Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.

5-Fluorouracil (5-FU) remains a cornerstone chemotherapeutic for colorectal cancer, exerting its antitumor effects primarily through disruption of DNA and RNA synthesis and subsequent induction of apoptosis. Nonetheless, its clinical efficacy is often compromised by prominent adverse effects, particularly mucositis. This study examines the potential of brown-strain Flammulina velutipes Singer (FVB) to alleviate 5-FU-associated intestinal damage in a mouse model, offering insights into its possible role in mitigating chemotherapy-induced toxicity. 5-FU treatment significantly exacerbated gastrointestinal toxicity, as evidenced by severe diarrhea, shortened colon length, villus atrophy, and architectural disorganization of the intestine. It also inhibited crypt cell proliferation and induced body weight loss. Mechanistically, 5-FU activated pro-inflammatory, apoptotic, oxidative stress, and EMT pathways and disrupted mucosal tight junctions. Notably, FVB administration mitigated these pathological changes, indicating its protective role against 5-FU-induced intestinal injury. In summary, this investigation presents novel evidence for the protective role of FVB in mitigating 5-FU-induced intestinal mucositis. The results highlight the therapeutic potential of FVB as an adjunct to chemotherapy, potentially reducing treatment-related toxicity and enhancing the clinical care and quality of life of individuals undergoing colorectal cancer therapy.