Methanol extract of Dicranopteris linearis L. leaves impedes acetaminophen-induced liver intoxication partly by enhancing the endogenous antioxidant system

Abstract

BackgroundThe present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats.MethodsA group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract’s vehicle) followed by treatment with 10% DMSO (hepatotoxin’s vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.ResultsPre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p < 0.05) increased in the level of serum liver enzymes of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), and significant (p < 0.05) decreased in the activity of endogenous antioxidant enzymes of catalase (CAT) and superoxide dismutase (SOD) in comparison to Group 1. Pre-treatment with MEDL, at all doses, significantly (p < 0.05) reduced the level of ALT and AST while the levels of CAT and SOD was significantly (p < 0.05) restored to their normal value. Histopathological studies showed remarkable improvement in the liver cells architecture with increase in dose of the extract. MEDL also demonstrated a low to none inhibitory activity against the respective LOX- and NO-mediated inflammatory activity. The HPLC and GCMS analyses of MEDL demonstrated the presence of several non-volatile (such as rutin, gallic acid etc.) and volatile (such as methyl palmitate, shikimic acid etc.) bioactive compounds.ConclusionMEDL exerts hepatoprotective activity against APAP-induced intoxication possibly via its ability to partly activate the endogenous antioxidant system and presence of various volatile and non-volatile bioactive compounds that might act synergistically to enhance the hepatoprotective effect.

Effect of Liposomal Curcumin on Acetaminophen Hepatotoxicity by Down-regulation of Oxidative Stress and Matrix Metalloproteinases

“…This fact may provide a new insight into studying novel therapeutic molecules that can provide hepatoprotection; one of the mechanisms could be represented by improving the level of thiols. Improving catalase levels in experimental APAP-induced hepatotoxicity could also provide a new approach for hepatoprotection strategies (50). Therefore, modulation of oxidative stress/antioxidant balance could be the target of nutraceuticals used to provide a hepatoprotective effect.…”

Aqueous Partition of Methanolic Extract of Dicranopteris linearis Leaves Protects against Liver Damage Induced by Paracetamol

“…Although not many traditional uses of this plant were recorded in Malay folklore medicine, its leaves were used as tonic or poultice to reduce body temperature [15,16]. Scientifically, D. linearis extracts have been reported to exert antinociceptive [15,16,18], antipyretic [16], anticancer [19,20], cytotoxic [17], hepatoprotective [21][22][23][24][25], and chemopreventive [26] activities. With regard to the hepatoprotective activity of D. linearis, preliminary studies using the chloroform, aqueous and methanol extracts of D. linearis leaf have successfully proven these extracts ability to attenuate PCM-and carbon tetrachloride-induced hepatotoxicity [21,22,24].…”

“…With regard to the hepatoprotective activity of D. linearis, preliminary studies using the chloroform, aqueous and methanol extracts of D. linearis leaf have successfully proven these extracts ability to attenuate PCM-and carbon tetrachloride-induced hepatotoxicity [21,22,24]. Further analyses by Kamisan et al [23] revealed that the methanol extract of D. linearis leaf (MEDL) possessed remarkable antioxidant activity when assessed using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-and superoxide anion-radical scavenging assays, oxygen radical absorbance capacity (ORAC) test and contained high total phenolic content (TPC) value, while Zakaria et al [25] successfully demonstrated the ability of MEDL to enhance the endogenous antioxidant activity in PCM-induced hepatotoxic rats.…”

“…Although several known bioactive compounds have been identified from MEDL [23,25] using the high pressure liquid chromatography (HPLC) and ultra-high pressure liquid chromatography-electrospray ionization coupled with high resolution mass spectrometry (UHPLC-ESI/HRMS) approaches, it is not possible to directly foretell the character of bioactive compounds that really contribute to the hepatoprotective effect of D. linearis. This could be due to the fact that methanol, being the solvent system for soaking D. linearis leaves, has the ability to dissolve all types of bioactive compounds regardless of their polarity.…”

“…Since there is a need to ascertain the effectiveness of each partition to attenuate liver injury, all partitions were subjected to the preliminary screening against the PCM-induced hepatotoxic effect in rats. Based on the preliminary findings (data not shown), the present study was designed to explore the hepatoprotective potential of the aqueous partition (AEDL) using the same animal models as reported by Zakaria et al [25].…”