Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat.

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220-280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

Herbal Remedies for Hepatic Inflammation: Unravelling Pathways and Mechanisms for Therapeutic Intervention.

Inflammation is a universal response of mammalian tissue to harm, comprising reactions to injuries, pathogens, and foreign particles. Liver inflammation is commonly associated with hepatocyte necrosis and apoptosis. These forms of liver cell injury initiate a sequence of events independent of the etiological basis for the inflammation and can result in hepatic disorders. It is also common for liver cancer. This review fundamentally focuses on the molecular pathways involved in hepatic inflammation. This review aims to explore the molecular pathways involved in hepatic inflammation, focusing on arachidonic acid, NF-κB, MAPK, PI3K/Akt, and JAK/STAT pathways. It investigates active compounds in herbal plants and their pharmacological characteristics. The review proposes a unique therapeutic blueprint for managing hepatic inflammation and diseases by modifying these pathways with herbal remedies.

Ameliorative Effect of Herbal Medicine in the Management of Hepatotoxicity.

Reactive oxygen species production, inflammation, an elevated serum profile, mitochondrial dysfunction, and up-regulation of proapoptotic mediators are the main mechanisms underlying chemotherapy-related hepatotoxicity, which results in hepatocyte disorders such as hepatitis, steatohepatitis, and fibrosis. The article aims to examine a prospective herbal remedy and its bioactive ingredients in terms of its antioxidant, anti-inflammatory, and anti-apoptotic capabilities, which offer superior protection against liver damage during chemotherapy administration. Plants including Silybum marianun, Nelumbo nucifera, Phyllanthus amarus, Plumbago zeylanica, Glycyrrhiza glabra, Citrus limon, and Nigella sativa may have hepatoprotective properties, according to the author. Last but not least, this will give aspiring scientists new knowledge for natural-based development in mitigating liver damage caused by chemotherapy medications.

Oral toxicity of the acetone extract of Coffea arabica var. Oro Azteca leaves in CD-1 mice.

The investigation of coffee leaves as a source of bioactive principles represents a relatively unexplored area of research. The study assesses the potential adverse effects of an aqueous acetone extract derived from Coffea arabica var. Oro Azteca leaves. The phenolic composition of the extract was identified and quantified by UPLC-MS/MS, and its acute and repeated-dose effects were evaluated in six-week-old CD-1 mice (n = 11 for acute evaluation and n = 20 female and n = 20 male for repeated-dose evaluation). The extract demonstrated no significant toxicity, maintaining consistent body weight and exhibiting a hepatoprotective effect by reducing ALT levels at a dose of 500 mg/kg. Some hyperactivity was observed at the highest doses, but overall, the extract enhanced the immune response and showed no histological alterations, except for mild inflammation in certain organs. The extract, which contains abundant quinic acid, chlorogenic acid, epicatechin, procyanidin B2, and mangiferin, has been deemed safe for consumption.

Discrimination of Abrus cantoniensis Hance and Abrus mollis Hance using UPLC-Q/TOF-MS and assessment of their in vivo hepatoprotective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: In Guangzhou and Guangxi, China, Abrus cantoniensis Hance (AH) is known for its liver-protective properties and is commonly used in herbal teas and soups. In the herbal market and pharmaceutical preparations, AH and Abrus mollis Hance (AMH) are often used interchangeable. Despite their morphological and usage similarities, distinguishing their differences is essential for scientific research and clinical practice. AIM OF THE STUDY: This study focuses on the morphological identification, chemical composition, and hepatoprotective effectiveness of AH and AMH. It aims to evaluate their interchangeable use and provide a rationale for this practice. This research helps regulate the market of AH medicinal materials, ensuring clinical safety and effectiveness. MATERIALS AND METHODS: Samples of AH and AMH roots, stems, leaves, and seeds were collected and photographed using a stereoscope and digital imaging system. The chemical components of AH and AMH were qualitatively analyzed using UPLC-Q/TOF-MS. Chemometric techniques, such as PCA and OPLS-DA, were employed to discern the componential differences between the two species. A CCl4-induced acute liver injury mouse model was developed to assess hepatoprotective effects. The hepatoprotective properties of AH and AMH were evaluated by analyzing the liver index, H&E staining, changes in serum liver function indicators (TBIL, ALT, AST), and concentrations of SOD, MDA in liver homogenate. RESULTS: The root color, texture, stem diameter, cross-sectional characteristics, leaf shape, and seed morphology of the two plants were observed. Notable differences were identified, which can be used for accurate identification. The UPLC-Q/TOF-MS identified 50 compounds in both species, which were classified into 3 alkaloids, 22 flavonoids, 2 triterpenes, 10 triterpene saponins, 10 amides, and 3 others, and 20 different compounds between AH and AMH were screened by chemometrics. By improving serum biomarkers (ALT, AST, TBIL) and regulating oxidative stress markers (SOD, MDA), the alleviating effect of AH and AMH extracts on liver injury was confirmed. Notably, AH showed a stronger liver protective effect, significantly reducing ALT and AST levels more than AMH. CONCLUSION: This study enhances understanding of the morphological identification, chemical profiling, and hepatoprotective effects of AH and AMH. It provides a reference for future scientific research and the clinical application of AH in treating liver damage.

Protective effect of Acanthus ilicifolius extracts against acute alcoholic liver injury via suppressing TLR4/NF-κB signal pathway and modulating intestinal microbiota in mice.

Excessive alcohol consumption is leading to increased rates of liver injury and disease. A new research strategy focuses on manipulating gut microbiota to lessen alcohol-induced harm. This study examined the hepatoprotective effects of extracts from Acanthus ilicifolius (EAI) on acute alcoholic liver injury by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal microbiota in mice. The results showed that EAI dose-dependently reduced alcohol-induced elevations of AST, ALT, and ALP levels. EAI showed significant inhibitory effects on the expressions of TLR4, NF-κB, and pNF-κB proteins. Furthermore, EAI caused a notable reduction in hepatic levels of IL-1ß, IL-6, and TNF-α. Supplementation with EAI could ameliorate alcohol-induced dysbiosis of intestinal bacteria. The levels of ALT, AST, and ALP levels were negatively correlated with Ligilactobacillus, Lactobacillus, and Alistipes, but positively correlated with Helicobacter and Bacteroides. Overall, EAI alleviated alcoholic liver injury in mice by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal bacteria.

An In-depth Review on Argemone mexicana in the Management of Liver Health and Liver Cancer.

INTRODUCTION: Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana. METHODOLOGY: A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer. RESULTS: The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy. CONCLUSION: In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.

Synthesis of Ganoderic Acids Loaded Zein-Chitosan Nanoparticles and Evaluation of Their Hepatoprotective Effect on Mice Given Excessive Alcohol.

Ganoderma lucidum, used in East Asia for its health benefits, contains ganoderic acids (GA) which have various pharmacological activities but are limited by poor water solubility and low oral bioaccessibility. This study synthesized and characterized ganoderic acids loaded zein-chitosan nanoparticles (GA-NPs), and investigated its advantages in alleviating alcoholic liver injury (ALI) in mice model. The GA-NPs demonstrated high encapsulation efficiency (92.68%), small particle size (177.20 nm), and a +29.53 mV zeta potential. The experimental results of alcohol-induced liver injury mouse model showed that GA-NPs significantly improved liver metabolic function, reduced alcohol-induced liver oxidative stress in liver by decreasing lactate dehydrogenase activity and malondialdehyde level, while increasing the activities of liver antioxidant enzymes and alcohol dehydrogenase. Moreover, GA-NPs were favorable to ameliorate intestinal microbiota dysbiosis in mice exposed to alcohol by increasing the proportion of probiotics such as Romboutsia, Faecalibaculum, Bifidobacterium and Turicibacter, etc., which were highly correlated with the improvement of liver function. Furthermore, GA-NPs modulated the mRNA expression related to ethanol metabolism, oxidative stress and lipid metabolism. Conclusively, this study revealed that GA-NPs have stronger hepatoprotective effects than non-encapsulated ganoderic acids on alleviating ALI by regulating intestinal microbiota and liver metabolism.

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 in vitro, in vivo, 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.

Hepatoprotective Effect of Camel Thorn Polyphenols in Concanavalin A-Induced Hepatitis in Mice.

OBJECTIVES: To explore the prophylactic and therapeutic effects of Alhagi maurorum ethanolic extract (AME) in concanavalin A (Con A)-induced hepatitis (CIH) as well as possible underlying mechanisms. METHODS: Polyphenols in AME were characterized using high performance liquid chromatography (HPLC). Swiss albino mice were divided into 4 groups. Normal group received intravenous phosphate-buffered saline (PBS); Con A group received 40 mg/kg intravenous Con A. Prophylaxis group administered 300 mg/(kg·d) AME orally for 5 days before Con A intervention. Treatment group received intravenous Con A then administered 300 mg/kg AME at 30 min and 3 h after Con A intervention. After 24 h of Con A injection, hepatic injury, oxidative stress, and inflammatory mediators were assessed. Histopathological examination and markers of apoptosis, inflammation, and CD4+ cell infiltration were also investigated. RESULTS: HPLC analysis revealed that AME contains abundant polyphenols with pharmacological constituents, such as ellagic acid, gallic acid, ferulic acid, methylgallate, and naringenin. AME alleviated Con A-induced hepatic injury, as manifested by a significant reduction in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (P<0.01). Additionally, the antioxidant effect of AME was revealed by a significant reduction in oxidative stress markers (nitric oxide and malondialdehyde) and restored glutathione (P<0.01). The levels of proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, and interleukin-6) and c-Jun N-terminal kinase (JNK) activity were reduced (P<0.01). Histopathological examination of liver tissue showed that AME significantly ameliorated necrotic and inflammatory lesions induced by Con A (P<0.01). Moreover, AME reduced the expression of nuclear factor kappa B, pro-apoptotic protein (Bax), caspase-3, and CD4+ T cell hepatic infiltration (P<0.01). The expression of anti-apoptotic protein Bcl-2 was increased (P<0.01). CONCLUSION: AME has hepatoprotective and ameliorative effects in CIH mice. These beneficial effects are likely due to the anti-inflammatory, antioxidant, and anti-apoptotic effects of the clinically important polyphenolic content. AME could be a novel and promising hepatoprotective agent for managing immune-mediated hepatitis.

Black garlic exhibited hepatoprotective effect against monosodium glutamate-induced hepatotoxicity in animal model.

Monosodium glutamate (MSG) is commonly used as a flavor-enhancing agent in foods, and studies have demonstrated its toxic effects in animal models. Black garlic is known for its antioxidant and anti-inflammatory properties; however, there is a lack of studies on the potential hepatoprotective effect of black garlic ethanol extract (BGE) against MSG-induced hepatotoxicity in rats. The aim of this study was to investigate the hepatoprotective effects of ethanol extract of black garlic against MSG-induced liver damage in animal model. Twenty-five male Wistar rats were randomly assigned to five groups (n=5): negative control, MSG only, and MSG with three different doses of BGE. The MSG only and MSG with BGE groups were orally administered with 8 mg/kg MSG daily. After MSG treatment, the MSG with BGE groups received BGE orally at daily doses of 200, 400, or 600 mg/kg body weight for 16 consecutive days. Subsequently, the levels of serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2) were measured. Our data indicated that the group treated with 200 mg/kg BGE had significant lower levels of AST and ALT significantly compared to the MSG-only group. The MSG-treated group had higher levels of the inflammatory markers COX-2 and IFN-γ, which were lowered by administration of 200 mg/kg BGE. In contrast, higher doses of BGE led to greater levels of COX-2 and IFN-γ compared to those in the MSG-only group. This study suggested that BGE might have hepatoprotective effects at low dose, potentially mitigating MSG-induced liver damage. However, the higher dose of black garlic extract did not alleviate inflammation, as shown by the higher levels of COX-2 and IFN-γ.

Comparison of kidney and hepatic outcomes among sodium-glucose cotransporter-2 inhibitors: a retrospective study using multiple propensity scores.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status. METHODS: Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values. RESULTS: Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively. CONCLUSIONS: Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status.

Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells.

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-ß1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects.

An updated overview of Gypsophila species: Phytochemical and pharmacological investigations.

Medicinal plants and their consituents play a crucial role in disease prevention and treatment. The genus Gypsophila (Caryophyllaceae family), comprising approximately 150 species of flowering plants, holds significant value in both ornamental and therapeutic fields. Traditional uses in various cultures highlight their potential in treating a range of conditions, such as liver disorders, diabetes, and kidney stones. These resilient plants, known for their delicate blooms and adaptability to diverse environments, are rich in chemical compounds, including non-volatile constituents such as phenolic compounds (e.g., flavonoids), terpenoids, saponins, cyclopeptides, and alkaloids. Additionally, monoterpenes and sesquiterpenes, the primary volatile constituents, exhibit significant insecticidal properties. Gypsophila species show a broad spectrum of pharmacological effects, including hepatoprotective, cytotoxic, anti-diabetic, antioxidant, cytotoxic, anti-inflammatory, diuretic, neuroprotective, and anti-obesity properties. This review underscores the promising therapeutic potential of Gypsophila and advocates for further research, particularly clinical trials, to thoroughly assess their efficacy and safety. By consolidating existing knowledge, it sheds light on the potential of Gypsophila species as valuable resources for human health and underscores the need for continued exploration to uncover novel treatments and interventions.

Hepatoprotective activity of Mentha rotundifolia aqueous extract against hepatocellular damage induced by CCL4 in rats.

This study aims to assess hepatoprotective properties of M. rotundifolia. Decoction was used to prepare the aqueous extract. The preliminary cytotoxicity evaluated against Caco 2 and RAW 264 cells demonstrate no cytotoxic effect. The preventive impact of the extract against liver damage was evaluated by examining blood levels of AST, ALT, ALP, total proteins, and histological alterations in liver tissues. Thirty albino rats were separated into five groups: the first served as normal group, the second was injected by olive oil (3 ml/kg), and the third was injected by CCL4 (3 ml/kg). However, groups IV and V received daily doses of 250 and 500 mg extract/kg bw, respectively before CCL4 injection. The results showed that the administration of the extract led to a marked improvement in plasma biochemical markers and a reduction in symptoms of CCL4-induced liver damage. The extract exhibits hepatoprotective activity, which may be attributed to its phytochemical components.

Hydrophilic extract of Pistacia vera pericarp protects against phenylhydrazine-induced hepatotoxicity and hemolytic anemia.

Objective: Pistacia vera is commonly used in traditional medicine to treat various disorders. This study aims to investigate the anti-anemia and hepatoprotective effects of Pistacia vera pericarp extract (PVPE) in a rat model of phenylhydrazine (PHZ)-induced anemia. Materials and Methods: PVPE was prepared using the maceration method. The extract was administered at doses of 20, 80, and 160 mg/kg for 28 days to normal and PHZ-treated rats. The effects of PVPE were evaluated in terms of changes in biochemical, histological, hematological, and molecular biomarkers in the liver and blood. Results: Administration of PVPE to the anemic animals significantly restored these deleterious effects on hematological parameters compared to the anemic group. Kupffer cell activation was seen in the liver tissue of the anemic rats. Administration of PVPE mitigated these deleterious effects. Conclusion: PVPE has potent antioxidant activity and may represent a promising treatment for anemia and liver protection in clinical settings.

Hepatoprotective effects of diosmin: a narrative review.

Liver diseases represent a formidable global health threat. Hesperidin, a flavonoid found in citrus fruits, is the source of diosmin (DS). The in vivo and in vitro investigations of the pharmacological effects of DS reveal that it exhibits tremendous beneficial effects, such as fighting against inflammation, oxidative stress, and fibrosis. These effects have been noticed in various disease models, emphasizing the potential therapeutic value of DS in tackling diverse pathological conditions. Interestingly, DS has promising liver-defense capabilities against a range of hepatic illnesses, such as radiation-induced hepatic injury, liver ischemia/reperfusion injury, alcoholic hepatic disease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Furthermore, DS demonstrates potential hepatoprotective effects against environmental toxins, such as heavy metals. DS activates PPAR-γ and Nrf2, leading to antioxidant effects that reduce oxidative stress. Moreover, DS suppresses NF-κB, NLRP3, MAPK activities, and cytokine production (TNF-α and IL-1ß), resulting in inflammation suppression. These anti-inflammatory effects are attributed to the activation of PPAR-γ and Nrf2, which are NF-κB inhibitors. This review aims to comprehensively discuss the hepatoprotective capacity of DS, elucidating the underlying mechanisms and identifying several research avenues that warrant further exploration to ascertain the prospective clinical advantages of DS intake as a viable strategy for the treatment of hepatic illnesses.

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.

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.

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-ß-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.