In silico and in vivo characterization of cabralealactone, solasodin and salvadorin in a rat model: potential anti-inflammatory agents
| Autor: | Mahwish Arooj, Sara Zahid, Tassadaq Hussain Jafar, Sulayman Waquar, Muhammad Usman Mirza, Sarfraz Ahmad, Siew Hua Gan, Fatima Zahid, Tariq M. Butt, Arif Malik |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
antioxidant
medicine.medical_treatment Anti-Inflammatory Agents Pharmaceutical Science Chemistry Medicinal 02 engineering and technology HEPATITIS-C Pharmacology medicine.disease_cause 01 natural sciences Solanaceous Alkaloids salvadorin chemistry.chemical_compound Lactones Coumarins HEPATOCELLULAR-CARCINOMA Drug Discovery Pharmacology & Pharmacy Carbon Tetrachloride Original Research cabralealactone anti-inflammatory Chemistry 021001 nanoscience & nanotechnology Malondialdehyde Molecular Docking Simulation medicine.anatomical_structure Liver Hepatocyte Toxicity HEPATOPROTECTIVE ACTIVITY 0210 nano-technology Life Sciences & Biomedicine Injections Intraperitoneal medicine.drug_class ALPHA-FETOPROTEIN Intraperitoneal injection INHIBITION CCL4 CARBON-TETRACHLORIDE INTOXICATION Naphthalenes 010402 general chemistry Anti-inflammatory solasodin In vivo medicine BREAST-CANCER Animals COX-2 inhibitor Science & Technology Drug Design Development and Therapy Tumor Necrosis Factor-alpha DNA 0104 chemical sciences Rats Disease Models Animal Oxidative Stress DNA-DAMAGE MOLECULAR-DYNAMICS Cyclooxygenase 2 INDUCED HEPATOTOXICITY Oxidative stress |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Arif Malik,1 Mahwish Arooj,2 Tariq Tahir Butt,3 Sara Zahid,4 Fatima Zahid,1 Tassadaq Hussain Jafar,1 Sulayman Waquar,1 Siew Hua Gan,5 Sarfraz Ahmad,1 Muhammad Usman Mirza6 1Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan; 2University College of Medicine and Dentistry (UCMD), University of Lahore, Lahore, Pakistan; 3Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan; 4Faculty of Pharmacy, University of Lahore, Lahore, Pakistan; 5School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia; 6Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, Leuven, Belgium Background: The present study investigates the hepato- and DNA-protective effects of standardized extracts of Cleome brachycarpa (cabralealactone), Solanum incanum (solasodin), and Salvadora oleioides (salvadorin) in rats. Materials and methods: Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied. Results: Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents. Conclusion: Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects. Keywords: cabralealactone, solasodin, salvadorin, antioxidant, COX-2 inhibitor, anti-inflammatory |
| Databáze: | OpenAIRE |
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