Abstract
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.
Acknowledgments.
The authors would like to thank the study participants; the staff of Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan; and ICCBS (International Center for Chemical and Biological Sciences), University of Karachi, for the realization of the in vitro part of this work.
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Research ethics: The experimental procedures have been approved by the local ethics committee and are in accordance with the guidelines for the study of pain in awake animals, published by the NIH (publication no. 85–23), “Principles of Animal Protection,” Laboratory, Study of Pain, Ministry of Scientific Research and Technology, which adopted the European Union Guidelines on Animal Care and Experimentation (EWC 86/609). For the donation of human blood samples, all processes of collecting blood are accepted by the Independent Ethics Committee, ICCBS, University of Karachi, No. ICCBS/IEC-008-BC-2015/Protocol/1.0. The blood donors were provided informed approval for the use of their blood for the purposes of this study.
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Informed consent: No applicable.
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Author contributions: NAE, AG, and MM designed the work. NAE, AG, MM, MKYK, YNW, FNZL and MMVM conducted the work and collected and analysed the data. NAE, AG, MM and YNW drafted the manuscript and revised it critically. All authors agree to be accountable for all aspects of the work.
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Competing interests: MM (PhD) is a Associate professor in the Department of Animal Biology, Faculty of Science, University of Dschang, Cameroon. AG (PhD) is a Professor in the Department of Animal Biology, Faculty of Science, University of Dschang, Cameroon. NAE, MKYK and FNZL are PhD students in the Department of Animal Biology, Faculty of Science, University of Dschang, Cameroon. ACF and MMVM are PhD in the Department of Animal Biology, Faculty of Science, University of Dschang, Cameroon. YNW is a senior lecturer in the Department of Biology of Animal Organisms, Faculty of Science, University of Douala, Cameroon. The authors declare that they have no conflicts of interest.
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Research funding: None declared.
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