Evaluation of the Effectiveness ofPiper cubebaExtract in the Amelioration of CCl4-Induced Liver Injuries and Oxidative Damage in the Rodent Model

Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness ofPiper cubebafruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model.Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT,γ-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile,in vivoantioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNFα, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations.Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNFαand IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene.

Download Full-text

In-vivo Hepatoprotective and Antioxidant Activities of Sphaeranthus amaranthoides Burm.f. Against Anti-Tubercular Drugs Induced Hepatotoxicity in Rats

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i25a31448 ◽

2021 ◽

pp. 15-23

Author(s):

M. R. Vinayakamurthi ◽

J. Anbu Jeba Sunilson ◽

A. V. Anita Gnana Kumari ◽

U. Aathilakshmi

Keyword(s):

Antioxidant Activity ◽

Liver Toxicity ◽

Methanolic Extract ◽

Antioxidant Activities ◽

Liver Homogenate ◽

Hepatoprotective Activity ◽

Thiobarbituric Acid Reactive Substance ◽

Enzymatic Antioxidants ◽

Drug Induced

Aim: To evaluate the hepatoprotective and antioxidant activity of Sphaeranthus amaranthoides Burm.f. against isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in rats. Study Design: Experimental study. Place and Duration: Research lab, Department of Siddha Medicine, Tamil University, Thanjavur, India, between March 2018 and November 2019. Methodology: Liver toxicity was induced by antitubercular drugs (Isoniazid; INH+Rifampicin; RIF) at a dose level of 50+100 mg/kg each, p.o for 15 days. Petroleum ether, Chloroform, Methanol, Aqueous extracts of Sphaeranthus amaranthoides Burm.f. (S. amaranthoides) (200 and 400 mg/kg bt.wt.) were administered orally once daily for 15 days. The hepatoprotective activity was assessed using various biochemical parameters SGOT, SGPT, ALP, bilirubin, total protein, albumin, total cholesterol, total bilirubin, direct bilirubin and LDH. The antioxidant activities such as the enzymatic activity of superoxide dismutase (SOD), and catalase (CAT), and the level of lipidperoxidation as thiobarbituric acid reactive substance (TBA-RS) were measured in liver homogenates and histological examinations were carried out to assess hepatoprotective activity. For Statistical analysis, the values were subjected to one way analysis of variance (ANOVA) followed by Tukey multiple compare test. Results were considered statistically significant when P<0.05. Results: The treatment with methanolic extract (400 mg/kg bt.wt.) of S. amaranthoides significantly prevented drug-induced increase in serum levels of liver enzymes (P<0.001). The antioxidant activity of a dose of 400 mg/kg of S. amaranthoides significantly prevented the decreases in the activity of enzymatic antioxidants (CAT & SOD) (P<0.01 and P<0.001) and inhibited the elevation of lipid peroxidation (TBA-RS) in the liver homogenate. Histopathology of liver tissue showed that S. amaranthoides attenuated the hepatocellular necrosis, regeneration and repair of cells toward normal. Conclusion: The methanolic extract of S. amaranthoides showed significant hepatoprotectivity and antioxidant activity against INH + RIF Anti TB drugs.

Download Full-text

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽

10.3390/molecules26092529 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2529

Author(s):

Haeyeop Kim ◽

Woo Seok Yang ◽

Khin Myo Htwe ◽

Mi-Nam Lee ◽

Young-Dong Kim ◽

...

Keyword(s):

Ethanol Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Tnf Α ◽

Anti Inflammatory ◽

Related Proteins ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Download Full-text

FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00542-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Dezhong Wang ◽

Yuan Yin ◽

Shuyi Wang ◽

Tianyang Zhao ◽

Fanghua Gong ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Metabolic Regulation ◽

Cardiac Injury ◽

Serum Levels ◽

Ros Generation ◽

Dependent Manner ◽

Cardiac Tissues ◽

Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

Download Full-text

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2015-0049 ◽

2016 ◽

Vol 27 (2) ◽

Cited By ~ 16

Author(s):

Ganiyu Oboh ◽

Veronica O. Odubanjo ◽

Fatai Bello ◽

Ayokunle O. Ademosun ◽

Sunday I. Oyeleye ◽

...

Keyword(s):

Leaf Extract ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Inhibitory Effect ◽

Seed Extract ◽

Persea Americana ◽

Dependent Manner ◽

Natural Treatment

AbstractAvocado pear (The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of FeThe extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID.The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Download Full-text

Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/4235695 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 7

Author(s):

Xinxin Yang ◽

Haibo Yang ◽

Fengdi Wu ◽

Zhipeng Qi ◽

Jiashuo Li ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Dependent Manner ◽

Protein Levels ◽

Key Factor ◽

Protein Sulfhydryl ◽

Mrna And Protein Expression ◽

The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

Download Full-text

Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22576 ◽

2015 ◽

Vol 10 (2) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Liaqat Hussain ◽

Muhammad Sajid Hamid Akash ◽

Madeha Tahir ◽

Kanwal Rehman

Keyword(s):

Liver Injury ◽

Serum Levels ◽

Therapeutic Effects ◽

Sapium Sebiferum ◽

Dependent Manner ◽

Protective Effects ◽

Drug Induced ◽

Standard Drug ◽

Hepatoprotective Effects ◽

Dose Dependent

Sapium sebiferum leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of S. sebiferum against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of S. sebiferum with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of S. sebiferum. We conclude that leaves of S. sebiferum have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.

Download Full-text

PASS-Predicted Hepatoprotective Activity ofCaesalpinia sappanin Thioacetamide-Induced Liver Fibrosis in Rats

The Scientific World JOURNAL ◽

10.1155/2014/301879 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 16

Author(s):

Farkaad A. Kadir ◽

Normadiah M. Kassim ◽

Mahmood Ameen Abdulla ◽

Behnam Kamalidehghan ◽

Fatemeh Ahmadipour ◽

...

Keyword(s):

Liver Fibrosis ◽

Transforming Growth Factor ◽

Antioxidant Activities ◽

Smooth Muscle Actin ◽

Immunohistochemical Analysis ◽

Hepatoprotective Activity ◽

Nuclear Antigen ◽

Sprague Dawley ◽

Liver Fibrogenesis

The antifibrotic effects of traditional medicinal herbCaesalpinia sappan(CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factorβ1 (TGF-β1),α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting.In vivodetermination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1,αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.

Download Full-text

Evaluation of Hepatoprotective activity of Methanol extract of Persicaria hydropiper: An in vivo screening

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.01012 ◽

2021 ◽

pp. 5819-5824

Author(s):

Pooja Kamra ◽

Mahaveer Singh ◽

Hardarshan Singh Lamba ◽

Birendra Srivastava

Keyword(s):

Carbon Tetrachloride ◽

Intraperitoneal Administration ◽

Hepatoprotective Activity ◽

Dependent Manner ◽

Standard Drug ◽

Whole Plant ◽

Dose Dependent ◽

Histopathological Investigation ◽

Different Doses

The present study aimed to evaluate the hepatoprotective potential of methanolic whole plant extract of Persicaria hydropiper in carbon tetrachloride (CCl4) induced hepatotoxicity model. Hepatotoxicity was induced in rats by intraperitoneal administration of carbon tetrachloride (CCl4) for seven days. The extract was thereafter administered at two different doses of 200 mg/kg and 400 mg/kg body weight for next seven days. Silymarin was used as a reference standard. The extract revealed hepatoprotective activity in dose dependent manner. The dose of 400 mg/kg exhibited maximum hepatoprotective ability as apparent from several evaluation parameters including liver function profile, bilirubin, antioxidant enzymes as well as histopathological investigation which was comparable to the standard drug Silymarin respectively. These findings sustenance the use of the extract as an adjuvant with existing therapy for treatment of liver ailments.

Download Full-text

EVALUATION OF HEPATOPROTECTIVE EFFECTS OF SELECTED FRUIT PEEL EXTRACTS AND THEIR POLY HERBAL MIXTURE ON CCL4 INDUCED HEPATOTOXICITY: AN IN VIVO STUDY

INDIAN DRUGS ◽

10.53879/id.57.09.12110 ◽

2020 ◽

Vol 57 (09) ◽

pp. 67-74

Author(s):

Gana Manjusha Kondepudi ◽

Battu Ganga Rao ◽

P Balakrishnaiah

Keyword(s):

Hepatoprotective Activity ◽

Serum Markers ◽

Albino Rats ◽

Dependent Manner ◽

Fruit Peel ◽

Herbal Mixture ◽

Wistar Albino Rats ◽

Dose Dependent ◽

Peel Extract

The main aim of this study was to screen the selected fruit peel extracts and their polyherbal mixture (PHM) for hepatoprotective activity. Male wistar albino rats (180-200 g), divided into 12 groups after induction of hepatotoxicity, were treated with selected fruit peel extracts and PHM and at the end of 14th day blood and liver samples were collected and analysed. The aqueous peel extract of Malus pumila was a better hepatoprotective among the selected peel extracts. The activities might be due to the conditioning of hepatocytes by protecting the integrity of the membrane from CCl4 induced leakage of serum markers into circulation. All the selected plant extracts and PHM were shown to revert back the liver enzymes to the normal values in diseased rats in a dose dependent manner. In conclusion, the selected fruit peel extracts and poly herbal mixture can be a potent hepatoprotective agent due to their antioxidant and anti-inflammatory actions.

Download Full-text

Hepatoprotective activity of a purified methanol extract and saponins from the roots of Chenopodium bonus-henricus L.

Zeitschrift für Naturforschung C ◽

10.1515/znc-2019-0002 ◽

2019 ◽

Vol 74 (11-12) ◽

pp. 329-337 ◽

Cited By ~ 2

Author(s):

Zlatina Kokanova-Nedialkova ◽

Paraskev Nedialkov ◽

Magdalena Kondeva-Burdina ◽

Rumyana Simeonova

Keyword(s):

High Performance ◽

High Resolution Mass Spectrometry ◽

Antioxidant Activities ◽

Rat Hepatocytes ◽

Hepatoprotective Activity ◽

Cellular Damage ◽

Medicagenic Acid ◽

Hepatoprotective Agents

Abstract An ultra-high-performance liquid chromatography-high-resolution mass spectrometry based profiling of a purified MeOH extract (PME) from the roots of Chenopodium bonus-henricus L. (Amaranthaceae) tentatively identified 15 saponins of six sapogenins. The PME exerts hepatoprotective and antioxidant activities comparable to those of flavonoid complex silymarin in in vitro (1 and 10 μg/mL) and in vivo (200 mg/kg/daily for 7 days) models of hepatotoxicity, induced by CCl4. The main constituents of PME, respectively saponins bonushenricoside A (1), 3-O-β-D-glucuronopyranosyl-bayogenin-28-O-β-D-glucopyranosyl ester (2), 3-O-β-D-glucuronopyranosyl-medicagenic acid-28-O-β-D-xylopyranosyl (1→4)-α-L-rhamnopyranosyl(1→2)-α-L-arabinopyranosyl ester (3), 3-O-β-D-glucuronopyranosyl-2β-hydroxygypsogenin-28-O-β-D-glucopyranosyl ester (4), 3-O-α-L-rabinopyranosyl-bayogenin-28-O-β-D-glucopyranosyl ester (6) and bonushenricoside B (8) (3 μg/mL each), compared to silymarin (5 and 50 μg/mL), significantly reduced the cellular damage caused by CCl4 in rat hepatocytes, preserved cell viability and glutathione level, decreased lactate dehydrogenase leakage and reduced lipid damage. The experimental data suggest that the glycosides of phytolaccagenin, bayogenin, medicagenic acid, 2β-hydroxygypsogenin, 2β-hydroxyoleanoic acid and oleanoic acid are a promising and safe class of hepatoprotective agents.

Download Full-text