Key Takeaways & Executive Findings
- •• DHC targets 20 genes involved in apoptosis, autophagy, and stress responses, suggesting a mechanistic link to vascular calcification. • Bioinformatics analysis reveals DHC's involvement in key signaling pathways (MAPK, ErbB, HIF-1, FoxO, sphingolipid) that are critical in vascular pathology. • DHC's anti-inflammatory, antioxidant, and anti-apoptotic properties may offer a novel therapeutic approach for vascular calcification. • This study provides a foundation for experimental validation of DHC as a potential drug to inhibit vascular calcification.
Abstract
Dihydrocapsaicin (DHC) is the primary pungent component of natural capsaicinoids in chili peppers, with diverse pharmacological properties including analgesia, anticancer, anti-inflammatory, antioxidant, and anti-obesity effects. Vascular calcification (VC) is a common adverse phenotype of various vascular lesions and an independent risk factor for disease occurrence, progression, and mortality. However, no effective therapeutic strategy currently exists to reverse or cure VC. This study hypothesized a potential connection between DHC and VC and utilized the Comparative Toxicogenomics Database (CTD) to extract experimental target genes of DHC. The results demonstrated that DHC has 20 target genes, including ATF4, CASP3, CASP4, CASP7, CAT, CDKN1A, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, DDIT3, EIF2S1, ERN1, HSPA5, IGF1, MAP1LC3A, MAPK1, MAPK3, and TP53. Chemical-phenotype analysis revealed cell death phenotypes such as apoptosis and autophagy. Disease analysis revealed necrosis, tumors, and cardiomyopathies. Gene Ontology (GO) and pathway analyses (KEGG, REACTOME) highlighted roles in metabolism, apoptosis, stress responses, and critical signaling pathways including MAPK, ErbB, HIF-1, FoxO, and sphingolipid signaling. These findings suggest that DHC may have therapeutic potential in vascular calcification, warranting further investigation.
1. Introduction
Dihydrocapsaicin (DHC, C18H29NO3; Figure 1A) is the primary pungent component of natural capsaicinoids in chili peppers. DHC has diverse pharmacological and physiological properties, such as analgesia, anticancer, anti-inflammatory, antioxidant, and anti-obesity effects [1]. These characteristics suggest its potential clinical applications in pain relief, cancer prevention, and weight loss, with benefits for the cardiovascular and gastrointestinal systems. Consequently, investigating the pharmacological and physiological effects and mechanisms of DHC has become a research hotspot in the food and pharmacological sciences.
Vascular calcification (VC) involves the accumulation and deposition of hydroxyapatite crystals within arterial wall cells, resulting in increased vascular wall stiffness, decreased compliance, thrombosis, and plaque rupture. VC is a common adverse phenotype of various vascular lesions; is a phenotypic feature of diseases such as atherosclerosis, hypertension, aortic valve stenosis, coronary artery disease, diabetes mellitus, and chronic kidney disease; and is an independent risk factor for disease occurrence, progression, and mortality [2]. Moreover, VC is also an independent risk factor and a sign of disease exacerbation and aging. Therefore, it is a life-threatening driver of human health. However, there is currently no acknowledged effective therapeutic strategy to reverse or cure VC clinically, particularly when a specific drug is lacking [3]. Thus, identifying a drug that inhibits VC holds significant importance and clinical value.
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Chenxi Li, Jiajun Chen, Zhiqing Liu, Hongling Zhu, Zeyu Huang, Qingyun Zhu, Lianyong Liu, Chaobao Zhang, Xiangqi Li (2026). Therapeutic potential of dihydrocapsaicin in vascular smooth muscle cell calcification. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2025143
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Frequently Asked Questions
What is dihydrocapsaicin (DHC)?
Dihydrocapsaicin (DHC) is the primary pungent component of natural capsaicinoids in chili peppers, known for its analgesic, anti-inflammatory, antioxidant, and anti-obesity properties.
What is vascular calcification?
Vascular calcification is the abnormal deposition of hydroxyapatite crystals in arterial walls, leading to increased stiffness, decreased compliance, and increased risk of cardiovascular events.
How was the study conducted?
The study used the Comparative Toxicogenomics Database (CTD) to identify experimental target genes of DHC, followed by Gene Ontology (GO), KEGG, and REACTOME pathway analyses to explore its potential role in vascular calcification.
What are the key findings?
DHC targets 20 genes involved in apoptosis, autophagy, and stress responses, and modulates pathways such as MAPK, ErbB, HIF-1, FoxO, and sphingolipid signaling, suggesting a potential therapeutic role in vascular calcification.
What is the significance of this study?
This study provides a bioinformatics-based rationale for further experimental investigation of DHC as a potential drug to inhibit vascular calcification, addressing an unmet clinical need.
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