Liver Injury In Rat Model Research Articles

Gelable and Adhesive Powder for Lethal Non‐Compressible Hemorrhage Control

AbstractHemostatic powders are widely used in clinical and emergency situations but often exhibit low wet adhesion, cytotoxicity concerns, and do not work well for lethal non‐compressible hemorrhage. Here a new kind of gelable and adhesive powder (GAP) is developed, which integrates chitosan microspheres (CM), tetra‐armed poly(ethylene glycol) amine (Tetra‐PEG‐NH2), and tetra‐armed poly(ethylene glycol) succinimidyl succinate (Tetra‐PEG‐SS). Upon application to the wound site, the macroporous CM can rapidly absorb the interfacial liquids, and meanwhile, the hydrated GAP turns into hydrogel (crosslinking between Tetra‐PEG‐SS and CM/Tetra‐PEG‐NH2) with stable and robust adhesion to the wet tissue though covalent bonding. The in vitro and in vivo results suggest that the GAP with optimized formulation exhibits strong tissue adhesive, high burst pressure, and enhanced blood clotting ability, as well as excellent biocompatibility and on‐demand removal properties. A significantly improved hemostatic efficacy is demonstrated in the rat liver, spleen, and femoral artery injury models compared to that of the CM, commercial fibrin glue, and Yunnan Baiyao (YB). The GAP can also halt the severe bleeding from pig visceral organs. Overall, the proposed GAP has many advantages including good biocompatibility, rapid and effective hemostasis, low cost, and ease of use, making it as a promising hemostat for lethal non‐compressible hemorrhage control.

Depletion of S-adenosylmethionine induced by arsenic exposure is involved in liver injury of rat through perturbing histone H3K36 trimethylation dependent bile acid metabolism

Long-term exposure to arsenic, a common environmental pollutant, can induce various types of liver injury, but the mechanism and treatment measures remain unclear. This study constructed a rat model of arsenic-induced liver injury, with methyl group donor S-adenosylmethionine (SAM) supplementation and Rosa roxburghii Tratt juice intervention, to explore the epigenetic mechanism and intervention method of arsenic-induced liver injury from the perspective of hepatic bile acid metabolism. The results showed that arsenic exposure induced the accumulation of total bile acids (TBA) in the liver and serum of rats, and the abnormalities in liver function and liver histopathology. Arsenic reduced histone H3K36 trimethylation (H3K36me3) in the liver via consuming methyl group donor SAM. The reduction of H3K36me3 was involved in arsenic-induced bile acid accumulation by inhibiting the transcription of negative feedback regulators Fxr and Fgfr4 for hepatic bile acid synthesis. SAM supplementation reversed arsenic-induced bile acid accumulation and liver injury by reactivating H3k36me3-dependent transcription of Fxr and Fgfr4. Moreover, this study found that Rosa roxburghii Tratt juice could rescue arsenic-induced SAM consumption, recover H3K36me3-dependent negative feedback regulation of hepatic bile acid synthesis, and alleviate arsenic-induced bile acid accumulation and liver injury. In conclusion, arsenic exposure perturbed H3K36me3-dependent hepatic bile acid metabolism via depleting SAM, thereby inducing hepatic bile acid accumulation and liver injury, which was ameliorated by the supporting effect of Rosa roxburghii Tratt juice on SAM. This study contributes to understanding the mechanism of arsenic-induced liver injury from the perspective of SAM-dependent epigenetics, providing new insight into its prevention and treatment.

Glutamate dehydrogenase combined with ferrochelatase as a biomarker of liver injury induced by antituberculosis drugs.

To explore the potential value of serum glutamate dehydrogenase (GLDH), ferrochelatase (FECH), heme oxygenase-1 (HO-1) and glutathione-S-transferase-α (GST-α) as diagnostic biomarkers for liver injury caused by antituberculosis drugs. We established a rat model of isoniazide-induced liver injury and recruited 122 hospitalized tuberculosis patients taking antituberculosis drugs. We detected the concentration of GLDH, FECH, HO-1 and GST-α by enzyme-linked immunosorbent assay. GraphPad Prism8 and SPSS 26.0 were used for statistical analysis. In the rat model, serum GLDH concentration gradually increased during isoniazid (INH) administration, while serum FECH, HO-1 and GST-α concentrations significantly increased after INH administration was stopped. The receiver operating characteristic curve showed that the areas under the curve (AUCs) of serum GLDH and FECH for the diagnosis of anti-tuberculosis (TB) drug-induced liver injury (anti-TB-DILI) were 0.7692 (95% confidence interval [CI] 0.5442-0.9943) and 0.7284 (95% CI 0.4863-0.9705) and the diagnostic accuracies were 81.25% and 78.79%, respectively. In clinical research, the AUCs of GLDH and FECH were 0.9124 (95% CI 0.8380-0.9867) and 0.6634 (95% CI 0.5391-0.7877), and the optimal thresholds were 10.40 mIU/mL and 1.304 ng/mL, respectively. The diagnostic accuracy, specificity and positive predictive value (PPV) of GLDH were 82.61%, 79.38% and 47.22%. We performed a joint diagnostic test for GLDH and FECH. The diagnostic accuracy (90.43%), specificity (91.75%) and PPV (65.21%) of serial tests were better than for GLDH and FECH alone. GLDH in the diagnosis of liver injury induced by anti-TB drugs has high sensitivity, but low specificity and low PPV. The combination of GLDH and FECH could significantly improve the specificity, PPV and diagnostic accuracy, and reduce the false-positive rate of anti-TB-DILI.

Flexible dual-functionalized hyaluronic acid hydrogel adhesives formed in situ for rapid hemostasis

Hydrogel adhesives integrating both rapid and strong adhesion to blooding tissues and biocompatibility are highly desired for fast hemostasis. Herein, a flexible hyaluronic acid hydrogel adhesive is fabricated via photocrosslinking of the solution originating from dopamine-conjugated maleic hyaluronic acid (DMHA) in situ. The introduction of acrylate groups with high substitutions into the hydrogel matrix endows the adhesive with rapid gelation and strong tissue adhesion properties through photopolymerization. Moreover, the high substitution of catechol groups with unoxidized state can not only induce red blood cell aggregation and platelets adhesion but also adhere to wound tissue to further enhance hemostasis. Based on its bio-adhesion and procoagulant activity, the DMHA hydrogel formed in situ reveals superior hemostatic performance in the rat liver injury model and noncompressible hemorrhage model, and rabbit femoral artery puncture model, compared to commercial products (gauze, absorbable gelatin sponge) and oxidized DMHA (SMHA) hydrogel. Besides, the hydrogel exhibited good adaptability, biodegradability, and superior cytocompatibility as well as negligible inflammation. This hydrogel adhesive is a promising biological adhesive for hemorrhage control.

Euryale ferox stem-inspired anisotropic quaternized cellulose/xanthan-based antibacterial sponge with high absorbency and compressibility for noncompressible hemorrhage

Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.

Sumc (Rhus coriaria L.) fruit ameliorates paracetamol-induced hepatotoxicity

Sumac [Rhus coriaria L. (Anacardiaceae)] is a widely used spice in the Middle East. In this study, the hepatoprotective effects of sumac fruit were evaluated using a rat model of paracetamol-induced liver injury. The experimental design relies on the pretreatment of rats with intraperitoneal sumac extract followed by a toxic dose of paracetamol. Tissue alterations, serum levels of oxidative stress markers, as well as gene expression of immunomarkers were evaluated. Rats pre-treated with sumac displayed attenuated signs of toxicity. Upon paracetamol intoxication, sumac-pretreated animals showed a minimal increase in liver enzyme levels. In parallel, serum albumin and total protein levels were close to normal. Moreover, pretreated sumac animals had preserved hepatocyte morphology, whereas unprotected animals had necrotic deformations. Importantly, these effects were dose-dependent and comparable to the silymarin-treated positive control group. In conclusion, sumac extract offers a potential hepatoprotective regimen against xenobiotic-induced hepatotoxicity and for oxidative stress management.

Semi-Targeted Profiling of Bile Acids by High-Resolution Mass Spectrometry in a Rat Model of Drug-Induced Liver Injury.

Using a semi-targeted approach, we have investigated the effect of acetaminophen on circulating bile acid profiles in rats, including many known bile acids and potential isomeric structures, as well as glucuronide and sulfate conjugates. The chromatographic separation was based on an optimized reverse-phase method exhibiting excellent resolution for a complex mix of bile acids using a solid-core C18 column, coupled to a high-resolution quadrupole time-of-flight system. The semi-targeted workflow consisted of first assigning all peaks detectable in samples from 46 known bile acids contained in a standard mix, as well as additional peaks for other bile acid isomers. The presence of glucuronide and sulfate conjugates was also examined based on their elemental formulae and detectable peaks with matching exact masses were added to the list of features for statistical analysis. In this study, rats were administered acetaminophen at four different doses, from 75 to 600 mg/kg, with the highest dose being a good model of drug-induced liver injury. Statistically significant changes were found by comparing bile acid profiles between dosing levels. Some tentatively assigned conjugates were further elucidated using in vitro metabolism incubations with rat liver fractions and standard bile acids. Overall, 13 identified bile acids, 23 tentatively assigned bile acid isomers, and 9 sulfate conjugates were found to increase significantly at the highest acetaminophen dose, and thus could be linked to drug-induced liver injury.

Interpenetrating network expansion sponge based on chitosan and plasma for ultrafast hemostasis of arterial bleeding wounds

Preventing arterial hemorrhage by intervening within the first few minutes is critical to the patient's life. Hemostatic materials have been developed over the last decades to address this issue, nevertheless these materials alone do not contribute to improve the survival effects in many extreme conditions, which is usually caused by penetrating arterial bleeding wounds that are incompressible and deep arterial bleeding with irregularly shapes. It is well known that, after calcium ion stimulation, many intriguing changes occurred in the major components of plasma, including the activation of several coagulation factors, such as the conversion of fibrinogen to fibrin, prothrombin to thrombin, and so on. Therefore, we constructed an expansion sponge with interpenetrating network based on chitosan and plasma, while various activated coagulation factors in plasma were also loaded into the pore structure of chitosan sponges. The prepared CS-PG sponge is capable of providing a simpler and more efficient method for treating high-pressure arterial bleeding wounds, which includes three steps: Rapid sealing and adhension, Thrombin catalysis and Activated autocoagulation. As the next generation bioactive materials, compared to conventional hemostatic materials, CS-PG sponge demonstrated superior hemostatic characteristics in both rabbit femoral artery damage and rat liver injury models.

On the development of modular polyurethane-based bioelastomers for rapid hemostasis and wound healing.

Massive hemorrhage may be detrimental to the patients, which necessitates the advent of new materials with high hemostatic efficiency and good biocompatibility. The objective of this research was to screen for the effect of the different types of bio-elastomers as hemostatic dressings. 3D loose nanofiber sponges were prepared; PU-TA/Gel showed promising potential. Polyurethane (PU) was synthesized and electrospun to afford porous sponges, which were crosslinked with glutaraldehyde (GA). FTIR and 1H-NMR evidenced the successful synthesis of PU. The prepared PU-TA/Gel sponge had the highest porosity and water absorption ratio. Besides, PU-TA/Gel sponges exhibited cytocompatibility, negligible hemolysis and the shortest clotting time. PU-TA/Gel sponge rapidly induced stable blood clots with shorter hemostasis time and less bleeding volume in a liver injury model in rats. Intriguingly, PU-TA/Gel sponges also induced good skin regeneration in a full-thickness excisional defect model as revealed by the histological analysis. These results showed that the PU-TA/Gel-based sponges may offer an alternative platform for hemostasis and wound healing.

A wet-adhesive carboxymethylated yeast β-glucan sponge with radical scavenging, bacteriostasis and anti-inflammatory functions for rapid hemostasis

Local hemostats still face obstacles to efficiently achieving hemostasis and promoting wound healing. Herein, a series of multifunctional well-degradable hemostatic sponges based-on carboxymethylated yeast β-glucan (CMYG) were fabricated by lyophilization. The porous CMYG sponge not only could absorb blood quickly (44.12 g/g), but also possessed unexpected tissue adhesion (∼30 kPa), and it represented good biocompatibility in vitro on fibroblasts and red blood cells. Notably, compared with the commercial Celox™, the CMYG sponge achieved more rapid hemostasis and significantly reduced blood loss in liver injury rat models by rapid wound block. Interestingly, the developed sponge showed an outstanding effect on antioxidant, anti-infection, anti-inflammatory, and cell proliferation, which are beneficial for further wound repair. Overall, these results suggest that the CMYG sponge is a promising candidate for the clinical management of uncontrollable hemorrhage and the further development of wound dressing materials throughout skin defect repair.

Protective effects of liposomes encapsulating ferulic acid against CCl4-induced oxidative liver damage in vivo rat model.

Antioxidants are useful for the treatment of oxidative stress mediated liver damage. A naturally occurring antioxidant γ-oryzanol is rapidly hydrolyzed to its active hydrophobic metabolite, ferulic acid, inside the body. Limitations associated with the hydrophobicity of ferulic acid can be overcome by encapsulating in a liposomal formulation. As intravenously administered nanoparticles (including liposomes) can effectively reach the liver, such systems may be suitable drug delivery carriers to treat liver injury. In this study, we prepared a liposomal formulation of ferulic acid (ferulic-lipo) and examined its effects on liver damage induced by CCl4. Ferulic-lipo were ~100 nm in size and drug encapsulation efficiency was about 92%. Ferulic-lipo showed potent scavenging efficacy against hydroxyl radical compared to α-tocopherol liposomes. Ferulic-lipo significantly prevented CCl4-mediated cytotoxicity in human hepatocarcinoma cells. Furthermore, intravenous administration of ferulic-lipo significantly reduced alanine aminotransferase and aspartate amino transferase levels in a rat model of liver injury. CCl4-mediated reactive oxygen species generation in liver was also reduced by intravenous administration of ferulic-lipo. Hepatoprotective effects of ferulic-lipo were demonstrated by histological observation of CCl4-induced liver tissue damage. Therefore, ferulic-lipo exhibit potent antioxidative capacity and were suggested to be an effective formulation for prevention of oxidative damage of liver tissue.

Pharmacokinetic Assessment of Isoniazid and Acetylisoniazid in Carbon Tetrachloride-Induced Liver Injury Model in Wistar Rats.

N-acetyl transferase 2 (NAT2) polymorphism testing could not see the light of success as a biomarker tool in tuberculosis management. Additionally, the antitubercular treatment (ATT) drug's reintroduction regimen variations exist because of the scarcity of robust preclinical evidence on ATT drug metabolism. The experiment was planned to understand the pharmacokinetic (PK) behavior of isoniazid and acetylisoniazid (AcINH) in a Wistar rat model of acute liver injury induced by carbon tetrachloride (CCl4) and preclinical drug-induced liver injury (DILI) model induced with CCl4 + anti-Tuberculosis (TB) drugs together. Thirty rats were used for the experiment and were divided into five groups. All rats were administered a single 0.5 ml/kg CCl4 intraperitoneal injection on day 0 to induce an animal model of DILI. Group I rats received CCl4 alone. Groups II-V were started on additional gavage feedings of isoniazid (H) alone, H plus rifampicin (R), H plus pyrazinamide (Z), and H, R, and Z together, respectively, daily for 21 days subsequently. Isoniazid and AcINH PK assessment was accomplished on day 20 of continuous once-daily dosing. Liver function test (LFT) monitoring was done at baseline on days 1, 7, and 21. On the last day of experiments, all experimental rats were sacrificed. Three-week ATT administration sustained the CCl4-induced LFT changes. Area under the curve (AUC) values for isoniazid and AcINH were found to be 2.24 and 1.69 times higher in the H + R group compared with the CCl4 + H group, respectively (P < 0.05). Isoniazid and AcINH maximum concentration (Cmax) reached the highest, while isoniazid clearance reached the lowest in the H + R group. AcINH AUC increased by double in the CCl4 + Isoniazid+Rifampicin+Pyrazinamide (HRZ) group compared with the CCl4 + H group (P < 0.05). Biochemical, histological, and antioxidant changes were consistent with the new liver injury model's development. Rifampicin almost doubles up the isoniazid and AcINH exposure, in presence if DILI.

Pharmacokinetic Assessment of Pyrazinamide and Pyrazinoic Acid in Carbon tetrachloride-induced Liver Injury Model in Wistar Rats.

We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury.

Ameliorating Effects of Croton Bonplandianus Leaves against Gentamicin Induced Acute Liver and Kidney Injury: A Biochemical and Histopathological Investigation

The utilization of natural constituents for the treatment of various medical complaints is well established. The members of the Euphorbiaceae family, especially the Croton genus, are reported to be rich in diterpenoids and showing various biological activities. Many activities of Croton bonplandianus are still unfolded therefore, current study is designed to evaluate the ameliorative effects of aqueous extract of C. bonplandianus against gentamicin-induced liver and kidney injuries in rats. The aqueous extract of leaves (27-81 mg/kg) was administered to albino rats Wistar strain for eight days with concurrent administration of gentamicin (100 mg/kg) daily. The protective effect of the aqueous extracts on the liver was determined by liver function tests (SGPT, ALT, GGT, Bilirubin) and kidney functions were evaluated by assessment of plasma biomarkers including urea, creatinine, uric acid and electrolytes (sodium, potassium, chloride and bicarbonate). Histopathological studies of liver and kidney tissue were carried out by Hematoxylin and Eosin (H&amp; E) staining confirmation of the consequences. Significant alterations in liver and kidney tissues treated groups with aqueous extracts of leaves were obtained in lower doses (27-54 mg/kg). Similarly, serum levels of SGPT, ALT, GGT, bilirubin, creatinine, and urea in the treated group were significantly reduced (P &lt; 0.01) at similar doses, whereas no significant changes were founded in levels of ions and uric acids. The histological examination of the liver and kidney confirmed the biochemical changes in treated rats. The underlying results demonstrate the protective effect of aqueous leave extracts Croton bonplandianus on an acute liver and kidney injury rat model. The hepato and renal protective effects of C. bonplandianus are certainly due to the presence of diterpenoids flavonoids and polyphenols exhibiting free radical or oxygen scavenging activities. Keywords: Croton bonplandianus , gentamicin, histopathological studies, nephroprotective effect. https://doi.org/10.55463/issn.1674-2974.50.3.15

Biomedical properties and hemostatic efficacy of polyvinyl alcohol (PVA) based hydrogel in experimental rat liver injury model.

Bleeding is a leading cause of mortality and morbidity in the trauma and surgery field, using effective hemostatic agents can help us reduce bleeding especially in parenchymal hemorrhage. Nowadays polyvinyl alcohol (PVA) is known as a safe candidate for wound dressing and maybe a hemostatic agent. PVA-based hydrogel is a popular biocompatible material in the biomedical field especially when it has high water absorption. In this study, we investigated the PVA hydrogel's mechanical and biological properties as well as its hemostatic potential in parenchymal bleeding. PVA hydrogel had made by the freeze-thawing approach, we used PVA hydrogel in comparison to standard treatment to investigate hemostatic potency. Also, we performed MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) tests to survey PVA cellular toxicity. After an acute liver injury, two groups of 12 rats were treated with PVA hydrogel or standard treatment with sterile gauze. The results including the time and volume of bleeding, and the time and survival rate of the rats were measured and compared. We saw that PVA hydrogel was safe with no cellular toxicity in the MTT assay. Regarding efficacy, PVA hydrogel increased rats' survival after bleeding from 75% to 91.7%, and decreased bleeding time (p: 0.015), and bleeding volume (p: 0.03) compared to the control group. Polyvinyl alcohol is safe. It has good biological properties with no cellular toxicity and has a significant hemostatic effect and can be regarded in control of parenchymal hemorrhage.

Sex differences in the hepatotropic effects of antiulcer drugs and placenta cryoextract in an experimental rat liver injury model

Background/Aim: Sex-related variances in drug metabolism provide a foundation for refining treatment protocols for prevalent conditions based on the patient's sex. Tailoring treatment strategies based on sex is particularly noteworthy among patients with comorbid illnesses due to the potential for drug interactions and the impact of concurrent diseases on clinical outcomes. Aim of this study was to assess the hepatotropic effects of antiulcer drugs (esomeprazole, clarithromycin and metronidazole - E/C/M) and placenta cryoextract (CEP) within a simulated model of tetrachloromethane (CCl4 )-induced hepatitis combined with underlying ethanol-induced liver cirrhosis (EILC), with a focus on the role of subjects' sex. Methods: Using 112 male and female rats, the research explored the effects of different sex hormone levels. Chronic EILC was induced by administering a 50.0 % CCl4 oil solution (8 mL/kg) twice a week, combined with a 5.0 % ethanol solution, over 45 days. Total protein (TP) levels and alkaline phosphatase (AP) activity were measured spectrophotometrically. Results: The research findings indicate that the onset of EILC and the administration of E/C/M resulted in a significantly greater 10.8 % (p = 0.03) reduction in TP levels among females compared to males, without altering hormonal status. Introducing CEP led to a noteworthy (p &lt; 0.001) rise in TP levels, by 30.8 % in males and 33.9 % in females, in the context of EILC and E/C/M administration, while maintaining hormonal status. Among male rats, the most elevated AP activity was observed with excess testosterone propionate administration (5.0 [5.0; 5.9] mmol/L), while the lowest level was recorded in rats after testectomy, measuring 3.8 [2.5; 4.7] mmol/L, exhibiting a significant 20.8 % decrease (p &lt; 0.05) compared to male rats without hormonal status changes. In female rats, the study revealed that against the backdrop of EILC and E/C/M administration, the highest AP level was seen in ovariectomised females, reaching 5.8 [5.1; 6.2] mmol/L, reflecting a substantial 9.4 % increase compared to rats without hormonal status changes. Conclusions: The administration of CEP under similar experimental conditions led to the recovery of the liver's protein-synthesising function in both male and female rats. When female sex hormones were introduced to sham-operated female rats, a significant 20.8 % greater reduction in AP levels was observed. Additionally, gonadectomy led to a more pronounced decrease in this enzyme's levels in male rats compared to female rats, indicating the cytoprotective properties of female sex hormones.

Exploring the Effective Components and Mechanism of Action of Japanese Ardisia in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification.

Japanese Ardisia is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese Ardisia and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese Ardisia in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese Ardisia were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese Ardisia were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound-target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese Ardisia mainly involved DNA-binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE-RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese Ardisia. Molecular docking showed that quercetin and kaempferol have good binding to AKT1, IL6, VEGFA, and CASP3. Animal experiments demonstrated that Japanese Ardisia could increase the expression of AKT1 and decrease the expression of CASP3 protein, as well as IL-6, in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese Ardisia in the treatment of AIH. At the same time, the effectiveness of Japanese Ardisia in treating AIH was verified by animal experiments.

Vinegar-baked Radix Bupleuri enhances the liver-targeting effect of rhein on liver injury rats by regulating transporters.

This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury. The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays. VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein. VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.

Ameliorating Potential of Marketed Formulations Containing Prebiotics And Probiotics Against Carbon Tetrachloride-Induced Hepatotoxicity in rats

In the present work, two marketed formulations VELGUT® (combination of prebiotic and probiotics) and VIZYLAC® (probiotic only) were assessed for a protective effect against carbon tetrachloride-induced chronic liver injury model in rats. Rats were randomly divided into four groups. Normal Control (treated with normal saline) and CCl4 treated group (treated with 1 ml/kg intraperitoneal injection of CCl4 once daily for 10 days followed by twice a week up to 49 days). Test groups composed of the oral treatment of VELGUT (1 mg kg-1) along with CCl4 (T1) and oral treatment of VIZYLAC (4 mg kg-1) along with CCl4. CCl4 treatment in the test group was similar to group 2. At the end of the treatment, various serum biochemical parameters like Alanine aminotransferase (ALT), Aspartate Aminotransferase, (AST), Alkaline Phosphatase (ALP), direct bilirubin, total protein, and albumin levels were measured. Serum cholesterol, glucose and malondialdehyde (MDA) levels were also measured. A small piece of the liver was collected to perform histopathological studies. Serum AST, ALT, ALP, and direct bilirubin were found to be significantly lower as compared to CCl4 intoxicated rats. The level of total protein and albumin was improved. The level of MDA, glucose and cholesterol was improved as compared to CCl4 treated group.

Preparation of methacrylated hyaluronate/methacrylated collagen sponges with rapid shape recovery and orderly channel for fast blood absorption as hemostatic dressing

Uncontrolled hemorrhage of deep, narrow, and non-compressible perforating wounds is responsible for many trauma deaths. In this study, a rapid hemostatic sponge with an orderly channel based on methacrylated collagen (ColMA) was prepared via directional freeze-drying technology. The methacrylated hyaluronate (HAMA) was added to further enhance the mechanical properties of the sponge. The sponge presents excellent mechanical strength, rapid shape recovery, and absorption speed, which was faster than those of many reported natural polymer hemostatic sponges. Moreover, ColMA/HAMA sponge showed much better blood-clotting capacity and superior hemostasis performance than commercially available collagen sponges in vitro and in the rat-liver injury model. This study demonstrated a feasible strategy to construct the rapid hemostatic sponge with an orderly channel for the deep and non-compressible perforating wound.