Modulation of Th1/Th2 Cytokine Balance by Extract of Male Papaya Leaves (Carica papaya L.) in an Experimental Autoimmune Disease Model

Lisa Savitri, Kharisul Ihsan, Elfred Rinaldo Kasimo

Abstract


Autoimmune diseases are characterized by dysregulated immune responses, particularly involving an imbalance between T helper 1 (Th1) and T helper 2 (Th2) cytokines. This imbalance contributes to chronic inflammation and progressive tissue damage. Modulation of Th1/Th2 balance has emerged as a promising therapeutic strategy; however, current treatments are often associated with significant side effects. This study aimed to evaluate the immunomodulatory effects of male papaya (C. papaya L.) leaf extract on Th1/Th2 cytokine balance in an experimental autoimmune disease model. An experimental approach was conducted using in vivo autoimmune models and ex vivo immune assays. Male papaya leaves were extracted using 70% ethanol and analyzed for phytochemical content. Experimental animals were induced with autoimmune disease and treated with different doses of the extract. Cytokine levels, including interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10), were measured using ELISA. Gene expression of transcription factors T-bet and GATA-3 was analyzed using qRT-PCR. Histopathological examination was performed to assess tissue inflammation and damage. The results showed that the extract significantly reduced Th1 cytokines (IFN-gamma and IL-2) and increased Th2 cytokines (IL-4 and IL-10), leading to normalization of the IFN-gamma/IL-4 ratio. The extract also downregulated T-bet expression and upregulated GATA-3, indicatingtranscriptional modulation. Histological findings confirmed reduced inflammatory infiltration and improved tissue structure in treated groups. In conclusion, male papaya leaf extract demonstrates significant potential as a natural immunomodulatory agent capable of restoring Th1/Th2 balance in autoimmune conditions. These findings provide a scientific basis for the development of plant-based therapies targeting immune regulation.


Keywords


autoimmune disease; C. papaya L.; cytokine balance; immunomodulation; Th1/Th2

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DOI: https://doi.org/10.14421/biomedich.2026.151.1543-1548

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Copyright (c) 2026 Lisa Savitri, Kharisul Ihsan, Elfred Rinaldo Kasimo



Biology, Medicine, & Natural Product Chemistry
ISSN 2089-6514 (paper) - ISSN 2540-9328 (online)
Published by Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity.

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This work is licensed under a CC BY-NC