Hepatoprotective Potential of Murraya koenigii (Curry Leaves) against Xenobiotics, Heavy Metals, and Hepatotoxic Agents: A Comprehensive Review.

Liver disease, responsible for two million annual deaths, causes Chronic Liver Disease (CLD) and cirrhosis, causing roughly a million deaths yearly. Treatment options for liver injury induced by hepatotoxicity vary, including medication (N-acetylcysteine, corticosteroids, and ursodeoxycholic acid), lifestyle changes, and sometimes liver transplant. However, effectiveness varies, and some treatments carry risks and side effects, highlighting the need for improved therapeutic approaches. Murraya koenigii (MK) is known for its hepatoprotective, antioxidant, anti-inflammatory, anti-microbial, nephroprotective, hepatoprotective, gastroprotective, cardioprotective, neuroprotective, wound-healing, anti-cancerous and immunomodulatory effects, etc. This review highlights the effectiveness of MK against liver damage induced by heavy metals, drug abuse, xenobiotics, etc. A comprehensive search across multiple databases like PubMed, Google Scholar, and others for articles on various hepatotoxicants and hepatoprotective activity of MK was conducted. The researchers applied specific search terms and limits, resulting in 149 eligible articles for final analysis, meeting predetermined inclusion criteria and excluding irrelevant studies. According to the available literature, the phytochemical components of MK, such as flavonoids, tannins, and alkaloids present in various extracts, play a crucial role in reversing the hepatotoxic effects by modifying oxidative and ER stresses, re-establishing the hepatic biochemical markers and enzymes involved in metabolism denoting ameliorative activity, and controlling the expression of pro-inflammatory cytokines. To conclude, this review highlights that MK has great potential as a natural hepatoprotective agent, providing a versatile defense against a range of injuries caused by heavy metals, xenobiotics, and common hepatotoxic agents.

Recent advances in the chemistry and biology of oleanolic acid and its derivatives.

The pentacyclic triterpenes represent a significant class of plant bioactives with a variety of structures and a wide array of biological activities. These are biosynthetically produced via the mevalonate pathway although occasionally mixed pathways may also occur to introduce structural divergence. Oleanolic acid is one of the most explored bioactive from this class of compounds and possesses a broad spectrum of pharmacological and biological activities including liver protection, anti-cancer, atherosclerosis, anti-inflammation, antibacterial, anti-HIV, anti-oxidative, anti-diabetic etc. This review provides an overview of the latest research findings, highlighting the versatile medicinal and biological potential of oleanolic and its future prospects.

Potential therapeutic effects of baicalin and baicalein.

Objective: Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects. Materials and Methods: An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established. Results: According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities. Conclusion: The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.

Enzyme-free method for preparation of sturgeon extracts with antioxidant, hepatoprotective and immune-enhancing functions.

Sturgeon has a long lifespan and slow evolutionary rate due to their powerful endogenous antioxidant system. This work aimed to assess the in vitro and in vivo antioxidant activity of sturgeon extracts from both muscle and roe. The extraction process without enzyme hydrolysis is not only simple, but also can produce extracts with better free radicals scavenging abilities than enzymatic hydrolysates in both cellular and in vivo experiments. Moreover, in mouse models with liver injury and immunosuppression treatment, the sturgeon extracts demonstrated strong hepatoprotective and immune-enhancing functions, comparable to vitamin C and ginseng extract supplements, which were attributed to abundant antioxidant peptides of the extracts. The 15 isolated peptides exhibited diverse free radical scavenging ability. Therefore, the sturgeon extracts showed high potential to be applied in food and biomedical industries.

A Systematic Review of Cardio-Metabolic Properties of Lonicera caerulea L.

In the light of growing concerns faced by Western societies due to aging, natality decline, and epidemic of cardio-metabolic diseases, both preventable and treatable, new and effective strategical interventions are urgently needed in order to decrease their socio-economical encumbrance. The recent focus of research has been redirected towards investigating the potential of haskap (Lonicera caerulea L.) as a novel functional food or superfruit. Therefore, our present review aims to highlight the latest scientific proofs regarding the potential of Lonicera caerulea L. (LC), a perennial fruit-bearing plant rich in polyphenols, in reversing cardio-metabolic dysfunctions. In this regard, a systematic search on two databases (PubMed and Google Scholar) from 1 January 2016 to 1 December 2023 was performed, the keyword combination being Lonicera caerulea L. AND the searched pharmacological action, with the inclusion criteria consisting of in extenso original articles, written in English. The health-enhancing characteristics of haskap berries have been examined through in vitro and in vivo studies from the 35 included original papers. Positive effects regarding cardiovascular diseases and metabolic syndrome have been assigned to the antioxidant activity, hypolipidemic and hypoglycemic effects, as well as to the hepatoprotective and vasoprotective potential. Latest advances regarding LCF mechanisms of action are detailed within this review as well. All these cutting-edge data suggest that this vegetal product would be a good candidate for further clinical studies.

Role of Arthrospira Platensis in Preventing and Treating High-Fat Diet-Induced Hypercholesterolemia in Adult Rats.

Hyperlipidaemia is a recognised risk factor for cardiovascular disease. In this study, the antihyperlipidaemic properties of spirulina (Arthrospira platensis, strain S2 from Serbia) were tested in adult Wistar rats before and after induction of hypercholesterolaemia by a high-fat diet (HFD) to compare the preventive with the curative effect. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured in the blood samples. The chemical composition (lipids, proteins and cholesterol) and the content of bile acids in the faeces of the animals were also analysed. Feeding rats with an atherogenic diet for 10 weeks led to the successful development of hyperlipidaemia, as serum TC and LDL-C levels as well as lipids, cholesterol and bile acids in the animals' faeces were significantly increased. Pre- and post-treatment with spirulina led to a reduction in serum LDL, TC and ALT levels. Administration of spirulina resulted in both a significant increase in primary bile acids excretion and a decrease in bile acids metabolism, with pre-treatment being more effective than post-treatment in some cases. These results suggest that increased excretion of bile acids as well as an effect on the gut microbiota may be the mechanism responsible for the anti-hyperlipidaemic activity of the tested spirulina strain.

Hepatoprotective Effect of Cannabidiol on the Progression of Experimental Hepatic Cirrhosis in Rats.

Introduction: Liver cirrhosis is a condition characterized by the gradual replacement of normal liver tissue with scar tissue, ultimately leading to liver failure. This slow and progressive disease begins with a chronic inflammatory process induced by a noxious agent. In its advanced stages, the disease lacks effective therapies. Research has demonstrated the significant involvement of the endocannabinoid system in the pathogenesis of this disease. This study evaluated the hepatoprotective effect of cannabidiol (CBD) in the progression of experimental hepatic cirrhosis induced by thioacetamide (TAA) in rats. Methods: A randomized experimental design was employed using Holtzman rats. Hepatic cirrhosis was induced by intraperitoneal administration of TAA at a dose of 150 mg/kg for 6 weeks, with treatment initiated additionally. The groups were as follows: Group 1: TAA + vehicle; Group 2: TAA + CBD 2 mg/kg; Group 3: TAA + CBD 9 mg/kg; Group 4: TAA + CBD 18 mg/kg; Group 5: TAA + silymarin 50 mg/kg; and Group 6: Healthy control. Serum biochemical analysis (total bilirubin, direct bilirubin, ALT, AST, alkaline phosphatase, and albumin) and hepatic histopathological study were performed. The Knodell histological activity index (HAI) was determined, considering periportal necrosis, intralobular degeneration, portal inflammation, fibrosis, and focal necrosis. Results: All groups receiving TAA exhibited an elevation in AST levels; however, only those treated with CBD at doses of 2 mg/kg and 18 mg/kg did not experience significant changes compared to their baseline values (152.8 and 135.7 IU/L, respectively). Moreover, ALT levels in animals treated with CBD showed no significant variation compared to baseline. The HAI of hepatic tissue was notably lower in animals treated with CBD at doses of 9 and 18 mg/kg, scoring 3.0 and 3.25, respectively, in contrast to the TAA + vehicle group, which recorded a score of 7.00. Animals treated with CBD at 18 mg/kg showed a reduced degree of fibrosis and necrosis compared to those receiving TAA alone (p ≤ 0.05). Conclusion: Our findings demonstrate that cannabidiol exerts a hepatoprotective effect in the development of experimental hepatic cirrhosis induced in rats.

The Ameliorative Effect of Litsea martabanica (Kurz) Hook. f. Leaf Water Extract on Chlorpyrifos-Induced Toxicity in Rats and Its Antioxidant Potentials.

Litsea martabanica root's antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

Bioactive peptides as a novel strategy to prevent alcoholic liver injury.

Alcohol intake has become one of the leading risks to human health and wellness, among which acute and/or chronic alcohol-induced liver injury is a leading threaten, with few therapeutic options other than abstinence. In recent years, studies suggested that certain bioactive peptides from food sources could represent natural and safe alternatives for the prevention of alcoholic liver injury. Hence, this chapter focus on the advanced research on bioactive peptides exerting hepatoprotective activity against alcoholic liver injury. The main sources of protein, strategies for the preparation of hepatoprotective hydrolysates and peptides, underlying mechanisms of peptides on hepatoprotection, and possible structure-activity relationship between peptides and hepatoprotective activity were summarized and discussed, aiming to give a systematic insight into the research progress of hepatoprotective peptides. However, more efforts would be needed to give a clearer insight into the underlying mechanisms and structure-activity relationship before using hepatoprotective peptides as functional food ingredients or dietary supplements.

Effects of compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid on relative metabolic enzymes and various biochemical indices in Wistar rats with isoniazid-induced liver injury.

Isoniazid (INH) is the first-line anti-tuberculosis drug in clinical practice, and its main adverse effect is drug-induced liver injury (DILI). This study aimed to investigate the hepatoprotective effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid (CAROL) and to provide a new strategy for the search of potential drugs against INH-induced liver injury in Wistar rats. Animal experiment was based on INH (100 mg/kg) induced liver injury to explore the intervention effects of CAROL at doses of 1.35, 2.70, and 5.40 mL/kg. LC-QTOF-MS/MS was used to identify hepatoprotective components in CAROL and its' exposed components in rat serum. The hepatoprotective effect of CAROL was evaluated by pathological observation of rat liver tissue and changes in levels of biochemical indices and cytokines in serum or liver tissue. Of the 58 hepatoprotective components identified, 15 were detected in the serum of rats with liver-injured treated by high-dose CAROL. Results of animal experiments showed that the levels of various biochemical indexes and cytokines were significantly reversed with CAROL intervention. In particular, the expression level of cytokeratin-18 and high-mobility group box 1, as specific and sensitive indicators of DILI, was significantly reduced in the serum of rats with CAROL intervention compared with the INH model group. The same reversal was observed in the levels of TBIL, ALP, ALT, and AST in serum, as well as in the levels of TNF-α, IL-6, SOD, and MDA in liver tissue. For INH-metabolizing enzymes, an evident expression inhibition was observed in N-acetyltransferase 2 and glutathione S-transferases with CAROL intervention, which may be the key to controlling INH hepatotoxicity. CAROL has a favorable hepatoprotective effect on INH-induced liver injury. This study takes the first step in studying the hepatoprotective mechanism of CAROL against INH hepatotoxicity and provides reference for wider clinical applications.

From petals to healing: consolidated network pharmacology and molecular docking investigations of the mechanisms underpinning Rhododendron arboreum flower's anti-NAFLD effects.

Rhododendron arboreum: Sm., also known as Burans is traditionally used as an anti-inflammatory, anti-diabetic, hepatoprotective, adaptogenic, and anti-oxidative agent. It has been used since ancient times in Indian traditional medicine for various liver disorders. However, the exact mechanism behind its activity against NAFLD is not known. The aim of the present study is to investigate the molecular mechanism of Rhododendron arboreum flower (RAF) in the treatment of NAFLD using network pharmacology and molecular docking methods. Bioactives were also predicted for their drug-likeness score, probable side effects and ADMET profile. Protein-protein interaction (PPI) data was obtained using the STRING platform. For the visualisation of GO analysis, a bioinformatics server was employed. Through molecular docking, the binding affinity between potential targets and active compounds were assessed. A total of five active compounds of RAF and 30 target proteins were selected. The targets with higher degrees were identified through the PPI network. GO analysis indicated that the NAFLD treatment with RAF primarily entails a response to the fatty acid biosynthetic process, lipid metabolic process, regulation of cell death, regulation of stress response, and cellular response to a chemical stimulus. Molecular docking and molecular dynamic simulation exhibited that rutin has best binding affinity among active compounds and selected targets as indicated by the binding energy, RMSD, and RMSF data. The findings comprehensively elucidated toxicity data, potential targets of bioactives and molecular mechanisms of RAF against NAFLD, providing a promising novel strategy for future research on NAFLD treatment.

Bithiophene and coumestan derivatives from Eclipta prostrata (L.) L. and their hepatoprotective activity.

One new bithiophene derivative, 5-(but-3-en-1-yn-1-yl)-5'-(methoxymethyl)-2,2'-bithiophene (1), along with twelve known compounds, senecioester (2), tiglinsaureester (3), 5-acetoxymethyl-2'-(but-3-en-1-yn-1-yl)-2,5'-bithiophene (4), 5-(4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (5), 5-hydroxymethyl-(2,5':2',5'')-terthienyl tiglate (6), 5-hydroxymethyl-(2,5':2',5'')-terthienyl agelate (7), 5- hydroxymethyl-2,5':2',5''-terthiophene dimethylacrylate (8), 5-methoxymethyl-2,2':5',2''-terthiophene (9), α-terthiophene (10), 1,3,8,9-tetrahydroxycoumestan 3-sulfate (11), demethylwedelolactone (12), and wedelolactone (13) were isolated from the methanol extract of aerial parts of Eclipta prostrata (L.) L. All isolated compounds were evaluated for the protective ability on the HepG2 cells. At the concentration of 100 µM, compounds 11-13 showed the highest hepatoprotective effects, with HepG2 cell viability ranging from 38.68% to 48.54%. Bithiophenes showed higher hepatoprotective cell viability than terthiophenes.

Green synthesis, characterization, and hepatoprotective effect of zinc oxide nanoparticles from Moringa oleifera leaves in CCl4-treated albino rats.

Hepatotoxin carbon tetrachloride (CCl4) causes liver injury. This research aims to create ZnO-NPs using green synthesis from Moringa oleifera (MO) leaves aqueous extract, and chemically prepared and confirming the synthesis by specialized equipment analysis. The sizes formed of ZnO-NPs were 80 and 55 nm for chemical and green methods, respectively. In addition, to study their ability to protect Wistar Albino male rats against oxidative stress exposed to carbon tetrachloride. MO leaf aqueous extract, green synthesized ZnO-NPs, and ZnO-NPs prepared chemically at 100 and 200 mg/kg BW per day were investigated for their hepatoprotective effects on liver enzyme biomarkers, renal biomarkers, antioxidant enzymes, lipid peroxidation, hematological parameters, and histopathological changes. Compared to the control group, all liver and kidney indicators were considerably elevated after the CCl4 injection. However, the activity of antioxidant enzymes in the liver was significantly reduced after the CCl4 injection. These outcomes indicate that MO leaf aqueous extract, greenly synthesized ZnO-NPs, and ZnO-NPs chemically prepared can restore normal liver and kidney function and activity, as well as hematological and antioxidant enzymes. The highest impact on enhancing the hepatoprotective effect was recorded for rats that received green synthesized ZnO-NPs. The increased drug delivery mechanism of green synthesized ZnO-NPs resulted in a higher protective effect than that of MO leaf aqueous extract.

Phytosterols and the Digestive System: A Review Study from Insights into Their Potential Health Benefits and Safety.

Phytosterols are a large group of substances belonging to sterols-compounds naturally occurring in the tissues of plants, animals, and humans. The most well-known animal sterol is cholesterol. Among phytosterols, the most significant compounds are ß-sitosterol, stigmasterol, and campesterol. At present, they are mainly employed in functional food products designed to counteract cardiovascular disorders by lowering levels of 'bad' cholesterol, which stands as their most extensively studied purpose. It is currently understood that phytosterols may also alleviate conditions associated with the gastrointestinal system. Their beneficial pharmacological properties in relation to gastrointestinal tract include anti-inflammatory and hepatoprotective activity. Also, the anti-cancer properties as well as the impact on the gut microbiome could be a very interesting area of research, which might potentially lead to the discovery of their new application. This article provides consolidated knowledge on a new potential use of phytosterols, namely the treatment or prevention of gastrointestinal diseases. The cited studies indicate high therapeutic efficacy in conditions such as peptic ulcer disease, IBD or liver failure caused by hepatotoxic xenobiotics, however, these are mainly in vitro or in vivo studies. Nevertheless, studies to date indicate their therapeutic potential as adjunctive treatments to conventional therapies, which often exhibit unsatisfactory efficacy or serious side effects. Unfortunately, at this point there is a lack of significant clinical study data to use phytosterols in clinical practice in this area.

Safety and Effectiveness of Liv.52 DS in Patients With Varied Hepatic Disorders: An Open-Label, Multi-centre, Phase IV Study.

Background The hepatoprotective function of polyherbal formulation Liv.52 in chronic liver diseases is well recognized in published literature. The objective of this open-label, phase IV study was to further strengthen and validate its safety and effectiveness using a large patient pool in a real-world scenario and provide scientific data on symptomatic improvement and supportive treatment in liver function with improvement in quality of life. Methods Adult patients of either sex with one or more clinical symptoms like fatigue, nausea, anorexia, abdominal pain or discomfort, muscle cramps, jaundice, or any other signs and symptoms with a history suggestive of mild-to-moderate hepatic disorders like alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), drug-induced hepatotoxicity, or hepatitis were treated with two Liv.52 DS tablets (oral) twice daily for 12 weeks. Results Out of the 1000 enrolled patients, 962 (96%) completed the study with the following subgroups ALD: 375 (38.9%), NAFLD: 379 (39.3%), drug-induced hepatotoxicity: 78 (8.1%), hepatitis: 130 (13.5%). The mean age of enrolled patients was 37.7 years, and the majority of them, 785 (78.5%) were men. The common adverse events observed (with >1.5% incidence) in the study were abdominal pain: 26 (2.6%) and headache: 17 (1.7%). Liv.52 showed statistically significant improvement (P<0.0001) in various clinical signs and symptoms in the majority of patients namely, fatigue: 357/723 (49%), anorexia: 485/620 (78.2%), jaundice: 48/52 (92%). Majority of the patients showed significant improvements from baseline to end of 12 weeks in the liver function test parameters namely, aspartate aminotransferase: 633/840 (75.36%), alanine aminotransferase: 592/729 (81.21%), serum bilirubin: 244/347 (70.32%), alkaline phosphatase: 279/355 (78.59%) with P<0.0001 for all parameters. Statistically significant improvement (P<0.005) was also seen in all the components of the chronic liver disease questionnaire (CLDQ) scores from baseline to 12 weeks. Conclusions The study demonstrated that Liv.52 was hepatoprotective and well tolerated in the study population after treatment for 12 weeks. Significant improvements were seen in clinical signs and symptoms, laboratory parameters of liver function, and CLDQ scores from baseline to 12 weeks. No significant or new safety signals emerged from this study.

Effects of Mactra chinenesis Peptides on Alcohol-Induced Acute Liver Injury and Intestinal Flora in Mice.

Food-borne bioactive peptides have shown promise in preventing and mitigating alcohol-induced liver injury. This study was the first to assess the novel properties of Mactra chinenesis peptides (MCPs) in mitigating acute alcoholic liver injury in mice, and further elucidated the underlying mechanisms associated with this effect. The results showed that MCPs can improve lipid metabolism by modulating the AMPK signaling pathway, decreasing fatty acid synthase activity, and increasing carnitine palmitoyltransferase 1a activity. Meanwhile, MCPs ameliorate inflammation by inhibiting the NF-κB activation, leading to reduced levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß). Additionally, a 16S rDNA sequencing analysis revealed that MCPs can restore the balance of gut microbiota and increase the relative abundance of beneficial bacteria. These findings suggest that supplementation of MCPs could attenuate alcohol intake-induced acute liver injury, and, thus, may be utilized as a functional dietary supplement for the successful treatment and prevention of acute liver injury.

Milk thistle protects against non-alcoholic fatty liver disease induced by dietary thermally oxidized tallow.

Non-alcoholic fatty liver disease (NAFLD) is a chronic condition caused by several factors including thermally oxidized tallow. Various strategies have been considered to ameliorate NAFLD. However, the role of milk thistle (MT) in ameliorating NAFLD caused by thermally oxidized tallow has not been reported. The purpose of this study was to evaluate the ability of milk thistle to protect rabbits from the toxicity of oxidized tallow (OT). The rabbits were given OT and an extract of MT. The composition of MT was analyzed using HPLC-DAD, and tallow samples were studied using GC-MS. The study also examined liver histology, antioxidant levels, liver-related inflammatory markers, and serum lipid profile. The results showed that the major components of the MT extract were silybin B, formononetin-glucuronic acid, proanthocyanidin B1, silychristin B, silydianin, and isosilybin A. The group given OT showed elevated lipid profiles, lower antioxidant status, higher levels of hepatic inflammatory markers, and lower levels of anti-inflammatory markers. This group also had higher fat storage in the liver compared to the control or treatment groups. However, when MT was supplemented, the pro-inflammatory cytokines (IL-1, IL-4, IL-6, and TNF-α) and antioxidant status (CAT, SOD, GSH-Px, GSH, and TBARS) of the liver returned to normal. This suggests that MT extract is an excellent source of hepatoprotective compounds. It protects the liver by increasing antioxidant enzymes, decreasing pro-inflammatory cytokines, and increasing anti-inflammatory markers.

The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition.

BACKGROUND: The liver serves as a metabolic hub within the human body, playing a crucial role in various essential functions, such as detoxification, nutrient metabolism, and hormone regulation. Therefore, protecting the liver against endogenous and exogenous insults has become a primary focus in medical research. Consequently, the potential hepatoprotective properties of multiple 4-phenyltetrahydroquinolines inspired us to thoroughly study the influence of four specially designed and synthesized derivatives on carbon tetrachloride (CCl4)-induced liver injury in rats. METHODS AND RESULTS: Seventy-seven Wistar albino male rats weighing 140 ± 18 g were divided into eleven groups to investigate both the toxicity profile and the hepatoprotective potential of 4-phenyltetrahydroquinolines. An in-vivo hepatotoxicity model was conducted using CCl4 (1 ml/kg body weight, a 1:1 v/v mixture with corn oil, i.p.) every 72 h for 14 days. The concurrent treatment of rats with our newly synthesized compounds (each at a dose of 25 mg/kg body weight, suspended in 0.5% CMC, p.o.) every 24 h effectively lowered transaminases, preserved liver tissue integrity, and mitigated oxidative stress and inflammation. Moreover, the histopathological examination of liver tissues revealed a significant reduction in liver fibrosis, which was further supported by the immunohistochemical analysis of α-SMA. Additionally, the expression of the apoptotic genes BAX and BCL2 was monitored using real-time PCR, which showed a significant decrease in liver apoptosis. Further investigations unveiled the ability of the compounds to significantly decrease the expression of autophagy-related proteins, Beclin-1 and LC3B, consequently inhibiting autophagy. Finally, our computer-assisted simulation dockingonfirmed the obtained experimental activities. CONCLUSION: Our findings suggest that derivatives of 4-phenyltetrahydroquinoline demonstrate hepatoprotective properties in CCl4-induced liver damage and fibrosis in rats. The potential mechanism of action may be due to the inhibition of autophagy in liver cells.

Identification of Hyperuricemia Alleviating Peptides from Yellow Tuna Thunnus albacares.

The development of food-derived antihyperuricemic substances is important for alleviating hyperuricemia (HUA) and associated inflammation. Here, novel peptides fromThunnus albacares (TAP) with strong antihyperuricemic activity were prepared. TAP was prepared by alkaline protease (molecular weight <1000 Da), with an IC50 value of xanthine oxidase inhibitory activity of 2.498 mg/mL, and 5 mg/mL TAP could reduce uric acid (UA) by 33.62% in human kidney-2 (HK-2) cells (P < 0.01). Mice were fed a high-purine diet and injected with potassium oxonate to induce HUA. Oral administration of TAP (600 mg/kg/d) reduced serum UA significantly by 42.22% and increased urine UA by 79.02% (P < 0.01) via regulating urate transporters GLUT9, organic anion transporter 1, and ATP-binding cassette subfamily G2. Meantime, TAP exhibited hepatoprotective and nephroprotective effects, according to histological analysis. Besides, HUA mice treated with TAP showed anti-inflammatory activity by decreasing the levels of toll-like receptor 4, nuclear factors-κB p65, NLRP3, ASC, and Caspase-1 in the kidneys (P < 0.01). According to serum non-targeted metabolomics, 91 differential metabolites between the MC and TAP groups were identified, and purine metabolism was considered to be the main pathway for TAP alleviating HUA. In a word, TAP exhibited strong antihyperuricemic activity both in vitro and in vivo.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms.

Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.