Protective Effect And Mechanisms Of Maltol On Polystyrene Nanoplastic-Induced Intestinal Injury

Maltol is the Maillard reaction product from red ginseng.It is a natural aromatic compound found in the breakdown of pine needles,roasted malt,chicory,wheat and soybeans.It’s created by the Maillard reaction.Maltol is widely regarded as a safe and reliable flavor enhancer,natural antioxidant and food preservative.Studies have shown that maltol can reduce apoptosis and protect the intestine,and has beneficial effects on growth performance,intestinal pathology,intestinal epithelial cell integrity and host immune response.Polystyrene is a commonly used thermoplastic whose degradation products are widely found in natural environments all over the world.Nanoplastics can infiltrate the food chain,water and/or enter the body by other means,greatly increasing the inevitable risk of intestinal exposure.Maltol is often used as a potential active ingredient for intestinal protection due to its extensive pharmacological activities.Therefore,this topic explores the protective effect and mechanism of natural product maltol in improving intestinal injury caused by polystyrene nanoplastics.In this study,the improvement effect of maltol on intestinal injury induced by polystyrene nanoplastics was investigated in vivo and in vitro from the aspects of autophagic lysosome,apoptosis and intestinal barrier,respectively.In addition,the regulation effect of maltol on intestinal microbial disturbance induced by polystyrene nanoplastics in mice was also explored,which provides a potential therapeutic approach for intestinal injury caused by environmental toxicants.The research contents are as follows:1.Improvement of maltol on intestinal injury induced by polystyrene nanoplastics in miceIn order to explore the protective mechanism of maltol against intestinal injury caused by polystyrene nanoplastics,the mice were tested in vivo.The results showed that maltol(50 mg/kg and 100 mg/kg)significantly inhibited the intestinal toxicity caused by polystyrene nanoplastics(100 mg/kg),and maltol could play a good role in intestinal protection.In addition,different doses of maltol could significantly reduce the level of diamine oxidase(DAO)in the intestinal tract of mice,recover the deterioration of intestinal barrier function,and increase the expression of tight junction proteins ZO-1 and Occludin.Maltol can promote TFEB translocation by activating AMPK and inhibiting m TOR signaling pathway.This process enhanced the acid environment of lysosome,enhanced the activity of lysosome membrane protein LAMP2,improved the activity level of lysosomal hydrolase CTSB,and then enhanced the catabolic ability of lysosome and the function of autophagy lysosome,and finally inhibited the autophagy dependent apoptosis of colon.It also inhibited the expression of Bax,Cleaved caspase3/Caspase 3 proteins associated with apoptosis.2.Ameliorating effect of maltol on damage of Caco-2 cells induced by polystyrene nanoplasticsIn order to further explore the protective effect and mechanism of maltol on intestinal injury induced by polystyrene nanoplastics,human colorectal adenocarcinoma cell(Caco-2)cells were used in this study.The model of polystyrene nanoplastics induced damage to Caco-2cells was established in vitro.The optimal dosage of maltol was 25 μM,50 μM and 100 μM by MTT test.The optimal dosage of maltol could protect Caco-2 cells from damage caused by polystyrene nanoplastics.In addition,the overproduction of reactive oxygen species,the depolarization of balanced mitochondrial membrane potential and the expression of Caspase 3protein could be regulated to alleviate the apoptosis induced by polystyrene nanoplastics.Maltol can ameliorate the deterioration of intestinal barrier function by increasing the expression of tight junction proteins ZO-1 and Occludin.The activation of AMPK/m TOR signaling pathway can also promote TFEB nuclear translocation,significantly restoring the impaired function of polystyrene nanoplastics lysosomes and dredging the autophagy flow.Maltol effectively reduced the damage of polystyrene nanoplastics induced Caco-2 cells,and immunofluorescence staining showed similar results.The results showed that maltol could alleviate the damage of Caco-2 cells induced by exposure to polystyrene nanoplastics by dredging autophagy flow,restoring lysosome function and reducing apoptosis.3.Regulation of maltol on intestinal flora disturbance induced by polystyrene nanoplastics in miceThrough the determination and analysis of intestinal microflora in mouse feces,the changes of maltol in improving intestinal microflora disturbance caused by polystyrene nanoplastics were explored.The results of maltol treatment showed that maltol treatment could effectively improve the decrease of Firmicutes and increase of Bacteroidetes in the intestinal flora of mice caused by polystyrene nanoplastics exposure.In addition,the relative abundance of short-chain fatty acid producing bacteria,such as Lachnospiraceae＿NK4A136＿group and Roseburia,decreased significantly after exposure to polystyrene nanoplastics.The relative abundance of short-chain fatty acid producing bacteria increased significantly.In addition,maltol treatment significantly reduced the pathogenic bacteria Proteobacteria.Meanwhile,maltol reversed the up-regulation of apoptosis-related gene abundance and down-regulation of butyric acid metabolism,propionic acid metabolism,lysosome and ABC transporter related functional genes after exposure to polystyrene nanoplastics.These results indicate that exposure to polystyrene nanoplastics can cause the imbalance of intestinal flora homeostasis,and maltol treatment can effectively improve the result.In conclusion,intestinal injury caused by polystyrene nanoplastics is multifactorial.As far as we know,the effect of maltol on intestinal injury induced by polystyrene nanoplastics and its possible molecular mechanism were investigated in this study.Our results clearly indicate that maltol can improve intestinal barrier function and maintain intestinal microbial homeostasis.Maltol promotes TFEB accumulation by activating AMPK/MTOR pathway,improves lysosome function,promotes autophagy and dregs autophagy flux,thereby reducing polystyrene nanoplastic-induced intestinal cell apoptosis.