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Antiphagocytic Properties of Polygallic Acid with Implications in Gouty Inflammation

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Abstract—

Polygallic acid (PGAL) has been used in vitro to protect synoviocytes from monosodium urate (MSU) crystals due to its anti-inflammatory properties. However, MSU crystals can also activate other cells of the synovial fluid (SF). We studied the impact of PGAL on the phagocytosis of MSU crystals, inflammation, and oxidative stress using an in vitro model with SF leukocytes and THP-1 monocyte cells. SF leukocytes were stimulated with PGAL and MSU crystals, proinflammatory cytokines and phagocytosis were assessed. In THP-1 cells, the effect of PGAL on the phagocytosis of MSU crystals and the levels of IL-1β, IL-6, TNF-α, and reactive oxygen species (ROS) was evaluated. PGAL was added to THP-1 cultures 24 h before MSU crystal addition as a pre-treatment, and IL-1β was measured. One-way ANOVA with Tukey's post hoc test was performed, and a P value < 0.05 was considered statistically significant. PGAL (100 µg/mL) decreased phagocytosis in SF leukocytes by 14% compared to cells exposed to crystals without PGAL. In THP-1 cells, 100 and 200 µg/mL PGAL reduced phagocytosis by 17% and 15%, respectively. In SF cells, there was a tendency to decrease IL-1β and IL-6. In THP-1 cells, decreases in IL-1β and TNF-α, as well as a slight decrease in ROS, were identified. PGAL pre-treatment resulted in a reduction of IL-1β. PGAL inhibits MSU phagocytosis by exerting an anti-inflammatory effect on cells exposed to crystals. The use of PGAL before an acute attack of gout suggests an important protective factor to control the inflammation.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

We would like to thank Jorge Cerna Cortés, Ph.D., from Instituto Politécnico Nacional (Mexico) for the reagents for carrying out cell culture assays and ELISAs.

Funding

This research received funding from the National Council of Science and Technology (CONACYT) for financing SEP-BASICA FSSEP02-C-2018-2 # A1-S-16109.

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Authors and Affiliations

  1. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Yessica Zamudio-Cuevas, Ambar López-Macay, Karina Martínez-Flores & Javier Fernández-Torres

  2. Unidad de Ingeniería de Tejidos Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Valentín Martínez-López, Carmen G. Hernández-Valencia & Roberto Sánchez-Sánchez

  3. División de Reconstrucción Articular de Cadera y Rodilla, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Nathalie Montaño-Armendáriz

  4. División de Reumatología, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Carlos Alberto Lozada-Pérez

  5. Departamento de Alimentos y Biotecnología, Facultad de Química, UNAM, Mexico City, Mexico

    Carmen G. Hernández-Valencia & Miquel Gimeno

  6. Escuela de Ingeniería y Ciencias, Departamento de Bioingeniería, Instituto Tecnólogico de Monterrey, C. Puente No 222, Colonia Arboledas Sur, 14380, Tlalpan, Mexico City, Mexico

    Roberto Sánchez-Sánchez

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  1. Yessica Zamudio-Cuevas
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Contributions

YZC and JFT contributed to the conception and design of the study, data collection, analysis, and interpretation, and writing and critical revision of the manuscript. VML and ALM, cell cultures, oxidative stress experiments, and data acquisition. NMA and CALP, provision of SF samples, collection of medical records and critical revision of the manuscript. KMF and CHV, pro-inflammatory molecules quantification and acquisition of data, writing and critical revision of the manuscript. YZC and RSS, statistical analysis, data interpretation and critical revision of the manuscript. MG, data interpretation and critical revision of the manuscript. All authors contributed to data analysis and interpretation as well as writing and critical revision of the article. All authors have approved the final version of the manuscript.

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Correspondence to Javier Fernández-Torres.

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This study was approved by the Ethics and Research Committee of the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra (registration number INR-27/20). All procedures performed in this study involving human participants were in accordance with the ethical standards of the INR-LGII-Institutional Research and Ethical Committee and with the Helsinki Declaration (1964). Informed consent was obtained from all individual participants included in the study.

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Zamudio-Cuevas, Y., Martínez-López, V., López-Macay, A. et al. Antiphagocytic Properties of Polygallic Acid with Implications in Gouty Inflammation. Inflammation 46, 1952–1965 (2023). https://doi.org/10.1007/s10753-023-01852-z

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