Hepatoprotective Activity In Rats Research Articles

Изучение эффективности применения пептидных препаратов при острых тяжёлых отравлениях этанолом

Severe poisoning plays a significant role in ethanol poisoning and is an important cause of increased mortality in the population. Existing treatment regimens for extremely severe ethanol poisoning have shown low effectiveness, necessitating the search for drugs among pharmacological groups that have not previously been used in severe cases of ethanol poisoning. Peptides, which have demonstrated high efficacy in treating critical conditions of the body accompanied by impaired central nervous system and liver function, can be the drugs of choice. The aim of this study was to investigate the effectiveness of peptide drugs with neuroprotective and hepatoprotective activities in rats with acute severe ethanol poisoning. The studies were conducted on male albino rats, in which 40% ethanol was administered intragastrically using a probe at a dose of 1.5 LD50. The investigated pharmacological correction agents included the peptide drug Semax and a hepatoprotective agent with a peptide component, Molixan. The survival rate, average lifespan, neurological status, and vital functions (respiratory rate, heart rate, and body temperature) of the animals were evaluated. The results showed that administration of Semax and Molixan peptides increased the survival rate of rats and had a favorable effect on neurological status and vital body functions in cases of acute severe ethanol intoxication at a dose of 1.5 LD50. This study demonstrated the potential of using peptide drugs in cases of acute severe ethanol intoxication.

Hepatoprotective Activity of Aqueous Extract of Cashew Apple Cake (Anacardium occidentale L.) in Rats and Mice

Aims: The aqueous extract of cashew apple cakes, rich in molecules of pharmacological interest, could be used against many diseases. Thus, the aim of the present work is to evaluate its hepatoprotective activity in rats and mice. 
 Methodology: Two batches of rats weighing between 200 and 300 grams, with five rats per batch, were pretreated for eleven days with the aqueous extract of cashew apple cakes at concentrations ranging from 150 to 300 mg.Kg-1 bw, then intoxicated with paracetamol at 2 g.Kg-1 bw, for three days. The blood of these rats was collected and submitted to biochemical analyses. 
 Two batches of mice weighing between 20 and 30 grams, with five mice per batch, were pretreated with the same test substance at concentrations also ranging from 150 to 300 mg.Kg-1 bw, then intoxicated with paracetamol before receiving phenobarbital. Afterwards, their sleep time was evaluated.
 Results: In rats, paracetamol intoxication materialized by the increase in serum ALT activity ranging from 109±5.19 to 571±20.28 IU.L-1 and that of AST ranging from 144±5.77 to 428±14.19 IU.L-1. Similarly, direct bilirubin increased from 0 to 1.08± 0.58 mg.dl-1. These increases in transaminase activity and bilirubin levels were significantly decreased in rats pretreated with the aqueous extract of cashew apple cake. In mice, the phenobarbital test showed a 29.82 to 38.59% decrease in sleep time in mice pretreated with the aqueous extract of cashew apple cakes.
 Conclusion: The aqueous extract of cashew apple cakes influencing biochemical parameters such as ALT, AST, bilirubin and sleep time, could therefore be used in the prevention of liver diseases, in traditional medicine.

Hepatoprotective Activity of Pirdot Leaves (Saurauia vulcani Korth) Ethanol Extract in Laboratory Rats (Rattus norvegicus) and Characterization of Bioactive Compounds Using a Molecular Docking Approach

AIM: The hepatoprotective activities of bioactive compounds Pirdot were investigated in vivo and in silico.
 METHODS: In this study, the completely randomized design non-factorial was experimentally to assess the value of SGPT and SGOT and twenty four adult male rats were divided into four groups : group G0, control group; group G1, a treated group received 0.1 ml sheep red blood cell; group G2, a treated group received 500 mg ethanol extract Pirdot; group G3, a group treated received 500 mg ethanol extract Pirdot and 0,1 ml sheep red blood cell. On thirty one days of treatment, the blood of all rats group were taken to value SGPT and SGOT using DiaLab kit. Furthermore, the molecular docking study was done to analyse molecular interaction that COX-2 and TNF-α were the primary target protein of bioactive compounds of Pirdot associated with hepatoprotective activities. In addition, it tends to be the target of non-steroidal anti-inflammatory drugs such as Ibuprofen.
 RESULTS: The results show SGOT and SGPT value significantly [p<0.05] decreased on Group G2 and G3. Moreover, the bioactive compounds of Pirdot, such as Pomolic acid and Ursolic acid tend to be the potential compound on liver protection. Moreover, Pomolic acid has a good binding affinity -14.6 kcal mol-1 with COX-2 Protein and the binding affinity of cis-3-O-p-hydroxycinnamoyl Ursolic acid was -15.1 kcal mol-1 associated with TNF-α Protein.
 CONLUSION: Pirdot Leaves (Saurauia vulcani Korth.) Ethanol Extract showed Hepatoprotective activity in rats (Rattus norvegicus). Molecular docking approach showed that pomolic acid has a good binding affinity with COX-2 Protein and TNF-α Protein.

Effects of nerol on paracetamol-induced liver damage in Wistar albino rats

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

Metabolic profiling and in vivo hepatoprotective activity of Malpighia glabra L. leaves.

Although Malpighia glabra Linn. fruits are well studied for their nutritional and medicinal prominence; little attention has been given to the leaves. Our study intends to investigate the leaves metabolic profile using Q-TOF LC/MS/MS (Quadrupole-Time-of-Flight-Liquid-Chromatography-Mass-Spectrometry), and to explore their in vivo hepatoprotective activity in rats using CCL4 -induced hepatic damage model and silymarin as standard. Fifty metabolites were characterized, belonging to different classes; coumarins (capensine, daphnoretin, and scopoletin), flavonoids (mainly quercetin and apigenin glycosides), phenolic acids (cinnamic acid and quinic acid derivatives) and amino acids (adenosine, homoisoleucine, and phenylalanine).These compounds are detected in the leaves for the first time. The hepatoprotective activity at three doses (200, 400, and 800mg/kg) was investigated. The dose of 800mg/Kg showed the highest hepatoprotective effect as it reduced the elevated serum levels of ALT, AST, NO, and TNF-α liver content by 26, 24, 23, and 42%, respectively, it also remarkably increased the serum level of catalase by 102%. All the tested doses showed higher reduction in serum level of TNF-α compared to silymarin which suggests their strong anti-inflammatory potential. M. glabra leaves are revealed to be a rich source of secondary metabolites and proved to possess significant hepatoprotective potential. PRACTICAL APPLICATIONS: The performed analyses in this study shows the richness of Malpighia glabra Linn. leaves in a plethora of beneficial and safe phytochemicals which are well-known to have a pivotal role in protection against different diseases including liver disorders. The carried-out investigations were done using Q-TOF LC/MS/MS analysis which is a reliable technique for the determination, characterization and identification of bioactive metabolites; in addition to evaluation of the hepatoprotective effect of the leaves. Therefore, this study may emphasize that Malpighia glabra Linn. leaves may have the same nutritional and medicinal importance as its fruits, and they could be incorporated into pharmaceuticals and foods instead of discarding them.

Hepatoprotective effect of Rhodomyrtus tomentosa fruit juice in rats fed with high fat high cholesterol diet

In this study we conducted experiments to prove the effectiveness of Rhodomyrtus tomentosa fruit juice as hepatoprotective agent in rats fed with high fat high cholesterol diet (HFHCD). The experiments were carried out using male albino rats which were fed with HFHCD for 15 days and at the same time orally supplemented with R. tomentosa fruit juice (RTFJ) in doses of 500, 1000 and 2000 mg/kg bw daily for 15 days. Simvastatin is used as a positive control. At the end of the experiment, the liver function markers in serum, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were determined as well as the histopathological image of the liver. Results of the experiments showed that HFHCD significantly induced hepatotoxicity showed by increase of sAST and sALT level. Supplementation of RTFJ significantly prevent the increase of sAST and sALT levels and maintained healthy histopathological image of liver tissue in rats fed with HFHCD, reduce fat accumulation and balloning hepatocytes as seen in untreated rats. From the results we concluded that R. tomentosa fruit juice possess significant hepatoprotective activity in rats fed with high fat high cholesterol diet, and therefore could be develop further as functional food to prevent hepatic diseases due to high fat high cholesterol diet.

HEPATOPROTECTIVE ACTIVITY OF CORDIA OBLIQUA AGAINST PARACETAMOL-INDUCED LIVER TOXICITY ON WISTAR RATS

Objective: The ethanolic extract of Cordia obliqua (EECO) Willd. leaves was evaluated for hepatoprotective activity in Wistar rats by inducing hepatic damage with paracetamol.
 Methods: The leaves of C. obliqua were dried under shade, segregated, pulverized by a mechanical grinder and passed through a 40 mesh sieve. The powdered plant materials were stored in an air-tight container. The above-powdered materials were successively extracted with ethanol by hot continuous percolation method in Soxhlet apparatus for 24 h. The extract was concentrated using a rotary evaporator and subjected to freeze drying in a lyophilizer till dry powder was obtained.
 Results: Treatment with EECO at 200 and 400 mg/kg showed significant decrease in serum glutamate-pyruvate transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, and total bilirubin levels and a significant elevation in the total protein, albumin, and globulin levels in serum when compared with paracetamol treated rats. In histological study of liver, the hepatocytes show moderate cytoplasm and moderately enlarged pleomorphic and hyperchromatic nuclei. The portal triads show mild periportal inflammation composed of lymphocytes, and central veins are normal.
 Conclusion: On the basis of results, we can conclude that the EECO leaves showed potential hepatoprotective activity in rats.

Anti-inflammatory and hepatoprotective potentials of the aerial parts of <i>Silene villosa</i> Caryophyllaceae methanol extract in rats

Purpose: To explore the anti-inflammatory and hepatoprotective potentials of Silene villosa Caryophyllaceae methanol extract in rats.Methods: Toxicity of S. villosa extract was evaluated in rats. Inflammation was induced in rats by injection of 0.1 mL carrageenan (1 %) in the left hind paws. Carbon tetrachloride (CCl4) was used to induce liver damage. Five groups of rat were used. The 1st (normal control) and 2nd (hepatotoxic) groups received the vehicle. The 3rd, 4th, and 5th groups received silymarin, 250 and 500 mg/kg of S. villosa extract, respectively, for 7 days. Liver injury was induced on the 7th day by intraperitoneal administration of 1 mL/kg of CCl4 to rats in groups 2 - 5.Results: The results showed that S. villosa is safe. It significantly reduced carrageenan-induced edema compared to normal (p < 0.01) and standard (p < 0.01) groups. The extract protected (p < 0.01) rats against the deleterious effect of CCl4. It decreased (p < 0.01) the elevated serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT) and alkaline phosphatase (ALP) as well as elevated serum levels of bilirubin (BRN), compared to CCl4 control rats. Reduced activities of the antioxidant enzymes were significantly increased (p < 0.01) in rat liver, compared with CCl4 control group. The results were confirmed by histological findings in rat liver as the extract reduced necrosis and hydropic degeneration of hepatic tissue compared to CCl4 control group.Conclusion: The results suggest that S. villosa possesses anti-inflammatory and hepatoprotective activities in rats, and therefore, has therapeutic potentials in humans.Keywords: S. villosa, anti-inflammatory, carrageenan, CCl4, antioxidant, hepatotoxicity.

High resolution UPLC-MS/MS profiling of polyphenolics in the methanol extract of Syzygium samarangense leaves and its hepatoprotective activity in rats with CCl4-induced hepatic damage

Oxidative stress plays a crucial role in the development of several liver diseases. Many natural polyphenols can attenuate oxidative stress and liver injury. In this study, a phytochemical profiling of a methanol extract from leaves of Syzygium samarangense revealed 92 compounds belonging to flavonoids, phenolic acids, condensed tannins, and ellagitannins. The S. samarangense extract exhibited a noticeable antioxidant activity with an EC50 of 5.80 μg/mL measured by DPPH scavenging capacity assay, 2632 Trolox equivalents, 10 mM Fe2+ equivalents/mg of samples by TEAC and FRAP assays, respectively. The total phenolic content was 419 mg gallic acid equivalent GAE/g extract. In a cell-based model (HaCaT cells), the extract completely inhibited ROS production induced by UVA, and prevented GSH-depletion and p38 phosphorylation. In addition, the extract exhibited a substantial antioxidant and hepatoprotective activities in CCl4-treated rats, with an increase in GSH (reduced glutathione) and SOD (superoxide dismutase) activities by 84.75 and 26.27%, respectively, and a decrease of 19.08, 63.05, 52.21, 37.00, 13.26, and 15.15% in MDA, ALT, AST, TB (total bilirubin), TC (total cholesterol), and TG (total glycerides), respectively. These results were confirmed by histopathological analyses. We believe that Syzygium samarangense is a good candidate for further evaluation as an antioxidant and liver protecting drug.

DNA fingerprinting, biological and chemical investigation of certain Yucca species

Yucca aloifolia, Y. aloifolia variegata, Y. elephantipes and Y. filamentosa were investigated. DNA sequencing was performed for the four plants and a genomic DNA fingerprint was obtained and provided. The cytotoxic activities against four human cancer cell lines were investigated. The ethanolic extracts of leaves of Y. aloifolia variegata prevailed, especially against liver cancer HepG-2 and breast cancer MCF-7. In vivo assessment of hepatoprotective activity in rats also revealed the hepatoprotective potential of the ethanolic extracts of the four plants against CCl4- induced rats’ liver damage. Qualitative and quantitative analysis of the flavonoid and phenolic content of the promising species was performed using HPLC. The analysis identified and quantified 18 flavonoids and 19 phenolic acids in the different fractions of Y. aloifolia variegata, among which the major flavonoids were hesperidin and kaemp-3-(2-p-coumaroyl) glucose and the major phenolic acids were gallic acid and protocatechuic acid.

A Phenylpropanoid and Biflavonoids from the Needles of Cephalotaxus harringtonia var. harringtonia

A phenylpropanoid [2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol] (1) together with four known biflavonoids namely 7, 4′, 7′″, 4′″-tetra- O-methyl amentoflavone (2); 7, 4′, 7″-tri- O-methyl amentoflavone (3); ginkgetin (4); sequoiaflavone (5) were isolated from the acetone soluble extract of needles of Cephalotaxus harringtonia var. harringtonia. Their structures were elucidated mainly on the basis of interpretation of 1D and 2D NMR spectroscopy and X-ray diffraction studies. The detailed spectral data of phenylpropanoid have been described for the first time. Ginkgetin (4) exhibited significant hepatoprotective activity in rat at 6 mg/kg oral dose level.

Role of Emblica officinalis (amla) in the prophylaxis of hepatic injury by carbon tetrachloride (CCl4) in albino rats

Background: The objective of the study was to evaluate the hepatoprotective activity of fruits extract of Emblica officinalis on carbon tetrachloride induced hepatotoxicity in Albino rats. Liver is vulnerable to wide variety of metabolic, toxic, microbial, circulatory and neoplastic insults. The dominant primary diseases of the liver are viral hepatitis, alcoholic liver disease and hepatocellular carcinoma. Due to absence of reliable drugs management of liver ailments in the modern medicine, plants and natural products are providing to be good hepatoprotectants as evident from voluminous published work on their hepatoprotective potentials.Methods: The required amount of fresh fruits of Emblica officinalis was collected and dried at room temperature. The dried fruit ground into powdered and was prepared by percolation method using 95% ethanol. Acute oral toxicity test of the fruits extract was performed as per OECD 423 guidelines. Carbon tetrachloride was used as the hepatotoxin. Silymarin suspension 100mg was used as a standard drug in this study.Results: The study was carried out with an attempt to evaluate the hepatoprotective activity of Emblica officinalis in carbon tetrachloride induced hepatic injury in albino rats. The results were analysed by using one way ANOVA followed by Dunnett’s test and (p <0.05) was considered significant.Conclusions: The present study shows that the Emblica officinalis has significant hepatoprotective activity in rats with carbon tetrachloride induced liver injury. Emblica officinalis is a commonly used traditional herb, which is safe, cost effective and grows widely in India and used by different ethnic groups for various diseases. That is why Emblica officinalis, a commonly used natural herb, deserve further consideration in order to establish its potential as safe economical hepatoprotective agent.

IN-VITRO ANTIOXIDANT AND IN-VIVO HEPATO PROTECTIVE ACTIVITY OF ETHANOL EXTRACTS FROM THE BARK OF SHOREA ROBUSTA (DIPTEROCARPACEAE) AGAINST CARBON TETRA CHLORIDE INDUCED LIVER TOXICITY IN RATS

ABSTRACT: The study is designed for the evaluation of in-vivo Hepato protective and in-vitro Anti oxidant activity of ethanol extracts from the bark of Shorea robusta (Dipterocarpaceae) by CCl4 induced hepatotoxicity in rats. Ethanol extracts from the bark Shorea robusta (EESR) was evaluated for hepatoprotective activity in rats by inducing liver damage by CCl4. The anti oxidant activity of EESR was assayed by various in-vitro antioxidant methods and activities were compared to standard ascorbic acid. Ethanol extracts at an oral dose 200mg/kg and 400mg/kg exhibited a significant (*p<0.005) protective effects by lowering the level of SGOT, SGPT, ALP, Serum bilirubin, total cholesterol and increasing the level of total proteins as compared to Silymarin (50mg/kg) used as positive control. The extracts exhibit significant anti oxidant activity in various in vitro anti oxidant models. From these studies we are concluding that, the ethanolic extracts of S.robusta have potent hepatoprotective effects and have anti oxidant properties, hence can be used as a natural product against liver damage.KEY WORDS: Anti oxidant, Carbon tetra chloride, Hepatoprotective, Shorea robusta

Isolation, identification, and in vivoevaluation of flavonoid fractions of chloroform/methanol extracts of Rheum emodi roots for their hepatoprotective activity in Wistar rats

Objective: Even though the rhizome of Rheum emodi (Chinese rhubarb) has been used since centuries as a traditional medicinal plant in treating a number of disease conditions, the bioactive components responsible for its hepatoprotective activity have not been identified. Therefore, we isolated, identified, and evaluated in vivo the compounds in chloroform/methanol extracts of Rheum emodi roots for their hepatoprotective activities in rats. Materials and Methods: Nine different fractions were collected by column chromatography and were further isolated and identified through thin layer chromatography (TLC) analysis for the presence of flavonoids. The isolated flavonoids containing fractions were then evaluated for their hepatoprotective activity in paracetamol-induced toxicity in male Wistar rats. Silymarin [50 mg/kg body weight (BW)] was used as a control hepatoprotective drug. To assess liver functions, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and bilirubin (total and direct) were determined. Results: Only five collected fractions (F 1 to F 5 ) showed the presence of different flavonoids and the fraction F 2 showed the presence of five different types of flavonoids. The isolated flavonoid containing fractions of Rheum emodi were significantly effective in decreasing the elevated the levels of ALT, AST, ALP, and bilirubin (total and direct) due to paracetamol-induced hepatotoxicity in Wistar rats. The fractions at dose level of 0.125 mL/kg BW showed significant hepatoprotective effects in rats. The fraction F 2 at a dose level of 0.5 mL/kg BW showed the maximum therapeutic efficacy followed by the same fraction at 0.25 mL/kg BW and 0.125 mL/kg BW, fractions F 1 , silymarin, F 3 , F 4 and F 5 . Conclusion: The results suggest that isolated fractions of Rheum emodi roots contained flavonoids, which showed significant hepatoprotective activity in Wistar rats. Further investigations are however, required for the identification of individual flavonoids as well as other bioactive components in Rheum emodi roots, and to establish their structure and mechanism of action for their hepatoprotective activity.

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats

Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties.Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage.Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses.Results: CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats.Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.

Mechanism of action involved in the hepatoprotective activities of methanol extract of Cassytha filiformis L. aerial parts in CCl4-induced liver damage

Cassytha filiformis alcohol decoction is used by traditional healers in Idem-Ogwa, Mbaitoli Local Government Area of Imo State, Nigeria, in the treatment of liver disorders ranging from hepatitis to susceptive poisoning and alcohol intoxication. The methanol extract of the aerial parts of Cassytha filiformis L. was investigated for hepatoprotective activity in rats challenged with carbon tetrachloride (CCl4). Apart from group 1 (normal), all other groups were pre-challenged with a single intraperitoneal injection of 0.7 ml of 20 % (v/v) CCl4 solution in olive oil. Group 2 (negative control) was given distilled water (10 ml kg−1, p.o.). Group 3 were treated with silymarin (35 mg kg−1 p.o.). Groups 4, 5, and 6 received oral treatments of 75, 150, and 300 mg kg−1 of the extract of C. filiformis respectively. All treatments were given by stomach intubation and at 12 h intervals for 7 days. Sodium pentobarbitone-induced sleeping time assay was carried out on the animals at 12 h after the last treatment on day 7 by intraperitoneal administration of Na-pentobarbitone (35 mg kg−1). Serum from individual animal was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, total protein and in vitro red blood cell membrane stability. The extract was safe up to 2000 mg kg−1 orally and did not induce overt clinical manifestation or death in rats. The extract significantly (p < 0.01) demonstrated potency at all test doses (75, 150, and 300 mg kg−1) in CCl4-challenged and treated animals when compared with prolonged Na-pentobarbitone-induced sleeping time observed in untreated CCl4-intoxicated rats. The methanol extracts of C. filiformis (150 and 300 mg kg−1) were also able to reduce hepatic tissue injury as revealed by a reduction in the serum levels of AST, ALT, ALP, and total bilirubin significantly (p < 0.05) but increased total serum protein significantly (p < 0.05) relative to values in untreated CCl4-induced liver damaged rats. Exposure of rat erythrocytes to varying saline concentrations (0.2–1.0 mg mL−1) of the extract did not produce observable measured increase in osmotic fragility in the red blood cell membranes. The findings suggest that the methanol extract of the aerial parts of C. filiformis could be useful in protecting hepatocytes from toxins especially from alcohol intoxication.

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, Phyllanthusniruri

The Role of Complementary and Alternative Medicine in Regenerative Medicine

Regenerative medicine is the process of replacing or regenerating animal cells, tissues, or organs to restore or establish normal function. This field has the potential to solve the problem of the shortage of organs available for donation and of organ transplant rejection. Recently, application of Complementary and Alternative Medicine (CAM) as a means to accelerate the process of regeneration is a new approach. The CAM therapies offer a natural and cost-effective intervention to change the course of chronic disease and may regenerate failing organ systems. The paper by Dr. Y.–J. Chen et al. explores how the Hepatitis B virus-encoded X regulates the expression of epidermal growth factor receptor, an important gene for growth of hepatocytes. Dr. H.–Y. Liu et al. demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy. Dr. S. –H. Hsu et al. prepared peripheral nerve conduits containing the negatively charged Tremella fuciformis polysaccharide (TF) and successfully used the TF-immobilized conduits to repair a large (15 mm) critical gap defect in rats. Y. Lee et al. found that L-glutamate-induced neurotoxicity could be suppressed by the treatment with constituents of Rhodiola rosea, indicating that the Rhodiola rosea may have therapeutic potential for the treatment of inflammation and neurodegenerative disease. Dr. B.–Y. Yang et al. tried to apply percutaneous electrical stimulation to improve bone remodeling and bone healing in rats. X-ray and micro-CT showed that the electrical treatment could increase the amount of newly formed cranial bone. W. Liu et al. examined the contribution of side population (SP) cells from kidney and bone marrow to the reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). They found that following renal IRI, kidney SP cells were acutely depleted and then progressively restorated to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing. Dr. F. Yahya et al. showed that methanol extract of Bauhinia purpurea leaves could exert potential hepatoprotective activity in rats via its antioxidant activity and high phenolic content. T. Jayakumar et al. reviewed the effects of andrographolide, a major bioactive chemical constituent in Andrographis paniculata (Burm.f.) Nees, against cardiovascular disease, platelet activation, infertility, and NF-kB activation. Dr. H.–M. Chiang et al. showed the antioxidant activity of a Neonauclea reticulata water extract against ultraviolet B (UVB) irradiation in human skin fibroblast cell cultures (Hs68) by inhibiting MMP-1, -3, and -9 expressions and increasing levels of collagen activity. Dr. W.–Y. Su et al. developed a biphasic calcium phosphate cement, consisting of α-tricalcium phosphate (α-TCP) and hydroxyapatite (HAP), which is a potential biomaterial for bone repair. C. Y. Ho et al. showed that acupuncture and electroacupuncture could have positive effects on regeneration of median nerve in rats. J. Xiao et al. demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) could ameliorate hepatic injury in a nonalcoholic fatty liver disease rat model. Dr. S.–C. Lee et al. investigated the effect of ferulic acid (FA) against peripheral nerve injury. They found that FA appears to promote peripheral nerve regeneration across a 15 mm critical defect gap in the rat sciatic nerve injury model. Suppression of macrophages by FA at the site of peripheral nerve injury may contribute to its nerve growth-promoting capability. By compiling these articles, we hope to stimulate our readers and researchers to provide continuing efforts to fully understand the effects of CAM therapies on regenerating tissues or organs. Yueh-Sheng Chen Wei-Chiang Lin Cheryl Miller

Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation

BackgroundThe purpose of this study was to develop a novel silymarin-loaded solid nanoparticle system with enhanced oral bioavailability and an ability to provide excellent hepatic protection for poorly water-soluble drugs using Shirasu porous glass (SPG) membrane emulsification and a spray-drying technique.MethodsA silymarin-loaded liquid nanoemulsion was formulated by applying the SPG membrane emulsification technique. This was further converted into solid state nanosized particles by the spray-drying technique. The physicochemical characteristics of these nanoparticles were determined by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Their dissolution, bioavailability, and hepatoprotective activity in rats were assessed by comparison with a commercially available silymarin-loaded product.ResultsFormulation of a silymarin-loaded nanoemulsion, comprising silymarin, castor oil, polyvinylpyrrolidone, Transcutol HP, Tween 80, and water at a weight ratio of 5/3/3/1.25/1.25/100 was accomplished using an SPG membrane emulsification technique at an agitator speed of 700 rpm, a feed pressure of 15 kPa, and a continuous phase temperature of 25°C. This resulted in generation of comparatively uniform emulsion globules with a narrow size distribution. Moreover, the silymarin-loaded solid nanoparticles, containing silymarin/castor oil/polyvinylpyrrolidone/Transcutol HP/Tween 80 at a weight ratio of 5/3/3/1.25/1.25, improved about 1,300-fold drug solubility and retained a mean size of about 210 nm. Silymarin was located in unaltered crystalline form in the nanoparticles. The drug dissolved rapidly from the nanoparticles, reaching nearly 80% within 15 minutes, indicating three-fold better dissolution than that of the commercial product. Further, the nanoparticles showed a considerably shorter time to peak concentration, a greater area under the concentration-time curve, and a higher maximum concentration of silymarin compared with the commercial product (P < 0.05). In particular, the area under the concentration-time curve of the drug provided by the nanoparticles was approximately 1.3-fold greater than that of the commercial product. In addition, the silymarin-loaded nanoparticles significantly reduced carbon tetrachloride-induced hepatotoxicity, indicating improved bioactivity compared with silymarin powder and the commercial product.ConclusionSilymarin-loaded nanoparticles developed using SPG membrane emulsification and spray-drying techniques could be a useful system for delivery of poorly water-soluble silymarin while affording excellent hepatic protection.

Antioxidant effect of celery against carbontetrachloride induced hepatic damage in rats

Ethanolic extract of celery (Apium graveolens) and its diet were evaluated for antioxidant and hepatoprotective activities in rats. Celery is valuable in weight loss diets and regulate lipid metabolism. Albino male rats were used to evaluate its antioxidant and hepatoprotective activities against carbon tetrachloride induced toxicity. Chromosomal aberration, sperm abnormalities, biochemical and molecular assay were used to evaluate its antioxidant activity. Liver damage was assessed by estimating biochemical parameters such as total soluble protein, DNA and RNA contents. Celery showed significant antioxidant effect by reducing chromosomal aberration, sperm abnormalities and increasing DNA bands number and pattern as the control. It also showed a significant hepatorotective effect by readjusting the toxic effect of CCL4 on the total soluble protein, DNA and RNA contents around that of the normal. Key words: Celery (Apium graveolens), albino male rats, carbontetrachloride, DNA and RNA contents and biochemical parameters.