Interleukin-1β (IL-1β) and Interleukin 10 (IL-10) Regulation Reduces Epithelial Inflammation in Mice Using a Topical Cream with Ficus minahassae
DOI:
https://doi.org/10.22146/ijp.23541Keywords:
inflammation, Ficus minahassae, carrageenan, gene expressionAbstract
Inflammation is an immune response contributing substantially to morbidity and mortality. However, anti-inflammatory treatments present limitations including availability of resources, high costs, and adverse reactions. Here, we investigated the anti-inflammatory properties of a traditionally used medicinal indigenous plant in the Philippines, Ficus minahassae (Hagimit), as a potential natural and cost-effective alternative in the form of a topical cream. We utilized a carrageenan-induced paw edema in mice and evaluated phenotypic, hematological, and genetic markers. Our findings demonstrated that the hagimit cream reduced paw edema comparable to a commercially available cream. After 8 hours, significant difference in paw temperature was observed among mice treated with mometasone furoate cream and F. minahassae cream which may suggest different mechanisms of inflammation resolution. The resolution of inflammation is parallel to the upregulation of Interleukin-1β (IL-1β) and Interleukin-10 (IL-10), pro and anti-inflammatory markers, respectively. This is corroborated by hematological parameters where neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and granulocyte (%) showed marked reduction. The upregulation of IL-1β and IL-10 reflects a systemic inflammatory resolution response, as evidenced by the hematological measurements. Our work underscores the therapeutic promise of hagimit as a natural, accessible, and sustainable anti-inflammatory agent and suggests the corresponding molecular mechanisms.
References
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Korniluk, A., Koper-Lenkiewicz, O. M., Kamińska, J., Kemona, H., & Dymicka-Piekarska, V. (2019). Mean platelet volume (MPV): New perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators of Inflammation, 2019, 1-14. https://doi.org/10.1155/2019/9213074
Korting, H. C., Unholzer, A., Schäfer-Korting, M., Tausch, I., Gassmueller, J., & H, K. (2002). Different skin thinning potential of equipotent medium‐strength glucocorticoids. Skin Pharmacol Appl Skin Physiol, 15(2), 85-91. https://doi.org/ 10.1159/000049394
Maramba-Lazarte, C. C. (2020). Benefits of mainstreaming herbal medicine in the Philippine healthcare system. Acta Medica Philippina, 54(1). https://doi.org/10.47895/amp.v54i1.1078
Mendes, L. F., Gaspar, V. M., Conde, T. A., Mano, J. F., & Duarte, I. F. (2019). Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-51113-z
Moosazadeh, M., Maleki, I., Alizadeh-Navaei, R., Kheradmand, M., Hedayatizadeh-Omran, A., Shamririan, A., & Barzegar, A. (2019). Normal values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio among Iranian population: Results of Tabari cohort. Caspian J Intern Med, 10(3), 320-325. https://doi.org/10.22088/cjim.10.3.320
Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M. Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies. Cells. 2021 Nov 4;10(11):3017. doi: 10.3390/cells10113017. PMID: 34831240; PMCID: PMC8616543.
Mukherjee, P., Roy, S., Ghosh, D., & Nandi, S. K. (2022). Role of animal models in biomedical research: A review. Laboratory Animal Research, 38(1). https://doi.org/10.1186/s42826-022-00128-1
Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034. doi: 10.1101/cshperspect.a000034. PMID: 20066092; PMCID: PMC2773619.
Ou, Z., Zhao, J., Zhu, L., Huang, L., Ma, Y., Ma, C., Luo, C., Zhu, Z., Yuan, Z., Wu, J., Li, R., & Yi, J. (2019). Anti-inflammatory effect and potential mechanism of betulinic acid on λ-carrageenan-induced paw edema in mice. Biomedicine & Pharmacotherapy, 118, 109347. https://doi.org/10.1016/j.biopha.2019.109347
Patil, K. R., Mahajan, U. B., Unger, B. S., Goyal, S. N., Belemkar, S., Surana, S. J., Ojha, S., & Patil, C. R. (2019). Animal models of inflammation for screening of anti-inflammatory drugs: Implications for the discovery and development of Phytopharmaceuticals. International Journal of Molecular Sciences, 20(18), 4367. https://doi.org/10.3390/ijms20184367
Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023 Aug;19(8):509-524. doi: 10.1038/s41581-023-00720-1. Epub 2023 May 10. PMID: 37165096; PMCID: PMC10171171.
Rafiyan, M., Sadeghmousavi, S., Akbarzadehmoallemkolaei, M., & Rezaei, N. (2023). Experimental animal models of chronic inflammation. Current Research in Immunology, 4, 100063. https://doi.org/10.1016/j.crimmu.2023.100063
Ren, K., & Torres, R. (2009). Role of interleukin-1β during pain and inflammation. Brain Research Reviews, 60(1), 57-64. https://doi.org/10.1016/j.brainresrev.2008.12.020
Rydell-Törmänen, K., & Johnson, J. R. (2019). The applicability of mouse models to the study of human disease. Methods in Molecular Biology, 3-22. https://doi.org/10.1007/978-1-4939-9086-3_1
Schäffer, M., & Barbul, A. (1998). Lymphocyte function in wound healing and following injury. Journal of British Surgery, 85(4), 444-460. https://doi.org/10.1046/j.1365-2168.1998.00734.x
Schmid, T., & Brüne, B. (2021). Prostanoids and resolution of inflammation – Beyond the lipid-mediator class switch. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.714042
Serra, M., Botelho, C., Almeida, H., Casas, A., Teixeira, J. A., & Barros, A. N. (2025). Stable and functional cosmetic creams enriched with grape stem extract: A sustainable skincare strategy. Antioxidants, 14(7), 784. https://doi.org/10.3390/antiox14070784
Shan, L., Tyagi, A., Ham, H., & Oh, D. H. (2024). Uncovering the anti-inflammatory potential of Lactiplantibacillus plantarum fermented Cannabis Sativa L seeds. Npj Science of Food, 8(1). https://doi.org/10.1038/s41538-024-00285-8
Spada, F., Barnes, T. M., & Greive, K. A. (2018). Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids. Australasian Journal of Dermatology, 59(3). https://doi.org/10.1111/ajd.12762
Takao, K., & Miyakawa, T. (2014). Genomic responses in mouse models greatly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences, 112(4), 1167–1172. https://doi.org/10.1073/pnas.1401965111
Tudurachi, B., Anghel, L., Tudurachi, A., Sascău, R. A., & Stătescu, C. (2023). Assessment of inflammatory hematological ratios (Nlr, plr, mlr, LMR and monocyte/hdl–cholesterol ratio) in acute myocardial infarction and particularities in young patients. International Journal of Molecular Sciences, 24(18), 14378. https://doi.org/10.3390/ijms241814378
Xu, Z., Zhou, J., Cai, J., Zhu, Z., Sun, X., & Jiang, C. (2012). Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema. Journal of Inflammation, 9(1). https://doi.org/10.1186/1476-9255-9-2
Yadav, V. R., Prasad, S., Sung, B., Kannappan, R., & Aggarwal, B. B. (2010). Targeting inflammatory pathways by Triterpenoids for prevention and treatment of cancer. Toxins, 2(10), 2428-2466. https://doi.org/10.3390/toxins2102428
Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007 Spring;45(2):27-37. doi: 10.1097/AIA.0b013e318034194e. PMID: 17426506; PMCID: PMC2785020
Al-Qahtani AA, Alhamlan FS, Al-Qahtani AA. Pro-Inflammatory and Anti-Inflammatory Interleukins in Infectious Diseases: A Comprehensive Review. Trop Med Infect Dis. 2024 Jan 4;9(1):13. doi: 10.3390/tropicalmed9010013. PMID: 38251210; PMCID: PMC10818686.
Bhatt D., Ghosh S (2014). Regulation of the NF-κB-mediated transcription of inflammatory genes. Front. Immunol. 5:71. doi: 10.3389/fimmu.2014.00071
Boy, H. I., Rutilla, A. J., Santos, K. A., Ty, A. M., Yu, A. I., Mahboob, T., Tangpoong, J., & Nissapatorn, V. (2018). Recommended medicinal plants as source of natural products: A review. Digital Chinese Medicine, 1(2), 131-142. https://doi.org/10.1016/s2589-3777(19)30018-7
Buonacera, A., Stancanelli, B., Colaci, M., & Malatino, L. (2022). Neutrophil to lymphocyte ratio: An emerging marker of the relationships between the immune system and diseases. International Journal of Molecular Sciences, 23(7), 3636. https://doi.org/10.3390/ijms23073636
Coondoo, A., Phiske, M., Verma, S., & Lahiri, K. (2014). Side-effects of topical steroids: A long overdue revisit. Indian Dermatology Online Journal, 5(4), 416. https://doi.org/10.4103/2229-5178.142483
Cordero, C. S., Meve, U., & Alejandro, G. J. (2023). Ethnobotany and diversity of medicinal plants used among rural communities in Mina, Iloilo, Philippines: A quantitative study. Journal of Asia-Pacific Biodiversity, 16(1), 96-117. https://doi.org/10.1016/j.japb.2022.12.003
Docherty, S., Harley, R., McAuley, J.J. et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Sci Med Rehabil 14, 5 (2022). https://doi.org/10.1186/s13102-022-003972
Elsayed, E. A., El Enshasy, H., Wadaan, M. A., & Aziz, R. (2014). Mushrooms: A potential natural source of anti-inflammatory compounds for medical applications. Mediators of inflammation, 2014, 805841. https://doi.org/10.1155/2014/805841
Elshafie, H. S., & Camele, I. (2017). An overview of the biological effects of some Mediterranean essential oils on human health. BioMed Research International, 2017, 1-14. https://doi.org/10.1155/2017/9268468
Foy, B. H., Sundt, T., Carlson, J. C., Aguirre, A. D., & Higgins, J. M. (2021). White blood cell and platelet dynamics define human inflammatory recovery. https://doi.org/10.1101/2021.06.19.21259181
Kodama, T., Ashitani, J., Matsumoto, N., Kangawa, K., & Nakazato, M. (2008). Ghrelin treatment suppresses neutrophil-dominant inflammation in airways of patients with chronic respiratory infection. Pulmonary Pharmacology & Therapeutics, 21(5), 774-779. https://doi.org/10.1016/j.pupt.2008.05.001
Korniluk, A., Koper-Lenkiewicz, O. M., Kamińska, J., Kemona, H., & Dymicka-Piekarska, V. (2019). Mean platelet volume (MPV): New perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators of Inflammation, 2019, 1-14. https://doi.org/10.1155/2019/9213074
Korting, H. C., Unholzer, A., Schäfer-Korting, M., Tausch, I., Gassmueller, J., & H, K. (2002). Different skin thinning potential of equipotent medium‐strength glucocorticoids. Skin Pharmacol Appl Skin Physiol, 15(2), 85-91. https://doi.org/ 10.1159/000049394
Maramba-Lazarte, C. C. (2020). Benefits of mainstreaming herbal medicine in the Philippine healthcare system. Acta Medica Philippina, 54(1). https://doi.org/10.47895/amp.v54i1.1078
Mendes, L. F., Gaspar, V. M., Conde, T. A., Mano, J. F., & Duarte, I. F. (2019). Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-51113-z
Moosazadeh, M., Maleki, I., Alizadeh-Navaei, R., Kheradmand, M., Hedayatizadeh-Omran, A., Shamririan, A., & Barzegar, A. (2019). Normal values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio among Iranian population: Results of Tabari cohort. Caspian J Intern Med, 10(3), 320-325. https://doi.org/10.22088/cjim.10.3.320
Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M. Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies. Cells. 2021 Nov 4;10(11):3017. doi: 10.3390/cells10113017. PMID: 34831240; PMCID: PMC8616543.
Mukherjee, P., Roy, S., Ghosh, D., & Nandi, S. K. (2022). Role of animal models in biomedical research: A review. Laboratory Animal Research, 38(1). https://doi.org/10.1186/s42826-022-00128-1
Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034. doi: 10.1101/cshperspect.a000034. PMID: 20066092; PMCID: PMC2773619.
Ou, Z., Zhao, J., Zhu, L., Huang, L., Ma, Y., Ma, C., Luo, C., Zhu, Z., Yuan, Z., Wu, J., Li, R., & Yi, J. (2019). Anti-inflammatory effect and potential mechanism of betulinic acid on λ-carrageenan-induced paw edema in mice. Biomedicine & Pharmacotherapy, 118, 109347. https://doi.org/10.1016/j.biopha.2019.109347
Patil, K. R., Mahajan, U. B., Unger, B. S., Goyal, S. N., Belemkar, S., Surana, S. J., Ojha, S., & Patil, C. R. (2019). Animal models of inflammation for screening of anti-inflammatory drugs: Implications for the discovery and development of Phytopharmaceuticals. International Journal of Molecular Sciences, 20(18), 4367. https://doi.org/10.3390/ijms20184367
Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023 Aug;19(8):509-524. doi: 10.1038/s41581-023-00720-1. Epub 2023 May 10. PMID: 37165096; PMCID: PMC10171171.
Rafiyan, M., Sadeghmousavi, S., Akbarzadehmoallemkolaei, M., & Rezaei, N. (2023). Experimental animal models of chronic inflammation. Current Research in Immunology, 4, 100063. https://doi.org/10.1016/j.crimmu.2023.100063
Ren, K., & Torres, R. (2009). Role of interleukin-1β during pain and inflammation. Brain Research Reviews, 60(1), 57-64. https://doi.org/10.1016/j.brainresrev.2008.12.020
Rydell-Törmänen, K., & Johnson, J. R. (2019). The applicability of mouse models to the study of human disease. Methods in Molecular Biology, 3-22. https://doi.org/10.1007/978-1-4939-9086-3_1
Schäffer, M., & Barbul, A. (1998). Lymphocyte function in wound healing and following injury. Journal of British Surgery, 85(4), 444-460. https://doi.org/10.1046/j.1365-2168.1998.00734.x
Schmid, T., & Brüne, B. (2021). Prostanoids and resolution of inflammation – Beyond the lipid-mediator class switch. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.714042
Serra, M., Botelho, C., Almeida, H., Casas, A., Teixeira, J. A., & Barros, A. N. (2025). Stable and functional cosmetic creams enriched with grape stem extract: A sustainable skincare strategy. Antioxidants, 14(7), 784. https://doi.org/10.3390/antiox14070784
Shan, L., Tyagi, A., Ham, H., & Oh, D. H. (2024). Uncovering the anti-inflammatory potential of Lactiplantibacillus plantarum fermented Cannabis Sativa L seeds. Npj Science of Food, 8(1). https://doi.org/10.1038/s41538-024-00285-8
Spada, F., Barnes, T. M., & Greive, K. A. (2018). Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids. Australasian Journal of Dermatology, 59(3). https://doi.org/10.1111/ajd.12762
Takao, K., & Miyakawa, T. (2014). Genomic responses in mouse models greatly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences, 112(4), 1167–1172. https://doi.org/10.1073/pnas.1401965111
Tudurachi, B., Anghel, L., Tudurachi, A., Sascău, R. A., & Stătescu, C. (2023). Assessment of inflammatory hematological ratios (Nlr, plr, mlr, LMR and monocyte/hdl–cholesterol ratio) in acute myocardial infarction and particularities in young patients. International Journal of Molecular Sciences, 24(18), 14378. https://doi.org/10.3390/ijms241814378
Xu, Z., Zhou, J., Cai, J., Zhu, Z., Sun, X., & Jiang, C. (2012). Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema. Journal of Inflammation, 9(1). https://doi.org/10.1186/1476-9255-9-2
Yadav, V. R., Prasad, S., Sung, B., Kannappan, R., & Aggarwal, B. B. (2010). Targeting inflammatory pathways by Triterpenoids for prevention and treatment of cancer. Toxins, 2(10), 2428-2466. https://doi.org/10.3390/toxins2102428
Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007 Spring;45(2):27-37. doi: 10.1097/AIA.0b013e318034194e. PMID: 17426506; PMCID: PMC2785020
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2026-09-08
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Manglal-lan, F. Y., Agcaoili, M. J. T., Fabia, J. Z. ., Balloyan, L. R., Beltran, K. G., Irapta, I. K., & Icalia-Gann, P. J. (2026). Interleukin-1β (IL-1β) and Interleukin 10 (IL-10) Regulation Reduces Epithelial Inflammation in Mice Using a Topical Cream with Ficus minahassae. Indonesian Journal of Pharmacy, 37(3), 636–646. https://doi.org/10.22146/ijp.23541
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