Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats

Context: Dicranopteris linearis L. (Gleicheniaceae) leaves have been reported to exert hepatoprotective activity. Objective: The hepatoprotective and antioxidant effects of ethyl acetate partition of D. linearis (EADL) are investigated. Materials and methods: EADL was subjected to antioxidant and anti-inflammatory studies, and phytochemical analyses. In vivo study involved six groups (n = 6) of overnight fasted Sprague Dawley rats. The test solutions [10% DMSO (normal), 10% DMSO (negative), 200 mg/kg silymarin (positive) or EADL (50, 250 or 500 mg/kg)] were administered orally once daily for 7 consecutive days followed by oral vehicle (only for normal) or hepatotoxic induction using 3 g/kg paracetamol (PCM). Results: EADL exerted ≈ 90% radical scavenging effects based on the DPPH and superoxide anion radical scavenging assays, high antioxidant capacity in the oxygen radical absorbance capacity assay (≈ 555,000 units), high total phenolic content (≈ 350 mg GAE/100 g extract) (p < 0.05), but low anti-inflammatory effect. EADL also attenuated PCM-induced liver intoxication as indicated by reduced level of serum liver enzymes; increased activity of endogenous enzymatic antioxidant (superoxide dismutase – 8.3 vs. 4.0 U/g tissue; catalase – 119 vs. 52 U/g tissue) and; reduced level of lipid peroxidation marker (2.7 vs. 5.0 µM). Preliminary screening of EADL revealed the presence of saponins, tannins and flavonoids with further HPLC analysis demonstrating the presence of rutin and quercetin. Discussion and conclusion: EADL exerted hepatoprotective and antioxidant activities; thus, these data support the potential use of D. linearis as a new source for future hepatoprotective drug development

Amelioration of paracetamol-induced hepatotoxicity in rat by the administration of methanol extract of Muntingia calabura L. leaves

Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n = 6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P < 0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations

Effect of methanol extract of Dicranopteris linearis leaves against paracetamol- and carbon tetrachloride (CCl4)-induced liver toxicity in rats

The present study aimed to determine the hepatoprotective activity of methanol extract of Dicranopteris linearis leaves (MEDL) using two models of liver injury in r ats. Rats (n = 6) received 10% DMSO(negative control), 200 mg/kg silymarin (positive control) or MEDL (50, 250, and 500 mg/kg) orally once daily for 7 days and 3 hours after the last adminis tration of the test solutions, they were subjected to the hepatotoxic induction either using carbon tetrachloride (CCl4) or paracetamol (PCM). The bloods and livers were collected and subjected to biochemical and microscopical analysis. From the data obtained, all doses of MEDL significantly (P < 0.05) reduced the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in CCl4-induced hepatotoxic rats while only the 500 mg/kg MEDL caused significant (P < 0.05) reduction in the level of both enzymes in the PCM-induced liver toxicity model. The histological results obtained were in line with the biochemical analysis. In conclusion, the MEDL-induced hepatoprotective activity is attributed partly to its free radicals scavenging and antioxidant activities and high flav onoids content

Hepatoprotective activity of methanol extract of Melastoma malabathricum leaf in rats

The present study aimed to determine the hepatoprotective activity of a methanol extract of Melastoma malabathricum leaves (MEMM) using two established rat models. Ten groups of rats (n = 6) were given a once-daily administration of 10% dimethyl sulfoxide (negative control), 200 mg/kg silymarin (positive control), or MEMM (50, 250, or 500 mg/kg) for 7 days followed by induction of hepatotoxicity either using paracetamol or carbon tetrachloride. Blood samples and livers were collected for biochemical and microscopic analysis. Based on the results obtained, MEMM exhibited a significant (p < 0.05) hepatoprotective activity against both inducers, as indicated by an improvement in the liver function test. These observations were supported by the histologic findings. In conclusion, M. malabathricum leaves possessed hepatoprotective activity, which could be linked to their phytochemical constituents and antioxidant activity; this therefore requires further in-depth studies

Effect of aqueous extract of Dicranopteris linearis leaves against paracetamol and carbon tetrachloride-induced liver toxicity in rats

The present study aimed to determine the hepatoprotective activity of Dicranopteris linearis L. (family Gleicheniaceae) leaf aqueous extract (DLAE) using two models of liver injury in rats. Rats were divided into ten groups (n=6) and received dH2O (negative control), 200 mg/kg silymarin (positive control) or DLAE (50, 250 and 500 mg/kg) orally once daily for 7 consecutive days and on the 8th day subjected to the hepatotoxic induction either using carbon tetrachloride (CCl4) or paracetamol (PCM). The bloods and livers were collected and subjected to biochemical and microscopical analysis. From the data obtained, only the highest dose of DLAE significantly (p<0.05) reduced the ALP, ALT and AST levels in CCl4-and PCM-induced hepatotoxic rats while the other doses caused significant (p<0.05) reduction only in the levels of ALT and AST. The histological results obtained were in line with the biochemical analysis wherein reduction in the CCl4- and PCM-induced tissue formation of necrosis, steatosis and inflammation occurred in a dose-dependent manner. In conclusion, the DLAE possesses hepatoprotective activity, which could be attributed to its free radicals scavenging and antioxidant activities, and high flavonoids content. Thus, in-depth studies regarding the hepatoprotective activity of DLAE are warranted

Gastroprotective activity of chloroform extract of Muntingia calabura and Melastoma malabathricum leaves

Context: Muntingia calabura L. (family Muntingiaceae) and Melastoma malabathricum L. (family Melastomaceae) are traditionally used to treat gastric ulcer. Objective: The present study determines the mechanisms of gastroprotective activity of the chloroform extract of leaves obtained from both the plants using several in vitro and in vivo assays. Materials and methods: Phytochemical screening, HPLC analysis, and antioxidant activity of the respective extract were carried out. Gastroprotective activity was determined using ethanol-induced gastric ulcer assay while the mechanisms of gastroprotection were determined using the pyloric ligation assay. The test solutions [8% Tween-80 (vehicle), 20 mg/kg omeprazole, and different doses of extracts (50, 250, or 500 mg/kg] were administered orally once daily for 7 consecutive days before the animals were subjected to ethanol induced gastric ulcers. Results: The chloroform-extracted M. calabura (CEMC) contains tannins, polyphenolics, triterpenes, and steroids while the chloroform-extracted M. malabathricum (CEMM) contains only triterpenes and steroids. CEMC, but not CEMM, exerted remarkably strong antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH)- (86% versus 16%) and superoxide- (73% versus 36%) radical scavenging assays. Both extracts demonstrated significant (p < 0.05) gastroprotection with the EC50 value recorded at 192.3 or 297.7 mg/kg, respectively. In the pylorus ligation assay, CEMC and CEMM significantly (p < 0.05) reduced the total and free acidity and volume; while increased the pH of gastric juice as well as the gastric wall mucus content in comparison with the vehicle-treated group. Discussion and conclusion: CEMC and CEMM exert gastroprotective effects in animals with ethanol-induced gastric ulcers via antioxidant and anti-secretory effects

Hepatoprotective activity of Dicranopteris linearis (Burm. f.) Underw. leaf methanol extract and its ethyl acetate fraction

Liver disease is a major global concern with extremely poor prognosis and high mortality rate due to the lack of effective preventive or treatment options. Besides,a reliable liver protective drug with fewer side effects is still lacking in modern medicines. Therefore, attempts are perpetually being made to investigate several alternative therapies that use natural plants. In the first part of the in vivostudy, methanol extract (MEDL) of Dicranopteris linearisleaves was investigated for hepatoprotective activity against carbon tetrachloride (CCl4)-induced and paracetamol (PCM)-induced liver damage. Rats (n=6) used in the study were divided into several groups and given a daily administration of 10% dimethyl sulfoxide (negative control group), 200 mg/kg Silymarin (positive control group) or MEDL (50, 250 or 500 mg/kg) for 7 days, followed by the induction of hepatotoxicity either CCl4or PCM. Crude methanolic extracts also were further partitioned using solvents of increasing polarity: petroleum ether <ethyl acetate <water. Semi-purified partitions were called petroleum ether (PEDL), ethyl acetate (EADL) and aqueous (AQDL) extracts. In the second part of in vivo study, these partitions were assayed on PCM-induced hepatotoxicity study. All the semi-purified partitions with intermediate doses (250 mg/kg) were tested on the PCM-induced hepatotoxicity model. The best partition proceeded with another two doses of 50 mg/kg and 500 mg/kg. Blood samples and livers were collected and subjected to biochemical and microscopic analyses. The crude and all the semi-purified partitions were also subjected to antioxidant assays, 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH), superoxide dismutase scavenging activity assay (SOD), and oxygen radical absorbance capacity assay (ORAC), and anti-inflammatory assays using lipoxygenase (LOX) and xanthine oxidase (XO) assay. Besides that, total phenolic content (TPC), phytochemical screening and high-performance liquid chromatography (HPLC) analysis and gas chromatography-mass spectrometer (GCMS) were also carried out. MEDL exhibited significant (p<0.05) hepatoprotective activity against both inducers. Pre- treatment of MEDL at a high dose markedly attenuated the increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and prevented a marked decrease in superoxide dismutase (SOD) and catalase (CAT) levels in CCl4-and PCM-induced hepatotoxic rats. These observations were supported by the histologic findings and scoring, where the liver tissues in groups pre-treated with MEDL and Silymarin showed mild necrosis and inflammation of the hepatocytes compared to the DMSO pre-treated group (negative control group). For the partition extracts, EADL partition exhibited the best activity in protecting the liver against PCM-induced toxicity. Interestingly, EADL, at a low dose (50 mg/kg) significantly (p<0.05) reduced ALP, ALT and AST to 198.5 ± 19.78 U/L, 108.7 ± 29.00 U/L and 313.0 ± 65.99 U/L, respectively and the total bilirubin levels (1.133 ± 0.1687 umol/L) in PCM-induced hepatotoxic rats. EADL also increased the activity of SOD (17.98 ± 0.09 U/g tissue) and CAT (116.9 ± 2.71 U/g tissue) while significantly attenuated the malondialdehyde (MDA) levels of the liver to 2.61 ± 0.70 μM in the liver homogenates. EADL partition also ameliorated histopathological changes to liver tissues by the PCM intoxication. In the in-vitro antioxidant assay, MEDL showed the highest DPPH- and superoxide anion-radical scavenging activity (98.94 ± 1.14% and 93.2 ±1.18%) as well as high TPC (1757.25 ± 29.39 mg/100g GAE) and ORAC ( 24 272.50 ± 2056.53 μM TE/ 100g) values, indicating a high antioxidant activity. In addition, EADL with low TPC (352.18 ± 48.40 mg/100g GAE) exhibited a high scavenging activity against DPPH- and superoxide anion with 93.68 ± 3.0% and 92.6 ± 2.17%, respectively. EADL was also the highest in ORAC value with 555 000 ± 12 700 μM TE/ 100g. The phytochemical screening of MEDL and EADL showed the present of saponins, flavonoids, tannins and polyphenolic compounds. HPLC analysis of MEDL also identified the presence of flavonoids, Rutin and Quercetin in the extracts. Moreover, GCMS analysis revealed the presence of 48 volatiles compounds in the MEDL extracts with some of them reported to exhibit antioxidant and anti-inflammatory activity. MEDL and EADL also exerted hepatoprotective activity that could be partly contributed by its antioxidant activity and high phenolic content, and the presence of various bioactive compounds that might act synergistically to enhance the hepatoprotective effect

Aqueous partition of methanolic extract of Dicranopteris linearis leaves protects against liver damage induced by paracetamol

This study aimed to determine the antioxidant and hepatoprotective activities of semi-purified aqueous partition obtained from the methanol extract of Dicranopteris linearis (AQDL) leaves against paracetamol (PCM)-induced liver intoxication in rats. The test solutions, AQDL (50, 250, and 500 mg/kg), were administered orally to rats (n = 6) once daily for seven consecutive days followed by the hepatotoxicity induction using 3 g/kg PCM (p.o.). Blood was collected for serum biochemical parameters analysis while the liver was collected for histopathological examination and endogenous antioxidant enzymes analysis. AQDL was also subjected to antioxidant determination and phytochemical analysis. Results obtained show that AQDL possessed high total phenolic content (TPC) value and remarkable radical scavenging activities. AQDL also significantly (p < 0.05) reduced the liver weight/body weight (LW/BW) ratio or serum level of ALT, AST, and total bilirubin while significantly (p < 0.05) increase the level of superoxide dismutase (SOD) and catalase (CAT) without affecting the malondialdehyde (MDA) in the liver indicating its hepatoprotective effect. Phytoconstituents analyses showed only the presence of saponins and triterpenes, but lack of flavonoids. In conclusion, AQDL exerts hepatoprotective activity via its high antioxidant potential and ability to modulate the endogenous enzymatic antioxidant defense system possibly via the synergistic action of saponins and triterpenes

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

Abstract Background The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. Methods A 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. Results Pre-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. Conclusion MEDL 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