Oxidative Stress In Liver Research Articles

Increased insulin resistance with reduced beta cell function in recovered COVID-19 Ghanaians

AimThis study compares levels of insulin resistance and beta-cell function and their relationship with liver enzymes in recovered COVID-19 participants and their uninfected counterparts in a cross-sectional study design in the Tamale metropolis of Ghana. MethodsBiochemical indices for liver function, lipid metabolism, inflammation and oxidative stress were assessed under fasting state in 110 recovered COVID-19 and 116 uninfected participants. The homeostatic model assessment of insulin resistance (HOMA-IR) and the triglyceride-glucose index (TyG) were employed for the assessment of insulin resistance. ResultsRecovered COVID-19 participants presented lower (P < 0.05) levels of fasting glucose, insulin, alkaline phosphatase, creatinine and beta-cell function but higher (P < 0.05) levels of alanine/aspartate transferase, total bilirubin, direct bilirubin, total cholesterol, high-density lipoprotein cholesterol and HOMA-IR than their uninfected counterparts. The mean levels of the remaining indices were comparable (P > 0.05) between the study groups. Prevalence of insulin resistance ranged from 61 % (71/116) to 81 % (89/110) for the uninfected and recovered COVID-19 participants respectively. Selected liver enzymes associated with HOMA-IR and TyG. ConclusionThe risk of developing type 2 diabetes mellitus appears higher in recovered COVID-19 participants than their uninfected counterparts despite the high prevalence of insulin resistance in both groups.

12 Amino Acid Nutrition in Dairy Cattle: Beyond Milk Protein

Abstract The transition from gestation to lactation, also known as the transition period, is a critical time for dairy cows. This phase is typically defined as 3 weeks before parturition through 3 weeks after parturition. Peak disease incidence (shortly after parturition) corresponds with the time of greatest negative energy balance (NEB) and negative protein balance (NPB), the peak in blood concentrations of nonesterified fatty acids, and the greatest acceleration of milk yield. Decreased fertility in the face of increasing milk production may be attributable to greater severity of postpartum NEB and NPB resulting from inadequate transition management or increased disease rates. The depth and duration of NEB and NPB are highly related to dry matter intake. Formulating and delivering appropriate diets that limit total energy intake to requirements but also provide proper intakes of all other nutrients [including the indispensable amino acids (IAA) Met and Lys] before calving can help lessen the extent of NEB and NPB after calving. Supplementation of rumen-protected methionine (RPM) during the transition period improved uterine immune function through improved glandular morphology, increased neutrophil infiltration after calving, and discovery of neutrophil extracellular trap formation in bovine endometrial tissue. Its supplementation has been reported to reduce the incidence of health complications, better lactation performance, and more favorable biomarker and plasma AA profiles, common in cows with increased liver functionality index. Cows supplemented with rumen-protected lysine (RPL) had decreased liver oxidative stress (SOD1, superoxide dismutase 1) and acute phase response (SAA3, serum amyloid A3) and reduced gene expression of NFKB1 (nuclear factor kappa B1) leading to increased proinflammatory IL1B postpartum, likely indicating improved immune activation when cows consumed RPL, a necessary component of early postpartum health. Our group has reported that a prepartum supply of RPL altered uteroplacental metabolism and glucose transport. This was demonstrated through increased expression of uterine transcripts involved in energy metabolism (GLUT3, glucose transporter 3; PCK1, phosphoenolpyruvate carboxykinase 1) and placental metabolism (FGF2, fibroblast growth factor 2; FGF2R, fibroblast growth factor 2 receptor; and PGF, placental growth factor). We also have demonstrated that RPL prepartum increased the placental protein abundance of FGF2 and LRP1 (low-density lipoprotein receptor-related protein 1), indicating possible enhanced placental metabolic activity, probably linked to trophoblast proliferation and migration processes. Finally, calves from dams fed RPL prepartum had improved overall growth and intake than calves from dams not receiving RPL. In conclusion, providing RPM and RPL during the transition period impacts dairy cows' health, uterine environment, and offspring.

Skimmianine attenuates liver ischemia/reperfusion injury by regulating PI3K–AKT signaling pathway-mediated inflammation, apoptosis and oxidative stress

Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established a mouse liver I/R model and an AML12 cell hypoxia-reoxygenation (H/R) model, both pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K–AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress, and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Moreover, Ski activated phosphorylation of PI3K–AKT pathway-related proteins after liver I/R and cell H/R. Importantly, the PI3K inhibitor LY294002 effectively reversed the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K–AKT pathway.

SIRT5 rs12216101 T>G variant is associated with liver damage and mitochondrial dysfunction in patients with non-alcoholic fatty liver disease

Sirtuin 5, encoded by the SIRT5 gene, is a NAD+-dependent deacylase that modulates mitochondrial metabolic processes through post-translational modifications. In this study, we aimed to examine the impact of the SIRT5 rs12216101T>G non-coding single nucleotide polymorphism on disease severity in patients with non-alcoholic fatty liver disease (NAFLD). The rs12216101 variant was genotyped in 2,606 consecutive European patients with biopsy-proven NAFLD. Transcriptomic analysis, expression of mitochondrial complexes and oxidative stress levels were measured in liver samples from a subset of bariatric patients. Effects of SIRT5 pharmacological inhibition were evaluated in HepG2 cells exposed to excess free fatty acids. Mitochondrial energetics invitro were investigated by high-performance liquid chromatography. In the whole cohort, the frequency distribution of SIRT5 rs12216101 TT, TG and GG genotypes was 47.0%, 42.3% and 10.7%, respectively. At multivariate logistic regression analysis adjusted for sex, age >50 years, diabetes, and PNPLA3 rs738409 status, the SIRT5 rs12216101T>G variant was associated with the presence of non-alcoholic steatohepatitis (odds ratio 1.20, 95% CI 1.03-1.40) and F2-F4 fibrosis (odds ratio 1.18; 95% CI 1.00-1.37). Transcriptomic analysis showed that the SIRT5 rs12216101T>G variant was associated with upregulation of transcripts involved in mitochondrial metabolic pathways, including the oxidative phosphorylation system. In patients carrying the G allele, western blot analysis confirmed an upregulation of oxidative phosphorylation complexes III, IV, V and consistently higher levels of reactive oxygen species, reactive nitrogen species and malondialdehyde, and lower ATP levels. Administration of a pharmacological SIRT5 inhibitor preserved mitochondrial energetic homeostasis in HepG2 cells, as evidenced by restored ATP/ADP, NAD+/NADH, NADP+/NADPH ratios and glutathione levels. The SIRT5 rs12216101T>G variant, heightening SIRT5 activity, is associated with liver damage, mitochondrial dysfunction, and oxidative stress in patients with NAFLD. In this study we discovered that the SIRT5 rs12216101T>G variant is associated with higher disease severity in patients with non-alcoholic fatty liver disease (NAFLD). This risk variant leads to a SIRT5 gain-of-function, enhancing mitochondrial oxidative phosphorylation and thus leading to oxidative stress. SIRT5 may represent a novel disease modulator in NAFLD.

Chromatographic Analyses of Spirulina (Arthrospira platensis) and Mechanism of Its Protective Effects against Experimental Obesity and Hepatic Steatosis in Rats.

Background and Objectives: Obesity is currently a major health problem due to fatty acid accumulation and excess intake of energy, which leads to an increase in oxidative stress, particularly in the liver. The main goal of this study is to evaluate the protective effects of spirulina (SP) against cafeteria diet (CD)-induced obesity, oxidative stress, and lipotoxicity in rats. Materials and Methods: The rats were divided into four groups and received daily treatments for eight weeks as follows: control group fed a standard diet (SD 360 g/d); cafeteria diet group (CD 360 g/d); spirulina group (SP 500 mg/kg); and CD + SP group (500 mg/kg, b.w., p.o.) according to body weight (b.w.) per oral (p.o.). Results: Our results show that treatment with a CD increased the weights of the body, liver, and abdominal fat. Additionally, severe hepatic alteration, disturbances in the metabolic parameters of serum, and lipotoxicity associated with oxidative stress in response to the CD-induced obesity were observed. However, SP treatment significantly reduced the liver alteration of CD feed and lipid profile disorder associated with obesity. Conclusions: Our findings suggest that spirulina has a marked potential therapeutic effect against obesity and mitigates disturbances in liver function parameters, histological alterations, and oxidative stress status.

Pectolinarigenin attenuates hepatic ischemia/reperfusion injury via activation of the PI3K/AKT/Nrf2 signaling pathway

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/AKT/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and apoptosis and could activate the PI3K/AKT/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/AKT/Nrf2 pathway.

Evaluation of the Protective and Regenerative Properties of Commercially Available Artichoke Leaf Powder Extract on Plasma and Liver Oxidative Stress Parameters.

Hepatocellular damage by the harmful effects of xenobiotics, which increase the production of free radicals, is a widespread phenomenon. The extract from the leaves of Cynara scolymus L. available as an artichoke preparation (natural source) of antioxidants may serve as a potential hepatoprotective factor. This study aimed to evaluate the impact of the protective and regenerative properties of artichoke preparation on the liver in three extract doses: 0.5; 1.0; and 1.5 g/kg bw/day. The evaluation was conducted by measuring the levels of oxidative stress parameters, including glutathione (GSH), glutathione S-transferases (GST), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), Trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx), paraoxonase 1 (PON1), SH- group, nitrosylated protein (RSNO), as well as such liver enzymes as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in the plasma and liver homogenate of rats with liver damage induced by CCl4 (1 mL/kg bw). Measurements were taken in plasma and liver homogenate. The results have demonstrated that the artichoke preparation, owing to its high antioxidative potential, exhibits protective and regenerative effects on the liver. This is supported by the observation of higher GSH levels in the plasma of rats treated with artichoke extract for two weeks before CCl4 exposure. Furthermore, the artichoke extract has shown regenerative properties, as evidenced by lower ALT, AST, and SOD activity in the group treated with artichoke extract after CCl4 exposure. These findings suggest that the in vivo administration of artichoke preparation may be beneficial for the protection and regeneration of the liver.

Lactobacillus intestinalis/Lactobacillus rhamnosus protects against AFB1-induced liver damage: involvement of intestinal mucosal barrier

Aflatoxin B1 (AFB1) is a widely spread mycotoxin that poses a threat to the healthy to human and animals. The liver is the main target organ for AFB1-induced damage, primarily causing inflammatory injury and oxidative stress. When AFB1 enters the body, it can damage the intestinal barrier function, and its metabolites are transported to the liver. Therefore, the damage to the liver is closely associated with intestinal barrier impairment. Lactobacillus plays a crucial role in mitigating liver damage by improving the intestinal barrier function. In our previous report, we reported that Lactobacillus reduces liver damage caused by AFB1. However, it is still unclear how the intestinal barrier contributes to the protective effects of Lactobacillus against AFB1. To investigate the protective effects and intestinal barrier mechanisms of Lactobacillus intestinals /rhamnosus against AFB1-induced liver damage, we orally administered AFB1 and Lactobacillus intestinals/rhamnosus to male SD rats. Then the body weight, organ index, histopathological changes in the liver and gut, liver and kidney function indicators, intestinal mucosal barrier indicators, serum AFB1 content and inflammatory factors, liver oxidative stress index, and short-chain fatty acids content were analyzed. Our findings demonstrate that exposure to AFB1 resulted in changes in liver histopathology and biochemical functions, altered inflammatory response and oxidative stress, compromised the intestinal mucosal barrier, and induced the accumulation of inflammatory factor and inflammation in the liver. However, supplementation with Lactobacillus intestinals or Lactobacillus rhamnosus significantly prevented AFB1-induced liver injury, alleviated histopathological changes and hepatic injury by the maintenance of intestinal mucosal barrier integrity.

Red Rice Seed Coat Targeting SPHK2 Ameliorated Alcoholic Liver Disease via Restored Intestinal Barrier and Improved Gut Microbiota in Mice.

Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativa L.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid-ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.

Thyroid Dysfunction Induced by Fungicide Famoxadone Exposure Contributes to Nonalcoholic Fatty Liver Disease in Male Mice: In Vivo, In Vitro, and In Silico Studies.

Thyroid dysfunction has become a serious public health problem, which is considered a trigger of nonalcoholic fatty liver disease (NAFLD). Pesticide exposure could contribute to thyroid dysfunction and NAFLD, but the relationship between these factors remains unclear. In this study, the effects of subchronic famoxadone exposure on thyroid and liver at no observed adverse effect level (NOEL) related concentrations were investigated using in vivo, in vitro, and in silico models. Famoxadone caused hepatic steatosis, lipid metabolism disorder, and liver oxidative stress and induced NAFLD in male mice. The suppression of hepatic fatty acid β-oxidation was the key factor of NAFLD, which was highly associated with hypothalamic-pituitary-thyroid (HPT) axis hormones disorder. Famoxadone disrupted thyroid hormone biosynthesis by causing thyroid follicle aberrations and abnormal HPT axis-related gene expression. In vitro studies confirmed that famoxadone inhibited the transport of thyroxine (T4) into hepatocytes and the conversion of T4 to triiodothyronine (T3). In silico studies verified that famoxadone interfered with the binding of thyroid hormones to proteins mediating thyroid hormone transport, conversion, and activation. This study comprehensively reported the association between NAFLD and thyroid dysfunction caused by famoxadone, providing new perspectives for the health risk evaluation of pesticides with a similar structure in mammals.

Phenolics and Terpenoids Profiling in Diverse Loquat Fruit Varieties and Systematic Assessment of Their Mitigation of Alcohol-Induced Oxidative Stress.

To compare and investigate the phenolic compounds in the peel and flesh of loquat (Eriobotrya japonica) and evaluate their ability to protect against alcohol-induced liver oxidative stress, we employed a combination of ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry (HRMS) to qualitatively and quantitatively analyze 22 phenolics and 2 terpenoid compounds in loquat peel and flesh extracts (extraction with 95% ethanol). Among these, six compounds were identified for the first time in loquat, revealing distinct distribution patterns based on variety and tissue. Various chemical models, such as DPPH, FRAP, ORAC, and ABTS, were used to assess free radical scavenging and metal ion reduction capabilities. The results indicate that peel extracts exhibited higher antioxidant capacity compared with flesh extracts. Using a normal mouse liver cell line, AML-12, we explored the protective effects of loquat extracts and individual compounds against ethanol-induced oxidative stress. The findings demonstrate the enhanced cell viability and the induction of antioxidant enzyme activity through the modulation of Nrf2 and Keap1 gene expression. In a C57/BL6 mouse model of alcohol-induced liver damage, loquat extract was found to alleviate liver injury induced by alcohol. The restoration of perturbed serum liver health indicators underscored the efficacy of loquat extract in reclaiming equilibrium. The culmination of these findings significantly bolsters the foundational knowledge necessary to explore the utilization of loquat fruit extract in the creation of health-focused products.

Ameliorative effect of hesperidin against high dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats

BackgroundThe clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days.ResultsIn the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated.ConclusionsHesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term.

Assessment of Liver Antioxidant Profile in Plasmodium Berghei Infected Mice Treated with Curative Ethanol Leaf extract of Musa paradisiaca.

The increasing resistance to most antimalarial drugs suggests a need for better alternatives. This study evaluated in vivo antimalarial and liver antioxidant profile of dry plantain leaf extract (Musa paradisiaca) on mice infected with Plasmodium berghei. Six groups of ten mice each grouped as control, P. berghei, artesunate, and P. berghei infected mice were orally administered 250,500 and 1000mg/kg Musa paradisiaca leaf extract for 5 days. Blood smears were evaluated for parasitaemia on the 10th day and the mice sacrificed. Catalase, Malondialdehyde, protein, Glutathione peroxidase and reduced glutathione was estimated using Colorimetric, Biuret and spectrophotometric methods respectively with data analyzed using SPSS version 21. Catalase activity (umol/ml/mins) was 24.62 ± 0.99, 10.04 ± 0.50, 19.35 ± 0.38, 22.13 ± 0.00, 22.79 ± 0.00 and 23.66 ± 0.20 while Glutathione Peroxidase(u/l) was 332.34± 0.64, 205.22± 4.61, 218.26± 0.63, 310.59± 0.00, 305.20± 0.00. and 295.97± 0.02 at Control, P.berghei, artesunate, 250mg, 500mg and1000mg extracts. Glutathione (mM) was 1.60 ± 0.12, 0.64 ± 0.09, 1.06 ± 0.16, 0.72 ± 0.00, 0.92 ± 0.00 and 1.26 ± 0.08 while Malondialdehye (uM) was 16.93 ± 3.59, 61.65 ± 1.72, 27.80 ± 0.26, 36.90 ± 0.00, 34.30 ± 0.00 and 32.68 ± 0.27 and Protein(g/dl) was 22.37 ± 1.87, 7.91 ± 0.13, 11.78 ± 1.19, 11.79 ± 0.00, 13.20 ± 0.00 and 17.04 ±0.03 at control, P.berghei, artesunate, 250mg, 500mg and1000mg respectively. The study suggested that ethanolic extract of Musa paradisiaca reduced liver oxidative stress caused by P.berghei.

UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Lamiophlomis Herba against hepatic fibrosis

BackgroundLamiophlomis Herba (LH) is a valuable traditional medicinal plant found on the Qinghai-Tibetan Plateau that promotes blood circulation, removes blood stasis, and has antibacterial and anti-inflammatory properties. The main components of LH are iridoid glycosides, phenethyl alcohol glycosides, flavonoids, and polysaccharides. PurposeTo investigate the mechanism of the anti-liver fibrosis effects of LH and screen for its bioactive compounds. Study designScreening LH marker components and validating the LH anti-liver fibrosis mechanism. MethodsThe active ingredients of LH were identified using UPLC-Q-TOF-MS, and HotMap combined with principal components analysis (PCA) was used to screen for marker components. Network pharmacology and molecular docking techniques were used to predict the potential anti-fibrotic targets of LH. Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting were used for experimental validation and mechanistic studies. ResultsFifteen compounds that actively contributed to the cluster were identified as marker compounds. Acteoside, 8-O-acetyl shanzhiside methyl ester (8-O-ASME), Luteolin, Shanzhiside Methyl ester (SME), Loganin, Loganate were the main active components. Network pharmacology and molecular docking studies have shown that LH might improve liver fibrosis, inflammation, and oxidative stress, which might be related to key targets such as PTGS2, MAPK, EGFR, AKT1, SRC, Fn1, Col3a1, Col1a1, and PC-III. The results of ELISA, RT-PCR and western blot experiments showed that Acteoside, 8-O-ASME, Luteolin, SME, Loganin, Loganate, and the LH group could reduce the levels of fibronectin, Col1a1, Col3a1, α-SMA, Col-Ⅳ, LN, and PC-Ⅲ. ConclusionLH improves liver fibrosis induced by HSC-T6 cells and inhibits the deposition of extracellular matrix (ECM) in hepatocytes, resulting in a decrease in the degree of liver fibrosis and a good anti-liver fibrosis effect.

Serum and urine metabolomics study revealed the amelioration of Gynura bicolor extract on high fat diet-fed and streptozotocin-induced type 2 diabetic mice based on UHPLC-MS/MS

Type 2 diabetes mellitus (T2DM) has been the most prevalent disease and has become a serious public health threat worldwide. Gynura bicolor (Willd.) DC. (GB) contains a variety of nutrients and possesses numerous activities, which might benefit those with diabetes. The current study aimed to confirm the improvement of metabolic disorders and explore the potential mechanism of GB in high fat diet-fed (HFD) and streptozotocin (STZ)-induced T2DM mice. The aboveground sample of GB was extracted with alcohol, and identified by highperformance liquid chromatography (HPLC) and liquid chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis. HFD and STZ-induced T2DM mice were administrated with GB extract. Biochemical and histopathologic examinations were conducted, and metabolomics evaluation was performed in serum and urine. GB significantly reduced body weight and liver weight, reversed hyperlipidemia, hyperglycemia, insulin resistance, oxidative stress and inflammation, improved hepatic histopathological changes and lipid deposition and mitigated liver injury in T2DM mice. Serum and urine metabolomics demonstrated a variety of significantly disturbed metabolites in T2DM and these changes were reversed after GB administration, including 13S-hydroxyoctadecadienoic acid, arachidonic acid, L-Valine and so on. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the overlapping enriched pathways in the normal control group and GB group were identified, including linoleic acid metabolism, PPAR signaling pathway, protein digestion and absorption, biosynthesis of amino acids and so on. This study demonstrates that the ethanol extract of GB remarkably attenuates metabolic disorders and maintains the dynamic balance of metabolites in T2DM, providing a scientific basis for GB in the treatment of T2DM and metabolism diseases.

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review.

To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs (ATDs) in the treatment of hyperthyroidism. Eight databases and three trial registries were searched from inception until May 2023. Randomized controlled trials (RCTs) were included and meta-analysis was conducted using RevMan 5.4 and Stata 14.0. The Cochrane risk of bias (ROB) tool 1.0 and GRADE tool was used for quality appraisal. The findings from case reports using mono-JWXYS and pharmacological studies were summarized in tables. Thirteen RCTs with 979 participants were included. The majority of the included studies were assessed as high risk of bias in one ROB domain. Compared with ATDs, JWXYS plus ATDs resulted in lower free triiodothyronine (FT3) (MD = -1.31 pmol/L, 95% CI [-1.85, -0.76]; low-certainty), lower free thyroxine (MD = -3.24 pmol/L, 95% CI [-5.06, -1.42]; low-certainty), higher thyroid stimulating hormone (MD = 0.42 mIU/L, 95% CI [0.26, 0.59]; low-certainty), higher effectiveness rate of traditional Chinese medicine syndrome (RR = 1.28, 95% CI [1.08, 1.52]; low-certainty), lower goiter score (MD = -0.66, 95% CI [-1.04, -0.29]; very low-certainty), lower thyrotrophin receptor antibody (SMD = -0.44, 95% CI [-0.73, -0.16]; low-certainty) and fewer adverse events (AEs) (RR = 0.34, 95% CI [0.18, 0.67]; moderate-certainty). Compared with regular dosage of ATDs, JWXYS plus half-dose ATDs resulted in fewer AEs (RR = 0.24, 95% CI [0.10, 0.59]; low-certainty). Compared with ATDs in 1 trial, JWXYS resulted in higher FT3, lower goiter score and fewer AEs. Three case reports showed that the reasons patients sought TCM-only treatment include severe AEs and multiple relapses. Three pharmacological studies demonstrated that JWXYS restored Th17/Treg balance, lowered deiodinases activity, regulated thyroid cell proliferation and apoptosis, and alleviated liver oxidative stress in mouse or rat models. JWXYS may enhance the effectiveness of ATDs for hyperthyroidism, particularly in relieving symptoms and reducing AEs. Mono-JWXYS is not recommended except in patients intolerant to ATDs. The findings should be interpreted with caution due to overall high risk of bias. Further pharmacological studies with more reliable models are needed. https://www.crd.york.ac.uk/prospero/, identifier CRD42023394923.

Aralia saponin A isolated from Achyranthes bidentata Bl. ameliorates LPS/D-GalN induced acute liver injury via SPHK1/S1P/S1PR1 pathway in vivo and in vitro

ObjectiveAcute liver injury (ALI) refers to a disease in which the liver is affected by factors such as chemical substances, alcohol, and virus infection in a short time, resulting in damage to liver cells. Achyranthes bidentata Bl. with the hepatoprotective activity has attracted great attention. In this study, a pentacyclic triterpenoid (Aralia saponin A, AsA) was isolated from roots of Achyranthes bidentata Bl. and its anti-ALI activity, as well as the mechanisms, were investigated for the first time. MethodsAsA (10 or 20 mg/kg, i.g.) was administered over a period of 1 weeks, following which liver injury was induced by LPS (10 µg/kg)/D-GalN (700 mg/kg). H&E staining of liver, Aspartate amino transferase (AST), Alanine transaminase (ALT) and cytokines was employed to investigate ALI relevant features. The mitochondrial morphology and levels of mitochondrial membrane potential (MMP), oxidative stress balance, apoptosis, average fluorescence intensity of 2-DG, natural killer (NK) cells in liver tissues were determined to assess the oxidative stress damage and inflammatory injury. Transcriptomics and metabonomics analysis were employed to clarify the mechanisms. Additionally, the mRNA and protein expression levels of Sphingosine 1-phosphate (S1P), Sphingosine kinase-1 (SPKH1), Sphingosine 1 phosphate receptor 1 (S1PR1), Sphingosine 1 phosphate receptor 3 (S1PR3), TNF receptor associated factor 2 (TRAF-2), Phospho-NF- kappaB p65 (p-P65), NF- kappaB p65 (P65), Proto-oncogene ras (Ras), Ras-related C3 botulinum toxin substrate (Rac), Phospholipase C (PLC), Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), Interleukin 1β (IL-1β), Vascular cell adhesion molecule 1 (Vcam1), CC chemokine ligand-2 (Ccl2) were analyzed. The mediating role of SPHK1 in the observed effects caused by AsA was assessed by investigatin SPHK1 transfection silencing/overexpression against AsA in AML12 cells induced by LPS/D-GalN. ResultsAsA can ameliorate liver function, inflammation, mitochondrial structure and oxidative stress in the ALI model. Meanwhile, AsA led to downregulated expression of proteins associated with sphingolipid signaling pathway. Silencing of SPHK1 led to enhanced protective effects of AsA, while over-expression of SPHK1 led to degraded protective effects of AsA in LPS/D-GalN-induced AML12 cells, suggesting that ALI is regulated by active molecules of AsA by means of SPHK1 mediation. ConclusionsAsA can ameliorate LPS/D-GalN-induced ALI by inhibiting inflammation and oxidative stress via the SPHK1/S1P/S1PR1 pathway. In this way, a molecular justification is provided for AsA application in ALI treatment.

Oxidized Soybean Oil Evoked Hepatic Fatty Acid Metabolism Disturbance in Rats and their Offspring.

The oxidation of fats and oils is an undisputed subject of science, given the effect of oxidized fats and oils on food quality and safety. This study aimed to determine whether maternal exposure to oxidized soybean oil (OSO) causes lipid metabolism disorders in the liver and whether this lipid metabolism disorder can be transmitted to offspring or even worsened. A total of 60 female Sprague-Dawley (SD) rats were divided randomly into four groups in this study. Treatment groups received a pure diet of OSO with a peroxide value of 200, 400, or 800 mEqO2/kg, while the control group received fresh soybean oil (FSO). As for our results, OSO affected serum biochemical parameters in the maternal generation (F0) and induced liver histopathology changes, inflammation, and oxidative stress. Moreover, the expression of genes related to the liver X receptor α (LXRα)─sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway was changed. Similar trends were found in the livers of offspring on postnatal days 21 and 56. In conclusion, exposure to OSO during gestation and lactation can affect liver lipid synthesis. Additionally, it is detrimental to the development of the offspring's liver, affecting fatty acid metabolism and causing liver damage.

Environmentally relevant lead alters nuclear integrity in erythrocytes and generates oxidative stress in liver of Anabas testudineus: Involvement of Nrf2-Keap1 regulation and expression of biomarker genes.

Genotoxic and hepatotoxic effects of lead (Pb) on a freshwater fish, climbing perch (Anabas testudineus) were studied at an environmentally relevant concentration (43.3 ppm). The genotoxic potential of Pb was confirmed by micronucleus study, with increased frequencies of erythrocytic nuclear alterations like lobed, blebbed, notched, fragmented, and micronuclei were observed in erythrocytes in treated groups as compared to control. Inorganic Pb induces oxidative stress which is a consequence of elevated level of Reactive Oxygen Species. Hepatotoxicity was assessed both by the oxidative stress and cellular responses that emerged due to the toxic assault of Pb in the liver, the most important detoxifying organ. Upregulation of xenobiotic metabolizing enzyme like catalase was evident after 15, 30, and 90 days of exposure, and a profound effect was observed on 30th days. The level of lipid peroxidation and reduced glutathione was increased after Pb exposure. Histoarchitectural damages of liver were distinctly evident in treated fish. Western blot analysis confirmed the expressional alterations of stress-responsive marker proteins like Nrf2, Keap1, Hsp70, and Nqo1. Pb exposure resulted in increased expression of Hsp70, Nrf2, and Nqo1, whereas Keap1 was downregulated, suggesting the involvement of Nrf2-Keap1 regulation as a cytoprotective mechanism against Pb toxicity.

Zafirlukast protects against hepatic ischemia-reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways.

Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its relevant protective mechanism. Thirty-two male Wistar albino rats were randomly allocated to four groups: sham, IRI, ZFK, and ZFK+IR groups. ZFK was administered orally in a dose of 80mg/kg/day for 10 consecutive days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) levels, and gamma glutamyl transferase (GGT) activity were estimated. Liver tissues were used to assess oxidative stress biomarkers including malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx), and reduced glutathione (GSH) contents. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-33 (IL-33), in addition to apoptosis biomarkers, BCL2 associatedXprotein (Bax), B-cell lymphoma 2 (Bcl2) and galactine-9 (GAL9) proteins were also assessed. Western blot analysis was performed for vascular endothelial growth factor (VEGF) and fibrinogen expressions. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and SMAD-4 was done in addition to histopathological examination. Our study revealed that ZFK pre-treatment resulted in liver function restoration and oxidative stress correction. Moreover, inflammatory cytokines were significantly reduced and a remarkable reduction of apoptosis, angiogenesis, and clotting formation has been indicated. Additionally, a significant reduction in SMAD-4 and NF-kB protein expressions was observed. These results were supported by hepatic architecture improvement. Our findings revealed that ZFK possesses a potential protective effect against liver IR possibly through its antioxidant, anti-inflammatory and anti-apoptotic properties.