Immunomodulatory Activity of Begonia Medicinalis Ethanolic Extract in Experimental Animals
Abstract
Benalu batu (B. medicinalis) is a plant endemic to Central Sulawesi that has been reported to possess anticancer, antioxidant, and antiviral activities. The mechanism of action of these activities is still unclear. This study aimed to evaluate the immunostimulatory effect of ethanol extract of B. medicinalis on an in vivo model by measuring the macrophage phagocytotic activity and cytokine production of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) on male mice and rats, respectively. The extract was obtained by the maceration method for 3 × 24 h using 70% ethanol. The doses of the extract were 60, 120, and 240 mg/kg body weight (bw). The percentage of macrophage phagocytosis and the TNF-α, and IFN-γ levels were measured on the eighth day, one hour after intraperitoneal injection of Staphylococcus aureus ATCC 25923. The result showed that ethanol extract of B. medicinalis activated macrophage phagocytosis in a dose-dependent manner, with a significant increase in cytokine expression of TNF-α and IFN-γ. The optimal dose was 240 mg/kg bw, with a higher percentage of phagocytic activity and higher levels of TNF-α and IFN-γ than Stimuno® as a positive control and other dosage treatments. This study suggests that B. medicinalis ethanol extract has the effect of an immunomodulator and provides a scientific basis for traditional usage of this herb plant.
References
Bhardwaj, J., Chaudhary, N., Seo, H. J., Kim, M. Y., Shin, T. S., & Kim, J. D. (2014). Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway. Immunopharmacology and Immunotoxicology, 36(3), 202–210. https://doi.org/10.3109/08923973.2014.909849
Block, K. I., & Mead, M. N. (2003). Immune system effects of echinacea, ginseng, and astragalus: A review. Integrative Cancer Therapies, 2(3), 247–267. https://doi.org/10.1177/1534735403256419
Brattig, N. W., Diao, G. J., & Berg, P. A. (1984). Immunoenhancing effect of flavonoid compounds on lymphocyte proliferation and immunoglobulin synthesis. International Journal of Immunopharmacology, 6(3), 205–215. https://doi.org/10.1016/0192-0561(84)90018-3
Catanzaro, M., Corsini, E., Rosini, M., Racchi, M., & Lanni, C. (2018). Immunomodulators inspired by nature: A review on curcumin and echinacea. molecules, 23(11), 2778. https://doi.org/10.3390/molecules23112778
Chaplin, D. D. (2010). Overview of the immune response. Journal of Allergy and Clinical Immunology, 125(2), S3–S23. https://doi.org/10.1016/j.jaci.2009.12.980
DeNardo, D. G., & Coussens, L. M. (2007). Inflammation and breast cancer. Balancing immune response: Crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Research, 9(4), 212. https://doi.org/10.1186/bcr1746
Espírito-Santo, R. F., Meira, C. S., Costa, R. dos S., Souza Filho, O. P., Evangelista, A. F., Trossini, G. H. G., Ferreira, G. M., Velozo, E. da S., Villarreal, C. F., & Pereira Soares, M. B. (2017). The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches. PLOS ONE, 12(6), e0179174. https://doi.org/10.1371/journal.pone.0179174
Fournier, B., & Philpott, D. J. (2005). Recognition of Staphylococcus aureus by the innate immune system. Clinical Microbiology Reviews, 18(3), 521–540. https://doi.org/10.1128/CMR.18.3.521-540.2005
Fristiohady, A., Jumadil, Wahyuni, Malaka, Muh. H., Harnita, W. O., Sadarun, B., Yodha, A. W. M., Saripuddin, Purnama, L. O. M. J., & Sahidin, I. (2020). Immunomodulatory activity of Xestospongia sp. Ethanolic extract towards Interferon-gamma (IFN- γ) and tumor necrosis factor-alpha (TNF-α) levels in Wistar male rats. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 6(2). https://doi.org/10.22487/j24428744.2020.v6.i2.15231
Hirayama, D., Iida, T., & Nakase, H. (2017). The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. International Journal of Molecular Sciences, 19(1), 92. https://doi.org/10.3390/ijms19010092
Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease. International Journal of Molecular Sciences, 20(23), 6008. https://doi.org/10.3390/ijms20236008
Khumaidi, A., Widodo, A., Nugrahani, A. W., & Fakhrudin, N. (2020). Profil Proliferasi Sel Limfosit Benalu Batu (Begonia medicinalis) Asal Kabupaten Morowali Utara Provinsi Sulawesi Tengah. 18, 7.
Kilani-Jaziri, S., Mokdad-Bzeouich, I., Krifa, M., Nasr, N., Ghedira, K., & Chekir-Ghedira, L. (2017). Immunomodulatory and cellular antioxidant activities of caffeic, ferulic, and p -coumaric phenolic acids: A structure–activity relationship study. Drug and Chemical Toxicology, 40(4), 416–424. https://doi.org/10.1080/01480545.2016.1252919
Labro, M. T. (2012). Immunomodulatory effects of antimicrobial agents. Part I: Antibacterial and antiviral agents. Expert Review of Anti-Infective Therapy, 10(3), 319–340. https://doi.org/10.1586/eri.12.11
Martínez, G., Mijares, M. R., & De Sanctis, J. B. (2019). Effects of flavonoids and its derivatives on immune cell responses. Recent Patents on Inflammation & Allergy Drug Discovery, 13(2), 84–104. https://doi.org/10.2174/1872213X13666190426164124
Qu, X., Tang, Y., & Hua, S. (2018). Immunological approaches towards cancer and inflammation: A cross talk. Frontiers in Immunology, 9, 563. https://doi.org/10.3389/fimmu.2018.00563
Wahyuni, W., Leorita, M., Fristiohady, A., Yusuf, M. I., Malik, F., Febriansyah, H., & Sahidin, S. (2019). Efek Imunomodulator Ekstrak Etanol Spons Xestospongia Sp. Terhadap Aktivitas Fagositosis Makrofag Pada Mencit Jantan Galur Balb/C. Jurnal Mandala Pharmacon Indonesia, 5(01), 15–30. https://doi.org/10.35311/jmpi.v5i01.38
Wahyuniati, N. (2017). Peran interferon gamma pada infeksi mycobacterium tuberculosis. Jurnal Kedokteran Syiah Kuala, 17(2), 126–132. https://doi.org/10.24815/jks.v17i2.8992
Wang, J., Shao, W., Niu, H., Yang, T., Wang, Y., & Cai, Y. (2019). Immunomodulatory effects of colistin on macrophages in rats by activating the p38/MAPK pathway. Frontiers in Pharmacology, 10, 729. https://doi.org/10.3389/fphar.2019.00729
Whiteside, T. L. (2007). Introduction to cytokines as targets for immunomodulation. In R. V. House & J. Descotes (Eds.), Cytokines in Human Health (pp. 1–15). Humana Press. https://doi.org/10.1007/978-1-59745-350-9_1
Zaidi, M. R., & Merlino, G. (2011). The two faces of interferon-γ in cancer. Clinical Cancer Research, 17(19), 6118–6124. https://doi.org/10.1158/1078-0432.CCR-11-0482
Zubair, M. S., Alarif, W. M., Ghandourah, M. A., & Anam, S. (2021). A new steroid glycoside from Begonia sp.: Cytotoxic activity and docking studies. Natural Product Research, 35(13), 2224–2231. https://doi.org/10.1080/14786419.2019.1669026
Zubair, M. S., Alarif, W. M., Ghandourah, M. A., Anam, S., & Jantan, I. (2020). Cytotoxic Activity of 2-O-β-glucopyranosil Cucurbitacin D from Benalu Batu (Begonia sp.) Growing in Morowali, Central Sulawesi. Indonesian Journal of Chemistry, 20(4), 766. https://doi.org/10.22146/ijc.43626
Zubair, M. S., Khairunisa, S. Q., Sulastri, E., Ihwan, Widodo, A., Nasronudin, & Pitopang, R. (2021). Antioxidant and antiviral potency of Begonia medicinalis fractions. Journal of Basic and Clinical Physiology and Pharmacology, 32(4), 845–851. https://doi.org/10.1515/jbcpp-2020-0476