title: Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats.
abstract: Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 ± 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI.
authors.affiliation: a Biotechnology Research Institute, Universiti Malaysia Sabah , Sabah , Malaysia ;
authors.forename: Charles
authors.initials: C
authors.lastname: Gnanaraj
authors.affiliation: a Biotechnology Research Institute, Universiti Malaysia Sabah , Sabah , Malaysia ;
authors.forename: Muhammad Dawood
authors.initials: MD
authors.lastname: Shah
authors.affiliation: b Department of Pathology , Queen Elizabeth Hospital , Sabah , Malaysia.
authors.forename: Jaafar Sadeq
authors.initials: JS
authors.lastname: Makki
authors.affiliation: a Biotechnology Research Institute, Universiti Malaysia Sabah , Sabah , Malaysia ;
authors.forename: Mohammad
authors.initials: M
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006842:Hydrocarbons, Brominated; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019684:Magnoliopsida; D008297:Male; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D006842:Hydrocarbons, Brominated; D018836:Inflammation Mediators; D010936:Plant Extracts; C031387:carbon tetrabromide
keywords: Antioxidant enzymes; electron microscopy; histopathology; immuno-histochemistry