Phytochemical constituents, antioxidant and chemopreventive effects of selected plants against carbon tetrachloride (CCI₄)- induced hepatic damage in rats

Muhammad Dawood Shah, (2016) Phytochemical constituents, antioxidant and chemopreventive effects of selected plants against carbon tetrachloride (CCI₄)- induced hepatic damage in rats. Post-Doctoral thesis, Universiti Malaysia Sabah.

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Abstract

Commelina nudiflora, Nephrolepis biserrata and Dillenia suffruticosa have been used in folk medicine for protection against different diseases such as jaundice, although their actual efficiency remains uncertain. The current experiment was designed to investigate the bioactive compounds and hepatoprotective potential of the selected plants against carbon tetrachloride (CCI₄)-induced hepatic oxidative damage in rats and their possible mechanism of action. The total phenolic and flavonoid contents, phytochemical constituents and antioxidant activates were determined in the methanolic extracts and methanolic fractions of plant samples. Phytochemical analysis was performed by gas chromatography and mass spectrometry (GCMS). In this in vivo study, Sprague Dawley rats were pre-treated with various doses of the methanolic extracts of the selected plants once daily for 14 days followed by two doses of CCI₄ (1ml/kg b. wt. ). After 24 hours of the last dosage, the rats were sacrificed and hepatoprotective analyses were performed on the rat's liver. The obtained data revealed that the methanolic extracts and methanolic fractions of C. nudiflora, N. biserrata and D. suffruticosa possessed strong antioxidant activities and have the ability to scavenge DPPH free radicals effectively. The GCMS analysis of the methanolic extracts and methanolic fractions of C. nudiflora, N biserrata and D. suffruticosa demonstrated the presences of different bioactive compounds of various natures. The identified bioactive compounds have been reported with antioxidant, anti-inflammatory and hepatoprotective properties. The animal studies indicated that the methanolic extracts of C. nudiflora, N biserrata and D. suffruticosa showed hepatoprotective effects against CCI₄- induced hepatic damage. The administration of Methanolic extracts of the plants depleted the elevation of enzymatic levels of serum transaminases, reduced the extent of malondialdehyde production, elevated the level of reduced glutathione and also increased the activities of antioxidant enzymes. The histopathological examination by light and electron microscopy indicated that these plant extracts protect the liver from the toxic effects of CCI₄ and healed lesions such as necrosis, fatty degeneration and hepatocyte injuries such as irregular lamellar organization and dilations in endoplasmic reticulum. The immunohistochemical studies revealed that the administration of plant extracts decreased the formation of 4- hydroxyl-2-nonenal (HNE) modified protein adducts and 8-hydroxy- 2- deoxygunosine (8-OHdG) as compared to the CCI4-intoxicated group. Furthermore, the overexpression of the pro-inflammatory markers TNF-a, IL-6 and PGE2 are also reduced. Collectively, these plants alleviated CCI₄- induced hepatic damage via modulation of hepatic metabolizing enzymes, suppression of oxidative stress, inhibition of inflammatory cytokines and PGE2 in liver. These findings exhibit the potential prospects of C. nudiflora, N biserrata and D. suffruticosa as functional ingredients to prevent ROS-related liver damage.

Item Type: Thesis (Post-Doctoral)
Uncontrolled Keywords: bioactive compounds, hepatoprotective potential, Sprague Dawley rats
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: SCHOOL > Biotechnology Research Institute (BRI)
Depositing User: Munira
Date Deposited: 28 Dec 2017 22:30
Last Modified: 28 Dec 2017 22:30
URI: http://eprints.ums.edu.my/id/eprint/6202

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