gamma-sitosterol and Chemical-and-Drug-Induced-Liver-Injury

The ability of plant polyisoprenoids (polyprenols and polyprenyl phosphates) to diminish the levels of serum cholesterol affecting its biosynthetic pathway are highlighted here. Possible mechanism of such process is discussed. It is also noted that polyisoprenoids can prevent toxic injuries of the liver and restore disturbed hepatic functions. The possibility of polyprenyl phosphates to reveal at the same time anti-inflammatory action suppressing lipoxygenase activity and lowering the levels of proinflammatory cytokines will be illustrated. Attention will be focused on the potential usefulness of plant polyisoprenoids in the course of prevention and treatment of hypercholesterolemia. High efficiency for combined use of polyprenyl phosphate and β-sitosterol, which leads to substantial enhancement of the ability to overcome hypercholesterolemia versus the individual constituents will be demonstrated.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Cholesterol; Humans; Hypercholesterolemia; Lipoxygenase; Phytotherapy; Plants; Sitosterols; Terpenes

The endoplasmic reticulum (ER) controls many biological functions besides maintaining the function of liver cells. Various studies reported the role of the ER stress and UPR signaling pathway in various liver diseases via triggering hepatocytes apoptosis. This study aims to investigate the suppressive effect of β-sitosterol (βS) on apoptosis associated with liver injury and ER stress.. Liver damage in rats was induced by TAA (150 mg/kg I.P twice a week/3 weeks) and γ-irradiation (single dose 3.5 Gy) and treated with βS (20 mg/kg daily for 30 days). Serum aminotransferase activity, lipid profile and lipid metabolic factors were measured beside liver oxidative stress and inflammatory markers. Moreover, the hepatic expression of ER stress markers (inositol-requiring enzyme 1 alpha (IRE1α), X-box-binding protein 1 (XBP1) and CCAAT/enhancer binding protein homologous protein (CHOP) and apoptotic markers were detected together with histopathological examination.. βS diminished the aminotransferase activity, the oxidative stress markers as well as the inflammatory mediators. Furthermore, βS lowered the circulating TG and TC and the hepatic lipotoxicity via the suppression of lipogenesis (Srebp-1c) and improved the β-oxidation (Pparα and Cpt1a) together with the mitochondrial biogenesis (Pgc-1 α). Moreover, the upregulated levels of ER stress markers were reduced upon treatment with βS, which consequently attenuated hepatic apoptosis.. βS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response.

Topics: Animals; Apoptosis; Chemical and Drug Induced Liver Injury; Endoplasmic Reticulum Stress; Endoribonucleases; Hepatocytes; Liver; Protein Serine-Threonine Kinases; Rats; Sitosterols; Thioacetamide; Transaminases

Of over 35 Saudi plants traditionally used to treat liver disorders, majority still lack scientific validations. We therefore, evaluated the anti-oxidative, anti-apoptotic and hepatoprotective potential of Solanum surattense leaves total ethanol-extract (SSEE).. Our findings suggest the therapeutic potential of S. surattense against chemical-induced oxidative stress and liver damage. However, isolation of the active principles and elucidation of mechanism of action remain to be addressed.

Topics: Animals; Antioxidants; Apoptosis; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Drug Evaluation, Preclinical; Hep G2 Cells; Humans; Liver; Plant Extracts; Rats, Wistar; Sitosterols; Solanum

Beta-sitosterol (Sit) widely exists in natural plants, is classed as phytosterol and known as the "key of life". Most pharmacological studies and clinical applications are limited because of the fact that Sit is difficult to be solved. Therefore, it is viable to enhance pharmacologic activities of Sit by using its derivatives which can be obtained through the modification of Sit. In this study, 4 kinds of new Sit derivatives were obtained by the esterification reaction. Further, the hepatoprotective effects of Sit and its derivatives were investigated against acute liver injury induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and its mechanism was illustrated by western blot analysis and real-time PCR. The results demonstrated that among its derivatives, 2-naphthoyl Sit ester (Sit-N) (50 mg/kg) showed the strongest activities against acute liver injury. Final experimental results showed that Sit-N significantly decreased the serum activity of aspartate transaminase (AST) and alanine aminotransferase (ALT); Sit-N also markedly reduced tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels. Meanwhile, Sit-N drastically improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and suppressed the expression of malondialdehyde (MDA). Results also displayed that over-expression of Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) induced by LPS/Gal N were inhibited by Sit-N. Meanwhile, the expression of nuclear respiratory factor2 (Nrf2) and heme oxygenase-1 (HO-1) were enhanced. The results all above verified the effectiveness of Sit-N against acute liver injury induced by LPS/GalN mediated by TLR4 and Nrf2 pathways.

Topics: Animals; Anti-Inflammatory Agents; Cell Survival; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Galactosamine; Inflammation; Lipopolysaccharides; Mice; Molecular Structure; Oxidation-Reduction; Sitosterols; Structure-Activity Relationship

Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported.. We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions.. Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03).. Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholesterol; Female; gamma-Glutamyltransferase; Humans; Infant; Inflammation; Intestinal Diseases; Liver; Male; Parenteral Nutrition; Phytosterols; Plant Oils; Portal Vein; Sitosterols; Stigmasterol; Triglycerides

Previous findings have demonstrated that β-sitosterol (BSS), an active component of Cistanches Herba, protected against oxidant injury in H9c2 cardiomyocytes and in rat hearts by enhancing mitochondrial glutathione redox cycling, possibly through the intermediacy of mitochondrial reactive oxygen species production. We therefore hypothesized that BSS pretreatment can also confer tissue protection against oxidant injury in other vital organs such as liver and kidney of rats. In this study, the effects of BSS pretreatment on rat models of carbon tetrachloride (CCl4) hepatotoxicity and gentamicin nephrotoxicity were investigated. The findings showed that BSS pretreatment protected against CCl4-induced hepatotoxicity, but not gentamicin nephrotoxicity in rats. The hepatoprotection afforded by BSS was associated with the improvement in mitochondrial glutathione redox status, presumably through the glutathione reductase-mediated enhancement in mitochondrial glutathione redox cycling. The hepatoprotection afforded by BSS was also accompanied by the improved mitochondrial functional ability in rat livers. The inability of BSS to protect against gentamicin nephrotoxicity was likely due to the relatively low bioavailability of BSS in rat kidneys. BSS may serve as potential mitohormetic agent for the prevention of oxidative stress-induced injury in livers.

Topics: Animals; Antioxidants; Biological Availability; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Female; Gentamicins; Glutathione; Glutathione Reductase; Kidney; Kidney Diseases; Liver; Mitochondria; Oxidants; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sitosterols

To investigate hepatoprotective activity of ethanol extract of Melothria heterophylla Lour Cogn. (EEMH) against CCl(4)-induced hepatic damage in rats.. β-sitosterol was isolated by column chromatography and characterized spectroscopically. Two different doses (200 and 400 mg/kg bw) of EEMH were administered orally in alternate days. The hepatoprotective activity was studied in liver by measuring biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein and total bilirubin. Lipid peroxidation product and different antioxidant enzyme activities were assessed in liver homogenate.. EEMH reduced all biochemical parameters and lipid peroxidation, as well as it increased the antioxidant enzyme activities in comparison with silymarin. The protective effect of the extract on CCl(4) induced damage was confirmed by histopathological examination of the liver.. This result strongly supports the protective effect of EEMH against acute liver injury, and may be attributed to its antioxidative activity.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cucurbitaceae; Lipid Peroxidation; Liver; Male; Oxidative Stress; Plant Extracts; Protective Agents; Rats; Rats, Wistar; Silymarin; Sitosterols

The purpose of this study was to study the hepatoprotective effects of the most promising extract of the root from Rubus aleaefolius Poir. and to isolate and identify the active components. Various crude forms of Rubus aleaefolius have been evaluated for their effects on CCl(4)-induced acute liver injury in mice vivo experimental model. Treatment groups contained 5 sub-groups that were ethanol crude extract; the high/low dosage ethyl acetate or n-butanol fraction; extracted with ethyl acetate or n-butanol after the residues and major constituent; intragastrically administrated with 35 mg/kg; 35, 4.6 mg/kg; 35, 5.8 mg/kg; 35 mg/kg and 3.5 mg/kg for 7 days. The serum samples were collected for biological analysis and also carried out histopathological studies. The low-dosage ethyl acetate fraction was the most active when the fractions were compared. It was found to decrease AST, ALT; to prevent formation of hepatic MDA, NO and intensify the activity of SOD. The histopathological changes induced by CCl(4) were also significantly reduced. The separation revealed the presence of six constituents by a bioassay-guided fractionation, beta-Sitosterol (1), 1beta-Hydroxyeuscaphic acid (2), Oleanolic acid (3), Myrianthic acid (4), Euscaphic acid (5), and Tomentic acid (6). Among them, compounds 2, 4, 5 in Rubus aleaefolius root is reported here for the first time. 1beta-Hydroxyeuscaphic acid (major constituent) showed a tremendous activity and the results confirm the traditional uses of Rubus aleaefolius in treating hepatitis.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Nitric Oxide; Oleanolic Acid; Phytotherapy; Plant Extracts; Plant Roots; Rosaceae; Sitosterols; Superoxide Dismutase; Triterpenes

To study the chemical constituents from Kalimeris indica.. Compounds were isolated and purified with silica gel and Sephadex LH-20 column chromatography, their structures were determined by using spectroscopic analysis including MS and NMR.. Nine compounds were isolated and identified as tritriacontane (I), hexadecanol (II), chrysophanol (III), vanillin (IV), physcion (V), beta-sitosterol (VI), stigmasterol (VII), leinoleic acid (VII), emodin (IX).. All of them, except compound IV, VI, are isolated from this genus for the first time. Compound III, IV had the protective effects with the toxicity of CCl4 on primary cultered hepatocytes.

Topics: Anthraquinones; Anti-Inflammatory Agents; Asteraceae; Benzaldehydes; Carbon Tetrachloride; Cell Survival; Cells, Cultured; Chemical and Drug Induced Liver Injury; Emodin; Fatty Alcohols; Hepatocytes; Magnetic Resonance Spectroscopy; Paraffin; Plants, Medicinal; Sitosterols