Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches
Background and Objectives. Leptadenia hastata is a liana from the family of Asclepiadaceae used in tropical Africa to treat diabetes mellitus. In this study, we investigated its hepatoprotective mechanisms on acetaminophen- (APAP-) induced toxicity through in vivo and in silico approaches. Materials...
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doaj-17c63522ca224fd78e2e07ce0244d5342020-11-25T03:05:32ZengHindawi LimitedBioMed Research International2314-61332314-61412020-01-01202010.1155/2020/38072343807234Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking ApproachesBorris R. T. Galani0Brice A. Owona1Dieudonné P. D. Chuisseu2Esaïe Machewere3Claude B. N. Ngantchouko4Paul F. Moundipa5Laboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454 Ngaoundere, CameroonLaboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812 Yaounde, CameroonLaboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812 Yaounde, CameroonLaboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454 Ngaoundere, CameroonDepartment of Pharmacy, Higher Institute of Health Sciences, Université des Montagnes, P.O. Box 208 Bangangte, CameroonLaboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812 Yaounde, CameroonBackground and Objectives. Leptadenia hastata is a liana from the family of Asclepiadaceae used in tropical Africa to treat diabetes mellitus. In this study, we investigated its hepatoprotective mechanisms on acetaminophen- (APAP-) induced toxicity through in vivo and in silico approaches. Materials and Methods. Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNFα)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME. Results. APAP administration significantly increased (p<0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p<0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels (p<0.05) and increased those of GSH, SOD, and CAT (p<0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant (p<0.001) decrease of TNFα levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. In silico studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNFα, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase. Conclusion. Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties.http://dx.doi.org/10.1155/2020/3807234 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Borris R. T. Galani Brice A. Owona Dieudonné P. D. Chuisseu Esaïe Machewere Claude B. N. Ngantchouko Paul F. Moundipa |
spellingShingle |
Borris R. T. Galani Brice A. Owona Dieudonné P. D. Chuisseu Esaïe Machewere Claude B. N. Ngantchouko Paul F. Moundipa Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches BioMed Research International |
author_facet |
Borris R. T. Galani Brice A. Owona Dieudonné P. D. Chuisseu Esaïe Machewere Claude B. N. Ngantchouko Paul F. Moundipa |
author_sort |
Borris R. T. Galani |
title |
Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches |
title_short |
Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches |
title_full |
Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches |
title_fullStr |
Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches |
title_full_unstemmed |
Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches |
title_sort |
hepatoprotective activity of leptadenia hastata (asclepiadaceae) on acetaminophen-induced toxicity in mice: in vivo study and characterization of bioactive compounds through molecular docking approaches |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2020-01-01 |
description |
Background and Objectives. Leptadenia hastata is a liana from the family of Asclepiadaceae used in tropical Africa to treat diabetes mellitus. In this study, we investigated its hepatoprotective mechanisms on acetaminophen- (APAP-) induced toxicity through in vivo and in silico approaches. Materials and Methods. Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNFα)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME. Results. APAP administration significantly increased (p<0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p<0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels (p<0.05) and increased those of GSH, SOD, and CAT (p<0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant (p<0.001) decrease of TNFα levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. In silico studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNFα, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase. Conclusion. Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties. |
url |
http://dx.doi.org/10.1155/2020/3807234 |
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