Synergistic anti-photoaging and anti-inflammatory effects of Eucommia ulmoides, Styphnolobium japonicum, and Portulaca oleracea extracts via TGF-β/Smad/IL-17 pathway
{"title":"Synergistic anti-photoaging and anti-inflammatory effects of Eucommia ulmoides, Styphnolobium japonicum, and Portulaca oleracea extracts via TGF-β/Smad/IL-17 pathway","authors":"Fangli Zhu, Liping Qu, Rui Xu, Yonglei Yuan, Shuhong Zhang, Yueyue Chen","doi":"10.1186/s40538-025-00856-1","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><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><h3>Results</h3><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><h3>Conclusion</h3><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><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":512,"journal":{"name":"Chemical and Biological Technologies in Agriculture","volume":"12 1","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chembioagro.springeropen.com/counter/pdf/10.1186/s40538-025-00856-1","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical and Biological Technologies in Agriculture","FirstCategoryId":"97","ListUrlMain":"https://link.springer.com/article/10.1186/s40538-025-00856-1","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Chemical and Biological Technologies in Agriculture is an international, interdisciplinary, peer-reviewed forum for the advancement and application to all fields of agriculture of modern chemical, biochemical and molecular technologies. The scope of this journal includes chemical and biochemical processes aimed to increase sustainable agricultural and food production, the evaluation of quality and origin of raw primary products and their transformation into foods and chemicals, as well as environmental monitoring and remediation. Of special interest are the effects of chemical and biochemical technologies, also at the nano and supramolecular scale, on the relationships between soil, plants, microorganisms and their environment, with the help of modern bioinformatics. Another special focus is the use of modern bioorganic and biological chemistry to develop new technologies for plant nutrition and bio-stimulation, advancement of biorefineries from biomasses, safe and traceable food products, carbon storage in soil and plants and restoration of contaminated soils to agriculture.
This journal presents the first opportunity to bring together researchers from a wide number of disciplines within the agricultural chemical and biological sciences, from both industry and academia. The principle aim of Chemical and Biological Technologies in Agriculture is to allow the exchange of the most advanced chemical and biochemical knowledge to develop technologies which address one of the most pressing challenges of our times - sustaining a growing world population.
Chemical and Biological Technologies in Agriculture publishes original research articles, short letters and invited reviews. Articles from scientists in industry, academia as well as private research institutes, non-governmental and environmental organizations are encouraged.