Hepatoprotective Agent Research Articles

Herbo-vitamin medicine Livogrit Vital ameliorates isoniazid induced liver injury (IILI) in human liver (HepG2) cells by decreasing isoniazid accumulation and oxidative stress driven hepatotoxicity

BackgroundTuberculosis (TB) is a leading cause of infection related mortality. Isoniazid is one of the frontline drugs for anti-TB therapy. Hepatotoxicity induced by isoniazid is a major cause of drug-discontinuation which may lead to development of resistant TB or increased mortality.PurposeTo characterize pharmacological properties of plant-based prescription medicine, Livogrit Vital (LVV) against isoniazid-induced liver injury (IILI) using HepG2 cells.MethodPhytometabolite characterization of LVV was performed by High-performance liquid chromatography (HPLC). The effects of LVV on cytosafety, IC50 shift, oxidative stress, ER stress, apoptosis, liver injury markers, and accumulation of isoniazid and hydrazine was performed on HepG2 cells induced with isoniazid. Silymarin was used as the positive control.ResultsHPLC based phytometabolite characterization of LVV revealed the presence of several anti-oxidant, anti-apoptotic, and hepatoprotective compounds. In isoniazid-induced HepG2 cells, LVV reduced cytotoxicity of isoniazid and shifted its IC50 value. Treatment with LVV reduced ROS generation and lipid peroxidation; enhanced GSH enzyme levels in isoniazid-induced HepG2 cells. As per the mechanistic evaluation, LVV modulated gene expression level of Caspase-3, FGF21, and IRE-1α. LVV treatment also normalized isoniazid-induced elevated Caspase-3 activity and cPARP1 protein levels, indicating its potentials to regulate liver cell apoptosis. Concomitantly, biomarkers of hepatotoxicity, ALT and GGT, also decreased by LVV treatment. Interestingly, LVV treatment reduced intracellular accumulation of isoniazid and its toxic metabolite hydrazine, in isoniazid-stimulated HepG2 cells.ConclusionTreatment of hepatic cells with the herbo-vitamin medicine, Livogrit Vital, regulates IILI by modulation of oxidative and ER stress, apoptosis, and bioaccumulation of isoniazid and hydrazine. Collectively, Livogrit Vital could well be explored as an adjuvant hepatoprotective agent alongwith anti-TB medicines.

The trans-differentiation promotion of parietal epithelial cells by magnesium isoglycyrrhizinate to improve podocyte injury induced by high fructose consumption

BackgroundPodocytes have limited proliferative capacity, which leads to irreversible glomerular injury in diverse kidney diseases. Magnesium isoglycyrrhizinate (MgIG), a hepatoprotective agent in clinic, has been reported to improve glomerular podocyte injury. However, the underlying mechanism of MgIG in ameliorating podocyte injury remains unclear. PurposeGlomerular parietal epithelial cells (PECs) are recognized as podocyte progenitors and play a pivotal role in the recovery following glomerular injury. This work aims to investigate the protective mechanisms of MgIG in mitigating glomerular injury by promoting PEC trans-differentiation. Study DesignA rat model of progressive glomerular podocyte injury, and in vitro models using the primary podocytes and primary PECs, were established to further explore the pharmacological mechanism of MgIG. MethodsFour-week-old male Sprague-Dawley (SD) rats were fed a 10% fructose solution for 3, 6, 9 and 12 weeks to induce glomerular injury. The effect of MgIG on the progressive changes in podocytes and PECs, and the correlation between PEC density and podocyte loss, were analyzed. The mechanism of MgIG in triggering PEC trans-differentiation was investigated, by examining adenosine secretion in injured podocytes, as well as the expression of cluster of differentiation 44 (CD44), nephrin, adenosine receptor A2B (ARA2B) and glucocorticoid receptor (GR) in PECs were examined both in vivo and in vitro. ResultsRats fed a high fructose diet exhibited progressive changes in glomerular PECs, including increased cell density and a preference for trans-differentiation. A positive correlation was observed between PEC density and podocyte loss. Co-culture experiments demonstrated that extracellular adenosine accumulation in injured podocytes induced by high fructose exposure promoted PEC trans-differentiation via ARA2B. MgIG significantly improved podocyte injury and exhibited effects similar to dexamethasone on nephrin upregulation activation and CD44 inhibition. Moreover, the inhibitory effect of MgIG on PEC ARA2B activation was more effective than that of dexamethasone. The co-expression of paired box 2 (PAX2)+-Nephrin+ in glomeruli indicated that MgIG induced PEC trans-differentiation and podocyte regeneration in model rats. Accordingly, podocyte loss and increased urine albumin-to-creatinine ratio (UACR) were also alleviated. Moreover, MgIG, which acts as a GR agonist to activate GR, reversed the upregulation of CD44 and decreased ARA2B induced by tumor necrosis factor-α (TNF-α) in primary PECs. The siRNA interference experiment manifested that MgIG exhibited a more pronounced enhancement of GR upregulation, in contrast to ARA2B activation, to promote PEC trans-differentiation. ConclusionThis work reports for the first time that PECs respond to the accumulation of extracellular adenosine from injured podocytes via activating ARA2B and focuses on the role of adenosine and adenosine receptors in the trans-differentiation of PECs. Furthermore, this study provides the first evidence that MgIG may promote podocyte regeneration by enhancing PEC trans-differentiation through GR activation, providing a research basis for investigating the glucocorticoid-like activity of MgIG in ameliorating glomerular podocyte injury.

Diammonium glycyrrhizinate alleviates iron overload-induced liver injury in mice via regulating the gut-liver axis

BackgroundEvidence indicates a close association between iron overload (IO) and the pathogenesis of chronic liver diseases, highlighting the potential for interventions targeted at IO to impede or decelerate the progression of chronic liver diseases. Diammonium glycyrrhizinate (DG), the medicinal form of glycyrrhizic acid, a principal constituent of licorice, has been clinically employed as a hepatoprotective agent; however, its protective effect against IO-induced liver injury and underlying molecular mechanisms remain elusive. PurposeThe aim of the present study is to investigate the hepatoprotective effect of DG against IO-induced liver injury with a focus on the gut-liver axis. Study design and methodsAnimal models of IO-induced liver injury and DG treatment have been established in vivo. Iron deposition, liver injury, intestinal barrier damage, and liver inflammation were assessed in mice treated with iron dextran or DG. The microbiome composition in feces was analyzed using 16S rRNA full-length sequencing. Bile acids (BAs) profiles in feces were detected by UPLC-Q-TOF-MS technique, and the expression levels of receptors, enzymes or transporters involved in BAs metabolism were also determined. ResultsDG partially reduced the iron deposition and the levels of ferrous ion in the livers of mice with IO, thereby mitigating oxidative damage. DG also improved gut microbiota dysbiosis, repaired intestinal barrier damage, inhibited endotoxin translocation to the liver, and subsequently suppressed TLR4/NF-κB/NLRP3 pathway-mediated liver inflammation caused by IO. Moreover, DG modulated BAs metabolism disorder in IO mice, reducing the accumulation of BAs in the liver. ConclusionDG alleviates IO-induced liver injury in mice by regulating the gut-liver axis. This study provides novel insights into the underlying mechanisms through which DG ameliorates liver injury caused by IO.

Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.

A novel immunopharmacological biocompound

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

High Fischer ratio oligopeptides from Antarctic krill: Ameliorating function and mechanism to alcoholic liver injury through regulating AMPK/Nrf2/IκBα pathways

In this study, we devoted attention to the hepatoprotective functions of high Fischer ratio oligopeptides (HFOPs) from Antarctic krill (HFOPs-AK) on alcoholic liver injury of mice. The results indicated that HFOPs-AK significantly improved the pathological state of mice liver and kidney, reduced alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, regulated lipid metabolism, and alleviated the burden on the liver. In addition, HFOPs-AK depicted anti-inflammatory and antioxidant effects by reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) contents and increasing superoxide dismutase (SOD) and catalase (CAT) activities to reduce malondialdehyde (MDA) level. The hepatoprotective mechanism of HFOPs-AK was further revealed by quantitative reverse transcription PCR (RT-qPCR) analysis, and the results proved that HFOPs-AK had the ability to stimulate the adenosine 5‘-monophosphate-activated protein kinase (AMPK)/nuclearrespiratoty factor 2 (Nrf2)/inhibitor of NF-κB (IκBα) signaling pathways, thereby regulating the expression levels of downstream factors. The activation of these signaling pathways is essential for the regulation of lipid metabolism as well as anti-inflammatory and antioxidant functions. This finding offers a novel approach for the development of innovative hepatoprotective agents utilizing HFOPs-AK.

LC-QTOF-MS/MS metabolic profiling and hepatoprotective effects of Litsea monopetala bark methanol extract against liver injury in rats and HepG2 cells.

Fresh stem bark decoction of Litsea monopetala has been practiced for the treatment of jaundice and other liver disorders by the tribal communities of Thakht-e-Sulaiman hills from West Pakistan. As per the folkloric claim, this study aims to identify the phytoconstituents and evaluate the hepatoprotective action of stem bark methanol extract of L. monopetala (LMME). The in-vitro hepatoprotective effect of L. monopetala was performed by H2O2-induced toxicity in the HepG2 cell line and in-vivo by cclt;sub>4-induced hepatotoxicity in Wistar albino rats taking Silymarin as standard drug. Phytoconstituents were identified using LC-QTOF-MS analysis followed by in-silico docking and validation. Molecular docking interactions between identified compounds of L. monopetala and two target proteins, namely 1VJY and 5HYK were presented. In this study, treatment with LMME at 100 µg/mL showed 67.73 % cell viability as compared to H2O2 (100 µM) treated alone i.e., 18.55 % in the HepG2 cell line. In-vivo treatment of LMME reversed the altered serum biochemical parameters and reduced the inflammatory response similar to that of the Silymarin-treated group supported by histopathological investigation. This research reveals that L. monopetala is a rich source of flavonoids and phenols which supports its hepatoprotective effects and is proposed for its usage as a promising hepatoprotective agent after controlled trials.

Antioxidant and Hepato-protective effects of Ginger in Comparison with Atorvastatin in Hyperlipidemic Albino mice.

Objective: This study was aimed to observe the effects of high fat diet on lipid levels and histomorphology of liver and detecting the preventive effects of ginger and atorvastatin on high fat diet induced hyperlipidemia in albino mice. Also the comparison between the two protective agents was observed.Methodology: This experimental study was conducted at Department of Anatomy and Pathology, LUMHS Jamshoro and Sindh Agriculture University Tando Jam for six months. This research comprised of 60 adult male mice, divided into four groups (each having 15 animals). Group A, normal control was given standard chow while Groups B, C and D were given high fat diet (cheese) along with chow for eight weeks followed by administration of ginger (15mg/30gm) to Group C and atorvastatin (0.3mg/30gms) to Group D for another eight weeks. Animals of Group B, hyperlipidemic control were left untreated. Weight of animals was measured weekly. Samples for serological and histological changes were taken before and after the induction of high fat diet and at the end of experiment.Results: The research revealed deranged lipid profile with increased total cholesterol, triglycerides, low density lipoprotein cholesterol and Alanine transaminases, decreased levels of high-density lipoprotein cholesterol and distorted hepatic architecture after high fat diet which were significantly improved by the administration of ginger in Group C animals and to a lesser extent by atorvastatin in Group D.Conclusion: Ginger only or concurrently with drug therapy proved to be effective hypolipidemic, antioxidant, and hepatoprotective agent, reducing the vulnerability to chronic co-morbidities. Keywords: Atorvastatin; Ginger rhizome; Hepatic ballooning; Lipid profile; Liver; Steatosis.

Hepatoprotective effects of ethanol extract of mobe leaves/eeml (artocarpus lacucha buch-ham.) against carbon tetrachloride induced hepatotoxicity in rats

This study evaluates the protective effects of ethanol extract of mobe leaves (Artocarpus lacucha Buch-Ham.) on ALT, AST, and bilirubin levels in rats induced with carbon tetrachloride (CCl4) on Liver. The ethanol extract was prepared by maceration using 96% ethanol. Results showed that administering 400 mg/kg BW of the extract significantly reduced total bilirubin, ALT, and AST levels in CCl4-induced rats. Phytochemical screening revealed bioactive compounds like flavonoids, alkaloids, tannins, saponins, triterpenoids, and glycosides, which are potential antioxidants and hepatoprotective agents. The study concludes that mobe leaf extract has potential as a therapeutic agent to protect the liver from toxic damage. The significant contribution of this research is providing a scientific basis for using mobe leaf extract as a natural hepatoprotective agent, highlighting its potential for safe and effective herbal medicine. Further research and clinical trials are recommended.

New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents

Introduction: To solve the problem of complex and safe pharmacological correction of metabolic disorders, including hyperlipidemia, hyperglycemia, and liver lesions is currently very important. With this in mind, the new derivatives of cyanothioacetamide with a dihydropyridine framework, with a potential effect on lipid and carbohydrate metabolism and the functioning of the liver are of great interest. Materials and Methods: To conduct an experiment, three samples were selected from an extensive library of new cyanothioacetamide derivatives, which, according to in silico studies, proved promising towards the positive effect on lipid and carbohydrate metabolism, as well as towards the protective effect on the liver. To study the compounds in vivo, metabolic disorders were simulated in Wistar rats by long -term alimentary and subsequent dexamethasone loads. The pharmacological efficacy of new compounds AZ-383, AZ-257, AZ-020 (administered in a dose of 1 mg/kg for 14 days) was assessed in comparison with metformin (300 mg/kg for 14 days) and vildagliptin (8 mg/kg for 14 days) by determining the biochemical indicators of blood (ALT, AST, total bilirubin, total cholesterol, triglycerides, and glucose), morphological and morphometric studies of the liver sections, and the study of immunohistochemical indicators of hepatocyte proliferation. The experimental results were statistically processed using the recognized methods of mathematical statistics. When processing the experimental data, the average arithmetic (AA) was determined. The statistical significance of the compared options was determined on the basis of the Student’s t-test, with the critical value of the Student’s t-test equal to 2.101 and the significance level α = 0.05. Results: The study shows that all the new compounds studied in the experiment – AZ-383, AZ-257, AZ-020 – have hypolipidemic and hepatoprotective properties, which manifested in the reduced levels of liver biochemical markers of blood, which had increased after simulating metabolic disorders, in the reduced concentration of total cholesterol and triglycerides in blood, in the normalization of liver microarchitecture, as well as in the proliferative activity of hepatocytes. Discussion: The hepatoprotective and hypolypidemic properties of the new derivatives of cyanothioacetamide with a dihydropyridine framework, which were determined while conducting the experiment, can be accounted for by their effects on the biotargets, identified for AZ-383, AZ-257, and AZ-020 in silico. According to the results, the most pronounced hepatoprotective activity was found in AZ-383 (intragastrically, 1 mg/kg for 14 days). The Ki-67 proliferation index under the influence of this compound was registered at the level of 1.48±0.03%, which exceeds this indicator in the control animals and proves a significant hepatoprotective activity of AZ-383. Conclusion: The results show good prospects and high efficacy of the new studied cyanothioacetamide derivatives, such as AZ-383, AZ-257, AZ-020 (in a dose of 1 mg/kg), in terms of comprehensive correction of metabolic disorders. Further study is needed for this class of compounds.

Hepatoprotective activity of medicinal plants, their phytochemistry, and safety concerns: a systematic review.

Medicinal plants and their derivatives represent a promising reservoir of remedies for various ailments. Especially secondary metabolites of these plants, including alkaloids, flavonoids, phenolic compounds, terpenoids, steroids, saponins, tannins, and anthraquinones, play crucial roles in hepatoprotection. Studies have identified several prominent phytoconstituents, such as silymarin, quercetin, luteolin, glycyrrhizin, curcumin, gallic acid, chebulic acid, catechin, aloin, emodin, liquiritin, liquiritigenin, cudraflavone B, and karaviloside, as effective agents for addressing hepatotoxicity. The mechanisms underlying their efficacy include antioxidant, anti-inflammatory, free radical scavenging, and the ability to block oxidative stress, cytokine production, and stabilize liver cell membranes. The application of natural products derived from medicinal plants in treating liver injuries is rooted in their efficacy, cost-effectiveness, and safety profile, contributing to their popularity. Many studies, encompassing invitro, invivo, preclinical, and clinical investigations, have demonstrated that the extracts of medicinal plants mitigate chemical-induced liver damage using animal models. However, intensive research efforts regarding the safety, regulatory standard, and quality control issues for using medicinal plants as hepatoprotective agents remain the strong task of scholars. The primary focus of this systematic review is to analyze the current state of the literature regarding treating liver ailments using extracts from medicinal plants, examining their phytochemical composition, and addressing associated safety considerations.

Putative role of 6-chogaol against tramadol-induced hepatotoxicity in albino rats via anti-inflammatory, antifibrotic, and antiapoptotic effects

Tramadol is a commonly used drug to relieve pain and avoid premature ejaculation in males with hepatotoxic effects, and 6-chogaol has potent anti-inflammatory and hepatoprotective properties.The work impetus is probing the hepatoprotective mechanisms of 6-chogaol against tramadol hepatoxicity. Twenty adult male rats were enrolled to obtain four equal groups [control group (G1), 6-chogaol group (G2), tramadol group (G3), and 6-chogaol+tramadol group (G4)]. Liver specimens were excised and processed to evaluate hepatocyte injury through histopathological (HP), immunohistochemical (IHC), flow cytometry, and biochemical investigations. The HP study exhibited hepatic injury in G3 hepatocytes (inflammatory cell infiltration, hepatic fibrosis, and disturbed liver structure). The IHC study showed a significant rise in caspase-3 and reduced PCNA immuno-expression (IE). Likewise, the flow cytometry and biochemical experiments exhibited a substantial elevation of apoptotic hepatocytes and the serum levels of IL-1β, IL-6, TNF-α, ALP, ALT, and AST in G3. In contrast, G4 rats significantly improved in all HP, IHC, flow cytometry, and biochemical parameters. Collectively, tramadol intake exerted harmful toxic effects on hepatocytes, whereas 6-Shogaol hampered these changes and served as a natural hepatoprotective agent. Therefore, we advise concurrent intake of 6-Shogaol supplement with tramadol to preserve the integrity of hepatic tissues.

Evaluation of Lemon Peel Extract as Hepatoprotective Agent against Paracetamol-Induced Liver Toxicity: Insights from Biochemical Studies

Evaluation of Lemon Peel Extract as Hepatoprotective Agent against Paracetamol-Induced Liver Toxicity: Insights from Biochemical Studies

Can Alpha-Pinene Prevent Methotrexate-Induced Cardiac and Hepatic Damage?

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy.

Hepatoprotective activity of Vitis vinifera L. fruit (V. vinifera) against acetaminophen induced oxidative damage

Liver-related diseases have become a global concern worldwide. Hepatic cells damage is mostly caused by a variety of toxic chemicals like carbon tetrachloride (CCl4), acetaminophen (APAP), antibiotics and thioacetamide. For the treatment of liver diseases, herbal based therapeutics have been used since long time in India and has become popular all over world. But in some places herbal medicines are still not acceptable for the treatment of liver diseases due to limiting factors. V. vinifera has numerous medicinal properties such as it acts as vasoprotective, astringent, diuretic and hepatoprotective activity. Various protocols were followed for the assessment of Vitis vinifera hepatoprotectivity properties including preparation of plants. Protocols include AST, ALT, LPO, GSH, urea, cholesterol, SOD, ATPase etc. The maximum recoupment was found with V. vinifera which was confirmed by % protection. V. vinifera ameliorated APAP induced cell death. It might be due to its antioxidant, radical scavenging and anti-inflammatory actions of V. vinifera. In this present study, we used V. vinifera as hepatoprotective agent which can be used as a good therapeutic agent against liver toxicity and also for the successful development of drug delivery in near future.

Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 μM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPARα and PPARγ protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74-86% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPARα, PPARγ, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPARα, PPARγ, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.

Pharmacological evaluation of the protective effect of hydroalcoholic extract of walnut (Juglans regia L.) leaf on 6-mercaptopurine-induced hepatotoxicity in rats

Chemical hepatotoxicity can cause liver illnesses like hepatitis and cirrhosis. Mercaptopurine, an anti-tumor medication, has potential myelotoxicity. Natural plants contain hepatoprotective phytoconstituents. The study aimed to explore the protective effect of J. Reia hydroalcoholic leaf extract against MTP-induced liver injury in rats. Seven groups of rats were randomly selected: Control received only distilled water and food; MP at 40 mg kg-1 b.w; Silymarin at 50 mg kg-1 b.w; Juglans Leaf extract 400 mg kg-1 b.w; Juglans Leaf extract 400 mg kg-1 and 6-MP 40 mg kg-1; Silymarin 50 mg kg-1 and 6-MP 40 mg kg-1; Juglans Leaf extract (200 mg kg-1); silymarin 25 mg kg-1, and 6-MP 40 mg kg-1. Blood samples were collected on days: zero, 10 and 21 days. Liver injury was assessed by serum biochemical parameters (SGOT, SGPT, ALP), bilirubin, albumin and total protein in addition to histopathology changes. Administration of J. Reia leaf extract significantly lowered SGOT, SGPT, ALP levels and bilirubin in MTP-treated rats. Histopathological evaluation of livers showed that J. Regia leaves extract reduced cell swelling, fatty degeneration, and inflammation in MTP-treated rats. These findings indicate that J. Regia extract has a protective impact on Oxidative injury in rat liver caused by MTP. Moreover, extract is an effective antioxidant and hepatoprotective agent for reducing hepatocellular damage.

Procyanidin B2-3'-O-Gallate Derived from Grape Seed Polymeric Procyanidins via the Galloyl-Attached Nucleophilic Degradation as a Potential Hepatoprotective Agent.

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'-O-gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.

Triterpenoid saponins from the roots of Panax notoginseng with protective effects against APAP-induced liver injury

Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1–5), together with eighteen known triterpenoid saponins (6–23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-β-d-glucose moiety from Panax species. Compounds 1–4, 7, 10, 12, 21–22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.

Green synthesis of pectin-functionalized silver nanocomposites using Carpesium nepalense and evaluation its bactericidal kinetics and hepatoprotective mechanisms

The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50–110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC50 of 223.7 μg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents.