A metabolomics study on the mechanisms of Gardeniae fructus against α-naphthylisothiocyanate-induced cholestatic liver injury.

Gardeniae fructus (GF) is known for its various beneficial effects on cholestatic liver injury (CLI). However, the biological mechanisms through which GF regulates CLI have not been fully elucidated. This study aimed to explore the potential mechanisms of GF against α-naphthylisothiocyanate (ANIT)-induced CLI. First, HPLC technology was used to analyze the chemical profile of the GF extract. Second, the effects of GF on serum biochemical indicators and liver histopathology were examined. Lastly, metabolomics was utilized to study the changes in liver metabolites and clarify the associated metabolic pathways. In chemical analysis, 10 components were identified in the GF extract. GF treatment regulated serum biochemical indicators in ANIT-induced CLI model rats and alleviated liver histological damage. Metabolomics identified 26 endogenous metabolites as biomarkers of ANIT-induced CLI, with 23 biomarkers returning to normal levels, particularly involving primary bile acid biosynthesis, glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. GF shows promise in alleviating ANIT-induced CLI by modulating multiple pathways.

Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin-Induced Organ Dysfunction in Rats: Comprehensive in†vivo and in silico Studies.

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.

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.

Hepatoprotective Principles from the Rhizomes of Picrorhiza kurroa.

A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.

Attenuation of methotrexate induced hepatotoxicity by epigallocatechin 3-gallate.

Methotrexate (MTX) is currently used as first-line therapy for autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematous. However, its use is limited by its hepatotoxic potential. Epigallocatechin-3-gallate (EGCG), an abundant catechin present in tea possesses potent antioxidant activity and effectively ameliorates oxidative stress-related disorders. This study aimed to investigate the hepatoprotective influence of EGCG in a MTX-induced rat model of hepatotoxicity. Sprague Dawley rats pretreated with EGCG (40 mg kg-1 b.w., p.o.) were administered a single dose of MTX (20 mg kg-1 b.w., i.p.) and its hepatoprotective efficacy compared with folic acid (1 mg kg-1 b.w., i.p.). On day 10, blood samples were collected to determine plasma levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), while the livers were examined for histopathogical changes along with levels of oxidative stress measured in terms of myeloperoxidase (MPO) activity, protein carbonylation (PCO), lipid peroxidation (LPO), and activities of cellular enzymatic antioxidants - superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). MTX significantly increased the plasma levels of AST, ALT, ALP, and LDH, which were prevented by pretreatment with EGCG, and was corroborated by histopathology. Additionally, MTX-induced hepatic oxidative stress as measured by increased generation of MPO, enhanced PCO, LPO, and decreased activities of antioxidant enzymes was mitigated by pretreatment with EGCG. The amelioration of MTX-induced hepatotoxicity by EGCG endorsed the inclusion of an anti-oxidant during chronic administration of MTX.

Hepatoprotective Effect of a New FFAR1 Agonist-N-Alkylated Isobornylamine.

Free fatty acid receptor-1 (FFAR1) is one of the possible therapeutic targets in the search for new hepatoprotective drugs. FFAR1 agonists were found to have hypolipidemic, antifibrotic, anti-inflammatory, antiproliferative and antioxidant effects in addition to hypoglycemic action. In this work, we conducted a study of the hepatoprotective effect of the compound QS-528 (previously discovered as an agonist of FFAR1) at doses of 60, 90, 120 and 150 mg/kg on carbon tetrachloride (CCl4)-induced liver injury. At the end of the experiment, a biochemical blood assay demonstrated that the introduction of QS-528 dose-dependently reduces the levels of liver enzymes (AST, ALT and ALKP). Histological and morphometric studies of animals' livers treated with QS-528 at doses of 120 and 150 mg/kg showed a decrease in degenerative/necrotic changes in hepatocytes and an increase in the regenerative activity of the liver. In addition, no toxicity at a single oral dose of 1000 mg/kg and an increase in HepG2 cell viability in vitro were found. Thus, the compound QS-528 was found to exhibit a hepatoprotective effect against CCl4-induced toxic liver damage.

Phytochemicals from Anneslea fragrans Wall. and Their Hepatoprotective and Anti-Inflammatory Activities.

Anneslea fragrans Wall., popularly known as "Pangpo tea", is an edible, medicinal, and ornamental plant of the Family Theaceae. The leaves of A. fragrans were historically applied for the treatment of liver and intestinal inflammatory diseases in China. This study aimed to explore the hepatoprotective agents from A. fragrans leaves through hepatoprotective and anti-inflammatory assessment. The phytochemical investigation of the leaves of A. fragrans resulted in the isolation and identification of a total of 18 chemical compounds, including triterpenoids, aliphatic alcohol, dihydrochalcones, chalcones, flavanols, phenolic glycoside, and lignans. Compounds 1-2, 4-6, 11-12, and 16-18 were identified from A. fragrans for the first time. Compounds 7 and 14 could significantly alleviate hepatocellular damage by decreasing the contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and inhibit the hepatocellular apoptosis in the HepG2 cells induced by N-acetyl-p-aminophenol (APAP). In addition, compounds 7 and 14 inhibited reactive oxygen species (ROS) and malondialdehyde (MDA) contents and increased the catalase (CAT) superoxide dismutase (SOD), and glutathione (GSH) levels for suppressing APAP-induced oxidative stress. Additionally, compounds 7, 13, and 14 also had significant anti-inflammatory effects by inhibiting interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) productions on LPS-induced RAW246.7 cells.

Effects of Banana (Musa spp.) Bract Flour on Rats Fed High-Calorie Diet.

Research background: The extensive cultivation of bananas (Musa sp.) is related to producing tons of residues, such as leaves, pseudostems and bracts (inflorescences). The banana bract is a commercially interesting residue due to its dietary fibre content and high antioxidant potential. With this in mind, this study evaluates the effects of administering banana bract flour in animal models fed a cafeteria diet. Experimental approach: Thirty-two male rats were divided into 4 groups: (i) control diet, (ii) control diet with 10 % banana bract flour, (iii) hypercaloric diet, and (iv) hypercaloric diet with 10 % bract banana flour. The study was conducted for 12 weeks and included analysis of phenolic compounds, assessment of the antioxidant effect of banana bract flour, determination of serum biochemical parameters (glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine transaminase (ALT), amylase, albumin, uric acid, creatine, total protein, and oral glucose), determination of faecal fat content, and histomorphological analysis of the liver, pancreas and adipose tissue. In addition, molecular parameters such as IL6, total and phosphorylated JNK, total and phosphorylated IKKß, TNFα, TLR4 and HSP70 were determined. Results and conclusions: The banana bract flour showed a high content of phenolic compounds and an antioxidant effect. The in vivo results suggest that the supplementation of a hypercaloric diet with banana bract flour prevented pathological damage by reducing total cholesterol and glucose amounts, which may imply a hepatoprotective effect of this supplement. Thus, using banana bract flour as a supplement can increase the consumption of fibre, antioxidants and bioactive compounds. Novelty and scientific contribution: The development of flour from banana waste and its inclusion in the diet can prevent and/or help treat obesity. In addition, the use of banana bracts can help protect the environment, as they are considered a source of waste by the food industry.

Formation of Maillard Reaction Products in Aged Sorghum Vinegar during Ageing and Protective Effects of Pure Vinegar Melanoidin Against CCl4-Induced Rat Hepatic Damage.

Research background: The processing method generally affects the toxicity and biological activity of aged sorghum vinegar. This study investigates the changes in the intermediate Maillard reaction products of sorghum vinegar during ageing and the in vivo hepatoprotective effects of pure melanoidin obtained from it. Experimental approach: High-performance liquid chromatography (HPLC) and fluorescence spectrophotometry were utilized to quantify intermediate Maillard reaction products. The CCl4-induced liver damage in rats was used to evaluate the protective role of pure melanoidin in rat liver. Results and conclusions: Compared with the initial concentration, the 18-month ageing process caused a 1.2- to 3.3-fold increase in the concentrations of intermediate Maillard reaction products, i.e. 5-hydroxymethylfurfural (HMF), 5-methylfurfural (MF), methyglyoxal (MGO), glyoxal (GO) and advanced glycation end products (AGEs). The concentrations of HMF in the aged sorghum vinegar were 6.1-fold higher than the 450 µM limit standard for honey, implying the need for shortening the ageing of the vinegar in practice for safety concerns. Pure melanoidin (Mr>3.5 kDa) demonstrated significant protective effects against CCl4-induced rat liver damage, as evidenced by normalized serum biochemical parameters (transaminases and total bilirubin), suppressing hepatic lipid peroxidation and reactive oxygen species, as well as increasing glutathione amount and restoring antioxidant enzyme activities. Histopathological analysis revealed that melanoidin in vinegar reduced cell infiltration and vacuolar hepatocyte necrosis in rat liver. The findings demonstrated that a shortened ageing process should be considered in practice to ensure the safety of aged sorghum vinegar. Vinegar melanoidin is a potential alternative for the prevention of hepatic oxidative damage. Novelty and scientific contribution: This study demonstrates that the manufacturing process had a profound influence on the generation of vinegar intermediate Maillard reaction products. In particular, it revealed the in vivo hepatoprotective effect of pure melanoidin from aged sorghum vinegar, and provides insight into the in vivo biological activity of melanoidin.

Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry-based plasma metabolomics study of hepatoprotective effect of cuscutae semen on CCl4 -induced liver injury model of rats.

Hepatic disorders are a serious health problem threatening human beings. Cuscutae semen (CS), a widely used Chinese medicine, is a tonic to nourish the liver and kidney. Our research aimed to assess the hepatoprotective effect of CS on CCl4 -induced liver injury rats using plasma metabolomics. Liver injury in rats was induced by 40% CCl4 in olive oil twice a week for 21 days. The CS group received 2 g/kg of CS every day for 21 days. The liver tissues were used for histological studies. The serum was used for the analysis of biochemical parameters. Plasma metabolomic analysis was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. CS could relieve hepatocyte necrosis and decrease the levels of serum biochemical parameters in comparison the with CCl4 group. Principal component analysis and orthogonal partial least squares-discriminant analysis on plasma metabolomes showed an obvious separation among the control, model, and CS groups. Heatmap showed that CS-administered mice had similar metabolite profiles as the control group. Seven influential pathways in plasma of the hepatoprotective effect impacted by CS were identified. This study confirmed the hepatoprotective effect of CS, and the related metabolic pathways were discussed.

The evaluation of hepatoprotective effects of flavonoids from Scorzonera austriaca Wild against CCl4-induced acute liver injury in vitro and in vivo.

Scorzonera austriaca Wild is a traditional herbal medicine; however, little is known with regard to the effect of flavonoids from S. austriaca (FSA) on liver injury induced by Carbon tetrachloride (CCl4), especially the mechanism remains unknown. Therefore, our paper was designed to investigate the hepatoprotective effect of FSA against CCl4-induced acute liver injury in vitro and in vivo, with focus on its potential mechanism. The purity of FSA prepared by using polyporous resin column chromatography could reach 94.5%, and seven flavonoid compounds in FSA were identified by using LC-ESI-MS analysis. In vivo results showed that FSA markedly decreased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and malonaldehyde (MDA) and increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Furthermore, in vivo and in vitro results confirmed that FSA could inhibit inflammatory response, as evidenced by decreasing the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) through inactivating toll-like receptor-4/nuclear factor-κB (TLR4/NF-κB) signaling pathway. FSA activated autophagy by increasing the ratio of LC3B-II/I and decreasing the protein level of p62 so as to exert its hepatoprotective effect. In general, these evidences suggested that FSA is likely to serve as a potential material for the drugs against chemical hepatic injury.

Hepatoprotective Effect of Oyster Peptide on Alcohol-Induced Liver Disease in Mice.

Alcohol-induced liver disease (ALD) has become one of the major global health problems, and the aim of this study was to investigate the characterization of the structure as well as the hepatoprotective effect and mechanism of oyster peptide (OP, MW < 3500 Da) on ALD in a mouse model. The results demonstrate that ethanol administration could increase the activities of aspartate aminotransferase (AST), alanine transaminase (ALT), γ-Glutamyl transferase (GGT), reactive oxygen species (ROS), malondialdehyde (MDA), and triglycerides (TG), as well as increase the interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) levels (p < 0.01), and reduce the activity of superoxide dismutase (SOD) and the concentration of glutathione (GSH). Those changes were significantly reversed by the application of different doses of OP. Furthermore, the mRNA expressions of nuclear factor elythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and quinone oxidoreductase1 (NQO1) were significantly up-regulated in OP groups, and the mRNA expressions of nuclear factor kappa-light chain enhancer of B cells (NF-κB), TNF-α, and IL-6 were markedly reduced in OP groups compared to that of the model group. Thus, OP had a significant protective effect on ALD through the enhancement of the in vivo antioxidant ability and the inhibition of the inflammatory response as possible mechanisms of action, which therefore suggests that OP might be useful as a natural source to protect the liver from alcohol damage.

Hepatoprotective Polysaccharides from Geranium wilfordii: Purification, Structural Characterization, and Their Mechanism.

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1ß, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.

Chantriolides F-P, Highly Oxidized Withanolides with Hepatoprotective Activity from Tacca chantrieri.

Eleven highly oxidized withanolides, chantriolides F-P (1-11), together with six known analogues (12-17), were isolated from the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were further confirmed by experimental ECD data and single crystal X-ray diffraction analysis. The structures of compounds 5-8 contained a chlorine atom substituted at C-3. Compounds 1 and 12 are a pair of epimers isomerized at C-24 and C-25, while compounds 9 and 16 are isomerized at C-1, C-7, C-24, and C-25. Next, the hepatoprotective effect of all the isolates was evaluated on tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes. Compounds 5-11 and 16 significantly enhanced cell viability. Compound 8 decreased reactive oxygen species accumulation and increased glutathione level in t-BHP injured AML12 hepatocytes through promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).

Effect of Hepatocyte Targeting Nanopreparation Syringopicroside on Duck Hepatitis B Virus and Evaluation of Its Safety.

Syringopicroside is a kind of iridoid monomer compound isolated from Syringa oblata exhibiting a potent effect against hepatitis B virus (HBV). The therapeutic effect and safety of syringopicroside-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SYR-NP) were studied on the model of HBV-infected ducklings and on cultured HepG2.2.15 cells. HBV DNA in ducklings was assessed by fluorescence quantitative PCR. In HepG2.2.15 cells, the content of HBsAg and HBeAg were assayed. Acute toxicity of SYR-NP was studied in ICR mice in 12 h and 7 days after SYR-NP administration. The serum levels of HBV DNA in ducklings treated with SYR-NP in a high dose was significantly lower than in the control. In HepG2.2.15 cells treated with different doses of SYR-NP, the concentrations of HBsAg and HBeAg were significantly below the control. Acute toxicity test showed high safety of SYR-NP. Thus, SYR-NP can inhibit replication of HBV DNA and protect the liver tissue.

Protective effect of surfactin on copper sulfate-induced inflammation, oxidative stress, and hepatic injury in zebrafish.

Surfactin, an antibacterial peptide, produced by various Bacillus subtilis strains, have broad-spectrum antibacterial and immune-enhancing functions. In this study, we investigated the anti-inflammatory, antioxidant, and hepatoprotective effect of surfactin on zebrafish (Danio rerio) larvae following their exposure to copper sulfate (CuSO4 ). The mature AB wild-type and a transgenic line of zebrafish larvae that expressed enhanced GFP (EGFP) named Tg (Lyz:EGFP) were exposed to 0, 20, 40, and 60 µg/mL surfactin after incubation with 3.2 µg/mL CuSO4 for 2 h from 72 h postfertilization (hpf). Different endpoints, such as migration of GFP-labeled neutrophils, analysis of inflammatory cytokines and transaminases, markers of oxidation, expression of certain genes, and histological changes of liver, were studied to evaluate the function of surfactin. The protein expression levels of NF-κBp65, TNF-α, cyclooxygenase-2 (COX-2), and iNOS were determined in murine macrophage RAW 264.7 cells by western blotting. Our results show that surfactin reduced migration of neutrophils and relieved hepatic injury. In addition, surfactin reduced the index levels of inflammatory factors, oxidative stress response, and improved hepatic function. Surfactin also significantly inhibited the expression of IL-1ß, IL-8, TNF-α, nitric oxide, NF-κBp65, COX-2, and iNOS, and increased the expression of IL-10. Thus, our results demonstrate that surfactin has anti-inflammatory, antioxidant, and hepatoprotective activities. Surfactin has potential as a novel inflammation and immune adjustment.

Protective effects and possible mechanisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies.

Drug-induced liver injury (DILI) has become a significant health care problem worldwide. Centella asiatica (L.) urban was traditionally used to prevent or treat various diseases, yet whether it works on hepatic injury remains unclear. In this study, multiple experimental models with different damage degrees and types of liver injury have been established to evaluate the hepatoprotective effects of an n-butanol extract of Centella asiatica (CA-BU). Our results revealed that CA-BU improved hepatocyte L02 cells survival from H2 O2 -induced oxidative damage in a concentration-dependent manner. We further verified the hepatoprotective effects of CA-BU in mice models of acetaminophen-induced acute liver injury (one of the most common DILIs clinically) and CCl4 -induced acute chemical liver injury, and a rat model of chronic alcoholic steatohepatitis. Furthermore, network pharmacology approaches were performed to explore the underlying mechanisms, and we predicted AKT1, EGFR, VEGFA, and STAT3 as the potential therapeutic targets. In follow-up studies, we will focus on targets verification and provide a deeper insight into the mechanisms of CA-BU against liver damage. Finally, we hope that these findings will provide new ideas and insights for the treatment of acute or chronic liver injury in the clinic.

Comparison of Chemical Constituents and Pharmacological Effects of Different Varieties of Chrysanthemum Flos in China.

Chrysanthemum Flos is the prestigious traditional Chinese medicinal material and the popular health drink. This article comprehensively evaluated the chemical constituents, antioxidant activity, and hepatoprotective effects of 25 common chrysanthemum varieties in China. Firstly, we analyzed the chemical compositions of water extracts of chrysanthemum using UPLC/Q-TOF-MS, and identified 29 chemical components. The results displayed that chrysanthemum was rich in chemical constituents, but there were significant differences in the contents of four phenolic acids and five flavonoids among different varieties, and the coefficient of variation (CVs) ranged from 35.96 % to 114.62 %. Then, the antioxidant activities of different chrysanthemums were investigated, respectively via 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and Ferric Reducing Antioxidant Power (FRAP) assays. The spectrum-effect relationships between nine main components and antioxidant activities were investigated to identify the antioxidant constitutes in chrysanthemums. Meanwhile, H2 O2 -induced hepatocyte injury testing showed wide variation in cultivar antioxidant capacity, with Tongchengju (TCJ) producing the best effect (90.32 %), followed by Chuju (CJ; 85.78 %). In addition, the hepatoprotective effects of 8 mainstream varieties were determined by the model of acute alcoholic liver injury. They protected liver from injury by affecting relevant liver function and antioxidant indexes. Huangshangongju (HSG) could decrease aspartate aminotransferase (AST) activity by 39.27 % in liver tissue; Hangju-Fubaiju (HJ-FBJ), Jinsihuangju (JSH), and Chuju (CJ) significantly decreased the malondialdehyde (MDA) content of liver tissue, which reduced by more than 40 %; Jinsihuangju (JSH) of used for tea could double the content of glutathione (GSH) and had the similar effect on superoxide dismutase (SOD) as the positive group, showing significant antioxidant capacity. Therefore, this study confirmed that chrysanthemums are potential resources as antioxidants, functional foods, and medicinal materials. Importantly, it may provide a scientific support for further development and utilization of chrysanthemum, and screen excellent varieties for different demands.

Toxicity of thioacetamide and protective effects of quercetin in zebrafish (Danio rerio) larvae.

Quercetin is a flavonoid compound with a variety of biological properties that is widely distributed throughout the plant kingdom. Studies have found that quercetin has anti-inflammatory, antioxidant, and liver-protective effects, while thioacetamide (TAA) can cause inflammation and liver damage in zebrafish larvae. The purpose of this study was to evaluate whether quercetin can prevent TAA-induced inflammation and liver damage in zebrafish larvae and to investigate the molecular mechanisms involved. Zebrafish Tg transgenic lines were used as the experimental animals. Behavioral, oxidative stress level, proliferative antigen chromogenic antibody, and western blot analyses were carried out on zebrafish larvae in the control group and groups treated with TAA and 12 µM quercetin. The results indicated that quercetin promoted the development of zebrafish larvae damaged by TAA, exhibited antioxidant and anti-inflammatory properties, and promoted cell proliferation. Quercetin reduced the expression of p53 protein in zebrafish larvae injured by TAA, resulting in decreased levels of Bax and increased levels of Bcl-2. The findings suggested quercetin has antiapoptotic action. Quercetin reduced the expression of DKK1 and DKK2 genes related to the Wnt signaling pathway in zebrafish larvae damaged by TAA and increased the expression of Lef1 and wnt2bb. Quercetin may regulate the development of zebrafish larvae damaged by TAA through the Wnt signaling pathway. This study provides the scientific basis for the development and utilization of quercetin and the development of new related drugs.

Development of herpetrione nanosuspensions stabilized by glycyrrhizin for enhancing bioavailability and synergistic hepatoprotective effect.

The objective of this study was to develop novel herpetrione (HPE) nanosuspensions stabilized by glycyrrhizin (HPE NSs/GL) for enhancing bioavailability and hepatoprotective effect of HPE. HPE NSs/GL were prepared by wet media milling method and then systemically evaluated by particle size analysis, scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), dissolution test, pharmacokinetics, and hepatoprotective effect. HPE-NSs stabilized by poloxamer 407 (HPE NSs/P407) were also prepared and used as a reference for comparison. HPE NSs/GL and HPE-NSs/P407 with similar particle sizes around 450 nm and PDI less than 0.2 were successfully prepared and both of them appeared to be spherical under SEM. The XRPD results demonstrated that HPE in both HPE NSs/GL and HPE NSs/P407 was presented in the amorphous state and the addition of GL or P407 and the milling process didn't alter the physical state of HPE. The dissolution and pharmacokinetic studies demonstrated that HPE NSs/GL exhibited significant enhancement in drug dissolution (72.44% within 24 h) and AUC0-t (24.91 ± 3.3 mg/L·h) as compared to HPE coarse suspensions (HPE CS, 34.19% & 13.07 ± 1.02 mg/L·h), but was similar with those of HPE NSs/P407 (80.06% & 26.75 ± 4.06 mg/L•h). Moreover, HPE NSs/GL exhibited significantly better hepatoprotective effect as compared to HPE CS and HPE NSs/P407 as indicated by the lowering of the elevated serum ALT and AST levels and the improvement of the hepatic morphology and architecture, which might be attributed to the improved bioavailability of HPE, and synergistic hepatoprotective effect of GL via alleviating inflammation evidenced by the significant decreased hepatic levels of inflammatory cytokines IL-1ß, IL-6 and TNF-α. It could be concluded that GL might be an effective stabilizer for preparing HPE NSs, and HPE NSs/GL is a potential formulation strategy for improving oral bioavailability and hepatoprotective effect of HPE.