Hepatoprotective Remedy Research Articles

Modulatory effect of quercetin on aspirin-induced hepatoxicity in Wistar rats

Objectives: Aspirin, also known as acetylsalicylic acid, is a non-steroidal anti-inflammatory drug medication. Aspirin has been shown to have a wide range of pharmacological effects, such as antipyretic, antiplatelet and analgesic effects. Although there is little known about how aspirin causes hepatotoxicity at the cellular level, this does happen and there is a need to look into some hepatoprotective remedies. The aim of this study was to assess how quercetin (QE) affects aspirin-induced hepatotoxicity in Wistar rats. Materials and Methods: Thirty-five male adult Wistar rats divided into seven experimental groups were used in this study. These groups received different treatments: Some were given varying concentrations of QE (30 mg/kg and 60 mg/kg), while others received aspirin (50 mg/kg). In addition, there were control groups that did not receive either aspirin or QE, with normal saline and corn oil being administered instead. The administration of treatments lasted for 30 days, after which the experiment was concluded, and the rats’ livers were removed for histological examination. Simultaneously, blood serum samples were collected for the biochemical analysis of liver enzyme markers. The level of significance was set at 0.05, and the data collected was analysed using the Statistical Package for the Social Sciences version 29. Results: It was found that aspirin increased the level of liver enzyme markers in the serum after 30 days of administration resulting from damage to the liver cells, this effect was most significant at an aspirin concentration of 50 mg/kg and QE at a concentration of 60 mg/kg was most effective in exhibiting hepatoprotective potentials. Conclusion: The results suggest that aspirin 50 mg/kg could be hepatotoxic due to the lessening of antioxidant effects, and QE has a modulating effect on aspirin-induced toxicity.

Ajuga reptans L. Herb Extracts: Phytochemical Composition and Pharmacological Activity Screening

The genus Ajuga (Lamiaceae family) comprises approximately 300 species, which are widely used in traditional medicine for their diaphoretic, antiseptic, hemostatic, and anti-inflammatory properties, but scarcely in official ones. Therefore, the study of Ajuga reptans holds promise for developing new medicinal products. In aqueous and aqueous-alcoholic soft extracts of the A. reptans herb, 16 amino acids, 20 phenolics, and 10 volatile substances were identified by HPLC and GC/MS. The assays of the main substances’ groups were also determined by spectrophotometry (vitamin K1, polyphenols, tannins, flavonoids, and hydroxycinnamic acids) and titrometry (ascorbic and organic acids). A. reptans herb extracts are practically non-toxic, exhibit hepatoprotective activity (dose 25 mg/kg) in experimental carbon tetrachloride-induced hepatitis, moderate anti-inflammatory activity (dose 100 mg/kg) in carrageenan-induced edema models, and possess significant local hemostatic (reducing bleeding time by 40.6%) and wound-healing properties (complete wound healing after 9 days). The aqueous-ethanolic soft A. reptans extract (extractant 50% ethanol) demonstrated the most pronounced hepatoprotective and anti-inflammatory effects. A. reptans extracts are capable of inhibiting the growth of microorganisms and showing higher activity against Gram-positive bacteria. A. reptans herb extracts are promising agents for implementation in official medicine as wound healing and hepatoprotective remedies after further preclinical and clinical studies.

Hepatoprotective Activity and Oxidative Stress Reduction of an Arctium tomentosum Mill. Root Extract in Mice with Experimentally Induced Hepatotoxicity

Background: The use of natural hepatoprotective remedies represents an important path in modern phytotherapy. Objectives: In this context, our research aims to evaluate the phytochemical composition and the hepatoprotective and oxidative stress reduction potential of an Arctium tomentosum Mill. root extract. Methods: The phenolic profile of the tested extract, prepared by the subcritical fluid-assisted method were qualitatively and quantitatively analyzed by spectrophotometrical and HPLC/DAD/ESI methods. In vitro antioxidant capacity was assessed using DPPH and FRAP assays. Hepatoprotective activity of the extract was assessed on a model of CCl4 experimentally induced hepatotoxicity in mice. Results: Phytochemical assays revealed the presence of important polyphenols, such as chlorogenic acid (17.20 ± 0.65 μg/mL) and acacetin 7-O-glucoside (56.80 ± 1.66 μg/mL). In vitro, the tested extract exhibited a significant oxidative stress reduction capacity, while in vivo it showed a dose-dependent hepatoprotective effect indicated by an improvement in plasma proteins profile and down-regulation of plasma transaminase activity (ALAT, ASAT, GGT). In liver tissue, the extract partially restored the activity of GPx, CAT, and SOD and attenuated lipid peroxidation. The protective effect of the A. tomentosum root extract was supported by the alleviation of histological injuries of the liver (centrilobular necrosis, granulocytic infiltrate, and fibrosis). Conclusions: The A. tomentosum subcritical fluid-assisted root extract proved to be able to provide a significant hepatoprotective effect mainly through an antioxidant mechanism.

Oligochaeta ramosa (Roxb.) Extract Regulates Lipid Metabolism and Exerts Hepatoprotective Effects in Cadmium-Induced Hepatic Injury in Rats.

Environmental pollutants present a potential source of toxicity when exposed to humans. The study was aimed at investigating the potential of Oligochaeta ramosa (Roxb.) as a hepatoprotective agent in cadmium-induced hepatotoxicity causing lipid profile disturbance. The aqueous methanolic (30 : 70 v/v) extract of O. ramosa Roxb. (AME.Or) was subjected to preliminary phytochemical analysis, whereas the antioxidant activity of its constituents was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The hepatoprotective and antihyperlipidemic effects of AME.Or was investigated by dividing animals into five groups (A-E). Animals were either treated with normal saline or CdCl2 (6.5 mg/kg, intraperitoneally) followed by treatment with silymarin (100 mg/kg), or AME.Or (200 mg/kg) and AME.Or (400 mg/kg) for consecutive three weeks. Blood samples were collected, and the serum lipid profile was assessed on the 11th and 21st day of treatment. Histopathological analysis was performed after euthanization. In vitro analysis of AME.Or revealed 64% inhibition as free radicals scavenging potential during DPPH, total phenolic content (TPC) (79.92 mgGAE/g), and total flavonoids content (TFC) (38.75 mgRE/g). The group intoxicated with CdCl2 showed significantly high (p ≤ 0.05) levels of the liver function indicators and lipid profile than in the control group. The higher dose of AME.Or (400 mg/kg) significantly decreased the aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin (p ≤ 0.001), decreased total cholesterol and triglycerides (p ≤ 0.01) while significantly increased high density lipoprotein (HDL; p ≤ 0.01) as compared to the intoxicated group. The histopathological analysis of the liver revealed signs of necrosis in the intoxicated group, while AME.Or treated groups showed marked improvement. The findings accentuate the therapeutic importance of O. ramosa (Roxb.) as a hepatoprotective remedy.

Holothuria arenicola Extract Attenuated Hepatic Steatosis in Splenectomized Rat Fed High Fat Diet

Background: Non-alcoholic fatty liver disease (NAFLD) is a considerable public health concern due to the excessive dietary consumption of high caloric diet and subsequent obesity. Additionally, splenectomy is considered one of the major common risk factors for NAFLD. Objective: Regardless of the non-alcoholic fatty liver disease (NAFLD) being the most common chronic disorder, there is no effective cure for it. Therefore, the current study aimed to investigate the efficacy of Holothuria arenicola extract (HaE) on hepatic steatosis in splenectomized (SPX) rats fed High fat diet (HFD). Methods: Male Wistar rats (n=28) were randomly assigned to four groups: sham rats fed a standard diet, sham rats+ HFD, SPX+HFD and SPX+HFD+HaE. The estimation of hematological and some biochemical parameters, as well as oxidative status, were analyzed. Results: Oral administration of HaE caused a significant amelioration in all hematological parameters relative to untreated splenectomized rats. Concerning lipid metabolism, HaE treatment caused a pronounced amelioration in lipid metabolism, as indicated by the decreased total cholesterol, triglycerides and LDL-cholesterol contents, as well as the increased HDL- cholesterol level. HaE treatment significantly enhanced hepatic function, as exhibited by the reduction in liver enzyme activities as well as the increase in protein and albumin content. Moreover, HaE could retard the hepatic oxidative stress via a pronounced increase in hepatic GSH content and antioxidant enzyme activities besides decreasing MDA, NO and H2O2 formation. Conclusion: HaE could be utilized as a potential alternative hepatoprotective remedy via lipid metabolism and oxidative damage attenuation.

Characterisation of Preformulation Parameters to Design, Develop and Formulate Silymarin loaded PLGA Nanoparticles for Liver Targeted Drug Delivery

Silymarin, a flavonolignan,derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. It inhibits the binding of hepatotoxins to receptor sites, protects hepatocyte membranes, enhances liver parenchyma regeneration and increases glutathione levels. The pharmacokinetic studies of past three decades revealed that Silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Typical oral adult dose of Silymarin is 240-800mg /day .It is a non-lipophilic and poorly water soluble compound with water solubility of 0.04mg/ml. Only 20-30% of oral Silymarin is absorbed from gastrointestinal tract where it undergoes extensive entero-hepatic circulation. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin to hepatocytes. A controlled release PNP of Silymarin was prepared by solvent evaporation method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer. Prior to the development of this novel dosage form, it is very important to identify fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder. This data helps in many of the subsequent events and approaches towards the development of a better formulation. Preformulation studies included determination of solubility, moisture content, partition coefficient, melting point , powder properties like tapped density, bulk density, compressibility index, flow properties like angle of repose, excipient compatibility, entrapment efficiency, release profile of nanoparticles like dissolution, stability studies like effect of temperature and humidity and analysis by scanning Electron Microscopy.

Preparation of Silymarin–quercetin Loaded Nanoparticles by Spontaneous Emulsification Solvent Diffusion Method Using D-alpha-tocopheryl Poly (Ethylene Glycol) 1000 Succinate

Silymarin, a flavonolignan, derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. The pharmacokinetic studies of past three decades revealed that silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Quercetin, a flavonoid present in edible vegetables and fruits, It is a potent antioxidant and shows a wide range of biological functions. Quercetin improves blood levels and efficacy of number of drugs since it is P-Glycoprotein inhibitor and also inhibits drug metabolizing enzymes. Both silymarin and quercetin were, poorly soluble in the water shows low bioavailability. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin-quercetin to hepatocytes. A controlled release PNPs of silymarin-quercetin were prepared by spontaneous emulsification solvent diffusion (SESD) method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer, D-alpha-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) used as a solubilizer, as an emulsifier. TPGS as an emulsifier and further as a matrix material blended with PLGA was used to enhance the encapsulation efficiency and improve the drug release profile of nanoparticles. Different formulations with various drug: polymer ratios and volume and concentration of surfactant, centrifugation time were evaluated. The effect of formulation parameters such as drug/polymer ratio, volume and surfactant content were evaluated. The surface morphology and size of the nanoparticles were studied by scanning electron microscopy (SEM) Transmission electron microscopy (TEM). Drug encapsulation efficiency and in vitro drug release profiles of nanoparticles were determined using UV spectrophotometry. The nanoparticles prepared with combination of both the drugs in this study were spherical with size range of 100–200 nm. It was shown that TPGS was a good emulsifier for producing nanoparticles of hydrophobic drugs and improving the encapsulation efficiency and drug loading and drug release profile of nanoparticles. Although the amount of the TPGS used had a significant effect on the nanoparticle size and morphology, the drug loading and release profile of nanoparticles

A Cross Over Trial Evaluating Combined Effect of Ruksha Virechana,Lashuna Erandadi Kashaya and Patolamooladi Kashaya in Diagnosed Patients of Non-Alcoholic Steatohepatitis

The change in living habits due to increasing popularity of fast foods, sedentary lifestyle have given rise to lifestyle disorders and Non Alcoholic Steatohepatitis is one among them. Non Alcoholic Steatohepatitis (NASH) is a spectrum of Non Alcoholic Fatty Liver Disease (NAFLD) characterized by the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis.There is no direct reference to NASH in Ayurvedic literature but based on the etiopathogenesis, signs and symptoms it can be correlated to Yakritodara.NASH has no FDA approved therapeutics, so, it is need of the hour to search an effective hepatoprotective remedy from Ayurvedic treasure of therapeutics. Hence, the present study was designed as cross over single blind clinical study with the objectives of evaluating the combined efficacy of Amapachana,Ruksha virechana and Shamanoushadhi with Lashuna Erandadi Kashaya and Patolamooladi Kashaya in the management of NASH. Overall study showed marked improvement in 60% of cases and Moderate improvement in 26.66%. Hence,it can be concluded that the combined effect of therapy with Amapachana,Ruksha virechana and Shamanoushadhis (Lashuna Erandadi Kashaya and Patolamooladi Kashaya) has shown a significant role in relieving the signs and symptoms of subjects diagnosed with Non Alcoholic Steatohepatitis

Identification of UDP-glucuronosyltransferases involved in the metabolism of silymarin flavonolignans

Silybum marianum (milk thistle) is a medicinal plant used for producing the hepatoprotective remedy silymarin. Its main bioactive constituents, including silybin and related flavonolignans, can be metabolized directly by phase II conjugation reactions. This study was designed to identify UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of six silymarin flavonolignans, namely silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin. UHPLC-MS analyses showed that all of the tested compounds, both individually and in silymarin, were glucuronidated by human liver microsomes, and that glucuronidation was the main metabolic transformation in human hepatocytes. Further, each compound was glucuronidated by multiple recombinant human UGT enzymes. UGTs 1A1, 1A3, 1A8 and 1A9 were able to conjugate all of the tested flavonolignans, and some of them were also metabolized by UGTs 1A6, 1A7, 1A10, 2B7 and 2B15. In contrast, no glucuronides were produced by UGTs 1A4, 2B4, 2B10 and 2B17. With silymarin, we found that UGT1A1 and, to a lesser extent UGT1A9, were primarily responsible for the glucuronidation of the flavonolignan constituents. It is concluded that the metabolism of silymarin flavonolignans may involve multiple UGT enzymes, of which UGT1A1 appears to play the major role in the glucuronidation. These results may be relevant for future research on the metabolism of flavonolignans in humans.

In Vitro Bioaccessibility, Human Gut Microbiota Metabolites and Hepatoprotective Potential of Chebulic Ellagitannins: A Case of Padma Hepaten® Formulation.

Chebulic ellagitannins (ChET) are plant-derived polyphenols containing chebulic acid subunits, possessing a wide spectrum of biological activities that might contribute to health benefits in humans. The herbal formulation Padma Hepaten containing ChETs as the main phenolics, is used as a hepatoprotective remedy. In the present study, an in vitro dynamic model simulating gastrointestinal digestion, including dialysability, was applied to estimate the bioaccessibility of the main phenolics of Padma Hepaten. Results indicated that phenolic release was mainly achieved during the gastric phase (recovery 59.38%–97.04%), with a slight further release during intestinal digestion. Dialysis experiments showed that dialysable phenolics were 64.11% and 22.93%–26.05% of their native concentrations, respectively, for gallic acid/simple gallate esters and ellagitanins/ellagic acid, in contrast to 20.67% and 28.37%–55.35% for the same groups in the non-dialyzed part of the intestinal media. Investigation of human gut microbiota metabolites of Padma Hepaten and pure ChETs (chebulinic, chebulagic acids) established the formation of bioactive urolithins (A, B, C, D, M5). The fact of urolithin formation during microbial transformation from ChETs and ChET-containing plant material was revealed for the first time. Evaluation of the protective effect of ChETs colonic metabolites and urolithins on tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in cultured rat primary hepatocytes demonstrated their significant reversion of the t-BHP-induced cell cytotoxicity, malonic dialdehyde production and lactate dehydrogenase leakage. The most potent compound was urolithin C with close values of hepatoprotection to gallic acid. The data obtained indicate that in the case of Padma Hepaten, we speculate that urolithins have the potential to play a role in the hepatic prevention against oxidative damage.

Silybum marianum: Beyond Hepatoprotection.

Silybum marianum is a medicinal plant that has long been used as hepatoprotective remedy. It has been used for the treatment of numerous liver disorders characterized by functional impairment or degenerative necrosis. Its hepatoprotective activity is unique and acts in different ways, including antioxidant and anti-inflammatory activities, cell permeability regulator and membrane stabilizer, stimulation of liver regeneration and inhibition of deposition in collagen fibers, which may lead to cirrhosis. Most of documented data with Silybum marianum are about liver disorders; however, recently several beneficial properties on a wide variety of other disorders such as renal protection, hypolipidemic and anti-atherosclerosis activities, cardiovascular protection, prevention of insulin resistance, especially in cirrhotic patients, cancer, and Alzheimer prevention. It is also used as a food remedy. This review article aims to present different aspects of Silybum marianum, especially the data in recently published articles about its effects on different diseases, apart from presenting the aspects of its hepatoprotection.

Gas chromatography-mass spectrometry analysis, hepatoprotective and antioxidant activities of the essential oils of four Libyan herbs

Following an ethnobotanical survey for hepatoprotective remedies, four Libyan medicinal plants from family Lamiaceae; Ajuga iva (L.) Schreber, Marrubium vulgare L., Rosmarinus officinalis L. and Thymus capitatus Hoff. et Link growing widely in Beida, Libya, were selected for our study. The chemical composition of essential oils hydrodistilled from the dried aerial parts, were analyzed by gas chromatography-mass spectrometry (GC-MS). The major constituents of the essential oils of A. iva and R. officinalis were carvacrol (35.07%) and 1,8-cineol (35.21%), respectively, thymol was the major constituent of the essential oil ofM. vulgare (20.11%) and T. capitatus (90.15%). The oil of M. vulgare had the most powerful antioxidant activity by restoring glutathione levels in the blood of alloxan-induced diabetic rats. The rats treated with the essential oils of M. vulgare, R. officinalis and T. capitatus (50 mg/kg) showed a significant decrease in liver enzymes which were elevated by CCl4 (p E‚ 0.01). The essential oil of M. vulgare had the most potent hepatoprotective activity. Key words: Ajuga iva, Marrubium vulgare, Rosmarinus officinalis, Thymus capitatusantioxidant, hepatoprotective.

Essential oils of four Rwandese hepatoprotective herbs: Gas chromatography–mass spectrometry analysis and antioxidant activities

Following an ethnobotanical survey in Southern Rwanda for hepatoprotective remedies, four food and medicinal plants, Crassocephalum vitellinum, Guizotia scabra, Microglossa pyrifolia and Ocimum lamiifolium, were selected for pharmacological and chemical investigations aiming to validate their reported properties. The chemical compositions of essential oils obtained from leaves were investigated by GC–MS; essential oils and methanolic extracts were evaluated for antioxidant activity by 1,1-diphenyl-2-picryhydrazyl (DPPH) and linoleic acid peroxidation assays. C. vitellinum [limonene (34.8%), (E)-β-ocimene (21.8%), β-pinene (8.5%), α-pinene (6.6%), myrcene (6.3%)], G. scabra [germacrene-d (25.5%), limonene (9.7%), (E)-β-ocimene (6.6%)], M. pyrifolia [germacrene-d (58.3%)] and O. lamiifolium [sabinene (12.2%), alpha phellandrene (11.6%)] volatile oils scavenge DPPH (10%, 39%, 27%, and 11% quercetin equivalents) and inhibit linoleic acid peroxidation (13%, 23%, 20%, and 13% Trolox® equivalents). The four methanolic extracts were quite active on the lipid peroxidation model (93%, 93%, 70%, and 67% Trolox equivalents) with modest activity on DPPH (5%, 10%, 8%, and 11% quercetin equivalents). These properties most probably participate in the four plants hepatoprotective activities reported in ethnopharmacological and/or pharmacological studies.

Absorption spectrum of iodine and bromine vapor at high temperatures

Following an ethnobotanical survey in Southern Rwanda for hepatoprotective remedies, four food and medicinal plants, Crassocephalum vitellinum, Guizotia scabra, Microglossa pyrifolia and Ocimum lamiifolium, were selected for pharmacological and chemical investigations aiming to validate their reported properties. The chemical compositions of essential oils obtained from leaves were investigated by GC–MS; essential oils and methanolic extracts were evaluated for antioxidant activity by 1,1-diphenyl-2-picryhydrazyl (DPPH) and linoleic acid peroxidation assays. C. vitellinum [limonene (34.8%), (E)-β-ocimene (21.8%), β-pinene (8.5%), α-pinene (6.6%), myrcene (6.3%)], G. scabra [germacrene-d (25.5%), limonene (9.7%), (E)-β-ocimene (6.6%)], M. pyrifolia [germacrene-d (58.3%)] and O. lamiifolium [sabinene (12.2%), alpha phellandrene (11.6%)] volatile oils scavenge DPPH (10%, 39%, 27%, and 11% quercetin equivalents) and inhibit linoleic acid peroxidation (13%, 23%, 20%, and 13% Trolox® equivalents). The four methanolic extracts were quite active on the lipid peroxidation model (93%, 93%, 70%, and 67% Trolox equivalents) with modest activity on DPPH (5%, 10%, 8%, and 11% quercetin equivalents). These properties most probably participate in the four plants hepatoprotective activities reported in ethnopharmacological and/or pharmacological studies.