Dendrobium huoshanense Improves Atherosclerosis in High-Fat-Induced ApoE Mice by Regulating Gut Microbiota and Serum Metabolite Profiles

Background Cardiovascular diseases, particularly atherosclerosis (AS), remain leading causes of mortality, with limited effective treatments available. Dendrobium huoshanense , a traditional medicinal herb, has shown promising anti-inflammatory and antioxidant effects, but its cardiovascular protective potential remains underexplored. Purpose This study aimed to explore the protective effects of Dendrobium huoshanense polysaccharides (DHP) against AS and elucidate the underlying mechanisms involved. Methods An ApoE(−/−) mice model of AS was established, and DHP was administered at different concentrations via gavage. After 14 weeks, serum and fecal samples were collected. The effects of DHP on lipid profiles, aortic plaques, matrix metalloproteinases (MMP-2 and MMP-9), and the Nrf2/HO-1 pathway were assessed. Additionally, metagenomic sequencing of fecal samples and untargeted metabolomics of serum were conducted and correlations between these findings were explored. Results DHP improved lipid profiles, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and enhanced superoxide dismutase (SOD) activity. It stabilized aortic plaques, suppressed MMP-2 and MMP-9 overexpression, and activated the Nrf2/HO-1 pathway. DHP also promoted gut microbiota balance, increasing Mucispirillum, Bifidobacterium , and Faecalibaculum while decreasing Desulfovibrionaceae and Eubacterium . Metabolomics revealed alterations in metabolites, including taurochenodeoxycholic acid and ursocolic acid, influencing amino acid, glycerophospholipid, and bile acid metabolism. Conclusions DHP effectively lowers lipid levels, stabilizes aortic plaques, restores gut microbiota balance, and corrects metabolic disturbances, thereby inhibiting the progression of atherosclerosis. These findings provide a scientific basis for the clinical use of DHP in AS prevention and treatment.