Evaluation of the Hepatoprotective Effects of the Flavonoid-Containing Ethyl Acetate Fraction Obtained after n-Hexane Defatting of Matoa (Pometia pinnata) Fruit Peel on a DMN-Induced Hepatic Fibrosis Model in Rats: A Histopathological and Serum Biomarker Approach

Authors

  • Emma Jayanti Besan Universitas Muhammadiyah Kudus
  • Atun Qowiyyah Universitas Garut
  • Korinus Suweni Poltekkes Kemenkes Jayapura
  • Yunita Kristina Universitas Cenderawasih
  • Ziza Putri Aisyia Fauzi Universitas Muslim Nusantara Al-Washliyah

Keywords:

Pometia Pinnata, Flavonoids, Liver Fibrosis, Hepatoprotection, DMN, Silymarin, Antioxidant

Abstract

Liver fibrosis is a progressive liver disorder and a major global health concern, prompting increasing interest in natural products with antifibrotic potential. Pometia pinnata, traditionally used to treat liver disorders, lacks sufficient experimental evidence supporting its hepatoprotective effects. This study evaluated the hepatoprotective and antifibrotic activity of a flavonoid-containing ethyl acetate fraction obtained after n-hexane defatting of Pometia pinnata fruit peel in a dimethylnitrosamine (DMN)-induced hepatic fibrosis rat model. Male rats were divided into six groups: normal control, DMN control, three treatment groups receiving the flavonoid fraction at doses of 50, 100, and 200 mg/kg body weight, and a silymarin-treated group (100 mg/kg). Dose selection was based on preliminary toxicity data and previous studies on flavonoid-rich extracts. Liver injury was assessed using serum biochemical markers (ALT, AST, ALP, and bilirubin), histopathological examination, and fibrosis scoring with Masson’s Trichrome staining. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05). DMN significantly induced hepatic injury and fibrosis, while flavonoid fraction treatment improved liver function and histological features in a dose-dependent manner. The highest dose showed effects comparable to silymarin and significantly reduced fibrosis scores (r = −0.91, p < 0.001). These findings indicate that Pometia pinnata fruit peel exhibits promising hepatoprotective and antifibrotic potential.

References

Abouelezz, H., Shehatou, G., Shebl, A., & Salem, H. (2023). A standardized pomegranate fruit extract ameliorates thioacetamide-induced liver fibrosis in rats via AGE–RAGE–ROS signaling. Heliyon, 9(5), e14256. https://doi.org/10.1016/j.heliyon.2023.e14256

Adrian, A., Syahputra, R., Lie, S., & Nugraha, S. (2021). Amelioration of cisplatin-induced liver injury by ethanol extract of Pometia pinnata. Open Access Macedonian Journal of Medical Sciences, 9(B), 678–685. https://doi.org/10.3889/oamjms.2021.6785

Ali, A., Gabbar, M., Abdel-Twab, S., Fahmy, E., Ebaid, H., Alhazza, I., & Ahmed, O. (2020). Antidiabetic potency, antioxidant effects, and mode of actions of Citrus reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin in nicotinamide/streptozotocin-induced Wistar diabetic rats. Oxidative Medicine and Cellular Longevity, 2020, 1730492. https://doi.org/10.1155/2020/1730492

Ammar, N., Hassan, H., Abdallah, H., Afifi, S., Elgamal, A., Farrag, A., El-Gendy, A., Farag, M. A., & Elshamy, A. (2022). Protective effects of naringenin from Citrus sinensis (Valencia) peels against CCl₄-induced hepatic and renal injuries in rats assessed by metabolomics, histological, and biochemical analyses. Nutrients, 14(8), 1602. https://doi.org/10.3390/nu14081602

Boye, A., Asiamah, E. A., Martey, O. N., & Ayertey, F. (2024). Citrus limon fruit peel extract attenuates carbon tetrachloride-induced hepatocarcinogenesis in Sprague–Dawley rats. BioMed Research International, 2024, 6673550. https://doi.org/10.1155/2024/6673550

Chen, Y., Liang, J., Sun, C., Wang, D., Chen, K., Zhao, J., Ji, S., Ye, X., Cao, J., Wang, Y., & Sun, C. (2024). Hepatoprotective potential of fruit extracts rich in structurally distinct flavonoids against alcohol-induced liver injury via the gut microbiota–liver axis. Food Chemistry, 460, 140460. https://doi.org/10.1016/j.foodchem.2024.140460

Jiang, J., Yan, L., Shi, Z., Wang, L., Shan, L., & Efferth, T. (2019). Hepatoprotective and anti-inflammatory effects of total flavonoids from Citrus changshan-huyou peel on non-alcoholic fatty liver disease via modulation of NF-κB and MAPK pathways. Phytomedicine, 64, 153082. https://doi.org/10.1016/j.phymed.2019.153082

Kumar, H., Dhanjal, D. S., Guleria, S., Nepovimova, E., Sethi, N., Dhalaria, R., & Kuča, K. (2024). Hepatoprotective effects of fruit pulp, seed, and peel against chemical-induced toxicity: Evidence from in vivo studies. Food and Chemical Toxicology, 188, 114742. https://doi.org/10.1016/j.fct.2024.114742

Lee, C. W., Bak, J. P., Yoon, S., & Moon, J. O. (2021). Protective effect of oligonol on dimethylnitrosamine-induced liver fibrosis in rats via JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways. Antioxidants, 10(3), 366. https://doi.org/10.3390/antiox10030366

Pulido-Hornedo, N., Ventura-Juárez, J., Guevara-Lara, F., González-Ponce, H., Sánchez-Alemán, E., Buist-Homan, M., Moshage, H., & Martínez-Saldaña, M. C. (2022). Hepatoprotective effect of Opuntia robusta fruit biocomponents in a rat model of thioacetamide-induced liver fibrosis. Plants, 11(15), 2003. https://doi.org/10.3390/plants11152003

Suzuki, T., Nagata, M., Kagawa, N., Takano, S., & Nomura, J. (2021). Anti-obesity effects of matoa (Pometia pinnata) fruit peel powder in high-fat diet-fed rats. Molecules, 26(21), 6733. https://doi.org/10.3390/molecules26216733

Toklu, H. Z., Sehirli, O., Şener, G., Dumlu, M. U., Ercan, F., Gedik, N., & Gökmen, V. (2007). Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats. Journal of Pharmacy and Pharmacology, 59(9), 1287–1295. https://doi.org/10.1211/jpp.59.9.0014

Wang, S., Li, W., Liu, W., Yu, L., Peng, F., Qin, J., Pu, L., Tang, Y., Xie, X., & Peng, C. (2023). Total flavonoids from Penthorum chinense Pursh attenuate CCl₄-induced hepatic fibrosis via inhibition of the TLR4/MyD88/NF-κB pathway. Frontiers in Pharmacology, 14, 1253013. https://doi.org/10.3389/fphar.2023.1253013

Wenbo, Z., Han, J., Hua, L., Lei, T., Chen, G., & Tian, M. (2024). The potential of flavonoids in hepatic fibrosis: A comprehensive review. Phytomedicine, 133, 155932. https://doi.org/10.1016/j.phymed.2024.155932

Xu, Y., Zhang, D., Yang, H., Liu, Y., Zhang, L., Zhang, C., Chen, G., Hu, Y., Chen, J., Zhang, H., Mu, Y., Liu, P., & Liu, W. (2021). Hepatoprotective effect of genistein against dimethylnitrosamine-induced liver fibrosis by regulating macrophage function and inhibiting the JAK2/STAT3/SOCS3 pathway. Frontiers in Bioscience, 26(12), 1572–1584. https://doi.org/10.52586/5050

Downloads

Published

2025-12-03

How to Cite

Emma Jayanti Besan, Atun Qowiyyah, Korinus Suweni, Yunita Kristina, & Ziza Putri Aisyia Fauzi. (2025). Evaluation of the Hepatoprotective Effects of the Flavonoid-Containing Ethyl Acetate Fraction Obtained after n-Hexane Defatting of Matoa (Pometia pinnata) Fruit Peel on a DMN-Induced Hepatic Fibrosis Model in Rats: A Histopathological and Serum Biomarker Approach. Fundamental and Applied Research in Medicine and Allied Sciences Indonesia, 1(2), 1–12. Retrieved from https://gpijournal.com/index.php/farmasi/article/view/389