Protective effects of exocarpium citri grandis extract and its flavonoid components against polystyrene...

Microplastics (MPs) pose potential risks to human health due to their persistence and biotoxicity, mainly by inducing oxidative stress, inflammation, and gut microbiota imbalance. Exocarpium Citri Grandis (ECG), a traditional Chinese medicine with both medicinal and dietary value, has shown notable anti-inflammatory and antioxidant activities. In this study, UHPLC-Q-TOF MS profiling combined with network pharmacology analysis was applied to identify the principal effective ingredients of ECG and to evaluate its protective effects on polystyrene microplastic (PS) -induced hepatic and intestinal toxicity in mice. ECG and its main parts, naringenin and naringin, greatly reduced the oxidative stress caused by PS. They also eased liver injury and improved the intestinal barrier. ECG was associated with reduced inflammation and oxidative stress, accompanied by changes in the TLR4/NF-κB/NLRP3 and Nrf2/HO-1 pathways. It also improved intestinal structural integrity by increasing the levels of tight junction proteins. Gut microbiota analysis revealed that ECG intervention significantly improved PS-associated disruptions in microbial diversity and enriched beneficial genera such as Lactobacillus, Bacteroides, and Blautia. Metabolomic profiling showed that ECG significantly altered 1,507 PS-associated metabolic features, notably inhibiting pro-inflammatory arachidonic acid metabolism and upregulating antioxidant-related ubiquinone biosynthesis. Correlation analysis further linked key microbial shifts (e.g., Clostridia) with specific metabolite changes. In summary, ECG significantly alleviates PS-induced hepatoenterotoxicity through multi-level modulation of inflammatory, antioxidant, and gut microbiota-metabolite interactions, antioxidant, and gut microbiota-metabolism effects, providing new insights into the use of natural products to prevent and control health risks associated with MPs.

The online version contains supplementary material available at 10.1007/s10616-026-00921-z.