Oxidative Stress In Liver Research Articles

Dendrobium nobile Lindl. alkaloids protect CCl4-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux.

Dendrobium nobile Lindl. alkaloids (DNLA) are considered important active ingredients of Dendrobium, which have a variety of pharmacological functions. Recent studies indicate that DNLA has beneficial activity in acute liver injury. However, the specific mechanism by which DNLA produces liver protective effects is stills unclear. This study was designed to determine whether regulation of autophagy is involved in the mode of action of DNLA in liver protection. Using CCl4-induced acute liver injury (ALI) and cell culture models, the molecular mechanism of DNLA-mediated autophagy regulation was studied. The results showed that DNLA significantly improved CCl4-induced liver damage and oxidative stress, which was confirmed in AML-12 cells. DNLA promoted autophagy in cells treated with CCl4, manifested by reduced protein expressions of p62 and LC3-II. Fluorescence imaging showed a decrease in the number of autophagosomes in AML-12 cells transfected with mCherry-GFP-LC3B. In addition, DNLA inhibited lysosomal membrane permeabilization by upregulating lysosomal associated membrane protein-1 (LAMP1), thereby promoting autophagy, preventing CCl4-induced mitochondrial dysfunction, and reducing the production of mitochondrial reactive oxygen species (ROS). While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl4 induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage.

Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis.

Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota

BackgroundIndividuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment.MethodsFifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels.ResultsLGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL.ConclusionLGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.

Maternal Dietary Improvement or Leptin Supplementation During Suckling Mitigates the Long-Term Impact of Maternal Obesogenic Conditions on Inflammatory and Oxidative Stress Biomarkers in the Offspring of Diet-Induced Obese Rats

This study investigates the impact of maternal nutrition during lactation on inflammation and oxidative stress in the offspring of diet-induced obese rats, along with the potential benefits of leptin supplementation during suckling. Dams were fed either a standard diet (SD), a western diet (WD) before and during gestation and lactation (WD-dams), or a WD switched to an SD during lactation (Rev-dams). Offspring were supplemented with leptin or vehicle during suckling and then fed an SD or WD until four months. Offspring of the Rev-dams exhibited improved metabolic indicators, including lower body weight, reduced plasma levels of TNF-alpha, a higher adiponectin/leptin (A/L) ratio, enhanced liver antioxidant defenses, and decreased inflammation markers in white adipose tissue (WAT) compared to WD-dams, with sex differences. Leptin supplementation further modulated these markers, reducing oxidative stress in liver and inflammation in WAT and liver (e.g., hepatic Tnfa expression decreased by 45% (males) and 41% (females) in the WD group on an SD), and improving the A/L ratio, with effects varying by maternal conditions and sex. In conclusion, this study underscores the importance of maternal nutrition and leptin intake during suckling in shaping long-term metabolic and inflammatory health in offspring, offering strategies to mitigate the adverse effects of maternal obesity on future generations.

Effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet

IntroductionThe aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet.MethodsA total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks.ResultsResults showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01) .DiscussionThis study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens.

Metabolic Effects of Loquat Juice (Eriobotrya japonica Lindl Mkarkeb Variety) on Lipid Homeostasis, Liver Steatosis, and Oxidative Stress in Hyperlipidemic Mice Fed a High-Fat–High-Fructose Diet

Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg−1 or fenofibrate at 4 mg·kg−1. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues.

Total minor ginsenosides exert anti-fatigue effects via antioxidant, anti-inflammatory, regulating gut microbiota and serum metabolism

Minor ginsenosides have demonstrated notable anti-fatigue capabilities. The aim of this study was to investigate the anti-fatigue mechanisms of total minor ginsenosides (TMGs) derived from a process involving probiotic fermentation and high-pressure steam treatment. The fatigue model was established in BALB/c male mice using weight-bearing swimming and TMGs were administered by orally at a dosage of 200 mg/kg for four weeks. The anti-fatigue mechanisms of TMGs were explored by assessing liver oxidative stress, skeletal muscle inflammation markers, as well as their impact on gut microbiota and serum metabolism. The results indicated that TMGs could significantly increase the levels of SOD, CAT, ATP and Na+-K+-ATPase and enhance the antioxidant capacity by modulating the PGC-1α/KEAP1/NRF2/HO-1 pathway. Meanwhile, TMGs reducing the levels of inflammatory factors TNF-α, IL-1β and IL-6 and inhibited inflammation by modulating the AMPK/TORC2/CREB/PGC-1α pathway. TMGs also regulated the gut microbiota, increasing the abundance of probiotic bacteria and the content of short-chain fatty acids (SCFAs) in the cecum. Serum metabolomics analyses have shown that TMGs can significantly affect the serum metabolic profile of fatigue model mice, regulating metabolic markers through affecting anti-fatigue-related metabolic pathways. In conclusion, TMGs exerted significant anti-fatigue effects through antioxidant and anti-inflammatory effects, and alleviate fatigue by regulating gut microbiota and serum metabolism.

Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.

Protective Effect and Mechanism of L-Theanine on Acute Alcoholic Liver Injury in Mice.

Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L-theanine (LTA), a compound found in tea leaves, mitigates the AALI-induced liver oxidative stress and inflammation. However, its relationship with alcohol metabolism and its liver-protective mechanism remains unexplored. This study investigates the protective mechanisms of LTA against AALI in mice. The results demonstrate that LTA mitigates liver tissue damage and reduces the serum levels of aspartate aminotransferase and alanine aminotransferase, and liver levels of triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, LTA enhances the activity of ethanol-metabolizing enzymes and decreases ethanol and acetaldehyde serum levels. Mechanistically, LTA accelerates alcohol metabolism by upregulating the hepatic expression of ADH6, ALDH1B1, ALDH2, CAT, and ACSS1 mRNA and protein in AALI mice, LTA downregulates the expression of CYP2E1 mRNA and protein and promoting antioxidative activities thus reducing the accumulation of ROS. This attenuated inflammation by inhibiting the phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα) and downregulating the hepatic expression of NF-κB p65, TNF-α, IL-1β, IL-6 mRNA, and protein. LTA is a beneficial dietary supplement that protects against AALI by modulating alcohol metabolism and the TNF-α/NF-κB pathway.

Effect of rapamycin on hepatic metabolomics of non-alcoholic fatty liver rats based on non-targeted platform

Rapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism.

Activation of Nrf2 and FXR via Natural Compounds in Liver Inflammatory Disease.

Liver inflammation is frequently linked to oxidative stress and dysregulation of bile acid and fatty acid metabolism. This review focuses on the farnesoid X receptor (FXR), a critical regulator of bile acid homeostasis, and its interaction with the nuclear factor erythroid 2-related factor 2 (Nrf2), a key modulator of cellular defense against oxidative stress. The review explores the interplay between FXR and Nrf2 in liver inflammatory diseases, highlighting the potential therapeutic effects of natural FXR agonists. Specifically, compounds such as auraptene, cafestol, curcumin, fargesone A, hesperidin, lycopene, oleanolic acid, resveratrol, rutin, ursolic acid, and withaferin A are reviewed for their ability to modulate both the FXR and Nrf2 pathways. This article discusses their potential to alleviate liver inflammation, oxidative stress, and damage in diseases such as metabolic-associated fatty liver disease (MAFLD), cholestatic liver injury, and viral hepatitis. In addition, we address the molecular mechanisms driving liver inflammation, including oxidative stress, immune responses, and bile acid accumulation, while also summarizing relevant experimental models. This review emphasizes the promising therapeutic potential of targeting both the Nrf2 and FXR pathways using natural compounds, paving the way for future treatments for liver diseases. Finally, the limitations of the clinical application were indicated, and further research directions were proposed.

Pueraria lobata extract ameliorates D-GalN/LPS-induced liver injury through targeting TLR4/NF-κB signalling pathway and regulating gut microbiota

AbstractKudzu root (Pueraria lobata), known for its dual role as a medicinal herb and food ingredient, has proven anti-inflammatory and antioxidant properties. This study explored the effects of P. lobata extract (PLE) on D-galactose/lipopolysaccharide (D-GalN/LPS)-induced liver inflammation and oxidative stress in mice, along with its impact on gut microbiota. The in vivo studies indicated that PLE significantly reduced hepatic levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6) and increased the anti-inflammatory cytokine interleukin-10. It also lowered serum aspartate aminotransferase and alanine aminotransferase activities, indicating reduced liver damage, and mitigated oxidative stress by decreasing malondialdehyde levels while restoring superoxide dismutase activity. Western blot analysis revealed that PLE inhibited the phosphorylation of NF-κB pathway proteins (p65 and IκB) and suppressed TLR4 expression, highlighting its role in this inflammatory pathway. Additionally, PLE ameliorated D-GalN/LPS-induced gut microbiota dysbiosis, reducing Proteobacteria abundance and promoting beneficial genera such as Lactobacillus, Bifidobacterium, and Akkermansia. These findings suggest that PLE protects against liver inflammation and oxidative stress, while improving gut microbiota composition, offering potential therapeutic strategies for liver-related diseases.

High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis.

Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.

The effect of anti‐imbalance on glycolipid metabolic homeostasis via the liver–gut axis intervened by 3′‐sialyllactose in obese mice

AbstractSialic acid could ameliorate disorders associated with glycolipid metabolism. 3′‐Sialyllactose (3′‐SL), a type of oligosaccharide, contains sialic acid. We examined the effects of 3′‐SL on glycolipid metabolism in obese mice with high fat diet and explore the underlying mechanisms. A total of 160 male C57BL/6J mice were fed with high‐fat diet for 8 weeks to construct obese mice model. Sixty successfully constructed obese mice were randomly divided three 3′‐SL dosage‐dependent groups, one free sialic acid N‐acetylneuraminic acid (Neu5Ac) group, and one blank control group. Each group of obese mice (n = 12) was continuously supplemented by 3′‐SL or Neu5Ac for 10 weeks. Ten‐week 3′‐SL supplementation and Neu5Ac supplementation both yielded remarkedly lower body weight, reduced fat content, increased energy expenditure and active daily exercises with improved glycolipid biomarkers, and attenuated proinflammation. 3′‐SL increased the colonic abundances of Akkermansia, Lactobacillus, and Solibacillus and reduced those of Enterobacter and Enterococcus. Changes were also observed in colonic and liver transcript and metabolites, which were mainly enriched in glycolipid metabolism, ameliorated immune function, and mitigated inflammatory signals, autophagy, bile acid metabolism, and insulin resistance. Akkermansia and Solibacillus were significantly associated with changes in colonic metabolites and transcriptome genes. The liver bile component and glucose metabolites were significantly correlated with transcriptional gene expression in the aforementioned differential pathways. Therefore, 3′‐SL can enhance the gut microbiota, regulate intestinal immunity and bile acid metabolism, reduce liver oxidative stress and autophagy processes, alleviate chronic inflammation levels, and improve islet function and lower blood sugar levels by acting through the gut–liver axis.

Curcumin's Protective Role in Heatstroke‐Induced Acute Liver Injury: Targeting Pyroptosis and Enhancing SIRT1 Expression

AbstractHeatstroke (HS) is a severe systemic condition that significantly impacts organ function, with the liver being particularly vulnerable. Sirtuin 1 (SIRT1), a crucial deacetylase, is implicated in various diseases' pathophysiology. Curcumin, a natural polyphenol, has been shown to modulate SIRT1 activity, offering therapeutic benefits. This study explores the impact of HS on hepatic SIRT1 expression and the protective mechanisms of curcumin against HS‐induced hepatic injury. Male C57BL/6 mice are divided into control and curcumin pretreatment groups, subjected to HS induction, and assessed for liver injury biomarkers, oxidative stress, and inflammatory cytokines. Results indicate that HS downregulates SIRT1, leading to liver damage and systemic inflammation. Curcumin pretreatment dose‐responsively attenuates these effects, with the highest dose providing optimal protection, potentially through SIRT1 restoration. The findings suggest that curcumin's hepatoprotective role in HS may be mediated by upregulating SIRT1, highlighting its therapeutic potential in heatstroke‐related liver damage.

Ameliorative effects of Penthorum chinense Pursh on insulin resistance and oxidative stress in diabetic obesity db/db mice.

Penthorum chinense Pursh (PCP), a medicinal and edible plant, has been reported to protect against liver damage by suppressing oxidative stress. Type 2 diabetes mellitus (T2DM) is associated with liver dysfunction and oxidative stress. In the present study, we aim to investigate the hypoglycemic effect of PCP on db/db mice and further explore the underlying mechanisms. Thirty-two db/db mice were randomized into four groups, including a diabetic model control group (MC) and three diabetic groups treated with low (LPCP, 300 mg/kg/d), medium (MPLP, 600 mg/kg/d), and high doses of PCP (HPCP, 1200 mg/kg/d), and the normal control group (NC) of eight db/m mice were included. Mice in the NC and MC groups received the ultrapure water. After four weeks of intervention, parameters of fasting blood glucose (FBG), insulin resistance (IR), blood lipid levels, hepatic oxidative stress, and enzymes related to hepatic glucose metabolism were compared in the groups. PCP administration significantly reduced FBG and IR in diabetic db/db mice, and improved hepatic glucose metabolism by increasing glucose transporter 2 (GLUT2) and glucokinase (GCK) protein expression. Meanwhile, PCP supplementation ameliorated hepatic oxidative stress by decreasing malonaldehyde content and increasing the activities of superoxide dismutase and glutathione peroxidase in db/db mice. Furthermore, PCP treatment reduced obesity and food intake in db/db mice, and improved dyslipidemia demonstrated by increasing high-density lipoprotein cholesterol (HDL-C) while decreasing total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (HDL-C). All doses of PCP treatment decreased the values of LDL-C/HDL-C in a dose-response relationship. PCP significantly alleviated hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity, inhibited hepatic oxidative stress, and enhanced hepatic glucose transport in T2DM mice. Based on the above findings, the hypoglycemic effect of PCP may be attributed to the activation of the GLUT2/GCK expression in the liver and the reduction of hepatic oxidative stress.

Evaluating the effectiveness of Toxfin and Novasil as dietary aflatoxin-binding agents in broilers for sustaining hepatic antioxidant capacity and intestinal health status during aflatoxin B1 exposure.

To assess the efficacy of Toxfin and Novasil as aflatoxin-binding agents in broilers exposed to aflatoxin B1 (AFB1) from 11 to 30days, 288 mixed-sex Ross 308 broiler chickens were randomly allocated to four dietary groups: control feed, control feed + 0.25mg/kg AFB1, AFB1 feed + 0.3% Toxfin, and AFB1 feed + 0.3% Novasil. The evaluation encompassed growth performance for the grower (11-20days), finisher (21-30days), and overall (11-30days) phases, carcass characteristics, serum biochemical components, liver function enzymes, hepatic antioxidant capacity, AFB1 residue in the liver and kidney, and ileal morphology at 30days, and apparent nutrient digestibility during 29-30days. Exposure to AFB1 significantly resulted in reduced growth efficiency, lowered carcass yields, liver hypertrophy, impaired metabolic and hepatic functions, liver oxidative stress, disrupted ileum architecture, diminished nutrient digestibility, and accumulated AFB1 in the liver and kidney. Conversely, supplementation of Toxfin or Novasil significantly augmented body weight gain (BWG) and reduced feed conversion ratio (FCR) during the finisher and overall phases, elevated BWG in the grower phase, heightened levels of glucose, hepatic protein, and glutathione peroxidase, declined malondialdehyde content, improved apparent metabolizable energy, and lowered AFB1 residues in the liver and kidney. Furthermore, Toxfin inclusion significantly reduced FCR during the grower phase, enhanced European production efficiency factor during the grower and overall phases, augmented dressing percentage, declined proportional liver weight, elevated concentrations of total protein, albumin, and total antioxidant capacity, heightened villus surface area, and boosted crude protein digestibility. To conclude, incorporating 0.3% Toxfin into broilers' feeds confers a more effectual safeguard than Novasil against the deleterious consequences of AFB1 exposure.

Therapeutic efficacy of praziquantel loaded-chitosan nanoparticles on juvenile Schistosoma mansoni worms in murine model

Praziquantel (PZQ) is the standard treatment for schistosomiasis; however, it is poorly effective on immature and juvenile worms. The present study aimed to evaluate the therapeutic efficacy of praziquantel loaded-chitosan nanoparticles (PZQ-CSNPs) on the 25 days old juvenile Schistosoma mansoni worms compared to PZQ and chitosan nanoparticles (CSNPs). It was conducted on 60 Swiss albino mice, including 20 control and 40 experimental mice. The control groups included healthy uninfected and infected non-treated mice. The experimental groups included mice infected treated on the 25th day with 400 mg/kg PZQ, 30 mg/kg CSNPs, 100 mg/kg, and 400 mg/kg PZQ-CSNPs. The results revealed that PZQ-CSNPs (100, 400 mg/kg) gave the best results substantiated by a remarkable decrease in worm burden, egg count, granuloma count and size compared to the other treatments. Moreover, it induced severe deformations of worm morphology regarding oral and ventral suckers, tegument, spines distribution, and male gynaecophoric canal. Liver enzymes and oxidative stress markers were significantly decreased while antioxidant activities were increased compared to control and other treated groups. In conclusion, a single dose of PZQ-CSNPs had significant antischistosomal therapeutic effects during the early maturation phase.

Qiwei Jinggan Ling regulates oxidative stress and lipid metabolism in alcoholic liver disease by activating AMPK

BackgroundAlcoholic liver disease (ALD) is a severe public health concern worldwide and there is still a lack of effective treatments. Qiwei Jinggan Ling (QJL) has protective effects against various liver injuries, but its pharmacological action on ALD has received little attention. PurposeTo investigate the effect and mechanism of QJL on ALD in vivo and in vitro. MethodsIn vivo, an ALD mouse model was established by alcohol combined with a high-fat diet (HFD) and treated with QJL. Biochemical indicators, HE staining, and Oil Red O staining were employed to assess hepatic oxidative stress, steatosis, and alcohol metabolism. RNA sequencing analysis was performed, and the results were verified by qRT-PCR and Western blot to elucidate the hepatoprotective mechanism of QJL. In vitro, HepG2 cells were co-stimulated with NaOA (sodium oleate) and EtOH (ethanol), followed by intervention with Compound C (CC, AMPK inhibitor) and QJL-containing serum. Oil Red O, BODIPY (boron-dipyrromethene), and ROS (reactive oxygen species) staining were applied to validate the efficacy and mechanism of QJL-containing serum. The expression of AMP-activated protein kinase (AMPK) pathway-related factors was analyzed through qRT-PCR and Western blot for additional corroboration. Moreover, the key pharmacodynamic components of QJL were identified by UPLC-MS/MS and molecular docking. ResultsIn vivo, QJL ameliorated liver structural disorders, steatosis, oxidative stress, and impaired alcohol metabolism, as indicated by biochemical indicators and histopathological assays. RNA sequencing analysis revealed that QJL reversed the expression of genes related to alcohol metabolism, fatty acid metabolism, and cholesterol metabolism. The results of qRT-PCR and Western blot were in line with those of RNA sequencing. Furthermore, it was discovered that QJL significantly upregulated the expression of p-AMPK and downregulated the expression of sterol regulatory element binding transcription factor 1 (SREBP-1c). In vitro, biochemical indicators and staining assays demonstrated that QJL-containing serum inhibited lipid accumulation and oxidative stress. The qRT-PCR and Western blot analysis revealed that QJL-containing serum markedly enhanced the expression of p-AMPK and carnitine palmitoyltransferase 1a (Cpt1a), while suppressing the expression of SREBP-1c, fatty acid synthase (Fasn), and acetyl-coenzyme A carboxylase 1 (ACC-1). However, CC inhibited the above pharmacological activities of QJL-containing serum. Additionally, (2S)-Liquiritigenin, Glycyrrhetinate, Isovitexin, Taxifolin, and Yohimbine were proved to be the key active components of QJL. ConclusionQJL had the potential to be a therapeutic drug for ALD by activating the AMPK pathway, thereby regulating lipid metabolism and inhibiting oxidative stress.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.