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Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages

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Abstract

In Hawaiian traditional medicinal practices, the indigenous ‘uhaloa, Waltheria indica var. Americana is one of the most recognized plants. Waltheria is also known in various cultures as a medicinal plant for the treatment of inflammatory conditions. Results in human subjects and cell and animal models supported anti-inflammatory activity for the Waltheria flavonoid quercetin, and for crude plant extracts, limited animal studies also confirmed anti-inflammatory effects. Yet no systematic studies have examined immune or inflammatory responses affected by these extracts. In order to gain insight into inflammatory cascades modulated by Waltheria extracts, and to uncover the mechanistic bases for the effective use of this medicinal plant as a natural anti-inflammatory agent, we have undertaken analyses of LPS and TNF-α/IF-γ-stimulated human macrophages treated with Waltheria extracts using targeted qRT-PCR and Inflammation Panels to test differential mRNA expression of two hundred immune-related genes, furthermore, ELISA assays and Inflammatory Protein arrays to determine extracts-modulated intracellular and secreted levels of prominent cytokines. Results demonstrate that Waltheria extracts inhibit key inflammatory cytokines and cytokine receptors including protein levels of IL-1B, IL-1ra, IL-8 and IL-6, reduce both mRNA and protein levels of TNF-α and protein levels of its receptor, TNF RII, predicting diminished TNF-α-associated inflammatory signaling that, together with significant reduction of NF-κB mRNA and protein, can effectively diminish activities of multiple pro-inflammatory signaling pathways and mitigate key processes in diseases with inflammatory components.

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Acknowledgement

Funding for this project was provided by Kamehameha Schools Outreach Program. We are grateful to Wenji Xu, Ph. D, for the RNA array Technical and Statistical Service at NanoString Technologies.

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Authors and Affiliations

  1. Department of Integrative Medicine and Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii, Honolulu, USA

    Rozalia Laczko, Andrew Chang, Lindsey Watanabe, Maria Petelo, Kimberly Kahaleua & Katalin Csiszar

  2. Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, USA

    Jon-Paul Bingham

Authors
  1. Rozalia Laczko
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  2. Andrew Chang
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  3. Lindsey Watanabe
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  4. Maria Petelo
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  5. Kimberly Kahaleua
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  6. Jon-Paul Bingham
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  7. Katalin Csiszar
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Contributions

RL performed the experiments, assisted with the design, analyzed and interpreted the data, and prepared the results and figures for publication, students AC, MP, LW and KK generated plant extracts and carried out some of the cytotoxicity and ELISA test, JPB contributed with HPLC analytical data, KC conceived, designed, and developed the study, analyzed and interpreted the results, and generated the manuscript.

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Correspondence to Katalin Csiszar.

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Laczko, R., Chang, A., Watanabe, L. et al. Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages. Inflammopharmacol 28, 525–540 (2020). https://doi.org/10.1007/s10787-019-00658-6

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