Significant Hepatoprotective Effect Research Articles

Effects of Baccharis dracunculifolia DC on an Innovative Animal Model of Cardiometabolic Syndrome

Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions are treated independently. This approach may be partially due to limited preclinical models to mimic the clinical conditions of CMS. Therefore, our study aims to present an innovative animal model of cardiometabolic syndrome and evaluate the effects of Baccharis dracunculifolia on the set of clinical alterations associated with the condition. Methods: Female Wistar rats were induced to develop diabetes, fed a cholesterol-enriched diet, and exposed to the smoke of 9 cigarettes/day for 6 weeks. During the last 2 weeks, the rats were treated with vehicle, B. dracunculifolia (30, 100, and 300 mg/kg), or a combination of simvastatin and insulin. At the end of the treatment, plasma lipid levels were measured, and the liver was analyzed histologically for hepatic lipid quantification and oxidative stress assessment. Results: Phytochemical analysis revealed seven phenolic acids and six flavonoids in the extract. B. dracunculifolia showed significant hepatoprotective effects, reducing AST and ALT levels and lowering both plasma and hepatic lipid levels. The extract also reversed hepatic steatosis and demonstrated antioxidant properties. Conclusions: These findings suggest that B. dracunculifolia may be a therapeutic option for the metabolic dysregulation present in CMS.

Oudemansiella radicata polysaccharides alleviated LPS-induced liver damage via regulating TLR4/NF-κB and Bax/Bcl-2 signaling pathways

The study was aimed to develop natural non-toxic substances to prevent LPS-induced liver damages and its complications. In present work, a pyranose polysaccharide of Oudemansiella radicata polysaccharides (ORP) with typical characteristics of α-type glycosidic linkage was isolated from the O. radicata fruiting body by physico-chemical analysis, and the potential impact against LPS-induced liver damage were performed in mice model. The results demonstrated that ORP showed significant hepatoprotective effects through its potential anti-oxidative, anti-inflammatory and anti-apoptosis activities via regulating the TLR4/NF-κB and Bax/Bcl-2 signaling pathway, independently or synergistically. These findings had established a robust theoretical framework for promoting the comprehensive utilization of ORP as supplements in the development of functional foods or drugs targeting LPS-induced liver damage and its associated complications.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Alcoholic Hepatitis: A Paradigm shift of Prevention and Treatment Analyzed at Cellular level by Histo/Pathological Micrometric Assessment.

Objective: To evaluate role of Vitamin C and Naproxen in Alcohol-induced liver toxicity by micrometric technique (hepatocyte count, size and nuclear diameter) in albino rats.Methodology: This experimental interventional study was conducted at the sheikh Zayed medical college and hospital Rahim yar khan from December 2022 to March 2023. 60 albino rats with equal gender distribution were selected based on the random probability sampling technique and placed in three groups of 20, again with an equal gender distribution (1:1). Group A (positive control) was given purified Ethanol for 10 days., Group B was given Vitamin C and NaproxenProphylaxis for 7 days and later intoxicated with Ethanol for 10 days and Group C was simultaneously Administered Vitamin C, Naproxen, and Ethanol for 10 days. The hepatocyte count, size and nuclear diameter of all the groups were recorded by micrometric technique using ocular and stage micrometric scales. Data analysis was conducted using SPSS 24.0 and P-Value of ≤0.05 considered Statistically Significant.Results: Group A animals experienced decreased number of hepatocyte count, increase in size of cell and decrease in nucleus size; Group B showed similar picture as group “A” but less in intensity and Group C showed nearly normal hepatic architecture with hepatocyte count, size and nuclear size close to normal ranges.Conclusion: The anti-oxidative and anti-inflammatory effects of Vitamin C and Naproxen demonstrated significant hepatoprotective effects on liver histologic architecture, providing safety from alcohol-induced liver injury. Keywords: Naproxen, Prophylaxis, liver toxicity, alcoholic liver disease, vitamin C.

Ursolic Acid Regulates Immune Balance, Modulates Gut Microbial Metabolism, and Improves Liver Health in Mice.

Ursolic acid (UA) has demonstrated significant immunomodulatory and hepatoprotective effects; however, the underlying mechanisms remain unclear. This study aims to analyze the impact of UA on the gut microbiome, metabolome, and liver transcriptome, investigate UA's role in maintaining gut immune homeostasis and liver health, and evaluate the potential contributions of gut microbes and their metabolites to these beneficial effects. Our findings indicate that UA enhances immune balance in the jejunum, fortifies intestinal barrier function, and promotes overall gut health. UA modulates the intestinal microbiota and its metabolic processes, notably increasing the abundance of beneficial bacteria such as Odoribacter and Parabacteroides, along with their metabolites, including ornithine and lactucin. Additionally, UA inhibits the expression of interleukin-1 receptor 1 (IL1R1) and calcium (Ca2+) voltage-gated channel auxiliary subunit beta 2 (CACNB2) while enhancing the synthesis pathways of retinol and ascorbic acid, thereby exerting a protective influence on liver function. In summary, UA enhances intestinal immune homeostasis and promotes liver health, with these advantageous effects potentially mediated by beneficial bacteria (Odoribacter and Parabacteroides) and their metabolites (ornithine and lactucin).

Polyherbal Formulation Development, Evaluation and Pharmacological Screening for Hepatoprotective Activity.

The current research work investigates the hepatoprotective action of polyherbal formulation prepared from ethanolic extracts of Azadirachta indica A. Juss, Moringa oleifera Lam, Cymbopogon citrates (DC.) Stapf, Tinospora cordifolia (Thumb.) Miers, Ricinus communis L., against experimental hepatotoxicity. The World Health Organization (WHO) is promoting herbal remedies derived from traditional medicinal plants in several countries. The main goal of this investigation was to create and evaluate the polyherbal formulation to protect albino Wistar rats against the hepatotoxic effects of CCl4. Three potential suspensions, polyherbal formulations A, B, and C, were formulated by trituration method using ethanolic extracts of specific medicinal plant components with different sodium carboxy methyl cellulose concentrations 1, 1.5, and 2%, respectively and evaluated the same for both certain physiochemical parameters, including organoleptic characteristics, pH, viscosity, sedimentation volume, redispersibility, density, specific gravity, zeta potential, and accelerated stability studies for three months and for hepatoprotective activity also. Evaluation parameters for Polyherbal Formulation-C have shown good results that met the specifications, with pleasant texture and appearance. Along with other physiochemical qualities, like pH, viscosity, flow rate and sedimentation, were all unchanged and showed significant hepatoprotective effects by reducing elevated serum enzyme levels SGOT, SGPT, ALP, total and direct bilirubin. It was discovered that each quality control parameter in the polyherbal suspension C formulation was thoroughly adequate and improved the recovery from hepatotoxicity caused by CCl4. These findings suggest that the produced polyherbal suspension C (containing ethanolic extracts of A. indica A. Juss, M. oleifera Lam, C. citrates (DC.) Stapf, T. cordifolia (Thumb.) Miers, R. communis L. may be stable, secure, and effective for use and exhibited notable hepatoprotective effects, possibly resulting from the combined impact of all these extracts.

Hepatoprotective Role of Aqueous Extract of Kasni Seeds in Alloxan-Induced Diabetic Mice

Background: Diabetes mellitus (DM) is a prevalent metabolic disorder characterized by chronic hyperglycemia, leading to various systemic complications, including liver damage. Traditional antidiabetic drugs are often associated with adverse effects, prompting interest in safer, natural alternatives like Kasni (Cichorium intybus) seeds, known for their hepatoprotective properties.Objective: This study aimed to evaluate the hepatoprotective effects of Kasni seed aqueous extract in alloxan-induced diabetic mice.Methods: Thirty-two male albino mice were divided into three groups: control, metformin-treated, and Kasni-treated. Diabetes was induced using alloxan monohydrate (150 mg/kg). The Kasni-treated group received 400 mg/kg of Kasni extract orally for 28 days. Blood glucose levels were monitored, and liver tissues were analyzed histologically to assess hepatocyte arrangement, central vein morphology, sinusoidal inflammation, and fatty globule presence.Results: The Kasni-treated group showed a significant reduction in blood glucose levels (140.2 ± 8.7 mg/dL) compared to the metformin group (180.4 ± 10.5 mg/dL) (p < 0.05). Histological analysis revealed restored hepatocyte arrangement, reduced fatty globules, and normalized central vein morphology in the Kasni-treated group.Conclusion: Kasni seed aqueous extract exhibits significant hepatoprotective effects in alloxan-induced diabetic mice, suggesting its potential as a natural therapeutic agent for managing liver complications in diabetes.

Lactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism

TGF-β1 activation of hepatic stellate cells (HSCs), transcriptional activator 3 (Stat3) activation and short chain fatty acids (SCFAs), metabolite of intestinal bacteria, is closely associated with hepatic fibrosis. Previous studies have shown that Lactucin has significant anti-inflammatory and hepatoprotective effects; however, the mechanism of Lactucin's role in liver fibrosis associated with SCFAs remains unknown. This study was intended to investigate whether effect of Lactucin on liver fibrosis was mediated by TGF-β1/Stat3 and SCFAs. We found that Lactucin induced apoptosis in HSC-T6 cells, and inhibition of nuclear translocation of Stat3 and p-Stat3. And Smad3 and TGF-β1 protein expression was significantly inhibited, while TLR4 and Smad7 protein expression was significantly enhanced. For in vivo experiments, we demonstrated that Lactucin alleviated liver fibrosis in mice, as evidenced by a reduction in inflammatory factors, collagen deposition, liver injury and fibrosis-related factors expression, especially the expression of Smad3 and TGF-β1 proteins was significantly suppressed and Smad7 protein expression was significantly increased in the liver. In addition, the levels of acetic acid, butyric acid and valeric acid in the intestine of Lactucin-treated mice were significantly higher than those in the intestine of liver fibrosis mice. In conclusion, based on the results of in vivo and in vitro experiments, preventive mechanism of Lactucin against liver fibrosis in mice may be to improve the enterohepatic circulation by regulating the metabolites of intestinal microorganisms, acetic acid and butyric acid, and to further regulate the Stat3 and TGF-β1 signaling pathway through the "gut-liver axis" to combat liver fibrosis.

Cystathionine gamma-lyase deficiency exaggerates diethylnitrosamine-induced liver damage in mice

Cystathionine gamma-lyase (CSE) is a key enzyme in reverse transsulfuration pathway and contributes to the majority of H2S generation in liver tissues via cysteine metabolism. Dysfunction of the CSE/H2S system is linked to both chronic and acute liver damage. This study investigated the regulatory role of CSE deficiency on diethylnitrosamine (DEN)-induced liver damage in mice. A single injection of DEN was administered into 4-week-old male CSE knockout (CSE-KO) mice and wild-type (WT) littermates, and the mice were sacrificed at 28 weeks of age. Compared to age-matched WT mice, CSE-KO mice spontaneously developed steatosis with increased oxidative stress and higher expressions of inflammation and fibrosis-related genes at 28-weeks of age. Following DEN injection, CSE-KO mice experienced more severe liver damage in comparison with the WT group as reflected by elevated levels of lipid accumulation, increased activities of alanine aminotransferase and aspartate aminotransferase, higher oxidative stress and fibrosis development, and increased expressions of inflammation and fibrosis-related genes. No visible tumors were observed in both types of mice with DEN treatment. In addition, the expression levels of the three H2S-generating proteins (CSE, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase) and the H2S production rate in liver tissues were unaffected by DEN. Taken together, our study demonstrates that CSE provides a significant hepatoprotective effect and deficiency of CSE exaggerates DEN-induced liver damage in mice. Based on these findings, it can be suggested that targeting the CSE/H2S signaling pathway could be a potential therapeutic target for the treatment of liver diseases.

MYELOID-DERIVED TLR4-TRIF SIGNALING PATHWAY MEDIATES OXIDATIVE STRESS IN LPS/D-GALN-INDUCED ACUTE LIVER FAILURE.

Background: Acute liver failure (ALF) is a severe clinical syndrome characterized by massive hepatocyte death in a short time due to viruses, drugs, alcohol, or other factors. Oxidative stress is an important pathogenic mechanism of ALF. LPS-induced internalization of toll-like receptor 4 (TLR4) and the subsequent activation of the toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) signaling pathway widely mediate inflammatory responses in a series of diseases. However, whether the TLR4-TRIF signaling pathway contributes to ALF by mediating oxidative stress processes remains unclear. Methods: An ALF mouse model was induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN). TLR4-TRIF systemic knockout mice and TLR4 conditional knockout mice were used to determine the role of the TLR4-TRIF signaling pathway in ALF. The effects of TLR4 or TRIF deficiency on oxidative stress were investigated. In addition, we examined the protective role of the clodronate liposomes (macrophage scavengers) and the antioxidant N-acetylcysteine (NAC) in ALF. Results: TLR4 or TRIF deficiency significantly alleviated LPS/D-GalN-induced lethality, hepatic dysfunction, and hepatic pathologic injury, which was dependent on myeloid-derived TLR4. Hence, macrophage clearance exhibits a similar protective effect. Mechanically, TLR4 or TRIF deficiency was observed to inhibit oxidative stress by increasing glutathione, while decreasing malondialdehyde, 8-hydroxy-2-deoxyguanosine, and γ-H2AX. Therefore, the pharmacologic antioxidant NAC exhibited significant hepato-protective effects. Conclusions: Targeting myeloid-derived TLR4-TRIF signaling pathway or antioxidant therapy may be a potential therapeutic direction to treat ALF.

Oral Supplementation of Ozonated Sunflower Oil Augments Plasma Antioxidant and Anti-Inflammatory Abilities with Enhancement of High-Density Lipoproteins Functionality in Rats.

Research on ozonated sunflower oil (OSO) is mostly restricted to its topical application, whereas the functional and toxicological assessment of oral OSO consumption is yet to be solved. Herein, OSO was orally supplemented in rats to assess the impact on plasma antioxidant status, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Also, the functionality of HDL from the OSO-supplemented rats (OSO-HDL) was tested against carboxymethyllysine (CML)- induced hyperinflammation in embryo and adult zebrafish. The results revealed that four weeks of OSO supplementation (3 g/kg BW/day) had no adverse effect on rats' hematological and blood biochemical profiles. Nonetheless, decreased interleukin (IL)-6, and LDL-C levels, along with enhanced ferric ion reduction ability (FRA) and sulfhydryl content, were observed in the plasma of OSO-supplemented rats compared to the control and sunflower oil (SO) supplemented group. In addition, OSO supplementation stabilized apoA-I/HDL and augmented HDL-allied paraoxonase (PON)-1 activity. The microinjection of OSO-HDL (10 nL, 2 mg/mL) efficiently prevented the CML (500 ng)-induced zebrafish embryo mortality and developmental deformities. Similarly, OSO-HDL thwarted CML-posed neurotoxicity and demonstrated a significant hepatoprotective effect against CML-induced fatty liver changes, hepatic inflammation, oxidative stress, and apoptosis, as well as exhibiting a noticeable influence to revert CML-induced dyslipidemia. Conclusively, OSO supplementation demonstrated no toxic effects on rats, ameliorated plasma antioxidant status, and positively influenced HDL stability and functionality, leading to a protective effect against CML-induced toxicity in zebrafish.

Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs’ in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1β and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Hepatoprotective effect of the ethanol extract of Detarium senegalense stem bark in albino Wistar

Aim: The hepatoprotective effect of Detarium senegalense ethanol stem bark extract was evaluated against paracetamol induced hepatic damage in albino rats. Material and methods: The ethanol stem bark extract of D. senegalense at doses of 100 mg/kg, 200 mg/kg and 400 mg/kg were orally administered once daily for 3 days.The liver function tests and biochemical investigation such as asparte transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and direct bilirubin were carried out against paracetamol induced hepatotoxicity in rats. Phytochemical investigation was performed to find active constituents of the plant extracts by the different phytochemical tests. Results: Pre-treatment with the ethanol stem bark extract significantly prevented the biochemical, histological, and changes induced by paracetamol in the liver. The extract showed significant hepatoprotective effects as evidenced by decreased serum enzyme activities such as AST, ALT,, ALP, TB and DB which was supported by histopatological assessment of the liver.The ethanol stem bark extract exhibited significant hepatoprotective activity comparable with silymarin, the standard drug as well as hepatotoxin agent, paracetamol. The phytochemical screening of the extract revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, cardiac glycosides, resins and balsam. Conclusion: The results of this study strongly show that ethanol stem bark extract of Detarium senegalense possess a potent hepatotoxicity activity against paracetamol induced hepatic damage in rats.

Salvianolic acid extract prevents Tripterygium wilfordii polyglycosides-induced acute liver injury by modulating bile acid metabolism

Ethnopharmacological relevanceTripterygium wilfordii polyglycosides (TWP) tablet is the most widely used traditional Chinese medicine preparation for the treatment of rheumatoid arthritis (RA), but the hepatotoxicity often limits its widespread application. In traditional use, Salvia miltiorrhiza has cardioprotective and hepatoprotective effects. Salvianolic acid extract (SA) is a hydrophilic component of Salvia miltiorrhiza and has significant antioxidant and hepatoprotective effects. Aim of the studyTo investigate the protective effects of SA on the TWP-induced acute liver injury in rats and to explore the related mechanisms by integration of metabolomics and transcriptomics. Materials and methodsSA and TWP extracts were identified by UPLC-Q/TOF-MS. SA (200 mg/kg) was administered for consecutive 7 days. On day 7, TWP (360 mg/kg) was administered by gavage to induce the acute liver injury in rats. Serum biochemical assay and H&E staining were used to evaluate liver damage. Liver metabolomics and transcriptomics were used to explore the potential mechanisms, and further molecular biological experiments such as qPCR and IHC were utilized to validate the relevant signaling pathways. ResultsSA can prevent liver injury symptoms caused by TWP, such as elevated liver index, elevated ALT and AST, and pathological changes in liver tissue. Liver metabolomics studies showed that TWP can significantly alter the content of individual bile acid in the liver and SA had the most significant impact on the biosynthetic pathway of bile acids. The transcriptomics results of the liver indicated that the genes changed in the SA + TWP group were mainly involved in sterol metabolism, lipid regulation and bile acid homeostasis pathways. The gene expression of Nr1h4, which encodes farnesoid X receptor (FXR), an important regulator of bile acid homeostasis, was significantly changed. Further studies confirmed that SA can prevent the downregulation of FXR and its downstream signaling induced by TWP, thereby regulating bile acid metabolism, ultimately preventing acute liver injury caused by TWP. ConclusionOur results demonstrated that SA could protect the liver from TWP-induced hepatic injury by modulation of the bile acid metabolic pathway. SA may provide a new strategy for the protection against TWP-induced acute liver injury.

Phytolacca Dodecandra (L' Herit) (Phytolaccaceae) Methanol Root Extract Protects Liver from Acetaminophen-Induced Injury in Rats.

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury.

Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.

Silybin (SLB), an important flavonoid from silymarin, displays significant hepatoprotective, anticancer, antioxidant, and neuroprotective effects. However, its therapeutic efficacy is limited by its low solubility and bioavailability. To address these challenges, we engineered bovine serum albumin (BSA) nanoparticles (NP) loaded with SLB (BSA-NP/SLB) using the coacervation method. BSA-SLB NP exhibited a spherical shape, a mean size of 197 nm, a polydispersity index of 0.275, a zeta potential of -34 mV, and an entrapment efficiency of 67%. X-ray diffraction analysis indicated amorphization of SLB upon encapsulation. Formulation stability was upheld over 180 days. In vitro release assays demonstrated controlled diffusion-erosion release, with approximately 40% SLB released within 0.5 h and 100% over 12 h. Intranasal administration of BSA-NP/SLB in rats improved SLB bioavailability by fourfold compared to free SLB. These findings highlight the promising potential of intranasally administered BSA-NP/SLB as an alternative approach to enhance SLB bioavailability, paving the way for innovative therapeutic applications.

Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.

Guided discovery of hepatoprotective polyhydroxy cembrane-type diterpenoids from the gum resin of Boswellia carterii by MS/MS molecular networking

Seven previously undescribed polyhydroxy cembrane-type diterpenoids, olibanols A-G (1–7) were obtained from the gum resin of Boswellia carterii by means of MS/MS molecular networking. Compound 2 possessed four hydroxy groups, 1, 3, 4, 5, and 6 had three hydroxy groups, 7 with one hydroxy group, among which 1 and 4 were a pair of epimers with double bond at C-3 and hydroxy at C-8. Structures of these previously undescribed compounds were determined by NMR analysis and ECD calculations. All the polyhydroxy cembrane-type diterpenoids obtained were assayed for their hepatoprotective effects against the anti-tuberculosis drug-induced hepatic damage to the HRZ-induced HepG2 cells. As results indicated, compounds 3, 4, and 6 showed significant hepatoprotective effects against the hepatic damage via the Nrf2 signal pathway, which could be developed as potential hepatoprotective agents against the anti-tuberculosis drug-induced hepatic damage.

Involvement of PI3K/HIF-1α/c-MYC/iNOS Pathway in the Anticancer Effect of Suaeda vermiculata in Rats.

Suaeda vermiculata Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment.