Species-Specific Ceramide Modulation by Natural Compounds in Metabolic Syndrome and Cardiovascular Disease: Mechanistic and Emerging Lipidomic Insights
| Author | Hassan Darvakh | en |
| Orcid | Hassan Darvakh [0000-0001-7325-6689] | en |
| Issued Date | 2026-05-31 | en |
| Abstract | Context: Ceramides are bioactive sphingolipids implicated in metabolic syndrome and cardiovascular disease (CVD), with species-specific roles in insulin resistance, inflammation, and endothelial dysfunction. Dysregulated ceramide metabolism is strongly associated with obesity, type 2 diabetes, and atherosclerotic cardiovascular disease, highlighting ceramide pathways as promising therapeutic targets. This narrative review assesses the therapeutic potential of natural compounds, including polyphenols, flavonoids, alkaloids, and isoflavones, in modulating ceramide metabolism in metabolic syndrome and CVD, with a particular focus on species-specific ceramide alterations, underlying mechanisms, and evidence from preclinical and clinical studies. Evidence Acquisition: A structured literature search was conducted in PubMed, Scopus, Web of Science, Embase, and Google Scholar to identify studies published up to January 2026. Preclinical and clinical studies evaluating the effects of natural compounds on ceramide synthesis, degradation, and signaling pathways were included. This review was conducted as a narrative synthesis, incorporating selected elements of the PRISMA guidelines to enhance transparency in study identification and selection. Results: A total of 67 studies were included in the synthesis. Natural compounds such as resveratrol, curcumin, epigallocatechin gallate (EGCG), quercetin, berberine, and genistein were reported to reduce total ceramide levels and selectively modulate pathogenic long-chain ceramides, particularly the C16:0 and C18:0 species. These effects were generally associated with improved insulin signaling and mitochondrial function, as well as reduced inflammation, oxidative stress, and apoptosis. Emerging clinical evidence suggests modest reductions in circulating long-chain ceramides, approximately 10 - 25% in some studies, accompanied by improvements in insulin sensitivity, lipid profiles, and endothelial function; however, these findings are based on heterogeneous, nonstandardized interventions. Conclusions: Natural compounds that target ceramide metabolism may represent a promising adjunctive strategy for the prevention and management of metabolic syndrome and CVD. However, the current evidence is largely derived from preclinical studies, and clinical data remain limited and heterogeneous. Future well-designed randomized controlled trials with standardized interventions and species-specific lipidomic endpoints are required to confirm these effects and support clinical translation. | en |
| DOI | https://doi.org/10.5812/jjnpp-171497 | en |
| URI | https://brieflands.com/journals/jjnpp/articles/171497 | en |
| Keyword | Ceramide | en |
| Keyword | Natural Compounds | en |
| Keyword | Phytochemicals | en |
| Keyword | Metabolic Syndrome | en |
| Keyword | Cardiovascular Disease | en |
| Keyword | Insulin Resistance | en |
| Keyword | Lipotoxicity | en |
| Keyword | Lipidomics | en |
| Publisher | Brieflands | en |
| Title | Species-Specific Ceramide Modulation by Natural Compounds in Metabolic Syndrome and Cardiovascular Disease: Mechanistic and Emerging Lipidomic Insights | en |
| Type | Review Article | en |
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