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Background <p>The skin plays a vital role in host defense against microorganisms, viruses, and environmental agents. Inflammatory skin conditions are initiated by increased expression of cytokines, interferons, and interleukins, which activate immune responses. TNF-α and lipopolysaccharide (LPS) are key inducers of skin inflammation, contributing to diseases, including psoriasis, ichthyosis, atopic dermatitis, and potentially melanoma. Protocatechuic acid (PCA), a natural anthocyanin with anticancer and anti-inflammatory properties, was chemically modified to synthesize PCA alkyl ester (PAE) derivatives to improve its anti-inflammatory efficacy.</p> Objective <p>This study aimed to investigate whether PAE derivatives more effectively inhibit TNF-α-induced inflammation in HaCaT keratinocyte cells compared to unmodified PCA. The expression levels of key downstream molecules in the Akt signaling pathway were assessed by western blotting, and the relative mRNA expression of muscle atrophy-related genes was analyzed using real-time PCR.</p> Results <p>We evaluated cytokine expression using ELISA, and MTT assays were performed to assess cytotoxicity. The PAE derivatives, particularly PAE-5, 6, and 7, significantly reduced IL-8 production at lower concentrations than PCA while maintaining low cytotoxicity. In contrast, PAE-12 exhibited reduced efficacy despite higher hydrophobicity, suggesting that excessive hydrophobicity may hinder biological activity. Moreover, PAE-5 and PAE-6 markedly suppressed LPS-induced expression of IL-6, IL-1β, and TNF-α, underscoring the importance of optimal alkyl chain length.</p> Conclusions <p>Our results provides that PCA alkyl ester derivatives are promising anti-inflammatory agents with low toxicity, offering potential applications in cosmeceutical formulations for treating inflammatory skin conditions.</p>

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Protocatechuic acid alkyl ester derivatives alleviate TNF-α and LPS-induced inflammation in HaCaT cells

  • 期刊论文

  • 发表日期：

    2025年8月19日

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  • Dong Young Kang,
  • Yunseul Park,
  • Heejoo Shin,
  • Yunkyeong Kwon,
  • Hyo Tae Kim,
  • Wooshik Shin,
  • Jaehoon Cho,
  • Se Won Bae,
  • Kyoung-Jin Jang

摘要

Background

The skin plays a vital role in host defense against microorganisms, viruses, and environmental agents. Inflammatory skin conditions are initiated by increased expression of cytokines, interferons, and interleukins, which activate immune responses. TNF-α and lipopolysaccharide (LPS) are key inducers of skin inflammation, contributing to diseases, including psoriasis, ichthyosis, atopic dermatitis, and potentially melanoma. Protocatechuic acid (PCA), a natural anthocyanin with anticancer and anti-inflammatory properties, was chemically modified to synthesize PCA alkyl ester (PAE) derivatives to improve its anti-inflammatory efficacy.

Objective

This study aimed to investigate whether PAE derivatives more effectively inhibit TNF-α-induced inflammation in HaCaT keratinocyte cells compared to unmodified PCA. The expression levels of key downstream molecules in the Akt signaling pathway were assessed by western blotting, and the relative mRNA expression of muscle atrophy-related genes was analyzed using real-time PCR.

Results

We evaluated cytokine expression using ELISA, and MTT assays were performed to assess cytotoxicity. The PAE derivatives, particularly PAE-5, 6, and 7, significantly reduced IL-8 production at lower concentrations than PCA while maintaining low cytotoxicity. In contrast, PAE-12 exhibited reduced efficacy despite higher hydrophobicity, suggesting that excessive hydrophobicity may hinder biological activity. Moreover, PAE-5 and PAE-6 markedly suppressed LPS-induced expression of IL-6, IL-1β, and TNF-α, underscoring the importance of optimal alkyl chain length.

Conclusions

Our results provides that PCA alkyl ester derivatives are promising anti-inflammatory agents with low toxicity, offering potential applications in cosmeceutical formulations for treating inflammatory skin conditions.