Markhamia lutea leaves aqueous and ethanolic extract with curative anti-inflammatory activity attenuates paclitaxel toxicity in rat's intestine.

OBJECTIVES:Markhamia lutea (M. lutea, Bignoniaceae) is mainly found in tropical/neotropical regions of America, Africa and Asia. The plant's leaves, stems or roots are used to treat anaemia, bloody diarrhoea, parasitic and microbial infections. This study evaluates anti-inflammatory properties (in vitro) of Markhamia lutea and their curative effects on paclitaxel-induced intestinal toxicity (in vivo). METHODS:The anti-inflammatory potential of Markhamia lutea was tested over cytokines (TNF-alpha, IL-6, IL-1β, IL-10), reactive oxygen species (ROS) and enzymes (cyclooxygenase and 5-lipoxygenase). While in vivo, intestinal toxicity was induced for 10 days by oral administration of paclitaxel (3 mg/kg, 0.05 mL). Animals in each group were further treated with aqueous (300 mg/kg) and ethanolic (300 mg/kg) leaves extracts of Markhamia lutea during 7 days and clinical symptoms were recorded, hematological, biochemical and histological analysis were subsequently performed. RESULTS:In vitro, aqueous (250 μg/mL) and ethanolic (250 μg/mL) extracts of Markhamia lutea inhibited the activities of cyclooxygenase 1 (56.67 % and 69.38 %), cyclooxygenase 2 (50.67 % and 62.81 %) and 5-lipoxygenase (77.33 % and 86.00 %). These extracts inhibited the production of intracellular ROS, extracellular ROS and cell proliferation with maximum IC50 of 30.83 μg/mL, 38.67 μg/mL and 19.05 μg/mL respectively for the aqueous extract, then 25.46 μg/mL, 27.64 μg/mL and 7.34 μg/mL respectively for the ethanolic extract. The extracts also inhibited the production of proinflammatory cytokines (TNFα, IL-1β and IL-6) and stimulated the production of anti-inflammatory cytokines (IL-10). In vivo, after administration of paclitaxel, the aqueous and ethanolic extracts of Markhamia lutea significantly reduced the weight loss, the diarrheal stools and the mass/length intestines ratio of the treated animals compared to the animals of the negative control group. Biochemically, the extracts lead to a significant drop in serum creatinine and alanine aminotransferase levels, followed by a significant increase in alkaline phosphatase. In addition to bringing the haematological parameters back to normal values after disturbance by paclitaxel, the extracts caused tissue regeneration in the treated animals. CONCLUSIONS:In vitro, aqueous and ethanolic extracts of Markhamia lutea showed anti-inflammatory properties (inhibition of COX1, COX2, 5-LOX activities, inhibition of ROS production and cell proliferation); in vivo, the same extracts showed curative properties against intestinal toxicity caused by paclitaxel.