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1.
Nat Prod Res ; : 1-6, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39092521

ABSTRACT

This study aims to assess hepatoprotective properties of M. rotundifolia. Decoction was used to prepare the aqueous extract. The preliminary cytotoxicity evaluated against Caco 2 and RAW 264 cells demonstrate no cytotoxic effect. The preventive impact of the extract against liver damage was evaluated by examining blood levels of AST, ALT, ALP, total proteins, and histological alterations in liver tissues. Thirty albino rats were separated into five groups: the first served as normal group, the second was injected by olive oil (3 ml/kg), and the third was injected by CCL4 (3 ml/kg). However, groups IV and V received daily doses of 250 and 500 mg extract/kg bw, respectively before CCL4 injection. The results showed that the administration of the extract led to a marked improvement in plasma biochemical markers and a reduction in symptoms of CCL4-induced liver damage. The extract exhibits hepatoprotective activity, which may be attributed to its phytochemical components.

2.
Avicenna J Phytomed ; 14(3): 375-387, 2024.
Article in English | MEDLINE | ID: mdl-39086862

ABSTRACT

Objective: Pistacia vera is commonly used in traditional medicine to treat various disorders. This study aims to investigate the anti-anemia and hepatoprotective effects of Pistacia vera pericarp extract (PVPE) in a rat model of phenylhydrazine (PHZ)-induced anemia. Materials and Methods: PVPE was prepared using the maceration method. The extract was administered at doses of 20, 80, and 160 mg/kg for 28 days to normal and PHZ-treated rats. The effects of PVPE were evaluated in terms of changes in biochemical, histological, hematological, and molecular biomarkers in the liver and blood. Results: Administration of PVPE to the anemic animals significantly restored these deleterious effects on hematological parameters compared to the anemic group. Kupffer cell activation was seen in the liver tissue of the anemic rats. Administration of PVPE mitigated these deleterious effects. Conclusion: PVPE has potent antioxidant activity and may represent a promising treatment for anemia and liver protection in clinical settings.

3.
Sci Rep ; 14(1): 16902, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043726

ABSTRACT

The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body's storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil's hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl4). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl4 by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1ß, osteopontin (OPN), and transforming growth factor-ß (TGF-ß)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl4 through suppressing OPN.


Subject(s)
Carbon Tetrachloride , Liver Cirrhosis , Osteopontin , Sildenafil Citrate , Animals , Sildenafil Citrate/pharmacology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/pathology , Osteopontin/metabolism , Osteopontin/genetics , Rats , Male , Down-Regulation/drug effects , Disease Models, Animal , Liver/drug effects , Liver/metabolism , Liver/pathology , Oxidative Stress/drug effects , Antioxidants/pharmacology , Gene Expression Regulation/drug effects , Rats, Wistar
4.
J Evid Based Integr Med ; 29: 2515690X241263063, 2024.
Article in English | MEDLINE | ID: mdl-39051594

ABSTRACT

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.


Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury , Liver , Phytolacca , Plant Extracts , Plant Roots , Animals , Acetaminophen/adverse effects , Plant Extracts/pharmacology , Male , Rats , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Female , Phytolacca/chemistry , Liver/drug effects , Liver/pathology , Liver/metabolism , Plant Roots/chemistry , Mice , Methanol/chemistry , Rats, Wistar
5.
Biomed Chromatogr ; : e5961, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054754

ABSTRACT

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

6.
Eur J Med Chem ; 276: 116619, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38981335

ABSTRACT

The pentacyclic triterpenes represent a significant class of plant bioactives with a variety of structures and a wide array of biological activities. These are biosynthetically produced via the mevalonate pathway although occasionally mixed pathways may also occur to introduce structural divergence. Oleanolic acid is one of the most explored bioactive from this class of compounds and possesses a broad spectrum of pharmacological and biological activities including liver protection, anti-cancer, atherosclerosis, anti-inflammation, antibacterial, anti-HIV, anti-oxidative, anti-diabetic etc. This review provides an overview of the latest research findings, highlighting the versatile medicinal and biological potential of oleanolic and its future prospects.

7.
Food Chem ; 459: 140327, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38986199

ABSTRACT

Sturgeon has a long lifespan and slow evolutionary rate due to their powerful endogenous antioxidant system. This work aimed to assess the in vitro and in vivo antioxidant activity of sturgeon extracts from both muscle and roe. The extraction process without enzyme hydrolysis is not only simple, but also can produce extracts with better free radicals scavenging abilities than enzymatic hydrolysates in both cellular and in vivo experiments. Moreover, in mouse models with liver injury and immunosuppression treatment, the sturgeon extracts demonstrated strong hepatoprotective and immune-enhancing functions, comparable to vitamin C and ginseng extract supplements, which were attributed to abundant antioxidant peptides of the extracts. The 15 isolated peptides exhibited diverse free radical scavenging ability. Therefore, the sturgeon extracts showed high potential to be applied in food and biomedical industries.

8.
Nat Prod Res ; : 1-11, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39021067

ABSTRACT

This study explored, for the first time, the antioxidant (total antioxidant content, reducing power, ferric ion reducing antioxidant power, hydroxyl radical scavenging, ferrous ion-chelating assays), anti-tyrosinase, anti-inflammatory properties, and hepatoprotective effect in HepG2 cell lines of Ochna integerrima (Loureiro) Merrill flowers and seeds. All extracts except n-hexane exhibited significant antioxidant activity, with high levels of tannin and proanthocyanidins. Luteolin (1), 6-γ,γ-dimethylallylkaempferol7-O-ß-d-glucopyranoside (2), 6-γ,γ-dimethylallylquercetin7-O-ß-d-glucopyranoside (3), and 6-γ,γ-dimethylallyldihydrokaempferol 7-O-ß-d-glucopyranoside (4) were isolated using semi-preparative HPLC. Compounds 1-3 demonstrated good anti-tyrosinase activity. The most active hepatoprotective extracts were found to be aqueous extracts. The flower extracts exhibited greater anti-inflammatory properties by the decrease of NO in RAW 264.7 cells and bovine serum albumin protein. Among them, the n-hexane and EtOAc extracts from flowers displayed promising anti-inflammatory activity. This was predicted by in silico analysis of 1-4. In summary, O. integerrima appears to be a promising natural source for antioxidant, anti-tyrosinase, and anti-inflammatory applications.

9.
Front Bioeng Biotechnol ; 12: 1400542, 2024.
Article in English | MEDLINE | ID: mdl-39007052

ABSTRACT

Introduction: This study explores the therapeutic potential of silver nanoparticles (Ag NPs) synthesized using a Helianthemum lippii extract in mitigating cadmium-induced hepatotoxicity in Wistar rats. Given the increasing environmental and health concerns associated with cadmium exposure, novel and eco-friendly therapeutic strategies are essential. Methods: Ag NPs were characterized using X-ray diffraction, UV-Vis spectrometry, and energy-dispersive X-ray spectroscopy with scanning electron microscopy, confirming their formation with a cubic crystal structure and particle sizes ranging from 4.81 to 12.84 nm. A sub-acute toxicity study of Ag NPs (2 mg/kg and 10 mg/kg) was conducted, showing no significant difference compared to untreated control rats (n = 3 animals/group). Subsequently, adult Wistar rats (n = 5/group) were divided into a control group and three experimental groups: Ag NPs alone, exposure to 50 mg/kg CdCl2 in drinking water for 35 days, and CdCl2 exposure followed by 0.1 mg/kg/day Ag NPs intraperitoneally for 15 days. Results: In the CdCl2-exposed group, there was a significant decrease in body weight and increases in alanine and aspartate transaminase levels (p < 0.05 vs. control), indicating hepatotoxicity. Additionally, antioxidant defenses were decreased, and malondialdehyde levels were elevated. Liver histology revealed portal fibrosis, inflammation, necrosis, sinusoid and hepatic vein dilation, and cytoplasmic vacuolations. Treatment with Ag NPs post-CdCl2 exposure mitigated several adverse effects on liver function and architecture and improved body weight. Discussion: This study demonstrates the efficacy of Ag NPs synthesized via a green method in reducing cadmium-induced liver damage. These findings support the potential of Ag NPs in therapeutic applications and highlight the importance of sustainable and eco-friendly nanoparticle synthesis methods. By addressing both toxicity concerns and therapeutic efficacy, this research aligns with the growing emphasis on environmentally conscious practices in scientific research and healthcare.

10.
Front Mol Biosci ; 11: 1440132, 2024.
Article in English | MEDLINE | ID: mdl-39021879

ABSTRACT

Licochalcone B (LicB), a chalcone derived from Glycyrrhiza uralensis and Glycyrrhiza glabra, has received considerable attention due to its diverse pharmacological properties. Accumulated data indicates that LicB has pharmacological effects that include anti-cancer, hepatoprotective, anti-inflammatory, and neuroprotective properties. The action mechanism of LicB has been linked to several molecular targets, such as phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, p53, nuclear factor-κB, and p38, and the involvements of caspases, apoptosis, mitogen-activated protein kinase-associated inflammatory pathways, and anti-inflammatory nuclear factor erythroid 2-related factor 2 signaling pathways highlight the multifaceted therapeutic potential of LicB. This review systematically updates recent findings regarding the pharmacological effects of LicB, and the mechanistic pathways involved, and highlights the potential use of LicB as a promising lead compound for drug discovery.

11.
Int J Biol Macromol ; : 133969, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39029849

ABSTRACT

In this study, an enzyme-assisted microwave extraction process was obtained by response surface method of polysaccharide from roots of Rubus crataegifolius Bunge. The optimized extraction process was as follow: enzyme dosage 2 %, enzymatic time was 3.6 h, enzymatic pH 4.9, and microwave time 4.7 min, with the extraction yield of 9.07 %. Four homogeneous polysaccharides (RCP-1, RCP-3, RCP-4 and RCP-5) were purified through column chromatography. Four polysaccharides have the relative higher molecular weights of 1.70 × 106 Da, 5.56 × 106 Da, 4.97 × 106 Da, and 9.80 × 106 Da and mainly consisted of GluN, GluA, Glu, Gal and Arab. FT-IR and NMR spectral analysis confirmed that the purified polysaccharides were polypyranose containing α- and ß-glycosidic bonds. RCP - 1 has a relative high crystallinity. Four purified polysaccharides contained triple helical conformations, and have good antioxidant activities. Among the purified polysaccharides, RCP - 1 was found to reduce the oxidative cell damage induced by H2O2 through increasing of cell viability, inhibition of AST and ALT levels, ROS production and cell apoptosis, increasing of the activities of antioxidative enzymes, as well as reduction of MDA content. Our findings would provide a foundation for purified polysaccharides efficient extraction and demonstrated that the polysaccharides from R. crataegifolius roots could be a promising hepatoprotective agent.

12.
Molecules ; 29(14)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39064870

ABSTRACT

Natural products have always played an important role in pharmacotherapy, helping to control pathophysiological processes associated with human disease. Thus, natural products such as oleanolic acid (OA), a pentacyclic triterpene that has demonstrated important activities in several disease models, are in high demand. The relevant properties of this compound have motivated re-searchers to search for new analogues and derivatives using the OA as a scaffold to which new functional groups have been added or modifications have been realized. OA and its derivatives have been shown to be effective in the treatment of inflammatory processes, triggered by chronic diseases or bacterial and viral infections. OA and its derivatives have also been found to be effective in diabetic disorders, a group of common endocrine diseases characterized by hyperglycemia that can affect several organs, including the liver and brain. This group of compounds has been reported to exhibit significant bioactivity against cancer processes in vitro and in vivo. In this review, we summarize the bioactive properties of OA and its derivatives as anti-inflammatory, anti-bacterial, antiviral, anti-diabetic, hepatoprotective, neuroprotective, and anticancer agents.


Subject(s)
Oleanolic Acid , Oleanolic Acid/chemistry , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/pharmacology , Humans , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry
13.
Plants (Basel) ; 13(14)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39065511

ABSTRACT

The hepatoprotective effects of natural products have been a significant focus in recent decades due to the growing demand for the help in the treatment of hepatic impairments. This review specifically delves into the findings of clinical trials involving 13 selected natural products, namely plants and their derived compounds (e.g., artichoke, berberine, and turmeric), algae (e.g., spirulina), probiotics, and other products like phospholipids and vitamin D. A literature search was performed in the Scopus database, PubMed, and Google Scholar, covering all articles found up to June 2024. Artichoke, berberine, chlorella, chicory, green tea, probiotics, phospholipids, schisandra, silymarin, spirulina, and vitamin D caused a decrease in liver enzymes, while for cinnamon and turmeric such an effect was either not observed or not convincing. The presented results indicate that some natural products might satisfactorily improve hepatic outcomes in NAFLD, NASH, and other liver disorders; however, further studies and metanalyses are needed to clearly demonstrate their effectiveness.

14.
Article in English | MEDLINE | ID: mdl-38982918

ABSTRACT

Liver disease, responsible for two million annual deaths, causes Chronic Liver Disease (CLD) and cirrhosis, causing roughly a million deaths yearly. Treatment options for liver injury induced by hepatotoxicity vary, including medication (N-acetylcysteine, corticosteroids, and ursodeoxycholic acid), lifestyle changes, and sometimes liver transplant. However, effectiveness varies, and some treatments carry risks and side effects, highlighting the need for improved therapeutic approaches. Murraya koenigii (MK) is known for its hepatoprotective, antioxidant, anti-inflammatory, anti-microbial, nephroprotective, hepatoprotective, gastroprotective, cardioprotective, neuroprotective, wound-healing, anti-cancerous and immunomodulatory effects, etc. This review highlights the effectiveness of MK against liver damage induced by heavy metals, drug abuse, xenobiotics, etc. A comprehensive search across multiple databases like PubMed, Google Scholar, and others for articles on various hepatotoxicants and hepatoprotective activity of MK was conducted. The researchers applied specific search terms and limits, resulting in 149 eligible articles for final analysis, meeting predetermined inclusion criteria and excluding irrelevant studies. According to the available literature, the phytochemical components of MK, such as flavonoids, tannins, and alkaloids present in various extracts, play a crucial role in reversing the hepatotoxic effects by modifying oxidative and ER stresses, re-establishing the hepatic biochemical markers and enzymes involved in metabolism denoting ameliorative activity, and controlling the expression of pro-inflammatory cytokines. To conclude, this review highlights that MK has great potential as a natural hepatoprotective agent, providing a versatile defense against a range of injuries caused by heavy metals, xenobiotics, and common hepatotoxic agents.

15.
Avicenna J Phytomed ; 14(1): 23-49, 2024.
Article in English | MEDLINE | ID: mdl-38948180

ABSTRACT

Objective: Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects. Materials and Methods: An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established. Results: According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities. Conclusion: The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.

16.
Mol Biol Rep ; 51(1): 835, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042283

ABSTRACT

Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Humans , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Animals , Signal Transduction/drug effects , Glucagon-Like Peptide 1/metabolism , Insulin/metabolism , Blood Glucose/metabolism , Blood Glucose/drug effects , Glucagon-Like Peptide-1 Receptor Agonists
17.
Foods ; 13(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38890923

ABSTRACT

Litsea martabanica root's antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

18.
Adv Food Nutr Res ; 110: 243-274, 2024.
Article in English | MEDLINE | ID: mdl-38906588

ABSTRACT

Alcohol intake has become one of the leading risks to human health and wellness, among which acute and/or chronic alcohol-induced liver injury is a leading threaten, with few therapeutic options other than abstinence. In recent years, studies suggested that certain bioactive peptides from food sources could represent natural and safe alternatives for the prevention of alcoholic liver injury. Hence, this chapter focus on the advanced research on bioactive peptides exerting hepatoprotective activity against alcoholic liver injury. The main sources of protein, strategies for the preparation of hepatoprotective hydrolysates and peptides, underlying mechanisms of peptides on hepatoprotection, and possible structure-activity relationship between peptides and hepatoprotective activity were summarized and discussed, aiming to give a systematic insight into the research progress of hepatoprotective peptides. However, more efforts would be needed to give a clearer insight into the underlying mechanisms and structure-activity relationship before using hepatoprotective peptides as functional food ingredients or dietary supplements.


Subject(s)
Liver Diseases, Alcoholic , Peptides , Humans , Liver Diseases, Alcoholic/prevention & control , Peptides/pharmacology , Peptides/chemistry , Protective Agents/pharmacology , Animals , Structure-Activity Relationship , Liver/drug effects
19.
J Pharm Biomed Anal ; 248: 116249, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38936169

ABSTRACT

Isoniazid (INH) is the first-line anti-tuberculosis drug in clinical practice, and its main adverse effect is drug-induced liver injury (DILI). This study aimed to investigate the hepatoprotective effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid (CAROL) and to provide a new strategy for the search of potential drugs against INH-induced liver injury in Wistar rats. Animal experiment was based on INH (100 mg/kg) induced liver injury to explore the intervention effects of CAROL at doses of 1.35, 2.70, and 5.40 mL/kg. LC-QTOF-MS/MS was used to identify hepatoprotective components in CAROL and its' exposed components in rat serum. The hepatoprotective effect of CAROL was evaluated by pathological observation of rat liver tissue and changes in levels of biochemical indices and cytokines in serum or liver tissue. Of the 58 hepatoprotective components identified, 15 were detected in the serum of rats with liver-injured treated by high-dose CAROL. Results of animal experiments showed that the levels of various biochemical indexes and cytokines were significantly reversed with CAROL intervention. In particular, the expression level of cytokeratin-18 and high-mobility group box 1, as specific and sensitive indicators of DILI, was significantly reduced in the serum of rats with CAROL intervention compared with the INH model group. The same reversal was observed in the levels of TBIL, ALP, ALT, and AST in serum, as well as in the levels of TNF-α, IL-6, SOD, and MDA in liver tissue. For INH-metabolizing enzymes, an evident expression inhibition was observed in N-acetyltransferase 2 and glutathione S-transferases with CAROL intervention, which may be the key to controlling INH hepatotoxicity. CAROL has a favorable hepatoprotective effect on INH-induced liver injury. This study takes the first step in studying the hepatoprotective mechanism of CAROL against INH hepatotoxicity and provides reference for wider clinical applications.


Subject(s)
Antitubercular Agents , Chemical and Drug Induced Liver Injury , Isoniazid , Liver , Rats, Wistar , Animals , Isoniazid/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/etiology , Rats , Male , Liver/drug effects , Liver/metabolism , Liver/pathology , Antitubercular Agents/toxicity , Orchidaceae/chemistry , Cytokines/metabolism , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Tandem Mass Spectrometry/methods , Administration, Oral
20.
Article in English | MEDLINE | ID: mdl-38885158

ABSTRACT

Introduction: Liver cirrhosis is a condition characterized by the gradual replacement of normal liver tissue with scar tissue, ultimately leading to liver failure. This slow and progressive disease begins with a chronic inflammatory process induced by a noxious agent. In its advanced stages, the disease lacks effective therapies. Research has demonstrated the significant involvement of the endocannabinoid system in the pathogenesis of this disease. This study evaluated the hepatoprotective effect of cannabidiol (CBD) in the progression of experimental hepatic cirrhosis induced by thioacetamide (TAA) in rats. Methods: A randomized experimental design was employed using Holtzman rats. Hepatic cirrhosis was induced by intraperitoneal administration of TAA at a dose of 150 mg/kg for 6 weeks, with treatment initiated additionally. The groups were as follows: Group 1: TAA + vehicle; Group 2: TAA + CBD 2 mg/kg; Group 3: TAA + CBD 9 mg/kg; Group 4: TAA + CBD 18 mg/kg; Group 5: TAA + silymarin 50 mg/kg; and Group 6: Healthy control. Serum biochemical analysis (total bilirubin, direct bilirubin, ALT, AST, alkaline phosphatase, and albumin) and hepatic histopathological study were performed. The Knodell histological activity index (HAI) was determined, considering periportal necrosis, intralobular degeneration, portal inflammation, fibrosis, and focal necrosis. Results: All groups receiving TAA exhibited an elevation in AST levels; however, only those treated with CBD at doses of 2 mg/kg and 18 mg/kg did not experience significant changes compared to their baseline values (152.8 and 135.7 IU/L, respectively). Moreover, ALT levels in animals treated with CBD showed no significant variation compared to baseline. The HAI of hepatic tissue was notably lower in animals treated with CBD at doses of 9 and 18 mg/kg, scoring 3.0 and 3.25, respectively, in contrast to the TAA + vehicle group, which recorded a score of 7.00. Animals treated with CBD at 18 mg/kg showed a reduced degree of fibrosis and necrosis compared to those receiving TAA alone (p ≤ 0.05). Conclusion: Our findings demonstrate that cannabidiol exerts a hepatoprotective effect in the development of experimental hepatic cirrhosis induced in rats.

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