Macroscopic Fungi in Grassland and Rubber Plantation Habitat Types in Special Purpose Forest Areas of Universitas Lambung Mangkurat, Indonesia
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Jun 30, 2025
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Abstract
Acute Kidney Injury (AKI) is a severe condition marked by a rapid decline in kidney function, often linked to inflammation and oxidative stress. Activation of the NLRP3 inflammasome triggers inflammation by releasing interleukin-18 (IL-18), exacerbating renal damage. Persea americana Mill. (avocado) contains bioactive compounds with known anti-inflammatory and antioxidant properties. This study aimed to evaluate the anti-inflammatory potential of P. americana leaves in inhibiting IL-18 mediated by the NLRP3 inflammasome using a bioinformatic approach. Active compounds were identified through The Indian Medicinal Plants, Phytochemistry And Therapeutics (IMPPAT) and KNApSAcK databases. Molecular docking simulations assessed their binding affinity to the NLRP3 inflammasome, while network pharmacology analysis explored interactions with inflammation-related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted the biological processes influenced by these compounds. The results showed that flavonoids such as luteolin and apigenin exhibited strong binding affinity to the NLRP3 inflammasome, with docking scores of -8.6850 kcal/mol and -8.2520 kcal/mol, respectively, indicating their potential to modulate inflammatory pathways. Network pharmacology analysis indicated that these compounds are linked to apoptosis and oxidative stress regulation, both critical in AKI progression. These findings suggest that P. americana leaves have promising anti-inflammatory potential by targeting IL-18 inhibition through modulation of the NLRP3 inflammasome, highlighting their value as a natural therapeutic agent for managing AKI.
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References
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Chen, X. J., Wu, M. Y., Li, D.-H., & You, J. (2016). Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-κB/MMP-9. Molecular Medicine Reports, 14(3), 2352–2358. https://doi.org/10.3892/mmr.2016.5460
Comella, F., Lama, A., Pirozzi, C., Annunziata, C., Piegari, G., Sodano, F., Melini, S., Paciello, O., Lago Paz, F., Meli, R., & Mattace Raso, G. (2024). Oleoylethanolamide attenuates acute-to-chronic kidney injury: in vivo and in vitro evidence of PPAR-α involvement. Biomedicine & Pharmacotherapy, 171, 116094. https://doi.org/10.1016/j.biopha.2023.116094
Dabas, D., Shegog, R., Ziegler, G., & Lambert, J. (2013). Avocado (Persea americana) Seed as a Source of Bioactive Phytochemicals. Current Pharmaceutical Design, 19(34), 6133–6140. https://doi.org/10.2174/1381612811319340007
Dash, R., Ali, Md. C., Dash, N., Azad, Md. A. K., Hosen, S. M. Z., Hannan, Md. A., & Moon, I. S. (2019). Structural and Dynamic Characterizations Highlight the Deleterious Role of SULT1A1 R213H Polymorphism in Substrate Binding. International Journal of Molecular Sciences, 20(24), 6256. https://doi.org/10.3390/ijms20246256
Deng, C., Liu, Q., Zhao, H., Qian, L., Lei, W., Yang, W., Liang, Z., Tian, Y., Zhang, S., Wang, C., Chen, Y., & Yang, Y. (2023). Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome. Bioengineering & Translational Medicine, 8(3). https://doi.org/10.1002/btm2.10517
Derkacz, A., Olczyk, P., Olczyk, K., & Komosinska-Vassev, K. (2021). The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases. Journal of Clinical Medicine, 10(5), 1122. https://doi.org/10.3390/jcm10051122
Dong, H., Li, M., Chen, H., Tian, L., Wei, W., Wang, S., Cheng, G., & Liu, S. (2023). Using network pharmacological analysis and molecular docking to investigate the mechanism of action of quercetin’s suppression of oral cancer. Journal of Cancer Research and Clinical Oncology, 149(16), 15055–15067. https://doi.org/10.1007/s00432-023-05290-0
Du, H., Hao, J., Liu, F., Lu, J., & Yang, X. (2015). Apigenin attenuates acute myocardial infarction of rats via the inhibitions of matrix metalloprotease-9 and inflammatory reactions. International Journal of Clinical and Experimental Medicine, 8(6), 8854. https://pmc.ncbi.nlm.nih.gov/articles/PMC4538101/
Du, J., Yuan, Z., Ma, Z., Song, J., Xie, X., & Chen, Y. (2014). KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol. BioSyst., 10(9), 2441–2447. https://doi.org/10.1039/C4MB00287C
Ge, S. X., Jung, D., & Yao, R. (2020). ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics, 36(8), 2628–2629. https://doi.org/10.1093/bioinformatics/btz931
Grynberg, K., Ma, F. Y., & Nikolic-Paterson, D. J. (2017). The JNK Signaling Pathway in Renal Fibrosis. Frontiers in Physiology, 8. https://doi.org/10.3389/fphys.2017.00829
He, Y., Hara, H., & Núñez, G. (2016). Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends in Biochemical Sciences, 41(12), 1012–1021. https://doi.org/10.1016/j.tibs.2016.09.002
Hoste, E. A. J., Kellum, J. A., Selby, N. M., Zarbock, A., Palevsky, P. M., Bagshaw, S. M., Goldstein, S. L., Cerdá, J., & Chawla, L. S. (2018). Global epidemiology and outcomes of acute kidney injury. Nature Reviews Nephrology, 14(10), 607–625. https://doi.org/10.1038/s41581-018-0052-0
Jang, S., Kelley, K. W., & Johnson, R. W. (2008). Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proceedings of the National Academy of Sciences, 105(21), 7534–7539. https://doi.org/10.1073/pnas.0802865105
Suresh, P. K., Sekar, G., Mallady, K., Wan Ab Rahman, W. S., Shima Shahidan, W. N., & Venkatesan, G. (2023). The Identification of Potential Drugs for Dengue Hemorrhagic Fever: Network-Based Drug Reprofiling Study. JMIR Bioinformatics and Biotechnology, 4, e37306. https://doi.org/10.2196/37306
Komada, T., & Muruve, D. A. (2019). The role of inflammasomes in kidney disease. Nature Reviews Nephrology, 15(8), 501–520. https://doi.org/10.1038/s41581-019-0158-z
Land, H., & Humble, M. S. (2018). YASARA: A Tool to Obtain Structural Guidance in Biocatalytic Investigations. In Bornscheuer, U., Höhne, M. (eds) Protein Engineering (Vol. 1685, pp. 43–67). Humana Press. https://doi.org/10.1007/978-1-4939-7366-8_4
Li, S., Huang, Q., Zhou, D., & He, B. (2022). PRKCD as a potential therapeutic target for chronic obstructive pulmonary disease. International Immunopharmacology, 113, 109374. https://doi.org/10.1016/j.intimp.2022.109374
Lim, S. H., Jung, S. K., Byun, S., Lee, E. J., Hwang, J. A., Seo, S. G., Kim, Y. A., Yu, J. G., Lee, K. W., & Lee, H. J. (2013). Luteolin suppresses UVB‐induced photoageing by targeting JNK1 and p90 RSK2. Journal of Cellular and Molecular Medicine, 17(5), 672–680. https://doi.org/10.1111/jcmm.12050
Lin, X., Yuan, J., Zhao, Y., & Zha, Y. (2015). Urine interleukin-18 in prediction of acute kidney injury: a systemic review and meta-analysis. In Journal of Nephrology (Vol. 28, Issue 1, pp. 7–16). Springer Science and Business Media, LLC. https://doi.org/10.1007/s40620-014-0113-9
Liu, Y., Liu, Q., Wang, X., He, Z., Li, D., Guan, X., Tao, Z., & Deng, Y. (2018). Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis. Kidney and Blood Pressure Research, 43(1), 246–255. https://doi.org/10.1159/000487678
Marwat, S. K., Fazal Ur Rehman, Khan, M. S., Ghulam, S., Anwar, N., Mustafa, G., & Usman, K. (2011). Phytochemical Constituents and Pharmacological Activities of Sweet Basil-Ocimum basilicum L. (Lamiaceae). Asian Journal of Chemistry, 23(9), 3773–3782. https://www.researchgate.net/publication/260096830
Ngbolua, K.-N. (2019). A mini-review on the Phytochemistry and Pharmacology of the medicinal plant species Persea americana Mill. (Lauraceae). Discovery Phytomedicine, 6(3). https://doi.org/10.15562/phytomedicine.2019.99
Ochoa-Zarzosa, A., Báez-Magaña, M., Guzmán-Rodríguez, J. J., Flores-Alvarez, L. J., Lara-Márquez, M., Zavala-Guerrero, B., Salgado-Garciglia, R., López-Gómez, R., & López-Meza, J. E. (2021). Bioactive Molecules From Native Mexican Avocado Fruit (Persea americana var. drymifolia): A Review. Plant Foods for Human Nutrition, 76(2), 133–142. https://doi.org/10.1007/s11130-021-00887-7
Pavlakou, P., Liakopoulos, V., Eleftheriadis, T., Mitsis, M., & Dounousi, E. (2017). Oxidative Stress and Acute Kidney Injury in Critical Illness: Pathophysiologic Mechanisms—Biomarkers—Interventions, and Future Perspectives. Oxidative Medicine and Cellular Longevity, 2017(1). https://doi.org/10.1155/2017/6193694
Petejova, N., Martinek, A., Zadrazil, J., & Teplan, V. (2019). Acute toxic kidney injury. Renal Failure, 41(1), 576–594. https://doi.org/10.1080/0886022X.2019.1628780
Podkowińska, A., & Formanowicz, D. (2020). Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease. Antioxidants, 9(8), 752. https://doi.org/10.3390/antiox9080752
Pratiwi, A., Agustina, D. R., Febrianti, N., & Eryati, E. (2024). Comparison of Antioxidant Activity of Methanol Extract of Young and Old Leaves of Avocado (Persea americana Mill.). Biota, 17(1), 14–22. https://doi.org/10.20414/jb.v17i1.493
Purwono, R. M., Syafitri, M., Widyastuti, R., Prasetyo, B. F., Andrianto, D., & Maulidia, D. (2024). In Silico Study of Avocado Leaves ( Persea americana Mill.) as Inhibitor of Calcium Oxalate Urolithiasis. IOP Conference Series: Earth and Environmental Science, 1359(1). https://doi.org/10.1088/1755-1315/1359/1/012130
Rapa, S. F., Di Iorio, B. R., Campiglia, P., Heidland, A., & Marzocco, S. (2019). Inflammation and Oxidative Stress in Chronic Kidney Disease—Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites. International Journal of Molecular Sciences, 21(1), 263. https://doi.org/10.3390/ijms21010263
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