Hepatoprotective Properties Research Articles

Silybin Derivatives Produced by γ-Irradiation and Their Tyrosinase Inhibitory Activities

Silybin, which belongs to the flavonolignan group, is the major component of the fruit extract of Silybum marianum (common name: milk thistle). Silybin is a medicinal compound with hepatoprotective, antioxidant, and anticancer properties. In this study, silybin derivatives were produced through γ-radiolysis, and their tyrosinase inhibitory activities were evaluated to explore the enhanced activities of silybin derivatives compared to silybin (1). Isosilandrin (2) and 2,3-dehydrosilybin (3) were obtained from a silybin sample irradiated at 300 kGy. The optimal dose showed significant changes in radiolysis product content. Compounds 2 and 3 exhibited an IC50 of 274.6 and 109.5 μM, respectively, which are more potent than that of 1 (IC50 > 500 μM). In addition, a molecular docking simulation revealed the binding affinity of these compounds to tyrosinase and their mechanisms of inhibition. Thus, γ-irradiation is an effective method for structural modification of silybin. We also demonstrated that 2,3-dehydrosilybin is a potential tyrosinase inhibitor.

Antiproliferative and Apoptotic Potential of Chicoric Acid, a Major Phytoconstituent of Cichorium intybus, against Colon Cancer Cells: A Possible Inhibition of CDC25 Phosphatases

Background: Over the years, plants have been utilized worldwide for the treatment of cancer in the traditional system of medicine, notably in the majority of developing nations. The use of chemotherapeutic drugs is frequently associated with lethal side effects when treating cancer. Therefore, the panacea to the vicious side effects linked to synthetic pharmaceuticals is the alternative usage of widely accessible and affordable therapeutic approaches. Chicoric acid, a major constituent of Cichorium intybus, has recently been shown to exhibit antioxidant, anti-inflammatory, antidiabetic, antiviral, neuroprotective, hepatoprotective, and anticancer properties. Purpose: Except for a few preliminary studies, no detailed study on the chemotherapeutic efficacy of chicoric acid against cancer cells has been done till now. Therefore, the aim of this study is to assess the potential of chicoric acid against colon cancer cells. Methods: Different in vitro assays like MTT, DAPI staining, rhodamine staining, H2DCFDA staining, caspase activity, and cell analysis were performed on colon cancer HCT116 cells to assess their growth inhibitory properties. Results: According to the results, chicoric acid dose-dependently suppressed the growth of colon cancer HCT116 cells by inducing cell cycle arrest at G0/G1 phase and apoptosis via both intrinsic and extrinsic pathways. In silico findings unveiled the cell cycle regulatory capacity of chicoric acid through binding CDC25 phosphatases, implying its potential as an antiproliferative agent capable of suppressing cell growth. Conclusion: Collectively, the results suggested strong chemopreventive potential of chicoric acid against colon cancer cells. Thus, chicoric acid may turn out to be an excellent anticancer agent, which may be explored in the future for the therapeutic drug development against cancer.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Postbiotics as Antiinflammatory and Immune-Modulating Bioactive Compounds in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Postbiotics, defined as products or metabolic byproducts secreted by live bacteria or released after bacterial lysis, are emerging as promising therapeutic agents for metabolic dysfunction-associated steatotic liver disease (MASLD). This review explores the antiinflammatory and immunomodulatory properties of various postbiotics, including exopolysaccharides, lipoteichoic acid, short-chain fatty acids, hydrogen sulfide, polyamines, tryptophan derivatives, and polyphenol metabolites. These compounds have demonstrated potential in mitigating steatotic liver infiltration, reducing inflammation, and slowing fibrosis progression in preclinical studies. Notably, postbiotics exert their beneficial effects by modulating gut microbiota composition, enhancing intestinal barrier function, optimizing lipid metabolism, reducing hepatic inflammation and steatosis, and exhibiting hepatoprotective properties. However, translating these findings into clinical practice requires well-designed trials to validate efficacy and safety, standardize production and characterization, and explore personalized approaches and synergistic effects with other therapeutic modalities. Despite challenges, the unique biological properties of postbiotics, such as enhanced safety compared to probiotics, make them attractive candidates for developing novel nutritional interventions targeting the multifactorial pathogenesis of MASLD. Further research is needed to establish their clinical utility and potential to improve liver and systemic outcomes in this increasingly prevalent condition.

20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells

20-Hydroxyecdysone (20E) is an arthropod steroid hormone that possesses a number of beneficial pharmacological activities in humans, including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties, etc. While several studies have explored the anabolic activity of 20E in muscle cells, they have concentrated on its effects on myofibril size, protein biosynthesis intensity, and myostatin expression, without assessing energy metabolism. In this research, we have demonstrated that 20E boosts both catabolism and anabolism, coupling energy-producing and biosynthetic metabolic processes in mouse myoblasts and fibroblasts in the same way. Using a transcriptomic approach, we identified the 20E-mediated up-regulation of genes involved in different metabolic processes. Further experiments revealed that 20E increased the levels of enzymes involved in glycolysis and one-carbon metabolism. It also increased the uptake of glucose, glycolysis, respiration, the production of ATP, and global protein biosynthesis in mouse myoblasts and fibroblasts. This phenomenon involves the PI3K/AKT/mTOR signaling pathway. Taken together, the observed 20E-dependent upregulation of energy metabolism may be the main reason for 20E’s well-known anabolic activity.

Investigating the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts in streptozotocin-induced diabetic rats

Diabetes is a major global health crisis, affecting millions of people worldwide and necessitating the search for effective and safe treatments, leading to various complications, including liver damage. This study investigated the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts (WBTP) in streptozotocin-induced diabetic rats.Propolis samples were collected from the West Black Sea Region of Turkey and prepared as -80 °C (PP-80) and -196 °C (PP-196) water extracts. Thirty male Wistar albino rats were divided into five groups: normal control, diabetic control, diabetic + PP-80 (250 mg/kg), diabetic + PP-196 (250 mg/kg), and diabetic + metformin (250 mg/kg). After 35 days of treatment, various parameters were evaluated, including body weight, blood glucose, glycated hemoglobin (HbA1c), serum biochemistry, antioxidant enzyme activities, and histopathology of the pancreas.The results showed that WBTP extracts, especially PP-80, significantly improved body weight and reduced blood glucose and HbA1c levels. Analysis of lipid profiles revealed improvements in HDL, LDL, triglycerides, and total cholesterol levels with WBTP treatment. The antioxidant defense systems were also enhanced in the WBTP-treated groups. Histopathological examination revealed that WBTP extracts mitigated pancreatic tissue damage in the diabetic rats.In conclusion, the WBTP extracts possess hepatoprotective and antidiabetic properties, suggesting a promising avenue for further research. It emphasizes the importance of addressing both diabetes and hepatopathologies concurrently and highlights WBTP extracts as natural and potentially safer alternatives to synthetic antidiabetic drugs. Specifically, PP-80 extracts demonstrate robust effects in managing diabetes and associated liver complications in streptozotocin-induced diabetic rats, indicating their therapeutic potential.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

Financial feasibility: developing and commercializing Turmeric Kombucha with the business model canvas

Turmeric Kombucha, a fermented drink combining the anti-inflammatory properties of turmeric, represents a promising product of functional beverage market. In order to successfully bring Turmeric Kombucha to market, it is essential to evaluate its commercialization potential. This involves assessing the Business Model Canvas (BMC) and financial feasibility metrics. This study aims to determine the feasibility and strategies for successfully commercializing Turmeric Kombucha for development a business plan with scale up the production of Turmeric Kombucha. The result indicate that Turmeric Kombucha has a viable business model with 9 elements. Based on financial shows that Net Present Value (NPV) of $ 13,405,417.62, an Internal Rate of Return (IRR) of 71.42 %, a Payback Period (PP) of 0.59 years, and Break-Even Point (BEP) metrics of 3,173 units and $ 4,914.46. The analysis shows strong financial viability and significant growth potential for Turmeric Kombucha, supported by sustainable and efficient supply chain partnerships. The features and characteristics of the obtained results in this study, namely: a) high consumer interest from health-conscious individuals over 18 years old; b) health benefits of Turmeric Kombucha include hepatoprotective, immunomodulatory, antidiabetic, and antioxidant properties; c) key resources include efficient production processes, user-friendly equipment, and adequate human and financial resources. The practical application of these results involves strategies for scale up of market expansion, quality standardization, and supply chain enhancement. Customer relationships are fostered through direct and indirect distribution channels such as marketplaces, word-of-mouth, and retail stores.

The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as non-alcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and hepatocellular carcinoma (HCC), face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects that make them unsuitable for patients with pre-existing liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions NAFLD, ALD and HCC. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative COVID-19 treatments.

Potential hepatoprotective properties of synthetic derivatives of thiourea — 2-aminobenzothiazole and IEM-2320

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

Toxicological evaluation of LivLonga®, a polyherbal combination, in rodents

There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about Curcuma longa, Garcinia indica and Piper nigrum which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga® using in vivo models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.

Portuguese Grapevine Leaves: A Neglected By-Product with High Potential

In Portugal, grapevine leaves are generally treated as agro-industrial waste, despite being rich in bioactive compounds that offer benefits to human health. This study compiles the most relevant and current data on the phytochemical composition and bioactive properties of grape leaves from both red and white varieties cultivated in the country. These by-products are abundant in flavonoid and non-flavonoid phenolic compounds, such as flavonols, derivatives of hydroxycinnamic acids, carotenoid pigments, and chlorophylls, as well as fatty acids, which have scientifically proven antioxidant, antimicrobial, anti-inflammatory, antidiabetic, cardio-, neuro- and hepatoprotective properties, among others. The combination of these beneficial properties, along with the low toxicity of their compounds, makes grapevine leaves a by-product with great potential for use in the food, pharmaceutical, and cosmetic industries. The key challenge is to develop sustainable methods to reintegrate this by-product into the supply chain, in alignment with the sustainability goals of the 2030 Agenda.

Effects of l-carnitine on frailty status in patients with liver cirrhosis: A randomized-controlled trial.

Frailty is a common complication in patients with liver cirrhosis, which is linked with augmented rates of morbidity and mortality. In this regard, timely nutritional assessment and intervention have gained scientific attention. L-carnitine may be a promising candidate with its potential to enhance energy metabolism, reduce inflammation, and act as an antioxidant. Therefore, we aimed to assess the impact of l-carnitine supplementation on frailty status and liver function in adults with liver cirrhosis. This double-blinded, randomized, controlled clinical trial study enrolled 77 patients with liver cirrhosis. Patients were randomly allocated into two groups: the control group (n = 42) and the l-carnitine group (n = 35). The l-carnitine group received 500 mg of l-carnitine orally three times a day for 8 weeks, while the control group did not receive any intervention. L-carnitine administration resulted in a significant decrease in alanine transaminase levels (p: 0.043) and partial thromboplastin time (p: 0.036). Furthermore, compared to the control group, l-carnitine treatment led to improvements in prothrombin time (p: 0.008) and international normalized ratio (p: 0.024). However, no significant improvement in the Liver Frailty Index, Freid Frailty Index, and Karnofsky Performance Status Scale (p > 0.05) was observed in the carnitine group after the 8-week intervention period. In conclusion, the administration of l-carnitine exhibited hepatoprotective properties and was correlated with lowered alanine transaminaselevels with improvement in coagulation status in liver cirrhosis patients. Nevertheless, our study indicated that the short-term use of l-carnitine might not significantly improve frailty in these patients.

Insights into the Phytochemical Profile and Therapeutical Potential of Withania Somnifera (L.) Dunal

Abstract: Withania somnifera (L.) Dunal (W. somnifera) is an herb commonly known by its English name Winter Cherry, and Ashwagandha in Hindi. It has been used as a traditional Rasayana herb for a long time. It is a rich reservoir of bioactive compounds known as withanolides, namely, withaferin-A and withanolide-D. Its current research covers many aspects of human health, which include anti-stress, anti-tumor, 9immuno-modulatory, hypocholesterolemic, hepatoprotective, hypoglycemic, diuretic, anti-convulsant, neurotropic, adaptogenic, and cardioprotective properties. This overview W. somnifera traditional uses, phytochemical, and pharmacological activities. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.

Effect of Particle Size on Physical Properties, Dissolution, In Vitro Antioxidant Activity, and In Vivo Hepatoprotective Properties of Tetrastigma hemsleyanum Diels et Gilg Powders

Objective: The aim of this study was to analyze the effects of different particle sizes of Tetrastigma hemsleyanum Diels et Gilg (TDG) powders on physical properties, dissolution, in vitro antioxidant activity, and in vivo hepatoprotective properties. Methods: The particle size of TDG coarse powders (TDG-CP), TDG fine powders (TDG-FP), and TDG micro powders (TDG-MP) were measured by a laser particle size analyzer. The physical properties were measured according to the latest version of the Chinese Pharmacopoeia (Committee Chinese Pharmacopoeia 2020). The content of the total flavonoids, total polysaccharides, kaempferol-3-O-rutinoside, and rutin of TDG powders were determined using the NaNO2-Al (NO3)3 colorimetric method, the sulphate-phenol colorimetric method, and HPLC, respectively. In vitro dissolution and antioxidant activity were determined by the paddle method in phosphate buffer (pH 6.8) and the DPPH radical scavenging method, respectively. In addition, the liver tissue pathology was evaluated by hematoxylin and eosin staining (H&E), and the AST and ALT activities were measured by automatic biochemical analyzer. The superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities were measured by using commercial analysis kits. Results: As the particle size decreases, the fluidity of TDG powders decreased and the porosity increased. In addition, there were no significant differences in physical properties between low temperature pulverized powders and room temperature pulverized powders. The final dissolution rates of the four bioactive ingredients in TDG-MP were found to be 85.06%, 85.61%, 83.88%, and 83.26%, respectively, whereas in TDG-CP, the dissolution rates were significantly lower at 18.79%, 17.96%, 22.46%, and 24.35%. The EC50 values of TDG-CP, TDG-FP, and TDG-MP on DPPH scavenging activity were 0.82, 0.31, and 0.10 mg/mL, respectively. The AST and ALT activities of the TDG-FP group and the TDG-MP group were significantly decreased and the SOD, CAT, and GSH activities were significantly increased when compared with that of the model group. The inflammatory cell infiltration and vacuolar degeneration of liver cells in the TDG-FP group and the TDG-MP group were significantly improved. Conclusions: The particle size of TDG powders had a significant effect on the physical properties and in vivo bioactivity. TDG pulverized to a fine particle size or smaller is a promising approach for clinical applications with improved physicochemical and biological properties.

Exploring the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models.

Medicinal plants are vital to healthcare, yet many remain unexplored. Marsdenia thyrsiflora Hook.f., from Bangladesh's Bhawal Forest, lacks research on its medicinal properties, especially its antioxidant capacities and protection against CCl4-induced liver toxicity. This study aims to evaluate the antioxidant properties of M. thyrsiflora leaf extract to determine its protective effects on rodents against CCl4-induced liver injury. After extraction, the total phenol, flavonoid content, and antioxidant capacity of the leaf extract were measured using established protocols. Free radical scavenging abilities were evaluated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) assays. Additionally, reducing power was assessed through cupric-reducing and ferric-reducing assays. Based on the OECD 420 recommendation, acute toxicity was tested on Swiss albino mice to establish an effective and safe dosage. For the hepatoprotective study, Sprague-Dawley rats were pre-treated with M. thyrsiflora leaf methanolic extract (MTLM) at 250 and 500mg/kg body weight, and CCl4 was administered to induce liver damage. Serum hepatic enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)), lipid profile (total cholesterol, triglycerides), total bilirubin, and markers of lipid peroxidation (Malondialdehyde (MDA)) were measured. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were also evaluated to assess oxidative stress. The results demonstrated that MTLM, rich in phenolic and flavonoid content, exhibits significant antioxidant activities in DPPH and NO radical scavenging assays, as well as in reducing power assays. The acute toxicity study confirmed the safety of MTLM, with no adverse effects observed even at high doses. For the hepatoprotective study, rats were administered CCl4 to induce liver damage, followed by treatment with MTLM. Results showed that MTLM significantly reduces liver damage markers such as elevated serum hepatic enzyme levels, lipid profile, total bilirubin, and lipid peroxidation and improves the activities of GSH and key antioxidant enzymes such as SOD and CAT. Histopathological analysis corroborated these findings, displaying reduced necrosis, inflammation, and edema in liver tissues treated with MTLM. MTLM extract exhibits potent antioxidant and hepatoprotective properties. Its ability to attenuate oxidative stress, enhance antioxidant enzyme activities, and facilitate histopathological changes in the liver highlights its potential as a natural therapeutic agent for liver damage. However, further investigation is required to understand its molecular processes, safety profiles, and active component characterization.

Network pharmacology and bioinformatic integrative analysis reveals candidate gene targets and potential therapeutic of East Kalimantan propolis against hepatocellular carcinoma

IntroductionHepatocellular Carcinoma (HCC) is commonly treated with surgery, liver transplantation, and chemotherapy, but recurrence and metastasis remain challenges. Natural complementary therapies like propolis, known for its hepatoprotective properties, are gaining interest due to limited efficacy and toxicity of conventional chemotherapy. This study aims to identify core targets for HCC, assess the therapeutic potential of East Kalimantan propolis (EKP) from stingless bees, and analyze the molecular interactions. MethodsEKP compounds were analyzed using target prediction tools related to HCC, alongside clinical data from the Gene Expression Omnibus (GEO) database, to identify overlapping genes with clinical relevance. The selected genes were then subjected to protein-protein interaction (PPI), GO and KEGG enrichment, immunohistochemical comparison and survival analysis to identify potential core targets and related pathways for HCC therapy. Furthermore, molecular docking and dynamics were conducted to verify the molecular interactions and stability of EKP compounds with targets. Results108 genes have been selected as HCC potential targets, which mostly associated with MicroRNAs in cancer, chemical carcinogenesis, and viral carcinogenesis pathways. These targets were obtained by overlapping genes from GEO clinical databases and target predictors. PPI network analysis revealed 4 main targets of propolis in HCC. Furthermore, differential expression genes, survival analysis, and Immunohistochemical analysis from databases suggested that AKR1C3 and MAPK1 promote HCC progression and shorten survival rate of HCC patients. Molecular docking and dynamic studies confirmed strong binding affinity and stability of Baicalein, Chrysin, Quercetin, and Myricetin with receptor targets within simulation time. ConclusionsThis study provides insight into the mechanism of action of EKP on HCC and identifies AKR1C3 and MAPK1 as candidate target treatments for future drug development.

A comparative study of DPPH radical scavenging property and antiproliferative potential on human hepatic cancer (HepG2) cells of methanolic extracts from different parts of <i>Ludwigia hyssopifolia</i> and <i>Ludwigia adscendens</i>

Ludwigia hyssopifolia and Ludwigia adscendens are two indigenous and common plant species in Vietnam with hepatoprotective property mentioned in numerous articles published in international journals. Therefore, the current paper aimed to evaluate the physicochemical parameters, total polyphenolic and flavonoid contents of the methanolic extracts from 04 parts of Ludwigia hyssopifolia and Ludwigia adscendens in Mekong delta, Vietnam. Most importantly, antioxidant properties by DPPH radial scavenging assay and antiproliferative potentials on human hepatic cancer (HepG2) cells of these multiple extracts also were determined in the in vitro models. These results showed that physicochemical parameters were within allowable limits according to the literatures. Among the investigated samples, the leaf and whole plant extract from Ludwigia hyssopifolia had the highest values of total phenolic and flavonoid contents being 196.55 ± 5.05 mg GAE/g and 64.72 ± 4.63 mg QE/g respectively. Additionally, the methanol whole plant extract of Ludwigia hyssopifolia and the methanol leaf extract of Ludwigia adscendens show the greatest antioxidant properties in DPPH scavenging assay with IC50 values of 44.48 ± 4.29 µg/mL and 26.11 ± 0.37 µg/mL respectively. Furthermore, the methanolic extract from Ludwigia hyssopifolia leaves displays the most potential anti-HepG2 activity among all surveyed samples. Therefore, the most promising extracts need further evaluation for potential herbal product developments.

Comparative hepatoprotective effects of flavonoids-rich fractions from flowers and leaves of Penthorum chinense Pursh in vitro

Ethnopharmacological relevancePenthorum chinense Pursh is a traditional Miao ethnomedicine rich in bioactive components, widely recognized for its hepatoprotective properties. However, the hepatoprotective effects of its flowers and leaves have not been individually elucidated. Aims of the studyThe objective of this study was to isolate and purify flavonoids-rich fractions from the flowers (PFF) and leaves (PLF) of P. chinense, and to assess their potential protective effects against oxidative, alcohol-induced, and free fatty acid (FFA) induced injury in hepatic cells. Materials and methodsThe P. chinense flowers and leaves flavonoids-rich fractions were extracted by the method optimized by response surface methodology, and the extracts were subsequently purified using petroleum ether and microporous column. The physical characteristics and component composition of PFF and PLF were analyzed by FT-IR and UPLC-MS/MS. The hepatoprotective activities of PFF and PLF were evaluated by the alcohol, H2O2, and FFA-induced hepatocyte injury cellular model in vitro. The protective effects of PFF and PLF on the hepatic cells were evaluated by assessing cell apoptosis rate, enzymes activities, mitochondrial membrane potential, and mRNA expression in relevant signaling pathways. ResultsThe results revealed that PFF was mainly composed of pinocembrin, quercitrin and quercetin, while PLF was predominantly composed of quercetin, pinocembrin, and kaempferol and their derivatives. PFF and PLF exhibited distinct effects on increasing the cell proliferation rate, regulating the MDA, GOT and GPT levels, and modulating the mRNA expression in apoptosis and antioxidant pathways in alcohol damaged LO2 cells. PFF exhibited superior efficacy in reducing cell apoptosis in alcohol-damage cells compared to PLF. Both PFF and PLF alleviated mitochondrial stress in H2O2-induced LO2 cells. Additionally, the PFF and PLF attenuated lipid accumulation and activated mRNA expressions in PPARα/ACOX1/CPT-1 lipid metabolism pathways, as well as Nrf2/ARE oxidative stress pathways. ConclusionThis study compared the hepatoprotective activities of flavonoids-rich fractions purified from the flowers and leaves of P. chinense. The results contribute to the enhanced development and utilization of various parts of P. chinense aimed at medical and health food applications.

Fagopyrum dibotrys extract improves nonalcoholic fatty liver disease via inhibition of lipogenesis and endoplasmic reticulum stress in high-fat diet-fed mice

ObjectiveThe prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, presenting a treatment challenge due to limited options. Endoplasmic reticulum (ER) stress and associated lipid metabolism disorders are main causes of NAFLD, making it important to inhibit ER stress for effective treatment. Fagopyrum dibotrys has hypolipidemic, anti-inflammatory and hepatoprotective properties, showing promise in treating NAFLD. However, its effects on ER stress in NAFLD remain unclear. This study used a high-fat diet (HFD) to establish NAFLD mouse models and supplemented with Fagopyrum dibotrys extract (FDE) to evaluate its therapeutic effect and underlying mechanisms.ResultsWe showed that FDE supplementation reduced the severity of hepatic steatosis and lowered triglycerides (TG) and total cholesterol (TC) levels in NAFLD mice. At the molecular level, FDE supplementation reduced hepatic lipid deposition by downregulating lipogenic markers (SREBP-1c, SCD1) and upregulating fatty acid oxidase CPT1α expression. Additionally, FDE treatment inhibited the overexpression of ER stress markers (GRP78, CHOP, and P-EIF2α) in NAFLD mice livers, and blocked the activation of the PERK-EIF2α-CHOP pathway, demonstrating its role in maintaining ER homeostasis. Considering that activation of the PERK pathway could exacerbate lipid deposition, our findings suggest that FDE has a protective effect against hepatic steatosis in NAFLD mice by attenuating ER stress, and the potential mechanism is through inhibiting the PERK pathway.