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Search Results (1,428)

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Keywords = hepatoprotective

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21 pages, 2777 KB  
Article
Protective Effects of Cuscuta australis Against CCl4-Induced Hepatic Injury in Rats: Antioxidant, Anti-Inflammatory, and In Silico Insights
by Hanen Baccari, Arij Bedoui, Anouar Feriani, Amal Bouallegue, Nihad Sahri, Sohaib Khatib, Mohamed Kharrat, Nizar Tlili, Mansour Sobeh, Moez Amri and Zouhaier Abbes
Pharmaceuticals 2025, 18(10), 1524; https://doi.org/10.3390/ph18101524 - 10 Oct 2025
Abstract
Background/Objectives: The search for new bioactive molecules increasingly extends beyond conventional medicinal plants, highlighting the importance of exploring alternative botanical sources. Parasitic plants represent a promising but underexploited reservoir of pharmacologically relevant compounds. Cuscuta australis (CA), a parasitic species with a history of [...] Read more.
Background/Objectives: The search for new bioactive molecules increasingly extends beyond conventional medicinal plants, highlighting the importance of exploring alternative botanical sources. Parasitic plants represent a promising but underexploited reservoir of pharmacologically relevant compounds. Cuscuta australis (CA), a parasitic species with a history of traditional use, remains poorly characterized. This study aimed to investigate its phytochemical composition and evaluate its antioxidant, anti-inflammatory, and hepatoprotective properties. Methods: The phytochemical profile of CA extract was characterized by LC-MS. Antioxidant capacity was assessed using DPPH and ABTS assays. In vivo hepatoprotection was evaluated in male rats subjected to CCl4-induced hepatotoxicity and treated orally with CA (30 or 60 mg/kg body weight). Biochemical, lipid, oxidative stress, and histological parameters were determined. Molecular docking was conducted to predict the binding of major identified compounds against selected protein targets. Results: CA significantly and dose-dependently improved biochemical and histological markers. At 60 mg/kg, ALT, AST, ALP, and bilirubin were reduced by 32%, 33%, 63%, and 51%, respectively. Lipid metabolism was improved by decreased TC, TG, and LDL-C with increased HDL-C. Antioxidant defense was enhanced through elevated CAT, SOD, and GPx activities, accompanied by reduced MDA levels. TNF-α and IL-6 decreased by 48% and 53%, respectively. Histopathology confirmed hepatoprotection and reduced fibrosis. Docking studies revealed strong binding affinities (−7.07 to −19.20 kcal/mol) for several metabolites, notably quercetin glucoside, diosmetin glucoside, caffeic acid glucoside, feruloylquinic acid, and isorhamnetin glucoside, against CYP450, IL-2, TNF-α, and IL-6. Conclusions: These findings demonstrate that C. australis is a promising source of bioactive compounds with hepatoprotective, antioxidant, antihyperlipidemic, and anti-inflammatory effects, supporting its potential as a natural therapeutic agent. Full article
(This article belongs to the Section Natural Products)
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24 pages, 4515 KB  
Article
Effects of the Polar Fraction of Lophocereus schottii on Gene Expression and Hepatocyte Proliferation in a Wistar Rat Model of Hepatocellular Carcinoma
by Marina Campos-Valdez, Jaime Sánchez-Meza, Arturo Orozco-Barocio, José A. Domínguez-Rosales, Juliana Marisol Godínez-Rubí, Sarai C. Rodríguez-Reyes, Erika Martínez-López, Miriam R. Bueno-Topete, Manuel A. Castro-García, Guillermo M. Zúñiga-González, Daniel Ortuño-Sahagún and Laura V. Sánchez-Orozco
Int. J. Mol. Sci. 2025, 26(19), 9788; https://doi.org/10.3390/ijms26199788 - 8 Oct 2025
Viewed by 25
Abstract
Hepatocellular carcinoma (HCC) remains a major global health problem for which there are few effective treatments. Phytochemicals from natural sources, such as those found in cacti, exhibit chemoprotective and hepatoprotective properties. In this study, the effect of the polar fraction of Lophocereus schottii [...] Read more.
Hepatocellular carcinoma (HCC) remains a major global health problem for which there are few effective treatments. Phytochemicals from natural sources, such as those found in cacti, exhibit chemoprotective and hepatoprotective properties. In this study, the effect of the polar fraction of Lophocereus schottii (LsPF) was investigated in a Wistar rat model of HCC induced by weekly administration of diethylnitrosamine (DEN, 50 mg/kg, i.p.) and 2-acetylaminofluorene (2-AAF, 25 mg/kg, i.g.) for 13 weeks. LsPF (50 mg/kg, i.g., three times per week) was administered either concurrently with HCC induction beginning in the first week or after seven weeks of HCC induction. LsPF did not lead to a significant improvement in macroscopic, biochemical or histologic results. However, when LsPF was administered after 7 weeks of HCC induction, it modulated the expression of genes related to liver carcinogenesis, including SOD, CAT, CYP2E1, TGFB1, AFP, and COL1A. In addition, co-administration of LsPF along with the damage treatment decreased the number of mitotic hepatocytes. These results suggest that LsPF can modulate gene expression and hepatocyte proliferation in HCC, with efficacy depending on the timing of administration, disease stage, and administration method. Further studies are needed to optimize its therapeutic potential. Full article
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12 pages, 552 KB  
Article
Cucurbitane Glycosides from Siraitia Grosvenorii and Their Hepatoprotective Activities
by Jia-Nan Mao, Hua-Xue Huang, Qing-Ling Xie, Guang-Yu Chen, Juan-Jiang Wu, Ying Deng, Shuang Zhan, Zhi Peng, Xu-Dong Zhou and Wei Wang
Molecules 2025, 30(19), 3983; https://doi.org/10.3390/molecules30193983 - 4 Oct 2025
Viewed by 179
Abstract
Siraitia grosvenorii (S. grosvenorii), a traditional medicine food homology plant, serves both dietary and medicinal purposes and is increasingly exploited for its bioactivities in pharmaceuticals and nutritional value. In this research, fifteen glycosides including three new cucurbitane-type triterpenoid glycosides named Luohanguosides [...] Read more.
Siraitia grosvenorii (S. grosvenorii), a traditional medicine food homology plant, serves both dietary and medicinal purposes and is increasingly exploited for its bioactivities in pharmaceuticals and nutritional value. In this research, fifteen glycosides including three new cucurbitane-type triterpenoid glycosides named Luohanguosides A–C (13) and twelve known ones (415) have been isolated from the aqueous extract of fresh S. grosvenorii fruits. A comprehensive analysis of 1D, 2D-NMR, HRESIMS techniques along with some other spectroscopic methods led to the elucidation of their chemical structures. Further investigation focused on the hepatoprotective activities of compounds 115. It turned out that compounds 1, 5, and 10 exhibited significant hepatoprotective activities compared to bicyclol under the same concentration (20 μM), providing scientific support for further research on S.grosvenorii products for their preventive potential of hepatic diseases. Full article
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19 pages, 4587 KB  
Article
Wet Media Milling Preparation and Process Simulation of Nano-Ursolic Acid
by Guang Li, Wenyu Yuan, Yu Ying and Yang Zhang
Pharmaceutics 2025, 17(10), 1297; https://doi.org/10.3390/pharmaceutics17101297 - 3 Oct 2025
Viewed by 365
Abstract
Background/Objectives: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development [...] Read more.
Background/Objectives: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development of drug formulations. This study investigates the preparation of a nano-UA suspension by wet grinding, researches the influence of process parameters on particle size, and explores the rules of particle breakage and agglomeration by combining model fitting. Methods: Wet grinding experiments were conducted using a laboratory-scale grinding machine. The particle size distributions (PSDs) of UA suspensions under different grinding conditions were measured using a laser particle size analyzer. A single-factor experimental design was employed to optimize operational conditions. Model parameters for a population balance model considering both breakage and agglomeration were determined by an evolutionary algorithm optimization method. By measuring the degree to which UA inhibits the colorimetric reaction between salicylic acid and hydroxyl radicals, its antioxidant capacity in scavenging hydroxyl radicals was indirectly evaluated. Results: Wet grinding process conditions for nano-UA particles were established, yielding a UA suspension with a D50 particle size of 122 nm. The scavenging rate of the final grinding product was improved to three times higher than that of the UA raw material (D50 = 14.2 μm). Conclusions: Preparing nano-UA suspensions via wet grinding technology can significantly enhance their antioxidant properties. Model regression analysis of PSD data reveals that increasing the grinding mill’s stirring speed leads to more uniform particle size distribution, indicating that grinding speed (power) is a critical factor in producing nanosuspensions. Full article
(This article belongs to the Special Issue Advanced Research on Amorphous Drugs)
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14 pages, 477 KB  
Article
Effect of Theracurmin Products for Alleviating Alcohol Hangovers in Healthy Adults
by Yeongtaek Hwang, Paul Kim, Minji Kwon, Sung-Vin Yim, Bo-Hyung Kim and Hyunjung Lim
J. Clin. Med. 2025, 14(19), 6996; https://doi.org/10.3390/jcm14196996 - 2 Oct 2025
Viewed by 400
Abstract
Background/Objectives: Excessive alcohol consumption leads to hangovers, which cause discomfort and reduce work efficiency, resulting in socioeconomic losses. Theracurmin, known for its antioxidant and hepatoprotective properties, may help mitigate these effects. We evaluated the efficacy and safety of two Theracurmin-based products in alleviating [...] Read more.
Background/Objectives: Excessive alcohol consumption leads to hangovers, which cause discomfort and reduce work efficiency, resulting in socioeconomic losses. Theracurmin, known for its antioxidant and hepatoprotective properties, may help mitigate these effects. We evaluated the efficacy and safety of two Theracurmin-based products in alleviating hangover symptoms in humans. Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted in 27 healthy adults, with a balanced distribution of men and women. Two formulations were tested: Ready Q, containing Theracurmin, Hovenia dulcis Thunb. extract powder, and L-glutathione yeast extract; and Theracurmin, containing only Theracurmin. The products were administered on designated visit days, followed by an alcohol challenge 30 min after administration. Blood and breath alcohol profiles were assessed 15 h post-consumption, and participants completed a hangover symptom questionnaire. Results: Compared to placebo, Ready Q resulted in a significantly lower area under the curve (AUC) for serum alcohol concentration (−94.92 mg·h/dL [−170.91, −18.93]), as well as lower AUC (−8.441 mg·h/dL [−11.713, −5.169]) for serum acetaldehyde. Theracurmin showed similar effects, with reduced AUC (−117.21 mg·h/dL [−194.20, −40.22]) for serum alcohol concentration, and lower AUC (−8.161 mg·h/dL [−12.597, −3.725]) for corrected serum acetaldehyde levels. Conclusions: These findings suggest that both products effectively enhance alcohol metabolism in healthy adults, underscoring their potential as interventions for alleviating alcohol hangovers. Full article
(This article belongs to the Section Mental Health)
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69 pages, 1993 KB  
Review
Glycyrrhizin (Glycyrrhizic Acid)—Pharmacological Applications and Associated Molecular Mechanisms
by Deepak Kumar Semwal, Ankit Kumar, Ruchi Badoni Semwal, Nand Kishor Dadhich, Ashutosh Chauhan and Vineet Kumar
Drugs Drug Candidates 2025, 4(4), 44; https://doi.org/10.3390/ddc4040044 - 30 Sep 2025
Viewed by 889
Abstract
Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on [...] Read more.
Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on its molecular targets. Methods: Scientific literature was thoroughly retrieved from reputable databases, including Scopus, Web of Science, and PubMed, up to 30 July 2025. The keywords “glycyrrhizin” and “glycyrrhizic acid” were used to identify relevant references, with a focus on pharmacological applications. Studies on synthetic analogs, non-English publications, non-pharmacological applications, and GL containing crude extracts were largely excluded. Results: Glycyrrhizin, the major bioactive constituent of Glycyrrhiza glabra, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, hepatoprotective, antitumor, neuroprotective, and immunomodulatory effects. These actions are primarily mediated through the inhibition of high-mobility group box 1 (HMGB1) and the modulation of key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and various cytokine networks. As a result of its therapeutic potential, GL-based formulations, including Stronger Neo-Minophagen C, and GL-rich extracts of G. glabra are commercially available as pharmaceutical preparations and food additives. Conclusions: Despite its therapeutic potential, the clinical application of GL is limited by poor oral bioavailability, metabolic variability, and adverse effects such as pseudoaldosteronism. Hence, careful consideration of pharmacokinetics and safety is essential for translating its therapeutic potential into clinical practice. Full article
(This article belongs to the Section Drug Candidates from Natural Sources)
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17 pages, 400 KB  
Review
A Comprehensive Review of Robinetin: Distribution, Biological Activity and Pharmacokinetic Parameters
by Katarzyna Jakimiuk
Int. J. Mol. Sci. 2025, 26(19), 9546; https://doi.org/10.3390/ijms26199546 - 30 Sep 2025
Viewed by 312
Abstract
Robinetin, a naturally occurring polyhydroxylated flavonol, has gained attention due to its broad spectrum of biological activities and potential therapeutic applications. This review presents a comprehensive summary of the current knowledge concerning the natural occurrence, extraction, spectroscopic characterization, and pharmacological properties of robinetin. [...] Read more.
Robinetin, a naturally occurring polyhydroxylated flavonol, has gained attention due to its broad spectrum of biological activities and potential therapeutic applications. This review presents a comprehensive summary of the current knowledge concerning the natural occurrence, extraction, spectroscopic characterization, and pharmacological properties of robinetin. Ethnobotanical evidence highlights its presence in various medicinal plants, particularly within the Fabaceae family, where it contributes to traditional treatments of infections, inflammation, and metabolic disorders. Robinetin exhibits diverse bioactivities, including antiviral, antibacterial, antiparasitic, antioxidant, anti-mutagenic, and enzyme-inhibitory effects. Notably, it inhibits HIV-1 integrase and acetylcholinesterase and demonstrates moderate antiproliferative activity in cancer cell lines. Despite limited water solubility, its redox behavior and metal-chelating capabilities support its antioxidant potential. Recent in vivo studies indicate its hepatoprotective and metabolic regulatory effects. Additionally, computational models reveal promising interactions with molecular targets such as CDK1. Collectively, these findings underscore the multifaceted therapeutic potential of robinetin and advocate for further pharmacokinetic and clinical investigations to validate its efficacy as a lead compound for the development of phytochemically derived pharmaceuticals. Full article
(This article belongs to the Special Issue Role of Natural Compounds in Human Health and Disease)
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22 pages, 12023 KB  
Article
Toxicological Assessment of Origanum majorana L.: Evaluation of Its Cytotoxicity, Genotoxicity, and Acute Oral Toxicity
by Ayfer Beceren, Ayse Nur Hazar-Yavuz, Ozlem Bingol Ozakpinar, Duygu Taskin, İsmail Senkardes, Turgut Taskin, Ozlem Tugce Cilingir-Kaya, Ahmad Kado and Hatice Kubra Elcioglu
Int. J. Mol. Sci. 2025, 26(19), 9461; https://doi.org/10.3390/ijms26199461 - 27 Sep 2025
Viewed by 301
Abstract
Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its [...] Read more.
Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields. Full article
(This article belongs to the Section Molecular Toxicology)
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15 pages, 1748 KB  
Article
Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3
by Maria Sotiropoulou, Ioannis Katsaros, Michail Vailas, Fotini Papachristou, Paraskevi Papakyriakopoulou, Nikolaos Kostomitsopoulos, Alexandra Giatromanolaki, Georgia Valsami, Alexandra Tsaroucha and Dimitrios Schizas
Life 2025, 15(10), 1523; https://doi.org/10.3390/life15101523 - 26 Sep 2025
Viewed by 413
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and progressive liver disorder linked to metabolic syndrome affecting over 30% of global population, currently lacking effective pharmacological treatment. Natural compounds like quercetin, silibinin, and crocetin have shown hepatoprotective potential. This study investigates [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and progressive liver disorder linked to metabolic syndrome affecting over 30% of global population, currently lacking effective pharmacological treatment. Natural compounds like quercetin, silibinin, and crocetin have shown hepatoprotective potential. This study investigates their therapeutic effect in a high-fat diet (HFD)-induced mouse model of MASLD. Methods: Ninety-five C57BL/6J (wild type) mice were fed an HFD for 12 weeks to induce hepatic steatosis and were then randomized into eight groups for a 4-week therapeutic intervention. Liver histopathology was assessed using the NAFLD Activity Score (NAS), and immunohistochemistry was conducted to quantify CD36 and PLIN3 expressions. Results: Both quercetin groups significantly reduced the prevalence of steatohepatitis (p-value < 0.05) and showed an increased PLIN3 expression. Silibinin also improved steatohepatitis, with the high-dose group reaching statistical significance (p-value 0.020), and demonstrated upregulation of PLIN3 along with significant CD36 downregulation. Crocetin groups markedly improved disease severity and showed the highest PLIN3 expression, though without significant changes in CD36. Conclusions: Quercetin, silibinin, and crocetin mitigate MASLD progression by reducing steatohepatitis. These effects are associated with distinct modulations of CD36 and PLIN3 protein expression, suggesting that these pathways are promising therapeutic targets in MASLD management. Natural compounds offer a multi-targeted hepatoprotective approach warranting further clinical investigation. Full article
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16 pages, 1228 KB  
Article
Supplementation Effects of Hibiscus sabdariffa L. Flower Aqueous Extract on Body Composition and Metabolism in Eutrophic and Obese Rats
by João Fernando Bernardo da Costa, Alana Louzada Millions Monteiro, Bruna Almeida Nascimento, Clarice Maia Vinagre de Oliveira, Karen Pereira Coutinho, Anderson Junger Teodoro, Barbara Elisabeth Teixeira-Costa and Mariana Sarto Figueiredo
Obesities 2025, 5(4), 67; https://doi.org/10.3390/obesities5040067 - 25 Sep 2025
Viewed by 359
Abstract
Obesity is a chronic, multifactorial disease characterized by excess body fat and is a major risk factor for various metabolic disorders. Bioactive compounds from the diet have been recognized for their role in preventing chronic non-communicable diseases and as adjuvants in managing endocrine–metabolic [...] Read more.
Obesity is a chronic, multifactorial disease characterized by excess body fat and is a major risk factor for various metabolic disorders. Bioactive compounds from the diet have been recognized for their role in preventing chronic non-communicable diseases and as adjuvants in managing endocrine–metabolic dysfunctions. Hibiscus sabdariffa L. (HSL) is rich in bioactive compounds with antioxidant, antihypertensive, and antihyperlipidemic properties. This study evaluated the effects of HSL flower extract supplementation on body composition, lipid profile, and biochemical parameters in both eutrophic and high-fat diet-induced obese rats. Thirty-two Wistar rats were assigned to four groups: control, control plus HSL extract, high-fat diet, and high-fat diet plus HSL extract. The extract was administered orally at 150 mg kg−1 for thirty days. Dual-energy X-ray absorptiometry revealed that HSL supplementation significantly attenuated fat mass gain (from 98 g to 75 g) and adiposity indices (10.23 to 8.86) in obese rats without altering total body mass. Moreover, the HSL extract improved lipid profiles by reducing LDL cholesterol from 23 to 13 mg dL−1 and exhibited potential hepatoprotective effects linked with decreased ALT (40 to 26.7 U L−1) and total bilirubin (0.12 to 0.07 mg dL−1) levels. Although glucose metabolism parameters had no significant differences, a trend toward improved insulin sensitivity was observed. These results suggest that the aqueous HSL extract may exert cardioprotective, hepatoprotective, and anti-obesity effects, supporting its potential as a complementary therapeutic agent in obesity and related metabolic disorders. Full article
(This article belongs to the Special Issue The Impact of Food Compounds on Obesity Mechanisms)
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16 pages, 3215 KB  
Article
Astaxanthin Alleviates Ochratoxin A (OTA)-Induced Spleen Dysfunction and Apoptosis in Broiler Chickens by Modulating the PTEN/PI3K/AKT Signaling Pathway
by Zhibi Cheng, Weilun Sang, Peng Li and Shuhua Yang
Antioxidants 2025, 14(10), 1160; https://doi.org/10.3390/antiox14101160 - 24 Sep 2025
Viewed by 316
Abstract
Ochratoxin A (OTA), a common mycotoxin contaminant, poses significant health risks through its multi-organ toxicity. While OTA is known to cause immune organ dysfunction leading to immunotoxicity, its precise mechanistic pathways remain unclear. The spleen is an important immune organ of the body [...] Read more.
Ochratoxin A (OTA), a common mycotoxin contaminant, poses significant health risks through its multi-organ toxicity. While OTA is known to cause immune organ dysfunction leading to immunotoxicity, its precise mechanistic pathways remain unclear. The spleen is an important immune organ of the body and plays a key role in immune defense and homeostasis maintenance. Astaxanthin (AST), a potent antioxidant with demonstrated immunomodulatory properties, exhibits a broad therapeutic potential including anti-inflammatory, wound-healing, anti-aging, and hepatoprotective effects. Therefore, this study aimed to explore the mechanism by which AST attenuates OTA-induced immunotoxicity using a chicken OTA/AST treatment model. Sixty 1-day-old, white-feathered, sex-undifferentiated chicks were randomly allocated into four groups (n = 15): (1) Control, (2) OTA (1 mg/kg), (3) AST (100 mg/kg), and (4) OTA + AST (1 mg/kg OTA + 100 mg/kg AST). The experiment lasted for 21 days to establish the model. Subsequently, serum ELISA, antioxidant capacity assays, qRT-PCR, and western blot (WB) analyses were employed to explore the protective role of AST against immunotoxicity. The results showed that AST increased splenic organ coefficients and serum immunoglobulin (IgM and IgG) concentrations (p < 0.01) and decreased the expression of inflammatory factors (IL-8, IL-6, and IL-1β) (p < 0.01). We found that OTA was involved in the expression of the PTEN/PI3K/AKT signaling pathway (PTEN, PI3K, AKT, p-AKT (Ser473)) and apoptotic genes (Bcl-2, Bax, Caspase3, Caspase9). Notably, AST significantly attenuated OTA-induced oxidative damage (ROS, MDA, T-AOC) in the spleen (p < 0.05), upregulated the expression of PI3K and p-AKT (Ser473) (p < 0.05) and inhibited the expression of PTEN and apoptosis-related genes (p < 0.05). In summary, AST attenuates OTA-induced immunotoxicity by alleviating oxidative stress and modulating the PTEN/PI3K/AKT signaling pathway. Full article
(This article belongs to the Special Issue Valorization of the Antioxidant Power of Natural Compounds)
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30 pages, 4182 KB  
Review
Advances in Extraction Technologies of Silybum marianum L. and Its Role in Protecting Against Skin Damage
by Oumayma Iraqi, Mariam Jalal, Issam El Mouzazi, Mourad Jbene, Youness Taboz and Amar Habsaoui
Cosmetics 2025, 12(5), 211; https://doi.org/10.3390/cosmetics12050211 - 21 Sep 2025
Viewed by 866
Abstract
Silybum marianum L., commonly known as milk thistle, is traditionally recognized for its hepatoprotective properties. This is primarily due to silymarin, a mixture of flavonolignans with strong antioxidant and anti-inflammatory activities. Although many studies have reported on its biological activities, critical syntheses that [...] Read more.
Silybum marianum L., commonly known as milk thistle, is traditionally recognized for its hepatoprotective properties. This is primarily due to silymarin, a mixture of flavonolignans with strong antioxidant and anti-inflammatory activities. Although many studies have reported on its biological activities, critical syntheses that compare extraction technologies and highlight its protective roles beyond liver health remain limited. Despite the abundant literature, the protective effects of milk thistle against skin damage remain largely unexplored. To address this gap, we performed a comprehensive literature search across PubMed, Scopus, Web of Science, and Google Scholar. Our research covered publications up to February 2025 and used predefined keywords, including extraction methods for the release of silymarin, in vitro, in vivo, and clinical studies relevant to its protective effects against skin damage. The evidence indicates that silymarin exerts protective effects on the skin, including the prevention of photoaging, the management of acne, the promotion of wound healing, and the defense against UV-induced damage, through the activation of Nrf2 and the preservation of the extracellular matrix. These results highlight the promising dermatological benefits of silymarin, as well as the need for further clinical studies and the optimization of environmentally sustainable extraction techniques for large-scale production. Full article
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20 pages, 5023 KB  
Article
Protective Effects of Methanolic Extract of Micromeria frivaldszkyana (Degen) Velen Against Acetaminophen-Induced Liver Toxicity in Male Wistar Rats
by Elisaveta Apostolova, Kristina Stavrakeva, Vesela Kokova, Ivica Dimov, Mariya Choneva, Delyan Delev, Ilia Kostadinov, Ilia Bivolarski, Maria Koleva, Rumen Mladenov, Plamen Stoyanov and Anelia Bivolarska
Int. J. Mol. Sci. 2025, 26(18), 9112; https://doi.org/10.3390/ijms26189112 - 18 Sep 2025
Viewed by 336
Abstract
Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar [...] Read more.
Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg/kg rosmarinic acid (RA); or 125 mg/kg silymarin. Liver toxicity was induced by oral application of 2000 mg/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA). Full article
(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)
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25 pages, 1864 KB  
Review
Food Minor Bioactive Compounds of Polyphenolic and Polyprenolic Nature Are Promising Agents for the Prevention and Therapy of Non-Alcoholic Fatty Liver Disease
by Anastasiya Balakina, Yuliya Sidorova, Nikita Petrov and Vladimir Shipelin
Molecules 2025, 30(18), 3791; https://doi.org/10.3390/molecules30183791 - 18 Sep 2025
Viewed by 618
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent liver disorders globally, affecting approximately 25% to 40% of the adult population. Closely associated with metabolic syndrome, obesity, insulin resistance, and dyslipidemia, NAFLD presents a growing burden due to its increasing incidence and [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent liver disorders globally, affecting approximately 25% to 40% of the adult population. Closely associated with metabolic syndrome, obesity, insulin resistance, and dyslipidemia, NAFLD presents a growing burden due to its increasing incidence and high healthcare costs. In this context, the development of effective preventive and therapeutic strategies remains a pressing challenge in modern medicine. This review aims to analyze current scientific evidence on bioactive plant compounds—particularly polyphenols and polyprenols—including their natural sources, mechanisms of action, and potential applications in the prevention and dietary management of NAFLD. A growing body of evidence demonstrates that both polyphenols and polyprenols exert hepatoprotective, antioxidant, anti-inflammatory, and hypolipidemic effects. These compounds modulate signaling pathways implicated in hepatic steatosis and fibrosis, positively influence gut microbiota composition, and affect bile acid metabolism. Studies have confirmed the efficacy of polyphenol-rich foods (naringenin, resveratrol, chlorogenic acid, etc.) and polyprenol-based formulations in reducing body weight and liver steatosis, improving biochemical markers and insulin resistance. The combined application of polyphenols and polyprenols may yield synergistic effects on multiple pathogenic pathways and represents a promising direction for the dietary prevention and management of NAFLD. Full article
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Article
Sinapic Acid Regulates the LXRα–ABCG5/8 Axis in the Hepatocytes: A Potential Strategy for Cholesterol Gallstone Management
by Sridevi Rajendran, Chitra Vellapandian, Bhupendra G. Prajapati and Himanshu Paliwal
Pharmaceuticals 2025, 18(9), 1388; https://doi.org/10.3390/ph18091388 - 17 Sep 2025
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Abstract
Background/Objective: Gallstone disease (cholelithiasis) is a prevalent hepatobiliary disorder with limited non-surgical therapeutic options. Sinapic acid (SINAP), a phenolic compound found in various dietary sources, has demonstrated anti-inflammatory and hepatoprotective effects. However, its role in gallstone dissolution has not been explored. This study [...] Read more.
Background/Objective: Gallstone disease (cholelithiasis) is a prevalent hepatobiliary disorder with limited non-surgical therapeutic options. Sinapic acid (SINAP), a phenolic compound found in various dietary sources, has demonstrated anti-inflammatory and hepatoprotective effects. However, its role in gallstone dissolution has not been explored. This study was designed to evaluate whether sinapic acid modulates hepatic cholesterol transport and enhances gallstone dissolution using a gallstone dissolution assay in artificial bile solution. Methods: The cytotoxicity of SINAP was assessed in HepG2 cells via the MTT assay. The mRNA and protein expression of lipid transporters (ABCG5, ABCG8, and LXRα) was quantified using qRT-PCR, ELISA, and Western blotting. Additionally, molecular docking was conducted to evaluate SINAP’s interaction with gallstone-related protein targets compared to that for the standard drugs (ursodeoxycholic acid and ezetimibe). Results: SINAP achieved a 53.71% gallstone weight reduction over 12 days, comparable to that with ursodiol (59.24%), and following 24 h of exposure, SINAP demonstrated minimal cytotoxicity, maintaining over 80% cell viability up to 50 µg/mL, with an IC50 value of 28 µg/mL. SINAP significantly upregulated ABCG5, ABCG8, and LXRα expression (p < 0.01), suggesting enhanced bile acid secretion. Docking studies confirmed the strong binding affinities of SINAP to key cholesterol transport proteins. Conclusions: These results indicate that SINAP may serve as a promising natural candidate for non-surgical management of cholelithiasis and support further preclinical investigation. Full article
(This article belongs to the Section Pharmacology)
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