Arginyl-fructosyl-glucose, a major Maillard reaction product of red ginseng mitigates cisplatin-evoked intestinal toxicity and .

Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, further causing gastrointestinal cell damage, diarrhea and vomiting. C. A. Meyer, a widely used medicinal and edible plant in China, shows many pharmacological activities. Nevertheless, the role of non-saponin is less known and has great potential in the treatment of severe toxic side effects related to the cisplatin treatment. The present work evaluates the efficiency of a major Maillard reaction product (MRP) of red ginseng, arginyl-fructosyl-glucose (AFG), against cisplatin-evoked intestinal toxicity and , and the underlying possible mechanisms are also explored. The cisplatin-treated mice (a dose of 20 mg kg for one time) showed serious intestinal mucosa damage accompanied by increased indicators of diamine oxidase (DAO) and decreased expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Moreover, cisplatin exposure increased intestinal cell apoptosis with decreased expression of Bcl-2 and increased expression of Bax and cleaved-caspase 3/9 as well as NF-κB related proteins. Interestingly, the supplements of AFG at doses of 40 and 80 mg kg day for 10 days significantly ameliorated these changes. It was also demonstrated in cultured IEC-6 cells that AFG enhanced the expression levels of apoptotic proteins during cisplatin exposure and reduced the sensitivity of IEC-6 cells to cisplatin by inhibiting the activation of GSK3β and up-regulating the protein expression of β-catenin. In conclusion, AFG exerted protective effects against cisplatin-induced intestinal toxicity, at least partially by the inhibition of NF-κB-mediated apoptosis, regulating Wnt/β-catenin signaling pathway.