional kunir asam yang dijual di pasar Kota Gede bulan Februari 2015. Pharm. Sci. Res. 2: 115-123. https://doi.org/10.7454/PSR.V2I3.3342

Zhan, C., Sindhu, R.K., Pang, J., Ehdaie, A. & Vaziri, N.D. 2004. Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. Journal of Hypertension 22(10): 2025-2033.

Zhang, Q., Qian, Z., Zhou, P., Zhou, X., Zhang, D., He, N. & Zhang, J. 2018. Effects of oral selenium and magnesium co-supplementation on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in rats fed a high-fat diet. Lipids Heal. Dis. 17(1): 165.

 

*Pengarang untuk surat-menyurat; email: nurkhasanah@pharm.uad.ac.id

 

 

 

 

 

   

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