Metabolic Profile and Hepatoprotective Efficacy of Carica Papaya Leaves in CCl4 Induced Oxidative Stress Albino Mice
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Hepatoprotective,
Metabolic profile
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Maryam Abdulkadir Usman
Hamza Ahmed Pantami
Muhammad Bappah Sani
Aliyu Ibrahim Lawan
Hajjagana Hamza
Abstract
Background: Hepatic disorder is fatal and require vital medication, orthodox cure is deleterious, so there is need for natural curative agents.
Aims: Bioactive phytochemical analysis and efficacy of Carica papaya leaves extracts versus CCL4 induced oxidative stress in mice.
Methods: The metabolite profile of Carica papaya leaves extract was analysed by LC-MS/MS analysis via GNPS. Liver aminotransferases were assessed, liver tissues and homogenates were assessed for histopathology and MDA, catalase, superoxide dismutase, and Glutathione S-Transferase activities, qRTPCR mRNA expression of hepatic tissue Glutathione S- Transferase was performed. Free radical scavenging activity of the extract were evaluated using invitro prototypes.
Results: Numerous metabolites were identified from crude extract. Observed weight loss in rats, liver damage through elevating serum variables (marker enzymes and bilirubin), decrease in total protein and albumin. A significant decrease in tissue catalase, GST, and superoxide dismutase activities and marked increase in MDA level (p<0.05) were also observed. The extract effectively ameliorated CCl4 effects with marked decrease in serum variables. GST mRNA expression of hepatic tissue and histopathological results also supported the biochemical findings. Extract exhibited radical scavenging activity with DPPH IC50 of 0.56mg/ml, FRAP IC50 of 0.52mg/ml, H2O2 IC50 of 0.58mg/ml and Phosphomolybdenum IC50 of 0.62.
Conclusion: Carica papaya leaves was beneficial in modulating the alterations induced in liver and serum variables of mice in CCL4 induced oxidative stress.
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Copyright (c) 2025 Maryam Abdulkadir Usman, Hamza Ahmed Pantami, Muhammad Bappah Sani, Aliyu Ibrahim Lawan, Hajjagana Hamza
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References
Airaodion, A. I., Okoroukwu, V. N., Ogbuagu, E. O., Ekenjoku, J. A., Ogbuagu, U., & Airaodion, E. O. (2019). Antifertility Effect of Ethanolic Leaf Extract of Carica papaya in Male Wistar Rats Antifertility Effect of Ethanolic Leaf Extract of Carica papaya in Male Wistar Rats. Merit Research Journal of Medicine and Medical Sciences. 7(10), 374-381. https://doi.org/10.5281/zenodo.3506541
Alamri, E.S.; El Rabey, H.A.; Alzahrani, O.R.; Almutairi, F.M.; Attia, E.S.; Bayomy, H.M.; Albalwi, R.A.; Rezk, S.M., 2022. Enhancement of the Protective Activity of Vanillic Acid against CCl4 Hepatotoxicity in Male Rats by the Synthesis of Silver Nanoparticles (AgNPs). Molecules, 27, 8308. https://doi.org/10.3390/molecules27238308
Allameh, Abdolamir, Reyhaneh Niayesh-Mehr, Azadeh Aliarab, Giada Sebastiani, and Kostas Pantopoulos (2023). Oxidative stress in liver pathophysiology and disease." Antioxidants 12(9), 1653. https://doi.org/10.3390/antiox12091653
Al-Seeni MN, El Rabey HA, Zamzami MA, Alnefayee AM. (2016). The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats. BMC Complement Altern Med. 16(1), 438. https://doi.org/10.1186/s12906-016-1422-4
Angeli, L., Morozova, K., & Scampicchio, M. (2023). A kinetic-based stopped-flow DPPH• method. Scientific Reports, 13, 7621. https://doi.org/10.1038/s41598-023-34382-7
Benjamaa, R., Khanchouch, A., Bouriche, H., & Kabouche, Z. (2024). Comparative evaluation of antioxidant activity in [sample type] using the phosphomolybdenum assay. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2024.1345340
Bhowmick, A., Sarkhel, S., & Basak, A. An Evaluative Review on Phytochemicals Present in Carica Papaya, Its Extraction Procedures And In Vivo Effects on Wistar Rat Model. International Research Journal of Modernization in Engineering Technology and Science, 32(212.7), 348-6. www.researchgate.net
Brol, M. J., Rösch, F., Schierwagen, R., Magdaleno, F., Uschner, F. E., Manekeller, S., ... & Trebicka, J. (2019). Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 317(2), G182-G194. https://doi.org/10.1152/ajpgi.00361.2018
Conde de la Rosa, L.; Goicoechea, L.; Torres, S.; Garcia-Ruiz, C.; Fernandez-Checa, J.C., (2022). Role of Oxidative Stress in Liver Disorders. Livers, 2, 283–314. https://doi.org/10.3390/livers2040023
Cortés, M. G., & García, A. G. (2022). Management of Pharmacologic Adverse Effects in Advanced Liver Disease. Clinical Drug Investigation, 42(s1), 57–62. https://doi.org/10.1007/s40261-022-01150-w
Delli Bovi, A. P., Marciano, F., Mandato, C., Siano, M. A., Savoia, M., & Vajro, P. (2021). Oxidative stress in non-alcoholic fatty liver disease. An updated mini review. Frontiers in medicine, 8, 595371. https://doi.org/10.3389/fmed.2021.595371
El-Boshy, M. E., Abdelhamidb, F., Richab, E., Ashshia, A., Gaitha, M., & Qustya, N. (2017). Attenuation of CCl4 induced oxidative stress, immunosuppressive, hepatorenal damage by fucoidan in rats. J Clin Toxicol, 7(3), 1-7. https://doi.org/10.4172/2167-7972.1000348
Gan, C., Yuan, Y., Shen, H., Gao, J., Kong, X., Che, Z., Guo, Y., & Wang, H. (2025). Liver diseases: epidemiology, causes, trends and predictions. Signal Transduction and Targeted Therapy, October 2024, 1–36. https://doi.org/10.1038/s41392-024-02072-z
Gulcin, I ̇.; Alwasel, S.H. (2025) Fe3+ Reducing Power as the Most Common Assay for Understanding the Biological Functions of Antioxidants. Processes, 13, 1296. https://doi.org/10.3390/pr13051296
Hajam, Y.A.; Rani, R.; Ganie, S.Y.; Sheikh, T.A.; Javaid, D.; Qadri, S.S.; Pramodh, S.; Alsulimani, A.; Alkhanani, M.F.; Harakeh, S.; et al., (2022). Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells, 11 (3), 552. https://doi.org/10.3390/cells11030552
Hamza, H. G., Saleh, A.I, Mohammed, Z. K & Ngadda, H. A. (2014). Effect of Aqueous Extract of Detarium microcarpum (Guill & Sperr) on Mycotoxin- Induced Tissue Damage in albino rats. 9(10), Committee of Publication ethics (COPE) and Journal donation project (JDP). 629–633. https://doi.org/10.22271/phyto.2020.v9.i4i.112990
Hariono, M., Julianus, J., Djunarko, I., Hidayat, I., Adelya, L., Indayani, F., Auw, Z., Namba, G., & Hariyono, P. (2021). The future of Carica papaya leaf extract as an herbal medicine product. Molecules, 26(22). https://doi.org/10.3390/molecules26226922
Hikmawanti, N. P. E., Fatmawati, S., & Asri, A. W. (2021, April). The effect of ethanol concentrations as the extraction solvent on antioxidant activity of Katuk (Sauropus androgynus (L.) Merr.) leaves extracts. IOP conference series: Earth and environmental science, 755(1), 012060. https://doi.org/10.1088/1755-1315/755/1/012060
Hussain, M. B., Hassan, S., Waheed, M., Javed, A., Farooq, M. A., & Tahir, A. (2019). Bioavailability and metabolic pathway of phenolic compounds. In Plant physiological aspects of phenolic compounds. IntechOpen. https://doi.org/10.5772/intechopen.84745
Ito F, Sono Y and Ito T., (2019). Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants, 8, 72; 1-28. https://doi.org/10.3390/antiox8030072
Jaffar HM., Al-Asmari F., | Khan FA., Abdul Rahim M., Zongo (2024). Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review Food Sci Nutr. 12:3097–3111. https://doi.org/10.1002/fsn3.4010 3097-3111
Jain, C., Khatana, S., & Vijayvergia, R. (2019). Bioactivity of secondary metabolites of various plants: a review. Int. J. Pharm. Sci. Res, 10(2), 494-504. https://doi.org/10.13040/IJPSR.0975-8232.10(2)
Jain Sb, N,, S. K., Hr, A., Champawat, P. S., Mogra, R., & Maherchandani, J. K. (2021). An overview of papaya: Phytochemical constituents and its therapeutic applications. The Pharma Innovation Journal, 10(9), 45–49. www.thepharmajournal.com
Jia, Hai, Yunchang Zhang, Xuemeng Si, Yuhang Jin, Da Jiang, Zhaolai Dai, and Zhenlong Wu. "Quercetin alleviates oxidative damage by activating nuclear factor erythroid 2-related factor 2 signaling in porcineenterocytes." Nutrients 13, no. 2 (2021): 375. https://doi.org/10.3390/nu13020375
Khor, B. K. K., Chear, N. J. Y., Azizi, J., & Khaw, K. Y. (2021). Chemical composition, antioxidant and cytoprotective potentials of Carica papaya leaf extracts: A comparison of supercritical fluid and conventional extraction methods. Molecules, 26(5). https://doi.org/10.3390/molecules26051489
Lawal, B., Shittu, O. K., Oibiokpa, F. I., Berinyuy, E. B., & Mohammed, H. (2017). African natural products with potential antioxidants and hepatoprotectives properties: a review. Clinical Phytoscience, 2(1). https://doi.org/10.1186/s40816-016-0037-0
Liedtke C., Luedde T., Sauerbruch T., Scholten D., Streetz K., Tacke F., Tolba R., Trautwein C., Trebicka J., and Li, Y., Li, Z., Li, C., Ma, X., Chang, Y., Shi, C., He, J., Li, R., Muhammad, I., & Liu, F. (2018). Evaluation of hepatoprotective activity of Syringa oblata leaves ethanol extract with the indicator of glutathione S-transferase A1. Revista Brasileira de Farmacognosia, 28(4), 489–494. https://doi.org/10.1016/j.bjp.2018.05.011
Liu XF, Xiang L, Zhou Q, Carralot J-P., Prunotto M., Niederfellner G and Pastan I., (2016). Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis. Proceedings Academy of Sciences, 113(38)1066-1071. https://doi.org/10.1073/pnas.1611481113
Ma S-C., Zhang J-Q.,Yan T-H Miao M-X., Cao Y-B., Zhang L-C and Li L.Novel. (2023). Strategies to reverse chemoresistance in colorectal cancer. Cancer Medicine, 12(10) 11073-11096. https://doi.org/10.1002/cam4.5594
Mas-Bargues C., Escriva C., Dromant M., Borras C., Vina J. (2021). Lipid peroxidation as measured by chromatographic termination of malondialdehyde. Human plasma reference values in health and disease. Biochem. Biophysics, 709(30). https://doi.org/10.1016/j.abb.2021.108941
Mehdi, S., Ahmad, F., Lodhi, A. H., Khurshid, U., Khalid, A. A., Sidiq, S. S., Hussain, L., & Baig, M. S. (2022). Protective Effects of p-CA Against Acute Liver Damage Induced by LPS / D-GalN in Wistar Albino Rats. Molecules, 3327–3342. https://doi.org/10.2147/DDDT.S380324
Mendoza, N., & Silva, E. M. E. (2018). Introduction to phytochemicals: Secondary metabolites from plants with active principles for pharmacological. Phytochemicals: Source of antioxidants and role in disease prevention, 25. https://doi.org/10.5772/intechopen.78226
Mondal, A., Gandhi, A., Fimognari, C., Atanasov, A. G., & Bishayee, A. (2019). Alkaloids for cancer prevention and therapy: Current progress and future perspectives. European journal of pharmacology, 858, 172472. https://doi.org/10.1016/j.ejphar.2019.172472
Musa M. Y., Daja A., Bababe A.B., Modu S., & Hamza HG (2021). Phytochemical analysis and in-vitro antioxidant activity of Xeromphis nilotica stem-bark extract. BIMA Journal of Science and Technology, 5(2), 138-147. www.ajol.info
Nugroho, A., Heryani, H., Choi, J. S., & Park, H. (2017). Asian Paci fi c Journal of Tropical Biomedicine scavenging activity. Asian Pacific Journal of Tropical Biomedicine, 7(3), 208–213. https://doi.org/10.1016/j.apjtb.2016.12.009
Ozawa, H., Miyazawa, T., Burdeos, G. C., & Miyazawa, T. (2022). Biological functions of antioxidant dipeptides. Journal of Nutritional Science and Vitaminology, 68(3), 162-171. https://doi.org/10.3177/jnsv.68.162
Pantami, H. A., Shaari, K., Bustamam, M. S. A., & Ismail, I. S. (2020). Metabolite Profiling of Different Solvent Extracts of the Microalgae Chlorella vulgaris Via 1H NMR-Based Metabolomics. Current Metabolomics and Systems Biology, 8(1), 61–74. https://doi.org/10.2174/2666338408999200819162931
Peñuelas, N., Laguna, A., & Vila, M. (2024). Hematoxylin and Eosin (H&E) Staining Protocol. protocols.io. https://doi.org/10.17504/protocols.io.ewov19deklr2/v1
Scholten, D., Trebicka, J., Liedtke, C., & Weiskirchen, R. (2015). The carbon tetrachloride model in mice. Laboratory animals, 49(1_suppl), 4-11. https://doi.org/10.1177/0023677215571192
Schwarz D. S., & Blower, M. D. (2016). The endoplasmic reticulum: structure, function and response to cellular signaling. Cellular and molecular life sciences, 73(1), 79-94. https://doi.org/10.1007/s00018-015-2052-6
Sharma, A., Sharma, R., Sharma, M., Kumar, M., Barbhai, M. D., Lorenzo, J. M., Sharma, S., Samota, M. K., Atanassova, M., Caruso, G., Naushad, M., Radha, Chandran, D., Prakash, P., Hasan, M., Rais, N., Dey, A., Mahato, D. K., Dhumal, S., … Mekhemar, M. (2022). Carica papaya L. Leaves: Deciphering Its Antioxidant Bioactives, Biological Activities, Innovative Products, and Safety Aspects. Oxidative Medicine and Cellular Longevity. 2022(1), 2451733. https://doi.org/10.1155/2022/2451733
Singh, P. G., Madhu, S. B., Shailasreesekhar, G. T. S., Basalingappa, K. M., & Sushma, B. V. (2020). In vitro antioxidant, anti-inflammatory and anti-microbial activity of Carica papaya seeds. Global Journal of Medical Research, 20, 19-38. https://doi.org/10.34257/GJMRBVOL20IS2PG19
Sun, W., & Shahrajabian, M. H. (2023). Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health. Molecules, 28(4), 1845. https://doi.org/10.3390/molecules28041845
Tibiri, A., Boria, S., Traoré, T. K., Ouédraogo, N., Nikièma, A., Ganaba, S., ... & Carraz, M. (2020). Countrywide survey of plants used for liver disease management by traditional healers in Burkina Faso. Frontiers in Pharmacology, 11, 563751. https://doi.org/10.3389/fphar.2020.563751
Ugbogu, E. A., Dike, E. D., Ebubechi, M., Etumnu, L. R., Okoro, B. C., Ugbogu, O. C., Adurosakin, O. E., Enyinna, C., Ohaeri, E., & I266weala, E. J. (2023). Pharmacological Research - Modern Chinese Medicine Ethnomedicinal uses, nutritional composition, phytochemistry and potential health benefits of Carica papaya. Pharmacological Research - Modern Chinese Medicine, 7(April), 100266. https://doi.org/10.1016/j.prmcm.2023.100
Uno, S., Kodama, D., Yukawa, H., Shidara, H., & Akamatsu, M. (2020). Quantitative analysis of the relationship between structure and antioxidant activity of tripeptides. Journal of Peptide Science, 26(3), e3238. https://doi.org/10.1002/psc.3238
Usunobun, U., Osaigbovo, J. O., & Okolie, N. P. (2020). Hepatoprotective and antioxidant effect of Rhaphiostylis beninensis ethanol root extract on carbon tetrachloride (ccl4)-induced hepatotoxicity and oxidative stress. Animal Research International, 17(2), 3781 – 3789. https://doi.org/10.5099/aj200300155
Wang, M., Carver, J. J., Phelan, V. V., Sanchez, L. M., Garg, N., Peng, Y., Nguyen, D. D., et al. (2016). Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology, 34(8), 828. https://doi.org/10.1038/nbt.3597
Xiao, F. (2020). Guidelines for antioxidant assays for food components. Food Science & Technology, 10. https://doi.org/10.1002/fft2.10
Yakkala, P. A., Penumallu, N. R., Shafi, S., & Kamal, A. (2023). Prospects of topoisomerase inhibitors as promising anti-cancer agents. Pharmaceuticals, 16(10), 1456. https://doi.org/10.3390/ph16101456
Yang, Nanxiang, Yongyan Pei, Yan Wang, Limin Zhao, Ping Zhao, and Zhanchao Li. "Identifying the antioxidant activity of tripeptides based on sequence information and machine learning." Chemometrics and Intelligent Laboratory Systems 238 (2023): 104845. https://doi.org/10.1016/j.chemolab.2023.104845
Zhu, H., Liang, Q. H., Xiong, X. G., Wang, Y., Zhang, Z. H., Sun, M. J., Lu, X., & Wu, D. (2018). Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, on Arthritis Model Rats. Evidence-Based Complementary and Alternative Medicine 2018. 1, 5198594. https://doi.org/10.1155/2018/5198594