Modulation of Autophagy and Mitochondrial Dynamics Gene Expression by Turmeric and Mangosteen Peel Extract

Diana Krisanti Jasaputra, Julia Windi Gunadi, Cliff Aaron Sutiono, Ronny Lesmana


High fat diet (HFD) induces oxidative stress and mitochondrial dysfunction which culminates in fatty liver disease. Autophagy and mitochondrial dynamics are affected by HFD. Turmeric and mangosteen have potential roles as antioxidants and regulators of mitochondrial function in the liver. The study aims to examine the effect of turmeric and mangosteen peel extract on autophagy and mitochondrial dynamics in the liver after HFD induction. Five groups of animals (n=5) as used: negative control, positive control (HFD), turmeric (HFD + 270 mg/kg BW turmeric extract), mangosteen (HFD + mangosteen 270 mg/kg BW peel extract), and fenofibrate (HFD + 15 mg/kg BW fenofibrate). HFD was given for 7 weeks, continued by another 7 weeks plus treatment. Liver sections were extracted to conduct semi-quantitative PCR. Autophagy (LC3, p62), mitophagy (Pink1, Parkin, Bnip3), mitochondrial fission (Drp1, Fis1), and mitochondrial fusion (Opa1, Mfn1, Mfn2) gene expression were measured. LC3 (p=0.048), p62 (p=0.043), Pink1 (p=0.012), Bnip3 (p=0.010), Mfn1 (p=0.015), and Mfn2 (p=0.035) gene expressions were differed significantly, while Parkin (p=0.098) Drp1 (p=0.962), Fis1 (p=0.570), and Opa1 (p=0.055) gene expressions did not differ between groups. Both turmeric and mangosteen peel extract have positive effects by activating autophagy, mitophagy, and mitochondrial fusion in rat liver induced by HFD.


autophagy, mitophagy, fusion, fission, HFD

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Adebayo, M., Singh, S., Singh, A. P., & Dasgupta, S. (2021). Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 35(6), e21620.

Alhusain, A., Fadda, L., Sarawi, W., Alomar, H., Ali, H., Mahamad, R., Hasan, I., & Badr, A. (2022). The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression. Dose-Response, 20(1), 15593258221078394.

Anding, A. L., & Baehrecke, E. H. (2017). Cleaning House: Selective Autophagy of Organelles. Developmental Cell, 41(1), 10–22.

Chao, H.-W., Chao, S.-W., Lin, H., Ku, H.-C., & Cheng, C.-F. (2019). Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 20(2).

Chen, Y., & Dorn, G. W. 2nd. (2013). PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science (New York, N.Y.), 340(6131), 471–475.

Fang, Y., Su, T., Qiu, X., Mao, P., Xu, Y., Hu, Z., Zhang, Y., Zheng, X., Xie, P., & Liu, Q. (2016). Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death. Scientific Reports, 6, 21018.

Feng, D., Zou, J., Su, D., Mai, H., Zhang, S., Li, P., & Zheng, X. (2019). Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE−/− mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. Nutrition & Metabolism, 16(1), 79.

Gluchowski, N. L., Becuwe, M., Walther, T. C., & Farese, R. V. J. (2017). Lipid droplets and liver disease: from basic biology to clinical implications. Nature Reviews. Gastroenterology & Hepatology, 14(6), 343–355.

Gunadi, J. W., Tarawan, V. M., Daniel Ray, H. R., Wahyudianingsih, R., Lucretia, T., Tanuwijaya, F., Lesmana, R., Supratman, U., & Setiawan, I. (2020). Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver. Heliyon, 6(5).

Haeussler, S., Köhler, F., Witting, M., Premm, M. F., Rolland, S. G., Fischer, C., Chauve, L., Casanueva, O., & Conradt, B. (2020). Autophagy compensates for defects in mitochondrial dynamics. PLoS Genetics, 16(3), e1008638.

John, O. D., Mouatt, P., Panchal, S. K., & Brown, L. (2021). Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats. In Nutrients (Vol. 13, Issue 2).

Khorolskaya, V. G., Gureev, A. P., Shaforostova, E. A., Laver, D. A., & Popov, V. N. (2020). The Fenofibrate Effect on Genotoxicity in Brain and Liver and on the Expression of Genes Regulating Fatty Acids Metabolism of Mice. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 14(1), 23–32.

Korovila, I., Höhn, A., Jung, T., Grune, T., & Ott, C. (2021). Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice. Antioxidants (Basel, Switzerland), 10(4).

Liao, C., Ashley, N., Diot, A., Morten, K., Phadwal, K., Williams, A., Fearnley, I., Rosser, L., Lowndes, J., Fratter, C., Ferguson, D. J. P., Vay, L., Quaghebeur, G., Moroni, I., Bianchi, S., Lamperti, C., Downes, S. M., Sitarz, K. S., Flannery, P. J., … Poulton, J. (2017). Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology, 88(2), 131–142.

Lionetti, L., Mollica, M. P., Donizzetti, I., Gifuni, G., Sica, R., Pignalosa, A., Cavaliere, G., Gaita, M., De Filippo, C., Zorzano, A., & Putti, R. (2014). High-lard and high-fish-oil diets differ in their effects on function and dynamic behaviour of rat hepatic mitochondria. PloS One, 9(3), e92753.

MacVicar, T. D. B., & Lane, J. D. (2014). Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation. Journal of Cell Science, 127(Pt 10), 2313–2325.

Mahmoudi, A., Moallem, S. A., Johnston, T. P., & Sahebkar, A. (2022). Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models. PPAR Research, 2022, 5805398.

Mashek, D. G. (2013). Hepatic fatty acid trafficking: multiple forks in the road. Advances in Nutrition (Bethesda, Md.), 4(6), 697–710.

Mizushima, N. (2018). A brief history of autophagy from cell biology to physiology and disease. Nature Cell Biology, 20(5), 521–527.

Oscarsson, J., Önnerhag, K., Risérus, U., Sundén, M., Johansson, L., Jansson, P.-A., Moris, L., Nilsson, P. M., Eriksson, J. W., & Lind, L. (2018). Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study. Journal of Clinical Lipidology, 12(6), 1390-1403.e4.

Otera, H., Ishihara, N., & Mihara, K. (2013). New insights into the function and regulation of mitochondrial fission. Biochimica et Biophysica Acta, 1833(5), 1256–1268.

Ramanathan, R., Ali, A. H., & Ibdah, J. A. (2022). Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 23(13).

Sathyabhama, M., Priya Dharshini, L. C., Karthikeyan, A., Kalaiselvi, S., & Min, T. (2022). The Credible Role of Curcumin in Oxidative Stress-Mediated Mitochondrial Dysfunction in Mammals. In Biomolecules (Vol. 12, Issue 10).

Shi, R.-Y., Zhu, S.-H., Li, V., Gibson, S. B., Xu, X.-S., & Kong, J.-M. (2014). BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neuroscience & Therapeutics, 20(12), 1045–1055.

Suttirak, W., & Manurakchinakorn, S. (2014). In vitro antioxidant properties of mangosteen peel extract. Journal of Food Science and Technology, 51(12), 3546–3558.

Tsai, S.-Y., Chung, P.-C., Owaga, E. E., Tsai, I.-J., Wang, P.-Y., Tsai, J.-I., Yeh, T.-S., & Hsieh, R.-H. (2016). Alpha-mangostin from mangosteen (Garcinia mangostana Linn.) pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis. Nutrition & Metabolism, 13, 88.

Wang, L., Ishihara, T., Ibayashi, Y., Tatsushima, K., Setoyama, D., Hanada, Y., Takeichi, Y., Sakamoto, S., Yokota, S., Mihara, K., Kang, D., Ishihara, N., Takayanagi, R., & Nomura, M. (2015). Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration. Diabetologia, 58(10), 2371–2380.

Williams, J. A., & Ding, W.-X. (2018). Mechanisms, pathophysiological roles and methods for analyzing mitophagy – recent insights. 399(2), 147–178.

Yaghoubi, M., Jafari, S., Sajedi, B., Gohari, S., Akbarieh, S., Heydari, A. H., & Jameshoorani, M. (2017). Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease. European Journal of Gastroenterology & Hepatology, 29(12), 1385–1388.

Yoshii, S. R., & Mizushima, N. (2017). Monitoring and Measuring Autophagy. International Journal of Molecular Sciences, 18(9).

Yu, R., Lendahl, U., Nistér, M., & Zhao, J. (2020). Regulation of Mammalian Mitochondrial Dynamics: Opportunities and Challenges . In Frontiers in Endocrinology (Vol. 11).



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