Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Santa Catarina, Brazil.
Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil.
Phytother Res. 2019 Jan;33(1):90-106. doi: 10.1002/ptr.6202. Epub 2018 Oct 3.
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 irinotecan-induced 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.
本研究评估了金凤花叶富含类黄酮部分(FRF-BF)对伊立替康诱导的肠道毒性的作用。这种植物的叶子在巴西民间医学中被用作茶,它富含类黄酮,主要是山奈酚。首先,在暴露于伊立替康的肠细胞(IEC-6 细胞)中评估了 FRF-BF 和山奈酚的化学预防作用。接下来,在小鼠中评估了它们对伊立替康诱导的粘膜炎的作用。最后,在 C57BL/6 小鼠中诱导黑色素瘤,以评估 FRF-BF 对伊立替康抗肿瘤活性的干扰作用。结果表明,FRF-BF 和山奈酚在 IEC-6 细胞中没有细胞毒性作用,并证实 FRF-BF 和山奈酚预处理对伊立替康诱导的细胞毒性具有化学保护作用。有趣的是,FRF-BF(100mg/kg,po)降低了小鼠的肠道蠕动,并减轻了与伊立替康诱导的肠道粘膜炎相关的参数,包括腹泻、组织学损伤、十二指肠 GSH 耗竭、TNF-α 量和小肠中的 MPO 活性。此外,FRF-BF 不干扰伊立替康的抗肿瘤活性,并在小鼠黑色素瘤中发挥抗肿瘤活性。总之,FRF-BF(100mg/kg,po)具有很大的药理学潜力,可以预防和减轻化疗期间肠道粘膜炎的严重程度,这与山奈酚的存在有关。