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
Received: 12 November
2022/Accepted: 16 August 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
REFERENCES
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.
*Corresponding
author; email: nurkhasanah@pharm.uad.ac.id
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