Steamed root of Rehmannia glutinosa Libosch. relieves methotrexate-induced intestinal mucositis in mice with manninotriose as a core mediator

Abstract

Chemotherapy-induced intestinal mucositis is a serious complication with few effective treatment options. In Traditional Chinese Medicine (TCM), this toxicity is attributed to Qi and Yin deficiencies, and the steamed root of Rehmannia glutinosa Libosch. (SRR) is commonly prescribed for its therapeutic benefits. This study aimed to evaluate SRR’s effects on methotrexate (MTX)-induced mucositis by modulating the gut microbiota. Mice were administered MTX (300 mg/kg) and SRR (1.56 g/kg), and gut microbiota changes were analysed by 16S rRNA sequencing. Network pharmacology was employed to identify SRR’s active components. SRR alleviated MTX-induced fatigue, diarrhea, weight loss, and intestinal villous damage, and modulated gut microbiota by reducing Clostridium levels, adjusting the Firmicutes/Bacteroidetes ratio, and promoting Gram-positive bacteria. SRR also reduced oxidative damage and inflammation markers (MDA, iNOS and NF-κB) without affecting MTX blood levels. Manninotriose was identified as one of the key active constituents. In conclusion, SRR alleviates MTX-induced intestinal mucositis by exerting antioxidative, anti-inflammatory, and gut microbiota-modulating effects.