Hepatoprotective activity of Phyllanthus niruri Linn. endophytes

Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats

Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels

Methanolic extract and fractions, ethylacetate (EtF) and butanol (BuF) of leaves of African mistletoe (Tapinanthus bangwensis, Engl. & K. Krause) were evaluated for their hepatoprotective potential using CCl4-induced hepatotoxicity in Wistar albino rats. The activities of the marker enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin were highest in rats treated with CCl4 alone. Oral administration at a fixed dose of 400 mg/kg body weight (BW) of the extract and fractions of T. bangwensis for seven days significantly (p ≤ 0.05) decreased the activity of marker enzymes and bilirubin. Total protein concentration increased significantly (p ≤ 0.05). These extracts also decreased the concentration of thiobarbituric acid reactive substances (TBARS) which indicated a reduction in lipid peroxidation. Histopathological examination of hepatocytes of rats administered methanolic extract (MeE) and fractions (EtF and BuF) showed normal architecture whereas rats treated with CCl4 alone was characterized by necrosis of the liver. Generally, among the three extracts, the BuF and EtF showed more hepatoprotective effect. The crude methanolic extract did not show any mortality up to a dose of 2000 g/kg BW. These findings suggest that T. bangwensis possesses strong antioxidant properties and hepatoprotective potentials against CCl4-induced hepatotoxicity in rats.

Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

Liver diseases pose a major challenge to international public health. Hepatic damage is associated with distortion of metabolic functions of the liver. The present study was carried out to evaluate the hepatoprotective effect of the ethanolic extract of whole plant of Andrographis paniculata in CCl4-induced hepatotoxicity in albino rats. Hepatotoxicity was induced in rats by single intraperitoneal injection of 30 % CCl4 suspended in olive oil (1 ml /kg b.w.) after every 72 h for 10 days (group II). Hepatotoxicity-induced rats were treated with 200 mg/kg b.w. of ethanolic extract of A. paniculata for 10 days, and also, CCl4 was given as in group II rats. The effect of the drug was compared with the standard drug silymarin. The effect of the ethanolic extract of whole plant of A. paniculata on marker enzymes, serum glucose, urea, creatinine, serum bilirubin total protein, A/G ratio, gamma-glutamyl transpeptidase, lipid profile and antioxidants was determined. Treatment with A. paniculata extract showed a significant reduction in blood glucose levels, marker enzymes and also lipid profile. The drug significantly increased the activity of antioxidant enzymes in the liver of hepatotoxic rats. The results of the present study suggest that treatment with A. paniculata extract enhanced the recovery from CCl4-induced hepatic damage due to its antioxidant and hepatoprotective property.

Aim: The current study was carried out to evaluate the hepatoprotective effects of aqueous extract of Adansonia digitata fruit pulp on carbon tetrachloride (CCl4) induced liver damage in rats.
 Place and Duration of Study: Department of Biochemistry, Faculty of Basic Medical Sciences, College of Health Science, between November 2017 and January 2018.
 Methodology: A. digitata fruit pulp was extracted by maceration using water; and a concentration of 100 mg/ml was used. Two doses of the aqueous extract (200 mg/kg and 300 mg/kg) and Livoline (25 mg/kg) were used to investigate their hepatoprotective effects on CCl4-induced hepatotoxicity in rats.
 Results: The two doses of the plant extract showed dose-dependent hepatoprotective effect on CCl4-induced hepatotoxicity, as evident by the significant reduction (P<0.05) in serum levels of AST, ALT, ALP and bilirubin along with the improved histopathological liver sections compared to CCl4-treated animals.
 Conclusion: Due to its hepatoprotective potentials, A. digitata extract may be used to develop standard treatment drugs against some liver disorders when it is further evaluated through extensive researches.

Phenolic compounds and hepatoprotective potential of Anastatica hierochuntica ethanolic and aqueous extracts against CCl4-induced hepatotoxicity in rats.

The hepatoprotective and anti-inflammatory effects of Terminalia catappa L. and Pergularia daemia hydroalcoholic extracts in albino rats with CCl4-induced liver damage (HAETC and HAEPD, respectively). The extracts significantly reduced the harm induced by CCl4 when given orally at a dosage of 200mg/kg. They also showed strong hepatoprotective and antioxidant properties. Wistar albino rats in good health were divided into seven groups, each with six animals. Group I acted as the control and received no treatment, whereas Group II was given 30% CCl4 (1ml/kg, intraperitoneally) to cause hepatotoxicity. After administering Silymarin (25 mg/kg, orally) as per protocol, Group III underwent CCl4 therapy. The CCl4-induced rats showed significant reductions in antioxidant enzymes like SOD, catalase, glutathione peroxidase (GPX), and glutathione-S-transferase (GST), as well as increases in serum marker enzymes like SGOT, SGPT, alkaline phosphatase (ALK), ACP, LDH, and lipid peroxidation (LPO) activity. However, rats given HAEPD and HAETC showed significant improvements, returning these parameters to levels that are almost normal (P 0.001).The hepatoprotective and antioxidant benefits of Terminalia catappa L. (HAETC) and Pergularia daemia (HAEPD) against CCl4-induced hepatotoxicity in rats were further validated by histopathological analysis of liver tissues. It encourages the use of pre-trained CNN architectures, such as VGG16 and ResNet (Residual Network), in the proposed method, which uses convolutional neural networks (CNNs) for histopathological image analysis to assess the hepatoprotective properties of Pergularia daemia and Terminalia catappa L. leaf extracts against CCl4-induced hepatotoxicity. These well-known CNN models may be modified for precise and effective histopathological image interpretation, assisting in the evaluation of the impact of plant extracts on liver health.

The available conventional remedies for the treatment of drug-induced liver diseases are highly inadequate and possess serious adverse effects; therefore, the development of new, effective drugs is considered necessary. This article explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC) and 7-methoxycoumarin (MOC) in CCl4-induced hepatotoxicity in rats. MC and MOC individually, at doses of 50 and 100 mg/kg body weight, were administered orally once-daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase (CAT)] levels were determined. Also, thiobarbituric-acid–related substances (TBARS) levels, along with histopathological studies of liver tissue, were scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and TB in the serum of CCl4-induced liver damaged rats in a dose-dependent manner. TA and TP levels in the serum were also restored significantly in all presupplemented MC and MOC groups. In addition, oxidative stress induced by CCl4 was prevented significantly; thereby, increasing SOD and CAT levels and decreasing TBARS levels in liver homogenates. Histopathological studies revealed the ameliorative natures of both the compounds. This study demonstrates the strong hepatoprotective activity of MC and MOC, which could be attributed to their potent antioxidant effects.

Hepatoprotective and antioxidant activity of pentagamavunon-0 against carbon tetrachloride-induced hepatic injury in rats

Objective: Punarnavashtak kwath (PNK) is a classical Ayurvedic formulation, mentioned in Ayurvedic literature Bhaishajya Ratnavali, for hepatic disorders and asthma. This study investigated the hepatoprotective activity of PNK to validate the traditional use of this formulation.Materials and methods: PNK was prepared in the laboratory according to the method given in Ayurvedic literature. Phytochemical screening was performed to determine the presence of phytoconstituents. Hepatoprotective activity was evaluated against CCl4-induced hepatotoxicity in rats and by its effect on the HepG2 cell line.Results: Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins, and a bitter principle in PNK. Administration of PNK produced significant hepatoprotective effect as demonstrated by decreased levels of serum liver marker enzymes such as aspartate transaminase, serum alanine transaminase, serum alkaline phosphatase, and serum bilirubin and an increase in protein level. Thiopentone-induced sleeping time was also decreased in the PNK-treated animals compared with the CCl4-treated group. It also showed antioxidant activity by increase in activity of glutathione, superoxide dismutase, and catalase and by a decrease in thiobarbituric acid reactive substance level compared with the CCl4-treated group. Results of a histopathological study also support the hepatoprotective activity of PNK. Investigation carried out on the HepG2 cell line depicted significant increase in viability of cells exposed to PNK as compared with CCl4-treated cells.Discussion and Conclusion: It can be concluded that PNK protects hepatocytes from CCl4-induced liver damages due to its antioxidant effect on hepatocytes. An in vitro study on HepG2 cell lines also supports its protective effect.

It has been proposed carbon tetrachloride (CCl4 ) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl4 -induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl4 (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl4 significantly inhibited alterations in the serum levels of AST, ALP (** P < 0.01), and ALT (*** P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl4 -induced hepatotoxicity in rats.

The current study was evaluated for the hepatoprotective activity of probiotics, prebiotics alone, and synbiotic of them. Animals were grouped into 12 groups (n = 6), i.e. normal control (NC), disease control (DC), treatment with prebiotics, probiotics alone, and synbiotic of them, and standard marketed hepatoprotective Silymarin along with Synbiotic 2000. All treatments were orally administered daily for 28 days. On the 28th day, all animals except the NC group received carbon tetrachloride (CCl4) (1 ml/kg, i.p.). Levels of serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, total protein, lactate dehydrogenase, and urea were evaluated. The tissues were evaluated for oxidative markers levels of catalase (CAT), lipid peroxidation (LPO), and glutathione (GSH), and total protein. Histopathology of tissues was carried out. Compositional analysis of intestinal microbiota was done by 16S amplicon sequencing. CCl4 caused elevation in SGPT, SGOT, ALP, total bilirubin, urea, and lactate dehydrogenase in the DC group which was prevented with pretreatment of prebiotics, probiotics, and synbiotics. Total protein was decreased in serum and tissues after administration of CCl4 which was restored with pretreatment of test substances. Oxidative marker LPO was increased in the DC group and catalase (CAT) and GSH were also depleted in liver tissue. These changes were prevented in pretreated test groups. The histological change in hepatic parenchyma and hepatocytes was minimal in test groups compared to DC. The 16S amplicon sequencing indicated that Lactobacillus acidophilus and prebiotic treatment effectively displaced Staphylococcus. Results suggested that the use of prebiotics, probiotics alone, and synbiotic of them has a protective effect against CCl4-induced hepatotoxicity in rats.

This study was conducted to investigate potentially protective and curative effects of Curcuma longa root (turmeric) powder on CCl4-induced hepatotoxicity in rats. Turmeric was administered before (preventive effect) or after (curative effect) treatment with CCl4. Total phenolic and flavonoid levels were 26.35mg GAE/g and 12.35mg CE/g, respectively. Using HPLC analysis, turmeric powder was rich in curcumin (62.97%), demethoxycurcumin (20.86%) and bisdemethoxycurcumin (16.17%). Curcuma longa powder showed important in vitro antioxidant activities. Results showed that the activities of aspartate aminotransaminase and alanine aminotransaminase, and the levels of bilirubin and serum lipids were increased in CCl4-treated animals. However, total protein and albumin levels and antioxidant enzyme activities were decreased. Turmeric administration, before or after CCl4 treatment, significantly decreased the activities of marker enzymes and lipid levels in serum. Moreover, total protein and albumin contents were restored to nearly normal levels after turmeric administration accompanied with increase of antioxidant enzymes activities.

Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. The other 4 groups were treated as indicated previously with induction of hepatic damage with CCl4; at the end of treatment period, rats were scarified, blood samples obtained and livers excised for the assessment of the oxidative stress parameters (MDA and GSH), cholesterol and triglycerides levels. Additionally, serum levels of total bilirubin, albumin, total protein and the activities of ALT, AST and ALP enzymes were evaluated before and after treatment with benfotiamine. Tissue sections were prepared for evaluation of histopathological changes. The results indicated that benfotiamine has the ability to protect hepatic tissue against the toxicity induced by CCl4, revealed through reduction of serum levels of TSB and liver enzymes, decrease in the hepatic tissue MDA levels and elevation of GSH there. Histological evaluation of tissue sections prepared for this purpose confirmed the previous finding. In conclusion, benfotiamine is capable to protect liver tissue against CCl4-induced toxicity in rats more than thiamine.&#x0D; Key words: Benfotiamine, CCl4, Hepatotoxicity