Liver Protective Effects Research Articles

Koumine regulates macrophage M1/M2 polarization via TSPO, alleviating sepsis-associated liver injury in mice

BackgroundTranslocator protein (TSPO) is an 18-kDa transmembrane protein found primarily in the mitochondrial outer membrane, and it is implicated in inflammatory responses, such as cytokine release. Koumine (KM) is an indole alkaloid extracted from Gelsemium elegans Benth. It has been reported to be a high-affinity ligand of TSPO and to exert anti-inflammatory and immunomodulatory effects in our recent studies. However, the protective effect of KM on sepsis-associated liver injury (SALI) and its mechanisms are unknown. Purpose: To explore the role of TSPO in SALI and then further explore the protective effect and mechanism of KM on SALI. MethodsThe effect of KM on the survival rate of septic mice was confirmed in mouse models of caecal ligation and puncture (CLP)-induced and lipopolysaccharide (LPS)-induced sepsis. The protective effect of KM on CLP-induced SALI was comprehensively evaluated by observing the morphology of the mouse liver and measuring liver injury markers. The serum cytokine content was detected in mice by flow cytometry. Macrophage polarization in the liver was examined using western blotting. TSPO knockout mice were used to explore the role of TSPO in sepsis liver injury and verify the protective effect of KM on sepsis liver injury through TSPO. ResultsKM significantly improved the survival rate of both LPS- and CLP-induced sepsis in mice. KM has a significant liver protective effect on CLP-induced sepsis in mice. KM treatment ameliorated liver ischaemia, improved liver pathological injuries, and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and proinflammatory cytokines in serum. Western blotting results showed that KM inhibited M1 polarization of macrophages and promoted M2 polarization. In TSPO knockout mice, we found that TSPO knockout can improve the survival rate of septic mice, ameliorate liver ischaemia, improve liver pathological injuries, and decrease the levels of ALT, AST, and LDH. In addition, TSPO knockout inhibits the M1 polarization of macrophages in the liver of septic mice and promotes M2 polarization and the serum levels of proinflammatory cytokines. Interestingly, in TSPO knockout septic mice, these protective effects of KM were no longer effective. ConclusionsWe report for the first time that TSPO plays a critical role in sepsis-associated liver injury by regulating the polarization of liver macrophages and reducing the inflammatory response. KM, a TSPO ligand, is a potentially desirable candidate for the treatment of SALI that may regulate macrophage M1/M2 polarization through TSPO in the liver.

Melatonin Prevents against Ethanol-Induced Liver Injury by Mitigating Ferroptosis via Targeting Brain and Muscle ARNT-like 1 in Mice Liver and HepG2 Cells.

The circadian clock acts a pivotal part in human daily physiology and metabolism. Excess alcohol consumption disturbs the circadian rhythm of several metabolism-related genes of the liver. Melatonin is a member of the foremost hormones secreted by the pineal gland with numerous pharmacological properties in quite a number of diseases. However, its potential roles and possible mechanisms in ethanol-induced ferroptosis are still not clear completely. Ethanol feeding studies were performed upon a chronic-plus-binge ethanol feeding protocol in C57BL/6 mice with or without intraperitoneal injection administration of melatonin. HepG2 cells and mice primary hepatocytes were subjected to investigation for ethanol and melatonin. The results showed that melatonin dramatically ameliorated liver injury and decreased ferroptosis makers induced by ethanol. Meanwhile, melatonin effectively reversed the circadian misalignment caused by ethanol. Additionally, melatonin accelerated Nrf2 nuclear translocation and further activated its downstream anti-ferroptosis proteins including FTH, FPN, HO-1, and SLC7A11 in ethanol-changed mice liver tissues and HepG2 cells. However, the impact of melatonin on liver protection and anti-ferroptosis was offset upon brain and muscle ARNT-like 1 (BMAL1) knockdown with the notably blocked Nrf2-ARE pathway. Altogether, this study revealed that melatonin could alleviate ethanol-induced liver injury by impeding ferroptosis via reprogramming the circadian protein BMAL1 and subsequently activating the Nrf2-ARE anti-ferroptosis pathway. The emergence of novel liver protective effects and mechanism of melatonin on ethanol-induced ferroptosis may provide a new dimension for prevention or intervention against liver injury associated with ethanol.

Liver protection and hemostatic effects of medicinal plant Arnebia euchroma (Royle) I.M.Johnst extract in a rat model

Ethnopharmacological relevanceArnebia euchroma (Royle) I.M.Johnst. (AE) is a Chinese medicinal herb that is traditionally used to treat various circulatory diseases. It exhibits certain effects, such as the promotion of blood circulation and cooling, rash clearance, and detoxification. Aim of the studyThis study was designed to explore the hepatoprotective and hemostatic effects of the ethyl acetate extract of AE in rats with carbon tetrachloride (CCl4)-induced liver injury. Materials and methodsWistar rats were treated via oral gavage with different doses of the ethyl acetate extract of AE (3.5, 7, or 14 g kg−1·day−1) for 14 consecutive days, following which hemostatic and liver function tests were conducted. For the hemostatic tests, the platelet count, blood platelet aggregation, blood platelet adhesion to fibrinogen, platelet factor 4 (PF-4) secretion from blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen levels were measured at the end of the treatment period. For the liver function tests, 0.25 mL/200 g (1.25 mL kg−1·day−1) of olive oil was injected into the abdominal cavity of the control rats, whereas 15% CCl4 plus olive oil (prescription: 7.5 mL CCl4 + 42.5 olive oil) was injected into that of the treated rats at 1 h after extract administration on day 6, 13, and 20. Additionally, food and water were withheld from all the animals. On the following day, the rats were anesthetized and their albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. Glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx) levels among the groups were determined using a one-way analysis of variance. ResultsThe platelet count and blood platelet aggregation, blood platelet adhesion to fibrinogen and PF-4 secretion levels were significantly increased in the (3.5 g kg−1 day−1) AE group as compared to those in the control group (all p < 0.001; for the 7 and 14 g kg−1 day−1 AE groups, all p > 0.05, respectively). Although the PT and aPTT were not affected by the AE extract (all p > 0.05), the TT was reduced and the FIB levels were significantly increased in all AE groups (p < 0.05). Liver function tests showed that CCl4 caused significant liver damage, thereby decreasing the albumin, SOD, CAT, GSH, GST, GR, and GPx levels, while increasing the AST, ALT, ALP, SGOT, SGPT, GGT, LDH, ROS, and MDA levels (all p < 0.001). By contrast, treatment with the different doses of AE extract reversed the CCl4 effects on all these parameters. Compared with the levels in the CCl4 group, the GSH and GR levels in the three AE groups (3.5, 7, and 14 g kg−1·day−1) were significantly higher (p < 0.05, p < 0.01, and p < 0.001, respectively), whereas the differences in the other parameters for these three groups were all at the significance levels of p < 0.05, p < 0.05, and p < 0.01, respectively. ConclusionsAE extracts administered orally exhibited hepatoprotective activity by affecting platelet production and blood coagulation and ameliorating liver function-damaging modifications. Specifically, a dosage of 3.5 g kg−1·day−1 resulted in the most optimal effects.

Effect of Chlorogenic Acid via Upregulating Resolvin D1 Inhibiting the NF-κB Pathway on Chronic Restraint Stress-Induced Liver Inflammation.

Chronic stress can cause chronic inflammatory injury to the liver. Chlorogenic acid (CGA) is known to have a wide range of biological activities and anti-inflammatory effects. Resolvin D1 (RvD1) is a polyunsaturated fatty acid derivative that has inhibitory effects on a variety of inflammatory diseases. However, whether CGA can inhibit liver inflammation in chronic stress through RvD1 remains unclear. In this work, male rats were subjected to restraint stress for 6 h every day and built a chronic stress model for 21 days. CGA (100 mg/kg) was administered intragastrically 1 h before restraint, with intraperitoneal injection of RvD1 inhibitor WRW4 (antagonist of FPR2, 0.1 mg/kg) or WRW4 solution every 2 days for 30 min before CGA administration. CGA reduced hepatic hemorrhage and inflammatory cell infiltration, alleviated hepatic injury, decreased the activation of the NF-κB pathway and the expression of interleukin 1β, interleukin 6, and tumor necrosis factor α in the liver, and increased RvD1 in the serum and liver. The therapeutic effect of CGA was blocked after WRW4 intervention. These results suggest that the protective effects of CGA mediate the NF-κB pathway by upregulating the generation of RvD1. Above all, this research demonstrates the liver protective effect of CGA and provides a potential treatment strategy for chronic inflammatory disease.

Galangin Nanoparticles Protect Acetaminophen-Induced Liver Injury: A Biochemical and Histopathological Approach.

One of the main causes of acute liver failure is overdose with acetaminophen. Excessive consumption of acetaminophen leads to the production of NAPQI (N-acetyl-p-benzoquinone imine) through the activity of the enzyme cytochrome c oxidase. For this purpose, the effect of galangin nanoparticles with antioxidant activities will be evaluated for the treatment of acetaminophen-induced hepatotoxicity. In this study, after the synthesis of galangin nanoparticles and particle size determination, mice were divided into six groups. Before treatment, a single dose (350 mg/kg) of acetaminophen was administered by gavage in all groups. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as biochemical factors FRAP and MDA in serum were measured and a histopathological study was performed. The prepared nanoparticles produced in this research were characterized by the SEM, DLS, and ZETA potential, and the average particle size was obtained in the range of 150 nm. Serum levels of liver enzymes (AST and ALT) in the nanoparticle group decreased significantly compared with the control group (P < 0.05). In the group without treatment, the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes increased significantly compared with the treatment groups. Also, galangin nanoparticles, at a dose of 20 mg/kg, improve cell damage in hepatocytes and preserve the tissue structure of the liver. Galangin nanoparticles reduce the acetaminophen-induced hepatotoxicity by reducing the number of liver function indices. According to our findings, the liver-protective effects of the nanoparticle may be due to its antioxidant properties.

Apocynin loaded silver nanoparticles displays potent in vitro biological activities and mitigates pyrogallol-induced hepatotoxicity

Drug-loaded nanoparticles are currently gaining attention due to their improved drug delivery properties. Apocynin, a natural polyphenolic compound, is a component of many plants. It has many medicinal and pharmacological properties. Pyrogallol is an anti-psoriatic agent. However, its clinical usage is limited due to its cumulative and dose-dependent hepatotoxicity. The objective of this study was to synthesize silver nanoparticles coated with Apocynin (Apo-AgNPs), and investigate the antioxidant and liver protective effects of Apo-AgNPs on pyrogallol-induced toxicity in rats. The nanoparticles were characterized and it was determined that the synthesis technique results in homogeneously dispersed core–shell Ag structures with spherical forms and an average diameter of 13 nm (6.3 nm). Our results showed that Apo-AgNPs exhibited potent antioxidant and excellent membrane stability activities in vitro. In rats, Apo-AgNPs (10 and 30 mg/kg) significantly prevented pyrogallol-induced elevations of alkaline phosphatase, gamma-glutamyl transferase, creatinine, urea, aspartate aminotransferase, alkaline aminotransferase, total bilirubin, and decreased blood levels of uric acid. Moreover, Apo-AgNPs restored the decreased activities of the liver antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, glutathione transferase, as well as non-enzyme antioxidant glutathione, as well as significantly decreased catalase activities which were induced by pyrogallol treatment. Histological studies indicated that pyrogallol -induced liver damage was alleviated following Apo-AgNPs treatment in rats. Apo-AgNPs significantly suppressed the up-regulation of Cyclooxygenase-2 (COX-2), Interleukin 6 (IL-6) and Nuclear factor-κB (NF-κB) protein expression. These results indicated that Apo-AgNPs protected the rats from damage via preserving the antioxidant defense systems, lowering pro-inflammatory cytokines, and expression of COX-2 and NF-κB in rats.

Comparison of antithyroid effects and hepatic complications of methimazole with catechin and its nanoencapsulation form in adult male rats

Methimazole is an antithyroid drug and is used clinically in hyperthyroidism. Liver dysfunction is one of the side effects of methimazole. Catechins are natural flavonoids and have antioxidant, antithyroid, and liver protection effects. Despite the wide range of biological properties of catechins, their effective use is limited due to poor water solubility, low stability, and low bioavailability. Catechin niosomal nanoencapsulation improves the properties of catechin and increases its antioxidant activities. Niosomal vesicles were synthesized by the Thin Film Hydration method and their physicochemical characteristics, morphology, and percentage of trapped catechin in them were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometry, respectively. In this study, 32 adult male rats were divided into 4 groups: control, 50 mg/kg methimazole, 100 mg/kg catechin, and 100 mg/kg nanocapsule niosomal form of catechin. The drugs were administered orally and the duration of treatment was 8 weeks. Then, the serum concentration of thyroid hormones and thyroid stimulating hormone (TSH) by enzyme-linked immunosorbent assay (ELISA) method, and serum liver function tests were performed using an autoanalyzer. The activities of hepatic oxidative enzymes were measured spectrophotometrically. Our study showed that the percentage of catechin encapsulation in the niosome was calculated to be 51%. A significant difference was observed in the catechin and encapsulated catechin treatment groups compared to the methimazole group (p <0.0001). In all three treatment groups of methimazole, catechin, and niosomal nanocapsule catechin, serum levels of TT3, TT4, FT3, FT4, body weight and daily consumption of water and food were significantly reduced compared to the control group (p <0.0001). The antithyroid effects of catechin and its encapsulated form were comparable to methimazole. Also, the encapsulation improved the hepatoprotective effects of catechin.

Irvingia gabonensis leaf extract scavenges nitric oxide and hydrogen peroxide in vitro and modulates arsenic-induced hepatic oxidative stress in wistar rats

BackgroundArsenic is a carcinogenic heavy metal that contaminates the environment, predisposing the exposed populace to its detrimental health effects. This study investigated the liver protective effect of ethanol leaf extract of Irvingia gabonensis (ELEIG) in sodium arsenite (SA)-exposed Wistar rats and its nitric oxide (NO.) and hydrogen peroxide (H2O2)-scavenging properties in vitro.MethodsEleven experimental groups made up of five (5) rats each (weight range 100 - 161 g) were used in this study. Group 1 (normal control) had normal rat chow and water. Group 2 received 4.1 mg/kg body weight (kgbw) of SA. Groups 3–8 received SA and graded doses of ELEIG and groups 9-11 had varied doses of ELEIG. Treatment, which spanned 14 days, was by oral gavage. Concentrations of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) as well as activities of liver enzymes (AST, ALT, ALP, and GGT) and concentrations of total bilirubin (TBIL) and direct bilirubin (DBIL) were determined using standard procedures. Standard methods were also used to determine the in vitro NO. and H2O2-scavenging properties of the extract.ResultsExposure to SA orchestrated significant (p ˂ 0.05) increases in CAT, MDA, AST, ALT, ALP and GGT and significant (p ˂ 0.05) decreases in SOD and GPx, relative to control. There were insignificant (p ˃ 0.05) differences in TBIL and DBIL concentrations, compared with control. Simultaneous and post-treatment with ELEIG at graded doses, alleviated the noxious effects of SA. In addition, ELEIG scavenged NO. and H2O2 in concentration-dependent manner.ConclusionThe results suggest that ELEIG possesses potent antioxidant property and combats SA-induced hepatic oxidative stress/toxicity in Wistar rats.

Dietary Goji Shapes the Gut Microbiota to Prevent the Liver Injury Induced by Acute Alcohol Intake.

Diet is a major driver of the structure and function of the gut microbiota, which influences the host physiology. Alcohol abuse can induce liver disease and gut microbiota dysbiosis. Here, we aim to elucidate whether the well-known traditional health food Goji berry targets gut microbiota to prevent liver injury induced by acute alcohol intake. The results showed that Goji supplementation for 14 days alleviated acute liver injury as indicated by lowering serum aspartate aminotransferase, alanine aminotransferase, pro-inflammatory cytokines, as well as lipopolysaccharide content in the liver tissue. Goji maintained the integrity of the epithelial barrier and increased the levels of butyric acid in cecum contents. Furthermore, we established the causal relationship between gut microbiota and liver protection effects of Goji with the help of antibiotics treatment and fecal microbiota transplantation (FMT) experiments. Both Goji and FMT-Goji increased glutathione (GSH) in the liver and selectively enriched the butyric acid-producing gut bacterium Akkermansia and Ruminococcaceae by using 16S rRNA gene sequencing. Metabolomics analysis of cecum samples revealed that Goji and its trained microbiota could regulate retinoyl β-glucuronide, vanillic acid, and increase the level of glutamate and pyroglutamic acid, which are involved in GSH metabolism. Our study highlights the communication among Goji, gut microbiota, and liver homeostasis.

Ursolic acid alleviates tetrandrine-induced hepatotoxicity by competitively binding to the substrate-binding site of glutathione S-transferases

BackgroundTetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, is the only approved medicine in China for silicosis. However, TET-induced hepatotoxicity has raised safety concerns. The underlying toxic targets and mechanism induced by TET remain unclear; there are no targeted detoxification strategies developed for TET-induced hepatotoxicity. Ursolic acid (UA), a pentacyclic triterpene with liver protective effects, may have detoxification effects on TET-induced hepatotoxicity. PurposeThis study aims to explore toxic targets and mechanism of TET and present UA as a potential targeted therapy for alleviating TET-induced hepatotoxicity. MethodsA TET-induced liver-injury model was established to evaluate TET toxicity and the potential UA detoxification effect. Alkenyl-modified TET and UA probes were designed to identify potential liver targets. Pharmacological and molecular biology methods were used to explore the underlying toxicity/detoxification mechanism. ResultsTET induced liver injury by covalently binding to the substrate-binding pocket (H-site) of glutathione S-transferases (GSTs) and inhibiting GST activity. The covalent binding led to toxic metabolite accumulation and caused redox imbalance and liver injury. UA protected the liver from TET-induced damage by competitively binding to the GST H-site. ConclusionThe mechanism of TET-induced hepatotoxicity is related to irreversible binding with the GST H-site and GST-activity inhibition. UA, a natural antidote, competed with TET on H-site binding and reversed the redox imbalance. This study revealed the hepatotoxic mechanism of TET and provided a targeted detoxifying agent, UA, to alleviate hepatotoxicity caused by GST inhibition.

Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFβ / p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity

Chronic liver disease is a worldwide health problem. Carbon tetra hydrochloride is an environmental toxin which is regarded as highly toxic and a potential human carcinogen. It can cause liver damage through the generation of metabolites and production of free radicals. Green tea contains catechins such as Epigallocatechin gallate which has been found to reduce the inflammation, oxidative stress, and fibrosis in experimental animal models. Hence, it represents a good source to prevent or ameliorate several chronic diseases. Silymarin is extracted from milk thistle seeds and has been found to be an effective agent to reduce the oxidative stress and free radical production and thereby exert protective effects in chronic liver conditions. The present study was planned to keep in view the above-mentioned facts. We included thirty rats in our study and divided them into five groups, each having six rats and the study continued for 8 weeks. Group I received normal saline; Group 2 received i.p. CCl4 injections; Group 3 received CCl4 i.p. injection and Epigallocatechin gallate (EGCG) oral gavage, Group 4 received CCl4 i.p. injection and silymarin by oral gavage; and Group 5 received CCl4 i.p. injection and combined EGCG + silymarin by oral gavage. The study found that in group 2, CCl4 induced significant elevation of ALT and MDA and reduced GSH thereby signifying increased oxidative stress. CCl4 also significantly increased inflammatory (TNFα, NFκB, IL1β, and TGFβ) as well as fibrotic markers (p-ERK and p-Smad1/2 protein expression). EGCG and silymarin significantly reversed the previously mentioned parameters either alone or in combination; however, the effect was more pronounced in case of EGCG. We conclude that EGCG and silymarin possess liver protective effects through their antioxidant, anti-inflammatory, and antifibrotic action.

Prunella vulgaris L. - A Review of its Ethnopharmacology, Phytochemistry, Quality Control and Pharmacological Effects.

Prunella vulgaris L. (PVL) is dried fruit spike of Lamiacea plant Prunella vulgaris L., which is a perennial herb with medicinal and edible homology used for thousands of years. PVL is bitter, acrid, cold, and belongs to the liver and gallbladder meridians. It clears the liver and dissipate fire, improve vision, disperse swelling, and has satisfactory clinical therapeutic effects on many diseases such as photophobia, dizziness, scrofula, goiter, breast cancer. The collection of information and data related to PVL comes from literatures retrieved and collated from various online scientific databases (such as CNKI, VIP, PubMed, Web of Science, Research Gate, Science Database), ancient books of traditional chinese medicine (Encyclopedia of Traditional Chinese Medicine, Classics of Traditional Chinese Medicine, Dictionary of Traditional Chinese Medicine), and Doctoral and Master’s Dissertations. Currently, the major chemical constituents isolated and identified from PVL are triterpenoids, steroids, flavonoids, phenylpropanoids, organic acids, volatile oils and polysaccharides. Modern pharmacological studies have shown that PVL has a wide range of pharmacological activities, including anti-inflammatory, anti-tumor, antibacterial and antiviral effects, as well as immune regulation, antihypertensive, hypoglycemic, lipid-lowering, antioxidant, free radical scavenging, liver protection, sedative and hypnotic effects. This paper reviewes the botany, ethnopharmacology, traditional application, phytochemistry, analytical methods, quality control, pharmacological effects of PVL. It can be used not only as medicine, but also gradually integrated into the “medicine and food homology” and “Chinese medicine health” boom. More importantly, it has great potential for drug resources development. This paper deeply discusses the shortcomings of current PVL research, and proposes corresponding solutions, in order to find a breakthrough point for PVL research in the future. At the same time, it is necessary to further strengthen the research on its medicinal chemistry, mechanism of action and clinical application efficacy in the future, and strive to extract, purify and synthesize effective components with high efficiency and low toxicity, so as to improve the safety and rationality of clinical medication.

Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models.

Nonalcoholic fatty liver disease (NAFLD) is initiated by excessive fat buildup in the liver, affecting around 35% of the world population. Various circumstances contribute to the initiation and progression of NAFLD, and it encompasses a wide range of disorders, from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Although several treatments have been proposed, there is no definitive cure for NAFLD. In recent decades, several medications related to other metabolic disorders have been evaluated in preclinical studies and in clinical trials due to the correlation of NAFLD with other metabolic diseases. Fenofibrate is a fibrate drug approved for dyslipidemia that could be used for modulation of hepatic fat accumulation, targeting peroxisome proliferator-activator receptors, and de novo lipogenesis. This drug offers potential therapeutic efficacy for NAFLD due to its capacity to decrease the accumulation of hepatic lipids, as well as its antioxidant, anti-inflammatory, and antifibrotic properties. To better elucidate the pathophysiological processes underlying NAFLD, as well as to test therapeutic agents/interventions, experimental animal models have been extensively used. In this article, we first reviewed experimental animal models that have been used to evaluate the protective effects of fenofibrate on NAFLD/NASH. Next, we investigated the impact of fenofibrate on the hepatic microcirculation in NAFLD and then summarized the beneficial effects of fenofibrate, as compared to other drugs, for the treatment of NAFLD. Lastly, we discuss possible adverse side effects of fenofibrate on the liver.

A GC–MS-Based Metabolomic Strategy to Investigate the Protective Effects of Mulberry Polysaccharide on CCl4-Induced Acute Liver Injury in Mice

BackgroundMulberry (Morus alba) fruits of the woody mulberry tree (family: Moraceae Morus) is a type of mulberry fruit grown in the southern Xinjiang region, which polysaccharides have antioxidant and liver protective effects. This article further preliminary study on the protective effects of mulberry polysaccharide (MP) on liver.MethodA detection kit was used to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver malondialdehyde (MDA), superoxide dismutase (SOD) and other indicators. Liver tissue sections were stained with hematoxylin and eosin (H&E) and observed under a microscope. The entire endogenous metabolite profiling was acquired via metabolomics strategy using gas chromatography-mass spectrometry (GC–MS) to assess the underlying protective mechanisms of MPs. ResultsResults indicated that MPs exerted a hepatoprotective effect on acute liver injury by decreasing serum ALT and AST levels, hepatic MDA, and restored hepatic SOD glutathione peroxidase (GSH-Px) activities. A total of 33 possible endogenous metabolites associated with lipid, glucose, and energy metabolism including amino acids, sugars, and fatty acids, were found.ConclusionThe results of the present study provide a reference for elucidating the protective mechanisms of MPs against acute liver injury.Graphical Abstract

Effects of water extracts of American cockroach ( Periplaneta americana ) on the growth and physiological and biochemical indices of genetically improved farmed tilapia ( Oreochromis niloticus )

New antioxidants as antibiotic substitutes are urgently required in aquaculture as their liver protection and anti-inflammatory effects. To explore the potential value of American cockroach (Periplaneta americana) powder water extract (ACPWE) as an antioxidant substitute for genetically improved farmed tilapia (GIFT, Oreochromis niloticus), different concentrations of ACPWE were added to the GIFT feed and its effects on growth performance, foregut histologic morphology, and some biochemical indices were measured. ACPWE had no significant effect on GIFT weight gain, feed conversion, specific growth rates, or condition factors. The viscerosomatic index of GIFT exposed to ACPWE was lower, indicating that ACPWE reduced the GIFT visceral mass. ACPWE had no significant effect on the length and width of foregut villi. At ACPWE concentrations >1.5 g/kg, serum aspartate aminotransferase (AST) and alanine aminotransferase, and liver AST concentrations decreased, whereas serum and liver total protein concentrations, catalase, total superoxide dismutase, and glutathione peroxidase activities, and total antioxidant capacity increased. Based on the observed serum and liver biochemical and antioxidant indices, adding 1.5 g/kg ACPWE to feed could improve GIFT antioxidant ability.

Hepatoprotective Native Plants Documented in Brazilian Traditional Medicine Literature: Current Knowledge and Prospects.

The native flora of Brazil covers a large biodiversity of plants, some of which have important pharmacological properties. Ethnobotanical studies have established that the folk use of plants for hepatobiliary disorders is very common in Brazil. This review aimed to compile, describe and discuss the main native Brazilian medicinal plants used as hepatoprotective agents listed on 25 books by authors from various regions in the country. Based on the 153 species found, a comprehensive analysis of the most relevant scientific studies is presented, including Piper umbellatum, Echinodorus macrophyllus, Fevillea trilobata and Achyrocline satureioides. Some medicinal plants share both a large number of citations and scientific evidence to corroborate their hepatoprotective effects, including Solanum paniculatum, Baccharis crispa and Phyllanthus niruri, which could be of interest to develop new phytomedicines. Additionally, some active ingredients are indicated as being responsible for the liver protective effects described, particularly phenolic compounds (flavonoids, coumestans and lignans).

The anti-inflammatory effect of Pien Tze Huang in non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease that may progress to nonalcoholic steatohepatitis (NASH), hepatic tissue fibrosis, liver cirrhosis, and hepatocellular carcinoma. In this study, we investigated the effects of Pien Tze Huang (PTH), a well-known traditional Chinese herbal formula with liver protective effect, in methionine-choline deficient diet (MCD)- and high-fat diet (HFD)-induced NASH mouse models. Our results showed that PTH could exert hepatoprotective effects by improving liver weight and steatosis and reducing the fibrosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) in both animal models. The effects of PTH was accompanied with the reduction of infiltrated macrophages, the inhibition of the expression of cytokines, and the induction of adiponectin expression. Mechanistically, we found that PTH could inhibit the activation of proinflammatory transcription factor nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor of κBα (IκBα). These results demonstrate that PTH can improve NAFLD largely due to its suppression of the NF-κB inflammatory pathway.

Procyanidin B2 Attenuates Nicotine-Induced Hepatocyte Pyroptosis through a PPARγ-Dependent Mechanism.

Procyanidin B2 (PCB2), a natural flavonoid, has been demonstrated to exert anti-oxidation and anti-inflammatory effects on hepatic diseases. Increasing evidence shows the hepatoxicity of nicotine. However, whether PCB2 protects against nicotine-induced hepatoxicity and the underlying mechanisms remains uncharacterized. Here, we reported that nicotine promoted hepatocyte pyroptosis, as evidenced by the elevation of propidium iodide (PI)-positive cells, the activation of Caspase-1 and gasdermin D (GSDMD), the enhanced expression of NOD-like receptor containing pyrin domain 3 (NLRP3) and the increased release of lactate dehydrogenase (LDH), interleukin (IL)-1β and IL-18. The silencing of GSDMD by small interfering RNA (siRNA) efficiently inhibited the release of LDH and the secretion of IL-1β and IL-18. In addition, rosiglitazone (RGZ) prevented hepatocyte pyroptosis induced by nicotine. Furthermore, we showed that PCB2 attenuated nicotine-induced pyroptosis through the activation of peroxisome proliferator-activated receptor-γ (PPARγ) in hepatocytes. Moreover, administration of PCB2 ameliorated liver injury and hepatocyte pyroptosis in nicotine-treated mice. Hence, our findings demonstrated that PCB2 attenuated pyroptosis and liver damage in a PPARγ-dependent manner. Our results suggest a new mechanism by which PCB2 exerts its liver protective effects.

Investigating the inter-individual variability of Astragali Radix against cisplatin-induced liver injury via 16S rRNA gene sequencing and LC/MS-based metabolomics

BackgroundCisplatin (CDDP), one of the widely used chemotherapeutic drugs, can induce a series of side effects, such as hepatotoxicity and gastrointestinal toxicity. Astragali Radix (AR) is widely used as the tonic herbal medicine in traditional Chinese medicine (TCM). However, there was no report about the hepatoprotective effect of AR against the cisplatin-induced hepatic damage. PurposeThis study aimed to investigate the protective effect and potential mechanism of AR water extract against the cisplatin-induced liver injury. MethodsCisplatin was utilized to induce the liver injury using ICR mice, and the protective effect of AR was evaluated by serum biochemistry indices and liver histopathology. Then UHPLC Q-TOF-MS/MS-based untargeted serum metabolomics approach combined with 16S rRNA-based microbiota analysis was used to explore the underlying biomarkers and mechanism about the liver-protective effect of AR. ResultsAR could decrease the serum AST and ALT, ameliorate hepatic pathological damages caused by cisplatin. Serum metabolomics indicated AR could regulate the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, purine metabolism, and fatty acid biosynthesis. In addition, 16S rRNA gene sequencing analysis showed that AR could regulate cisplatin-induced gut microbiota disorder, especially the inflammation-related bacteria (p_Deferribacteres, g_Enterococcus, and g_Alistipes, etc.), and the short chain fatty acids (SCFAs)-producing bacteria (g_Alloprevotella, g_Intestinimoas, and g_Flavonifractor). Moreover, 7 mice (AR-7) showed better liver protective effect than the other 3 mice (AR-3), and their regulatory effect on the gut microbiota and serum metabolites were also different, indicating the presence of inter-individual variability for the liver protective effect of AR. ConclusionsThis study revealed the protective effect and the potential mechanisms of AR against cisplatin-induced liver injury, and found that inter-individual variability of the liver protective effect of AR was related to the host microbiome and metabolome. These findings provided new insight into the health effect of dietary AR as a functional food for cisplatin-based chemotherapy.

Discovery of 5,7-Dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one with Lipid Lowering Effects in Hepatocytes.

The population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing. However, no medicine is indicated for treating these diseases clinically nowadays. Therefore, there is an urgent need to develop a new drug to overcome NAFLD and NASH. Capillarisin, a 2-phenoxychromone originating from Artemisia capillaris Thunb., is well-known for its liver-protective effects. As a result, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells by means of high-content screening. In the light of the results, the compounds with trimethoxy groups on the phenyl ring possessed better inhibitory properties against lipid accumulation in Huh7 cells, compared to other functional groups on the same ring. Nonetheless, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one (7e), with an IC50 value of 32.2 ± 2.1 μM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.