PHYTOMEDICINE
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2025
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IF 8.3
Jun-Han Wang,Min Li,Peng-Fei Xie,Jia-Yao Si,Zhen-Jie Feng,Chuan-Feng Tang,Jian-Mei Li
Background Aging-related skin fibrosis (SF) is a complex condition with limited treatment options. Procyanidin C1 (PCC1), a natural polyphenolic compound with demonstrated senolytic activity, has emerged as a potential therapeutic agent for fibrotic disorders through its selective elimination of senescent cells. However, its therapeutic efficacy and mechanisms in aging-related SF remain unclear. Purpose This study aimed to investigate the mechanisms of PCC1 in aging-related SF. Results In D-galactose-induced L929 cells, PCC1 treatment significantly attenuated the expression of both senescence-associated markers (IL-1β, P16, P21 and LMNB1) and fibrosis-related markers (α-SMA, LOXL2 and COL1). Network pharmacology and experimental validation (molecular docking, DARTS, CETSA, MST) identified EGFR as a primary target, with PCC1 directly binding to and inhibiting EGFR phosphorylation. Furthermore, PCC1 treatment effectively down-regulated TGFβ1 expression and suppressed SMAD2/3 phosphorylation in D-galactose-induced L929 cells. Notably, PCC1 blocked NSC228155-induced EGFR phosphorylation and inhibited ERK/MAPK, AKT/mTOR and TGFβ/SMAD pathway activation. In bleomycin-induced SF mice, PCC1 significantly attenuated epidermal hyperplasia, improved collagen structure, restored the collagen I/III ratio, and reduced EGFR phosphorylation along with TGFβ1 expression and SMAD2/3 phosphorylation. Conclusion This study elucidates that PCC1 exerts its anti-fibrotic effects through dual mechanisms: resistance to cellular senescence and modulation of fibroblast heterogeneity. By directly binding to EGFR and inhibiting its phosphorylation, PCC1 subsequently suppresses multiple downstream signaling cascades, ultimately ameliorating TGFβ/SMAD-mediated SF. These findings establish PCC1 as a promising therapeutic candidate for aging-related skin fibrosis, offering a novel approach through targeted EGFR inhibition and comprehensive pathway modulation .
研究领域:
医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Min Li,Jia-Yao Si,Peng-Fei Xie,Zhen-Jie Feng,Sheng-Jie Li,Feng Zhou,Jian-Mei Li
The global aging crisis has increased the risk of atherosclerosis (AS), positioning vascular senescence as a critical therapeutic target. Procyanidin C1 (PCC1), a bioactive polyphenol from hawthorn, demonstrates dual senolytic and longevity-enhancing effects. This study explored the regulatory role and mechanisms of PCC1 in AS using an ApoE −/− mouse model fed a high-fat diet (HFD) and a D-galactose (D-Gal)-induced cellular senescence model. Hawthorn oligomeric proanthocyanidins (HOPCs), as well as PCC1, showed potent anti-atherosclerotic and anti-aging effects by improving serum lipid metabolism and reducing aortic root plaque, vascular senescence markers and inflammatory adhesion molecules. Metabolomic analysis demonstrated that PCC1 significantly suppresses key enzymes in arachidonic acid (AA) metabolism, thereby decreasing downstream pro-inflammatory mediators. Target identification studies, including drug affinity responsive target stability (DARTS) assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS), cellular thermal shift assay (CETSA), and molecular docking, identified heat shock protein 90 (HSP90) as a direct target of PCC1, leading to inhibition of its downstream signaling. In vitro, PCC1 selectively cleared senescent cells, suppressed the senescence-associated secretory phenotype (SASP), enhanced endothelial nitric oxide synthase (eNOS) phosphorylation, and inhibited the toll-like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) pathway, demonstrating multimodal anti-aging and anti-inflammatory effects. Together, these findings indicate that PCC1 mitigates atherosclerosis by targeting both metabolic and inflammatory pathways through senescent cell clearance and HSP90-mediated blockade of the TLR2/NF-κB signaling axis. This dual mechanism highlights PCC1 as a promising vasoprotective agent and supports the potential application of hawthorn extracts in functional foods aimed at preventing aging-related cardiovascular diseases.
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PubMed
高影响因子
Journal of Translational Medicine
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2024
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IF 6.1
Wenbin Hua,Lin Xie,Chenpeng Dong,Guoyu Yang,Shouyuan Chi,Zhiqiang Xu,Cao Yang,Huiwen Wang,Xinghuo Wu
Intervertebral disc degeneration (IVDD) is a common cause of low back pain. Procyanidin C1 (PCC1) has been demonstrated to exert a protective effect on nucleus pulposus (NP) cells, and therefore, plays a critical role in the prevention and therapy of IVDD. Clarifying the pathophysiological characteristics and molecular mechanisms of IVDD may be helpful in establishing novel preventive and therapeutic strategies. This study aimed to investigate the probable mechanisms underlying the protection against acidic pH stress induced human NP cell injury. In vitro, acidic pH stress induced degeneration, mitochondrial dynamics imbalance, mitophagy, and mitochondria-mediated apoptosis in NP cells, all of which were ameliorated by PCC1. Autophagy inhibition partially eliminated the protective effects of PCC1 on mitochondrial homeostasis in NP cells. Moreover, PCC1 activated the sirtuin 3 (SIRT3)/forkhead box O3 (FOXO3) signaling pathway, a pivotal signaling pathway involved in the regulation of mitochondrial homeostasis in NP cells. In vivo, PCC1 ameliorated IVDD in a rat model and preserved the extracellular matrix of NP cells. Consequently, the protective effects of PCC1 on NP cells may inhibit IVDD progression via regulation of the SIRT3/FOXO3 signaling pathway. Therefore, regulation of the SIRT3/FOXO3 signaling pathway may be a novel preventive and therapeutic strategy for IVDD.
研究领域:
骨科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Linyan Duan,Zhizhong Hao,Rong Ji,Xingfan Li,Hao Wang,Yujing Su,Fangxia Guan,Shanshan Ma
Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo . Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aβ deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1β pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD.
研究领域:
神经科学
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药理学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Zhihao Liu,Qihao Li,Fu Zhao,Dapeng Zhang,Xinyue Li,Daozheng Fang,Haimeng Li,Qixiang Shang,Fengyan Chen,Zhiyuan Zhen,Yong Zhu,Chang-An Geng,Jianbo Xiao,Jihang Chen
Procyanidin C1 (PCC1) is a biologically relevant oligomeric small molecule and a trimeric epicatechin with the potential to modulate gut microbiota. However, how it reshapes microbiota-linked phosphatidylcholine homeostasis in the context of insulin resistance remains insufficiently defined, limiting the establishment of mechanism-informed design principles for microbiota-directed metabolic modulation. Here, PCC1 improved systemic glucose and insulin sensitivity, promoted hepatic glycogen accumulation, reduced hepatic steatosis, attenuated skeletal muscle fibrosis, and decreased lipid deposition in adipose tissues. Notably, 16S rRNA sequencing revealed that PCC1 treatment enriched Lactobacillus johnsonii and depleted Leptogranulimonas caecicola , which were positively associated with elevated GPCho (16:0/20:5) and circulating eicosapentaenoic acid (EPA) identified by untargeted metabolomics, indicative of enhanced α-linolenic acid metabolism and a gut microbiota-driven contribution to EPA biosynthesis. Meanwhile, lipidomics revealed that PCC1 reduced diacylglycerols, triacylglycerols, ceramides, and lysophosphatidylcholines, while restoring EPA-containing phosphatidylcholines. Transcriptomics further demonstrated that PCC1 induced tissue-specific metabolic reprogramming, activating PPAR signaling in liver, enhancing oxidative phosphorylation in brown adipose tissue (BAT), and stimulating AMPK signaling in skeletal muscle. Importantly, PCC1 reversed HFD-induced phospholipase A2 dysregulation, upregulating Pla2g2d in skeletal muscle and downregulating Pla2g7 in liver and BAT, two genes implicated in EPA release and phospholipid remodeling. Together, integrated multi-omics analyses identify PCC1 as an oligomeric small-molecule modulator associated with improved insulin sensitivity across multiple tissues and implicate an EPA-linked phosphatidylcholine signaling axis that connects microbiota remodeling with host metabolic responses.
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高影响因子
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