Abstract
This study investigated the restorative effect of Leea macrophylla ethanol root extract (LMERE) in carbon tetrachloride (CCl4) induced hepatic injury. It also tried to unfold the underlying mechanism through ligand-receptor interactions. Prior to conduct the CCl4 induced animal model study, the in vitro antioxidative capacities of LMERE were investigated. Gas chromatography mass spectroscopy (GC–MS) was accomplished to identify the prevalent bioactive compounds. The molecular docking was performed using Schrödinger Suites 2017-1. Results showed the promising antioxidative potentials of LMERE in in vitro models. Upon treatment of CCl4 intoxicated animals with LMERE, serum ALT and AST were found to be significantly (p < 0.05) reduced compared to the CCl4 control while LMERE50 was noted as the best dose in restoring the hepatic markers. Serum lipids and total protein were significantly restored compared to control. Remarkable changes of cell necrosis, apoptosis and sinusoidal dilution were noticed in histopathological assay of liver tissue. mRNA expression for superoxide dismutase (SOD1) and catalase was multifold increased which are statistically significant compared to reference drug, silymarin. In docking study, octadecanoic acid showed the lowest binding energy and highest binding affinity with the protein (ID: 1VKX) which is a crystallized structure of NF-κB p50/p65 heterodimer involved in cytokine production. The findings demonstrate that LMERE restores the hepatic damage by the mRNA expression of antioxidative enzymes while LMERE50, at a glance, seems the most suitable dose.
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Abbreviations
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- CHL:
-
Cholesterol
- LDL:
-
Low density lipoprotein
- TSP:
-
Total serum protein
- TG:
-
Triglycerides
- SEM:
-
Standard error for mean
- LMERE:
-
Leea macrophylla ethanol root extract
- ROS:
-
reactive oxygen species
- SOD1:
-
Super oxide dismutase 1
- CAT:
-
Catalase
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- LMERE 50:
-
Leea macrophylla ethanol root extract 50 mg per kg body weight
- LMERE 100:
-
Leea macrophylla ethanol root extract 100 mg per kg body weight
- LMERE 200:
-
Leea macrophylla ethanol root extract 200 mg per kg body weight
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Acknowledgements
The authors are grateful to the Department of Biochemistry and Molecular Biology, University of Chittagong, Bangladesh, for providing the facilities to conduct this research work. The authors are also thankful to Dr. Sheikh Bokhtear Uddin, Professor, Department of Botany, University of Chittagong, for identifying the plant. Moreover, we appreciate the tremendous technical supports from laboratory of Eukaryotic Gene Expression and Function (EuGEF), Department of Biochemistry and Molecular Biology, University of Chittagong.
Funding
This research has been partially funded by Ministry of Science and technology, Bangladesh under the special allocation for research with the Grant Number BS-176/180/MOST.
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This work was carried out in collaboration between all authors. Authors MRHB collected the plant materials (root) and carried out the study design, data collection, data interpretation, manuscript preparation and statistical analysis. Author MAR supervised the study design and data interpretation as well as contributed in manuscript preparation and statistical analysis. MAR also acted for all correspondences. Author MZR contributed in histopathological scoring of liver tissue sections. MK and MA contributed in phytochemical analysis especially GC–MS preparation and interpretation of the relevant data. MAHC has conducted all the in vitro antioxidative works on LMERE. TBE and MAI participated in the manuscript draft and has thoroughly checked and revised the manuscript for necessary changes in format, grammar and English standard. All authors read and approved the final version of the manuscript. SK has arranged the in silico docking study.
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Animals were handled and maintained according to the guidelines of Institutional Animal Ethics Committee of the Faculty of Biological Science of the University of Chittagong, Bangladesh (AERB/FBS/UC/02, 2015).
Conflict of interest
Md. Rakibul Hassan Bulbul has no conflict of interest. Md. Atiar Rahman has no conflict of interest. Md. Zillur Rahman has no conflict of interest. Talha Bin Emran has no conflict of interest. Mirola Afroze has no conflict of interest. Mala Khan has no conflict of interest. Muhammad Abid Hasan Chowdhury has no conflict of interest. Mohammed Auwal Ibrahim has no conflict of interest. Mohammed Sohel Chowdhury has no conflict of interest.
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Bulbul, M.R.H., Rahman, M.A., Rahman, M.Z. et al. Leea macrophylla (Roxb.) root extract reverses CCl4 induced liver injury through upregulation of antioxidative gene expression: a molecular interaction for therapeutic inception. ADV TRADIT MED (ADTM) 20, 35–52 (2020). https://doi.org/10.1007/s13596-019-00380-2
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DOI: https://doi.org/10.1007/s13596-019-00380-2