Preliminary phytochemical screening and Evaluation of hepatoprotective activity of ethanolic extract of whole plant of Evolvulus alsinoides using CCl4 induced model in experimental animals

Present study was conducted to evaluate the preliminary phytochemical screening and hepatoprotective activity of whole plant of Evolvulus alsinoides. The whole plant was defatted with petroleum ether and then extracted with 90 % ethanol. The phytochemical screening was done for ethanol extract using standard procedures. Acute toxicity was done using OECD 423 guidelines and the extract was found to be practically non-toxic upto a dose of 1500mg/kg b.w. when given orally. Hepatoprotective activity was evaluated using Carbon tetra chloride induced model in rats. In CCl4 induced mothod of 90% Ethanolic extract of whole plant of Evolvulus alsinoides (75 & 150mg/kg b.w.) produced significant dose dependent hepatoprotective activity. Histopathological studies could be carried out to assess the degree of damage. The hepatoprotective effect of the aforesaid extract was substantiated by pentobarbital sleeping time experiment in mice. The effect of the extracts at 150 mg/kg was compared to that of the reference drug, Silymarin (50 mg/kg). In vitro antioxidant studies were conducted to confirm the antioxidant mechanism involved in their hepatoprotective activity in CCl4-induced in rats. The presence of flavonoids could be responsible for hepatoprotective activity

IN VITRO HEPATOPROTECTIVE ACTIVITY OF EXTRACTS OF VIBURNUM PUNCTATUM BUCH-HAM EX D.DON AGAINST CARBON TETRACHLORIDE INDUCED TOXICITY

Objective: The study was aimed to evaluate of in vitro hepatoprotective activity of Chloroform and Methanol extracts of Viburnum punctatum (200 and 400 μg/ml) against carbon tetrachloride induced toxicity. Methods: The screening of hepatoprotective activity was based on the protection of human liver derived Chang liver cells against CCl4 induced damage determined by MTT assay [(3-(4,5 dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromide assay] using Silymarin as standard. Results: The chang liver cells were treated with different concentrations of chloroform and methanol extracts of Viburnum punctatum, showed a dose dependent increase in percentage viability and the results were highly significant (P<0.001, when compared with CCl4 induced group). The percentage viability ranged between 62 to 84% at 200-400µg/ml concentrations. The methanolic extract exhibited more hepatoprotective activity when compared to chloroform extract. Conclusion: The results clearly demonstrate that Viburnum punctatum possess promising hepatoprotective effects and hence suggests to isolate and identify the active principle involved in the hepatoprotective activity

Models of hepatoprotective activity assessment

Liver diseases are a major health problem worldwide, making it necessary to develop new molecules that help counteract or prevent such diseases. On account of this fact, investigations aiming to obtain natural and/or synthetic compounds possessing hepatoprotective activity have been undertaken. The development of new drugs consists of a variety of steps, ranging from the discovery of the pharmacological effects in cellular and animal models, to finally demonstrate their efficacy and safety in humans. Different models for assessment of the hepatoprotective activity in vitro, ex vivo and in vivo can be found in medical literature. The purpose of this review is to show the features, main advantages and disadvantages of each of the models, the hepatotoxic agents most commonly used (CCl4, acetaminophen, ethanol, dgalactosamine, t-BuOOH, thioacetamide) as well as the biochemical parameters useful to assess liver damage in the different models

Analgesic and Hepatoprotective Activity of Methanolic Leaf Extract of Ocimum gratissimum (L.).

The methanolic extract of Ocimum gratissimum (L.) leaves was screened for analgesic and hepatoprotective activity in albino rats, respectively. The use of the hot-plate method to study central analgesic activity of the leaves extract in albino rats indicated that the extract possesses the ability to significantly reduce pain threshold and also increase the response latency period to thermal stimuli in albino rats, similar to the reference drug acetylsalicylic acid. After treatment reaction time of albino rats was significantly increased to 10.92 sec with 40 mg kg-1 of leaves extract, whereas acetylsalicylic acid also increased reaction time to 12.53 sec with 25 mL kg-1. A decline in the reaction time beyond 1.61 sec was observed by the reference drug and leaves extract. Albino rats whose livers were damaged with a hepatotoxin-Carbon tetrachloride (CCl4) 0.5 mL kg-1 i.p. were used to test for hepatoprotective properties of the plant leaves extract. It reduced significantly (p<0.05) liver enzyme levels for animals treated with CCL4 (0.5 mL kg-1) and the methanolic plant leaf extract (40 mg kg-1) concurrently compared to animals treated with CCL4 only. Many histopathological changes in the liver such as marked dilation of the central vein, blood vessel congestion and inflammatory leucocytic infiltrations which were observed in the CCl4 treated animals were not observed in the CCl4 + plant extract treated animals. No apparent disruptions of the normal liver structure by histological and enzyme activities assessment were observed. The results show that the methanolic leaf extract is a potent analgesic and antihepatotoxic agent

Hepatoprotective studies of floral extracts of Gomphrena serrata L. and piperic acid on CCl4 induced hepatotoxicity

The present investigation aims to isolate, characterise and evaluate the phytoconstituents of Gomphrena serrata L. responsible for hepatoprotective activity in carbon tetrachloride-induced hepatotoxicity models both in vitro and in vivo. The plant species has not been explored for various therapeutic activities. HPLC analysis of subfraction of plant extract showed the presence of piperine, which was isolated and further hydrolysed to piperic acid. The results of the study indicate that the plant hydroalcoholic, acetone extracts at 500 mg/kg and compound piperic acid at 0.5 mg/kg exhibited better results in the regeneration of damaged hepatocytes and reduction of biochemical marker enzymes. The hepatoprotective activity might be due to inhibition of cytochrome P450 2E induced ER and oxidative stress. The present study reveals that the hepatoprotective activity of floral extracts might be due to in situ conversion of piperine into piperic acid. As piperic acid showed the equipotent potential to standard drug silymarin, it can be further developed as a hepatoprotective drug

Hepatoprotective studies of floral extracts of Gomphrena serrata L. and piperic acid on CCl4 induced hepatotoxicity

238-251The present investigation aims to isolate, characterise and evaluate the phytoconstituents of Gomphrena serrata L. responsible for hepatoprotective activity in carbon tetrachloride-induced hepatotoxicity models both in vitro and in vivo. The plant species has not been explored for various therapeutic activities. HPLC analysis of subfraction of plant extract showed the presence of piperine, which was isolated and further hydrolysed to piperic acid. The results of the study indicate that the plant hydroalcoholic, acetone extracts at 500 mg/kg and compound piperic acid at 0.5 mg/kg exhibited better results in the regeneration of damaged hepatocytes and reduction of biochemical marker enzymes. The hepatoprotective activity might be due to inhibition of cytochrome P450 2E induced ER and oxidative stress. The present study reveals that the hepatoprotective activity of floral extracts might be due to in situ conversion of piperine into piperic acid. As piperic acid showed the equipotent potential to standard drug silymarin, it can be further developed as a hepatoprotective drug

HEPATOPROTECTIVE ACTIVITY OF SAPONIN FRACTION OF OYONG SEED FLESH AND ITS COMBINATION AGAINST CCl4-INDUCED CHRONIC LIVER DAMAGE IN MALE WISTAR RAT

Saponin fraction of seed flesh of Oyong (Luffaacutangula [L.]Roxb) has been investigated to have a hepatoprotective activity in rats with fibrotic chronic liver damage. This research was conducted to evaluate whether saponin fraction of Oyongseed flesh has a hepatoprotective activity in CCl4-induced acute liver damage. Hepatoprotective activity was determined by measuring the activity of liver enzymes (SGOT, SGPT, LDH), total nitrite/nitrate level, liver index and liver histology. Saponin fraction of Oyong flesh seeds 10mg/kg BW and meniran extract 400mg/kg BW alone showed hepatoprotective activity. Administration of saponin fraction 10mg/kb BB decreased SGPT and LDH significantly over untreated group. Group given meniran extract at dose of 200mg/kg BW showed decreased on LDH, while at dose of 400mg/kg BW decreased SGPT, SGOT, and LDH significantly. Hystological observation revealed any improvement in liver morphology especially after treated with saponin fraction 10mg/kg BWand meniran extract at dose of 400mg/kg BW. However, all groups treated with combination of saponin and meniran did not show improvement both at biochemical parameter and liver histology. In conclusion, saponin extract with dose of 10mg/kg BW and meniran extract at dose of 400mg/kg BW showed hepatoprotector activity. In contrast, combination of both did not show any hepatoprotective effect and it was suspected that they have antagonist effects.Key words:hepatoprotective, CCl4-induced liver fibrosis, Luffaacutangula, Phyllanthusnirur

Hepatoprotective Effect of Adenema hyssopifolium G. Don (Gentianaceae) in Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Purpose: The effects of oral administration of ethyl acetate, ethanol and aqueous extracts of Adenema hyssopifolium G.Don (Gentianaceae) on carbon tetrachloride-induced liver disorders were investigated.Methods: Rats were individually treated daily with 300 and 600 mg/kg dose of either ethyl acetate, ethanol or aqueous extracts of A. hyssopifolium, respectively, following induction of liver damage with the hepatotoxin, carbon tetrachloride. The hepatoprotective activity of the extracts was assessed by estimating the levels of serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP) and total bilirubin (TBL) in the rats. Silymarin was used as the reference hepatoprotective agent. Acute toxicity test on the extracts in male mice was also carried out.Results: At doses of 300 and 600 mg/kg p.o., the ethyl acetate and ethanol extracts showed significant (p < 0.001 and p < 0.01) dose-dependent hepatoprotective activity, showing decreases in serum levels of ASAT, ALAT, ALP and TBL. The aqueous extract, however, did not exert any significant effect on hepatoprotective activity. All three extracts, up to a dose of 3000 mg/kg p.o. each, did not cause mortality in the acute toxicity test.Conclusion: The ethyl acetate and ethanol extracts showed significant hepatoprotective activity when compared to untreated (normal) control group while the aqueous extract did not. The active extracts could find future use in countering hepatic damage.Keywords: Hepatoprotection; Iridoid glycosides; Hepatotoxicity

Preparation, Characterisation and In Vivo Evaluation of Silybin Nanoparticles for the Treatment of Liver Fibrosis

Purpose: To formulate and characterize nanoparticles containing silybin, and evaluate their activity against carbon tetrachloride (CCl4)-induced liver toxicity.Methods: Silybin nanoparticles were formulated by o/w emulsion solvent evaporation technique using poly-å-caprolactone as polymer. Four different nanoparticle formulations (NP1, NP2, NP3 and NP4) were prepared by varying the drug/polymer ratio. The particles were characterized for particle size, drug content and in vitro drug release. The pharmacokinetics and pharmacodynamics of the silybin formulations in male Wistar rats were evaluated following i.v. administration, using silybin solution asreference. The hepatoprotective activity of the formulations was also determined in a CCl4-treated rat model.Results: Silybin nanoparticles were successfully prepared using o/w emulsion solvent evaporation technique. The nanoparticles sustained the release of the drug both in vitro and in vivo for up to 10 days and offered better pharmacokinetic properties than the free drug itself. Intravenous nanoparticulate administration reversed serum liver enzyme levels by 95 % compared to only 50 % for the drug solution.Conclusion: The developed silybin nanoparticles showed superior pharmacokinetic properties and hepatoprotective activity to silybin solution.Keywords: Silybin, Nanoparticles, Pharmacokinetics, Pharmacodynamics, Hepatoprotective activity