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Background <p><i>Eucommia ulmoides</i> Oliv. (PE), <i>Styphnolobium japonicum</i> (L.) Schott (PS) and <i>Portulaca oleracea</i> L. (PP) are well-characterized medicinal botanicals with established therapeutic profiles. PE exhibits anti-psoriatic and anti-aging properties through bioactive constituents, as demonstrated in vitro and in vivo research. PS flowers contain sophoricoside, a validated modulator of atopic dermatitis pathways, while PP displays broad-spectrum anti-inflammatory and antioxidant activities. Given their complementary mechanisms and the limited efficacy of single-agent approaches against UVB-driven oxidative stress/inflammation, we hypothesized that a tripartite extract (ESP: PE/PS/PP) would demonstrate synergistic photoprotection. This study evaluated the efficacy of ESP through integrated experimental cell models, a murine model of acute UVB-induced photoaging, and transcriptome analysis.</p> Results <p>ESP extracts demonstrated synergistic antioxidant and photoprotective activities through multi-target mechanisms, effectively attenuating UVB-induced photoaging in vitro and in vivo. LC-QTOF-MS analysis identified major bioactive components comprising organic acids, polysaccharides, iridoids, and flavonoids. In a paracrine signaling model using conditioned medium from UVB-exposed HaCaT cells to stimulate HFF cells, ESP significantly inhibited UVB-induced secretion of inflammatory mediators (PGE2, TNF-α, IL-1α, IL-6). Transcriptome sequencing coupled with RT-qPCR validation revealed that ESP attenuated photoaging via the IL-17 signaling pathway, downregulating key mediators including matrix metalloproteinases (MMP1/3/13), chemokines (CXCL3/8, CCL7), and colony-stimulating factors (CSF2/3). Furthermore, ESP reduced mitochondrial ROS generation, stabilized membrane potential, activated the TGF-β/Smad pathway, and upregulated COL1A1 and COL3A1 expression. Significantly, in a murine model of acute UVB-induced photoaging, ESP treatment produced dose-dependent restoration of UVB-damaged skin. It markedly attenuated epidermal hyperplasia, and increased collagen density. Concurrently, it improved skin elasticity and barrier function (TEWL), while suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-17) and MMP3 expression, and upregulating collagen genes (COL1A1, COL3A1). These findings demonstrated that ESP inhibits photoaging through four integrated pathways: (1) attenuating inflammatory cytokines, (2) scavenging ROS, (3) enhancing collagen synthesis, and (4) restoring structural and functional integrity to the skin.</p> Conclusion <p>Our data established ESP as a potent anti-photoaging agent that protects against UVB-induced damage via coordinated modulation of the TGF-β/Smad pathway and IL-17 signaling. Its dose-dependent efficacy, demonstrated through effective ROS scavenging, enhanced collagen synthesis, and significant anti-inflammatory activity, validates ESP as a novel, multi-target strategy against skin aging.</p> Graphical Abstract <p></p>

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Synergistic anti-photoaging and anti-inflammatory effects of Eucommia ulmoides, Styphnolobium japonicum, and Portulaca oleracea extracts via TGF-β/Smad/IL-17 pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • Fangli Zhu,
  • Liping Qu,
  • Rui Xu,
  • Yonglei Yuan,
  • Shuhong Zhang,
  • Yueyue Chen

摘要

Background

Eucommia ulmoides Oliv. (PE), Styphnolobium japonicum (L.) Schott (PS) and Portulaca oleracea L. (PP) are well-characterized medicinal botanicals with established therapeutic profiles. PE exhibits anti-psoriatic and anti-aging properties through bioactive constituents, as demonstrated in vitro and in vivo research. PS flowers contain sophoricoside, a validated modulator of atopic dermatitis pathways, while PP displays broad-spectrum anti-inflammatory and antioxidant activities. Given their complementary mechanisms and the limited efficacy of single-agent approaches against UVB-driven oxidative stress/inflammation, we hypothesized that a tripartite extract (ESP: PE/PS/PP) would demonstrate synergistic photoprotection. This study evaluated the efficacy of ESP through integrated experimental cell models, a murine model of acute UVB-induced photoaging, and transcriptome analysis.

Results

ESP extracts demonstrated synergistic antioxidant and photoprotective activities through multi-target mechanisms, effectively attenuating UVB-induced photoaging in vitro and in vivo. LC-QTOF-MS analysis identified major bioactive components comprising organic acids, polysaccharides, iridoids, and flavonoids. In a paracrine signaling model using conditioned medium from UVB-exposed HaCaT cells to stimulate HFF cells, ESP significantly inhibited UVB-induced secretion of inflammatory mediators (PGE2, TNF-α, IL-1α, IL-6). Transcriptome sequencing coupled with RT-qPCR validation revealed that ESP attenuated photoaging via the IL-17 signaling pathway, downregulating key mediators including matrix metalloproteinases (MMP1/3/13), chemokines (CXCL3/8, CCL7), and colony-stimulating factors (CSF2/3). Furthermore, ESP reduced mitochondrial ROS generation, stabilized membrane potential, activated the TGF-β/Smad pathway, and upregulated COL1A1 and COL3A1 expression. Significantly, in a murine model of acute UVB-induced photoaging, ESP treatment produced dose-dependent restoration of UVB-damaged skin. It markedly attenuated epidermal hyperplasia, and increased collagen density. Concurrently, it improved skin elasticity and barrier function (TEWL), while suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-17) and MMP3 expression, and upregulating collagen genes (COL1A1, COL3A1). These findings demonstrated that ESP inhibits photoaging through four integrated pathways: (1) attenuating inflammatory cytokines, (2) scavenging ROS, (3) enhancing collagen synthesis, and (4) restoring structural and functional integrity to the skin.

Conclusion

Our data established ESP as a potent anti-photoaging agent that protects against UVB-induced damage via coordinated modulation of the TGF-β/Smad pathway and IL-17 signaling. Its dose-dependent efficacy, demonstrated through effective ROS scavenging, enhanced collagen synthesis, and significant anti-inflammatory activity, validates ESP as a novel, multi-target strategy against skin aging.

Graphical Abstract