ArticleFrontiers in cellular and infection microbiology2025
Car@PLGA-NPs target gut microbiota-ER stress axis to combat diabetes.
Article in Frontiers in cellular and infection microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Previous studies have demonstrated that carvacrol (Car) ameliorates vascular and hepatic injury in db/db mice, but its low bioavailability limits clinical translation. Methods: To address this, this study constructed carvacrol-loaded polymeric nanoparticles (Car@PLGA-NPs) to enhance carvacrol bioavailability and fully explore its novel mechanisms of action on islet function and gut homeostasis in a diabetic model. We used C57BL/6J db/db mice to measure serum fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance (ITT), and lipid profiles. Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota composition and its correlation with host indices. Pancreatic and intestinal tissues underwent histopathological staining, immunofluorescence, and Western blotting to detect endoplasmic reticulum (ER) stress-related protein expression levels (p-IRE1α, XBP1S, PERK, p-ElF2α). Results: Results demonstrated that Car@PLGA-NPs, compared to free carvacrol, significantly improved insulin sensitivity, reduced fasting blood glucose, ameliorated dyslipidemia, attenuated inflammation, and mitigated oxidative stress in db/db mice. 16S rRNA sequencing revealed that Car@PLGA-NPs remodeled the gut microbiota composition, with Conclusions: Collectively, this study confirms that the PLGA nanocarrier effectively enhances carvacrol bioavailability. Car@PLGA-NPs improve islet function and intestinal homeostasis in diabetic mice by remodeling the gut microbiota and subsequently inhibiting ER stress in pancreatic and intestinal tissues, providing a novel nano-drug delivery system and a "microbiota-ER stress" regulatory axis for diabetes treatment.
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