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.

Pharmaceutical Care by Clinical Pharmacists can Effectively Improve the Use of Antibacterials and Hepatoprotective Drugs during Perioperative Period in Urology Department: A Retrospective Study.

BACKGROUND: The management of medication for patients undergoing urological surgery is a subject of ongoing controversy, especially in elucidating the effect of clinical pharmacists on medication rationality. This study aims to assess the influence of clinical pharmacist service on the utilization of antibacterial and hepatoprotective drugs in urological surgery patients during the perioperative period. METHODS: Patients undergoing urological surgery in our hospital from January 2020, to January 2023, were consecutively selected. The patients were divided into control group (routine procedure) and observation group (routine procedure + clinical pharmacist service). The baseline data were balanced by 1:1 propensity score matching (PSM). The t test and chi-square test were used to compare the drug use, adverse reactions, and hospitalization-related indicators between the two groups. RESULTS: A total of 292 patients were included, with 100 patients in each group after PSM. No significant difference was found in the baseline data between the two groups (p > 0.05). The rationality of drug use (drug type, administration time, course of treatment, and combination) in the observation group was significantly better than that in the control group (χ2 = 8.489, 10.607, 10.895, 10.666; p = 0.004, 0.001, 0.001, 0.001). The incidence of adverse reactions (6.00%) and postoperative complications (7.00%) was significantly lower (χ2 = 4.903, 5.531; p = 0.027, 0.019). The length of hospital stay and total cost were similar (p > 0.05). The use time and cost of antibacterial and hepatoprotective drugs in the observation group were lower than those in the control group (t = 2.935, 3.450, 3.243, 3.532; p = 0.004, 0.001, 0.001, 0.001). The types and rates of antibacterial and hepatoprotective drugs in the observation group were significantly lower than those in the control group (p < 0.05). CONCLUSIONS: Clinical pharmacist service can effectively improve the rationality of drug use in urological surgery patients and reduce adverse reactions and postoperative complications, hence its clinical promotion value.

Network medicine-based analysis of the hepatoprotective effects of Amomum villosum Lour. on alcoholic liver disease in rats.

Alcoholic liver disease (ALD) is characterized by high morbidity and mortality, and mainly results from prolonged and excessive alcohol use. Amomum villosum Lour. (A. villosum), a well-known traditional Chinese medicine (TCM), has hepatoprotective properties. However, its ability to combat alcohol-induced liver injury has not been fully explored. The objective of this study was to investigate the hepatoprotective effects of A. villosum in a rat model of alcohol-induced liver disease, thereby establishing a scientific foundation for the potential preventive use of A. villosum in ALD. We established a Chinese liquor (Baijiu)-induced liver injury model in rats. Hematoxylin and eosin (HE) staining, in combination with biochemical tests, was used to evaluate the protective effects of A. villosum on the liver. The integration of network medicine analysis with experimental validation was used to explore the hepatoprotective effects and potential mechanisms of A. villosum in rats. Our findings showed that A. villosum ameliorated alcohol-induced changes in body weight, liver index, hepatic steatosis, inflammation, blood lipid metabolism, and liver function in rats. Network proximity analysis was employed to identify 18 potentially active ingredients of A. villosum for ALD treatment. These potentially active ingredients in the blood were further identified using mass spectrometry (MS). Our results showed that A. villosum plays a hepatoprotective role by modulating the protein levels of estrogen receptor 1 (ESR1), anti-nuclear receptor subfamily 3 group C member 1 (NR3C1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). In conclusion, the results of the current study suggested that A. villosum potentially exerts hepatoprotective effects on ALD in rats, possibly through regulating the protein levels of ESR1, NR3C1, IL-6, and TNF-α.

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.

Hepatoprotective effects of fruits pulp, seed, and peel against chemical-induced toxicity: Insights from in vivo studies.

The liver is a vital organ in human physiology positioned in the upper right quadrant of the peritoneal cavity, which plats a critical role in metabolic processes, detoxification of various substances and overall homeostasis. Along with these critical functions, hepatic diseases impose as significant global health threat. Liver illness is the cause of two million fatalities every year, or 4% of all deaths. Traditionally, healthcare providers have prescribed antibacterial and antiviral medications to address liver illness. Nephrotoxicity is a frequently observed negative reaction to drugs, with the majority of such events happening in individuals who have advanced cirrhosis. Thus, recognizing this gap, there is a dire need of exploration of pharmaceutical alterative for hepatic diseases, with special focus on their efficacy and reduced toxicity. Fruits have long been known to therapeutic impact on human health, thus exploration of fruits components namely pulp, seeds and peels containing phytochemicals have emerged as a promising avenue for hepatoprotective interventions. Thus, review comprehends the information about worldwide burden of chemical induced toxicity and injuries as well as highlight the on-going challenges in hepatic disease management. It also shed light on the valuable contributions fruit parts and their phytocompounds obtained from different components of fruits. Fruit pulp, especially when rich in flavonoids, has demonstrated significant potential in animal model studies. It has been observed to enhance the activity of antioxidant enzymes and reduce the expression of pro-inflammatory markers. The methanolic and ethanolic extracts have demonstrated the most favorable outcomes. Further, this review also discusses about the safety assessments of fruits extracts for their utilization as hepatoprotective agents.

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.

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.

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.

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.

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.

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.

Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review.

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as 'Bhumyamalaki' (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.

Deferiprone-resveratrol hybrid attenuates iron accumulation, oxidative stress, and antioxidant defenses in iron-loaded human Huh7 hepatic cells.

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-ß-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells. In the findings, DFP-RVT dose dependently bound Fe(II) and Fe(III) and exerted stronger ABTS•- and DPPH•-scavenging (IC50 = 8.0 and 164 µM, respectively) and anti-RBC hemolytic activities (IC50 = 640 µM) than DFP but weaker than RVT (p < 0.01). DFP-RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP-RVT diminished the level of redox-active iron (p < 0.01) and decreased the non-heme iron content (p < 0.01) in iron-loaded Huh7 cells effectively when compared without treatment in the order of DFP-RVT > RVT ∼ DFP treatments (50 µM each). Moreover, the compound decreased levels of hepatic ROS in a dose-dependent manner and the level of malondialdehyde, which was stronger than DFP but weaker than RVT. Furthermore, DFP-RVT restored the decrease in the GSH content and GPX and SOD activities (p < 0.01) in iron-loaded Huh7 cells in the dose-dependent manner, consistently in the order of RVT > DFP-RVT > DFP. Thus, the DFP-RVT hybrid possesses potent iron chelation, antioxidation, anti-lipid peroxidation, and antioxidant defense against oxidative liver damage under iron overload.

Protective effects of esculetin against doxorubicin-induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies.

Doxorubicin (DOX) is widely used in cancer treatment but the dose-related toxicity of DOX on organs including the liver limit its use. Therefore, there is great interest in combining DOX with natural compounds with antioxidant properties to reduce toxicity and increase drug efficacy. Esculetin is a natural coumarin derivative with biological properties encompassing anti-inflammatory and antioxidant activities. In light of these properties, this study was meticulously crafted to investigate the potential of esculetin in preventing doxorubicin (DOX)-induced hepatotoxicity in Sprague-Dawley rats. The rats were divided into a total of six groups: control group, DOX group (administered DOX at a cumulative dose of 5 mg/kg intraperitoneally every other day for 2 weeks), E50 group (administered 50 mg/kg of esculetin intraperitoneally every day), E100 group (administered 100 mg/kg of esculetin intraperitoneally every day) and combined groups (DOX + E50 and DOX + E100) in which esculetin was administered together with DOX. The treatments, both with DOX alone and in combination with E50, manifested a reduction in catalase (CAT mRNA) levels in comparison to the control group. Notably, the enzymatic activities of superoxide dismutase (SOD), CAT, and glutathione peroxidase (GPx) witnessed significant decreases in the liver of rats treated with DOX. Moreover, DOX treatment induced a statistically significant elevation in malondialdehyde (MDA) levels, coupled with a concurrent decrease in glutathione (GSH) levels. Additionally, molecular docking studies were conducted. However, further studies are needed to confirm the hepatoprotective properties of esculetin and to precisely elucidate its mechanisms of action.

Hepatoprotective effects of leaf extract of Annona senegalensis against aflatoxin B1 toxicity in rats.

Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.

Profiling of two Lampranthus species using LC-ESI/MS with evidence of their hepatoprotective activity.

Lampranthus glaucus and Lampranthus glaucoides are only reported to have significant cytotoxic activity against certain cancer cell lines with phytochemical investigation of their petroleum ether and the ethyl acetate extracts. Further investigation was suggested concerning their hepatoprotective activity and relating it to the metabolic profile of their defatted methanol extracts using LC-ESI/MS analysis. Hepatoprotective activity was evaluated through assessment of three liver parameters as well as liver histopathological examination in thioacetamide-induced hepatotoxicity model. Sixty-eight and 26 phytochemicals were tentatively identified in L. glaucoides and L. glaucus, respectively, with phenolic compounds as the major class. Both plants showed significant inhibition of serum GPT and GOT levels, inhibition of tissue IL-1ß and TNF-α levels and inhibition of tissue NF-κß and caspase-3 gene expression proving hepatoprotective action. Liver treated with L. glaucoides showed lesion scoring range between negative to mild, whereas L. glaucus showed a range between mild to moderate.

Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation.

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs' in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

Ten cyclopentanoid monoterpenes from the whole plant of Rehmannia piasezkii maxim.

Ten new cyclopentanoid monoterpenes (1-10) were isolated from the whole plant of Rehmannia piasezkii. The structures of these compounds were elucidated based on spectroscopic data analysis. In in-vitro assays, compounds 3, 7, and 9 exhibited weak hepatoprotective activities against APAP-induced HepG2 cell damage. Compound 9 exhibited protective effect on hapassocin carbon tetrachloride model.