Flavonoid‐rich fraction of Bauhinia forficata Link leaves prevents the intestinal toxic effects of irinotecan chemotherapy in IEC‐6 cells and in mice

Abstract

This study evaluated the effects of flavonoid-rich fraction from Bauhinia forficata leaves (FRF-BF), against intestinal toxicity induced by irinotecan. The leaves of this plant are used like tea in Brazilian folk medicine, and it is rich in flavonoids, mainly kaempferitrin.First, the chemopreventive effects of FRF-BF and kaempferitrin were evaluated in intestinal cells (IEC-6 cells) exposed to irinotecan. Next, the effects were evaluated against irinotecan-induced mucositis in mice. Lastly, melanoma was induced in C57BL/6 mice to evaluate FRF-BF interference on irinotecan antitumor activity. The results showed that FRF-BF and kaempferitrin exert no cytotoxic effects in IEC-6 cells and confirmed that pretreatment with FRF-BF and kaempferitrin displays chemoprotective effects against cytotoxicity induced by irinotecan. Interestingly, the FRF-BF (100 mg/kg, p.o) reduced the intestinal motility in mice and attenuated parameters linked to irinotecaninduced intestinal mucositis, including diarrhea, histological damage, depletion of duodenal GSH, amount of TNF-α, and MPO activity in the small intestine. Also, FRF-BF does not interfere in the antitumor activity of irinotecan and exerted antitumoral activity in murine melanoma. In conclusion, FRF-BF (100 mg/kg, p.o) presents promising pharmacological potential to prevent and attenuate the severity of intestinal mucositis during chemotherapy treatment, related to the presence of kaempferitrin.

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

“…However, the results are not consistent among the studies involving chemoprevention treatments. Studies performed by Cheah et al [31] and Cechinel-Zanchett et al [32], for example, demonstrated that flavonoids could not prevent the progressive weight loss induced by chemotherapy, even though their efficacy was shown in reversing histological changes, oxidative stress, and inflammatory process induced during mucositis. Weight loss is a side effect caused by the activation of inflammatory responses followed by gastrointestinal dysfunction [33].…”

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

“…The therapeutic success and quality of life of the cancer patient also depend on an early diagnosis and management of the complications of anticancer therapy. Nowadays, different strategies are used to treat mucositis and, among them also products from natural sources, which possess anti-apoptotic, anti-inflammatory and antioxidant properties [ 13 , 14 , 15 ].…”

Promising Medicinal Plants with Diuretic Potential Used in Brazil: State of the Art, Challenges, and Prospects

“…We also investigated the role of kaempferitrin in vasorelaxation in NTR and SHR aortic rings, and both 3 and its aglycone, kaempferol (0.001-0.3 µg/mL), were able to induce vasorelaxation by 34.70 % and 40.54 %, respectively [57]. There have been few studies on the toxic potential of this compound, but in vitro investigations have shown that despite being cytotoxic to cancer cell lines [58], kaempferitrin did not exert any toxicity in intestinal epithelial cells (IEC-6 lineage) [59].…”