Structure of POU2AF1 recombinant protein and it affects the progression and treatment of liver cancer based on WGCNA and molecular docking analysis.

Hepatocellular carcinoma, also referred to as HCC, is the most frequent form of primary liver cancer. It is anticipated that the discovery of the molecular pathways related with HCC would open up new possibilities for the treatment of HCC.WGCNA (Weighted gene co-expression network analysis) and molecular docking analysis were used to study the structural characteristics of POU2AF1 recombinant protein and its interaction with related proteins. Normal samples were placed in one group, and tumor samples were placed in another group inside the GEO database. We continued our investigation of the DEGs by performing an enrichment analysis using GO and KEGG. The GSCA platform is utilized in the process of doing an analysis of the connection between gene expression and medication sensitivity. In the end, the core target and the active molecule were both given the green light for a molecular docking investigation. POU2AF1 is being considered as a possible therapeutic target for HCC, and the results of our work have presented novel concepts for the treatment of HCC.

Exploring anti-diabetic potential of compounds from roots of Dendrobium polyanthum Wall. ex Lindl. through inhibition of carbohydrate-digesting enzymes and glycation inhibitory activity.

Eight compounds, including one anthraquinone, two bibenzyls, one phenanthrene, three dihydrophenanthrenes, and one flavonoid, were isolated from the roots of Dendrobium polyanthum Wall. ex Lindl. Among these, six compounds were investigated for inhibitory activities against alpha-glucosidase, alpha-amylase, and advanced glycation end products (AGEs) production. Additionally, molecular docking was conducted to analyze the interactions of the test compounds with alpha-glucosidase. Moscatin, the only isolated phenanthrene, displayed the strongest anti-alpha-glucosidase activity with an IC50 of 32.45 ± 1.04 µM, approximately 10-fold smaller than that of acarbose. Furthermore, moscatilin most strongly inhibited alpha-amylase and AGEs production with IC50 values of 256.94 ± 9.87 and 67.89 ± 9.42 µM, respectively. Molecular docking analysis revealed the effective binding of all substances to alpha-glucosidase with smaller lowest binding energy values than acarbose. Moscatin was selected for kinetics studies, and it was identified as a non-competitive inhibitor with approximately 9-fold greater inhibitory capability than acarbose. This study represents the first report on the phytochemical constituents and antidiabetic potential of compounds derived from the roots of D. polyanthum Wall. ex Lindl.

Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids.

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC50 1.0-9.0 µM in the tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition test. Lupane derivatives - 1-oxime 7, 1,10-seco-hydroxynitrile 11 and furanoterpenoid 14 - were selected as those expected to be the most promising compounds. The results of molecular modeling evinced the strongest binding of compound 11 to the active site of Tdp1 compared to the reference drug. Simultaneously, only compound 11 at subtoxic concentration (10 µM) produced a synergetic effect on the topotecan activity against HeLa-V cells.

Catalpol reduced LPS induced BV2 immunoreactivity through NF-κB/NLRP3 pathways: an in Vitro and in silico study.

Background: Ischemic Stroke (IS) stands as one of the primary cerebrovascular diseases profoundly linked with inflammation. In the context of neuroinflammation, an excessive activation of microglia has been observed. Consequently, regulating microglial activation emerges as a vital target for neuroinflammation treatment. Catalpol (CAT), a natural compound known for its anti-inflammatory properties, holds promise in this regard. However, its potential to modulate neuroinflammatory responses in the brain, especially on microglial cells, requires comprehensive exploration. Methods: In our study, we investigated into the potential anti-inflammatory effects of catalpol using lipopolysaccharide (LPS)-stimulated BV2 microglial cells as an experimental model. The production of nitric oxide (NO) by LPS-activated BV2 cells was quantified using the Griess reaction. Immunofluorescence was employed to measure glial cell activation markers. RT-qPCR was utilized to assess mRNA levels of various inflammatory markers. Western blot analysis examined protein expression in LPS-activated BV2 cells. NF-κB nuclear localization was detected by immunofluorescent staining. Additionally, molecular docking and molecular dynamics simulations (MDs) were conducted to explore the binding affinity of catalpol with key targets. Results: Catalpol effectively suppressed the production of nitric oxide (NO) induced by LPS and reduced the expression of microglial cell activation markers, including Iba-1. Furthermore, we observed that catalpol downregulated the mRNA expression of proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß, as well as key molecules involved in the NLRP3 inflammasome and NF-κB pathway, including NLRP3, NF-κB, caspase-1, and ASC. Our mechanistic investigations shed light on how catalpol operates against neuroinflammation. It was evident that catalpol significantly inhibited the phosphorylation of NF-κB and NLRP3 inflammasome activation, both of which serve as upstream regulators of the inflammatory cascade. Molecular docking and MDs showed strong binding interactions between catalpol and key targets such as NF-κB, NLRP3, and IL-1ß. Conclusion: Our findings support the idea that catalpol holds the potential to alleviate neuroinflammation, and it is achieved by inhibiting the activation of NLRP3 inflammasome and NF-κB, ultimately leading to the downregulation of pro-inflammatory cytokines. Catalpol emerges as a promising candidate for the treatment of neuroinflammatory conditions.

Computational drug repurposing effort for identifying novel hits for the treatment of diseases such as endometriosis, uterine fibroids, and prostate cancer.

This research aimed to identify potential drug compounds from the ZINC15 molecule database that could effectively treat GnRH1R-related diseases. The study utilized molecular docking and molecular dynamics methods to achieve this goal, which is crucial in drug repurposing research. The virtual screening process involved analyzing known drug compounds using molecular docking. Additionally, molecular dynamics simulations and MM-GBSA were employed to evaluate the stability of the complexes and determine the interactions between the compounds and protein structure. As a result, this study provides significant insights for treating diseases such as endometriosis, uterine fibroids, and prostate cancer related to GnRH1R. The study also involved designing new drugs and identifying necessary molecular scaffolds.

Chemical Composition, Anti-bacterial Activity and Molecular Docking Studies of Essential Oil Isolated from Sa Sam Nam (Launaea sarmentosa).

Launaea sarmentosa, also known as Sa Sam Nam, is a widely used remedy in Vietnamese traditional medicine and cuisine. However, the chemical composition and bioactivity of its essential oil have not been elucidated yet. In this study, we identified 40 compounds (98.6% of total peak area) in the essential oil via GC-MS analysis at the first time. Among them, five main compounds including Thymohydroquinone dimethyl ether (52.4%), (E)-α-Atlantone (9.0%), Neryl isovalerate (6.6%), Davanol D2 (isomer 2) (3.9%), and trans-Sesquisabinene hydrate (3.9%) have accounted for 75.8% of total peak area. The anti-bacterial activity of the essential oil against 4 microorganisms including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa has also investigated via agar well diffusion assay. The results showed that the essential oil exhibited a strong antibacterial activity against Bacillus subtilis with the inhibition zones ranging from 8.2 to 18.7 mm. To elucidate the anti-bacterial effect mechanism of the essential oil, docking study of five main compounds of the essential oil (Thymohydroquinone dimethyl ether, (E)-α-Atlantone, Neryl isovalerate, Davanol D2 (isomer 2), and trans-Sesquisabinene hydrate) against some key proteins for bacterial growth such as DNA gyrase B, penicillin binding protein 2A, tyrosyl-tRNA synthetase, and dihydrofolate reductase were performed. The results showed that the main constituents of essential oil were highly bound with penicillin binding protein 2A with the free energies ranging -27.7 to -44.8 kcal/mol, which suggests the relationship between the antibacterial effect of essential oil and the affinity of main compounds with penicillin binding protein. In addition, the free energies of main compounds of the essential oil with human cyclooxygenase 1, cyclooxygenase 2, and phospholipase A2, the crucial proteins related with inflammatory response were less than diclofenac, a non-steroidal antiinflammatory drug. These findings propose the essential oil as a novel and promising anti-bacterial and anti-inflammatory medicine or cosmetic products.

Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase.

Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

Putative Probiotic Ligilactobacillus salivarius Strains Isolated from the Intestines of Meat-Type Pigeon Squabs.

This study aims to screen for potential probiotic lactic acid bacteria from the intestines of meat-type pigeon squabs. Ligilactobacillus salivarius YZU37 was identified as the best comprehensive performed strain. Being acid- and bile salt-tolerant, it displayed growth-inhibition activities against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, and Salmonella typhimurium SL1344, exhibited sensitivity to 6 commonly used antibiotics, and endowed with good cell surface hydrophobicity, auto-aggregation property, and anti-oxidant activities. Results of in vitro experiments indicated that the bacteriostatic effects of this strain were related to the production of proteinaceous substances that depend on acidic conditions. Whole-genome sequencing of L. salivarius YZU37 was performed to elucidate the genetic basis underlying its probiotic potential. Pangenome analysis of L. salivarius YZU37 and other 212 L. salivarius strains available on NCBI database revealed a pigeon-unique gene coding choloylglycine hydrolase (CGH), which had higher enzyme-substrate binding affinity than that of the common CGH shared by L. salivarius strains of other sources. Annotation of the functional genes in the genome of L. salivarius YZU37 revealed genes involved in responses to acid, bile salt, heat, cold, heavy metal, and oxidative stresses. The whole genome analysis also revealed the absence of virulence and toxin genes and the presence of 65 genes distributed under 4 CAZymes classes, 2 CRISPR-cas regions, and 3 enterolysin A clusters which may confer the acid-dependent antimicrobial potential of L. salivarius YZU37. Altogether, our results highlighted the probiotic potential of L. salivarius YZU37. Further in vivo investigations are required to elucidate its beneficial effects on pigeons.

Deciphering the inhibitory mechanisms of betanin and phyllocactin from Hylocereus polyrhizus peel on protein glycation, with insights into their application in bread.

Protein glycation closely intertwines with the pathogenesis of various diseases, sparking a growing interest in exploring natural antiglycation agents. Herein, high-purity betacyanins (betanin and phyllocactin) derived from Hylocereus polyrhizus peel were studied for their antiglycation potential using an in vitro bovine serum albumin (BSA)-glucose model. Notably, betacyanins outperformed aminoguanidine, a recognized antiglycation agent, in inhibiting glycation product formation across different stages, especially advanced glycation end-products (AGEs). Interestingly, phyllocactin displayed stronger antiglycation activity than betanin. Subsequent mechanistic studies employing molecular docking analysis and fluorescence quenching assay unveiled that betacyanins interact with BSA endothermically and spontaneously, with hydrophobic forces playing a dominant role. Remarkably, phyllocactin demonstrated higher binding affinity and stability to BSA than betanin. Furthermore, the incorporation of betacyanins into bread dose-dependently suppressed AGEs formation during baking and shows promise for inhibiting in vivo glycation process post-consumption. Overall, this study highlights the substantial potential of betacyanins as natural antiglycation agents.

Purification and characterization of betacyanin monomers from Hylocereus polyrhizus peel: A comparative study of their antioxidant and antidiabetic activities with mechanistic insights.

Betacyanins have garnered escalating research interest for their promising bioactivities. However, substantial challenges in purification and separation have impeded a holistic comprehension of the distinct bioactivities of individual betacyanins and their underlying mechanisms. Herein, betanin and phyllocactin monomers with purity exceeding 95% were successfully obtained from Hylocereus polyrhizus peel using a feasible protocol. These monomers were subsequently employed for comparative bioactivity assessments to uncover underlying mechanisms and illuminate structure-activity relationships. Interestingly, phyllocactin exhibited superior antioxidant activities and 36.1% stronger inhibitory activity on α-glucosidase compared to betanin. Mechanistic studies have revealed that they function as mixed-type inhibitors of α-amylase and competitive inhibitors of α-glucosidase, with interactions predominantly driven by hydrogen bonding. Notably, phyllocactin demonstrated a greater binding affinity with enzymes than betanin, thereby substantiating its heightened inhibitory activity. Overall, our results highlight novel bioactivities of betacyanin monomers and provide profound insights into the intricate interplay between structures and properties.

Unveiling Glucosinolate Diversity in Brassica Germplasm and In Silico Analysis for Determining Optimal Antioxidant Potential.

This study explored the glucosinolate (GSL) content in Brassica plants and utilized in silico analysis approach to assess their antioxidant capabilities. GSLs, present abundantly in Brassica vegetables, offer potential health advantages, including antioxidant effects. Employing Ultra-Performance Liquid Chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS), major GSLs were identified in 89 accessions from diverse species and subspecies. Statistical analysis and principal component analysis unveiled significant GSL variation and potential correlations among the Brassica germplasms. This study unveils the dominance of aliphatic GSLs over aromatic and indolyl compounds in all the accessions. Notably, Gluconapin (GNA) (33,049.23 µmol·kg-1 DW), Glucobrassicanapin (GBN) (9803.82 µmol·kg-1 DW), Progoitrin (PRO) (12,780.48 µmol·kg-1 DW) and Sinigrin (SIN) (14,872.93 µmol·kg-1 DW) were the most abundant compounds across the analyzed accessions. Moreover, in silico docking studies predicted promising antioxidant activity by evaluating the interactions of each GSL with antioxidant enzymes. Specifically, Sinigrin and Gluconapin exhibited a notably weaker influence on antioxidant enzymes. This provides key insights into the antioxidant potential of Brassica germplasm and highlights the importance of in silico analysis for evaluating bioactive properties. In general, the results of this study could be utilized in breeding programs to maximize GSL levels and antioxidant properties in Brassica crops and for developing functional foods with enhanced health benefits.

Exploring the Therapeutic Potential of Ammodaucus leucotrichus Seed Extracts: A Multi-Faceted Analysis of Phytochemical Composition, Anti-Inflammatory Efficacy, Predictive Anti-Arthritic Properties, and Molecular Docking Insights.

Ammodaucus leucotrichus exhibits promising pharmacological activity, hinting at anti-inflammatory and anti-arthritic effects. This study investigated seed extracts from Ammodaucus leucotrichus using methanol and n-hexane, focusing on anti-inflammatory and anti-arthritic properties. The methanol extract outperformed the n-hexane extract and diclofenac, a reference anti-inflammatory drug, in trypsin inhibition (85% vs. 30% and 64.67% at 125 µg/mL). For trypsin inhibition, the IC50 values were 82.97 µg/mL (methanol), 202.70 µg/mL (n-hexane), and 97.04 µg/mL (diclofenac). Additionally, the n-hexane extract surpassed the methanol extract and diclofenac in BSA (bovine serum albumin) denaturation inhibition (90.4% vs. 22.0% and 51.4% at 62.5 µg/mL). The BSA denaturation IC50 values were 14.30 µg/mL (n-hexane), 5408 µg/mL (methanol), and 42.30 µg/mL (diclofenac). Gas chromatography-mass spectrometry (GC-MS) revealed 59 and 58 secondary metabolites in the methanol and n-hexane extracts, respectively. The higher therapeutic activity of the methanol extract was attributed to hydroxyacetic acid hydrazide, absent in the n-hexane extract. In silico docking studies identified 28 compounds with negative binding energies, indicating potential trypsin inhibition. The 2-hydroxyacetohydrazide displayed superior inhibitory effects compared to diclofenac. Further mechanistic studies are crucial to validate 2-hydroxyacetohydrazide as a potential drug candidate for rheumatoid arthritis treatment.

Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species.

In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between -6 and -8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from -5.5 to -8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within -6.5 to -8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.

Characterization of four new cycloartane triterpenoids from Swietenia macrophylla and their angiotensin-I-converting enzyme inhibitory activity.

Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1-4) and one known (5) cycloartane triterpenoids were isolated from the leaves of Swietenia macrophylla by chromatographic techniques and identified by their spectroscopic data and a comprehensive comparison of published data. The triterpenoids were evaluated for their ACE inhibitory potential using in vitro inhibition assays and in silico methods. The inhibition assay and enzyme kinetics results showed that the most active triterpenoid, compound 4, inhibited ACE in a mixed-type manner with an IC50 value of 57.7 ± 6.07 µM. Computer simulations revealed that compound 4 reduces the catalytic efficiency of ACE by competitive insertion into the active pocket blocking the substrate, and the binding activity occurs mainly through hydrogen bonds and hydrophobic interactions. The study showed that S. macrophylla can be a source of bioactive material and the ACE inhibitory triterpenoid could be a potential antihypertensive agent.

Molecular Docking Analysis at the Human α7-nAChR and Proliferative and Evoked-Calcium Changes in SH-SY5Y Cells by Imidacloprid and Acetamiprid Insecticides.

Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking. Additionally, NNI effects were analyzed in neuroblastoma SH-SY5Y cells, as they naturally express α-7 nAChRs. Functional studies included proliferative/cytotoxic effects (MTT test) in undifferentiated SH-SY-5Y cells and indirect measurements of [Ca2+]i transients in retinoic acid-differentiated SH-SY-5Y cells loaded with Fluo-4 AM. Docking analysis showed that the binding of IMI and ACE occurred at the same aromatic cage that the specific α-7 nAChR agonist EVP-6124. IMI showed a better docking strength than ACE. According to the MTT assays, low doses (10-50 µM) of IMI better than ACE stimulated neuroblastoma cell proliferation. At higher doses (250-500 µM), IMI also prevailed over ACE and dose-dependently triggered more abrupt fluorescence changes due to [Ca2+]i mobilization in differentiated SH-SY5Y neurons. Indeed, only IMI blunted nicotine-evoked intracellular fluorescence stimulation (i.e., nicotine cross-desensitization). Summarizing, IMI demonstrated a superior docking strength and more robust cellular responses compared to ACE, which were likely associated with a stronger activity at α-7nAChRs. Through the interaction with α-7nAChRs, IMI would demonstrate its high neurotoxic potential for humans. More research is needed for investigating the proliferative effects of IMI in neuroblastoma cells.

Effects of fermentation with Lactiplantibacillus plantarum NCU116 on the antihypertensive activity and protein structure of black sesame seed.

Effects of fermentation by Lactobacillus Plantarum NCU116 on the antihypertensive potential of black sesame seed (BSS) and structure characteristics of fermented black sesame seed protein (FBSSP) were investigated. Angiotensin-I-converting enzyme (ACE) inhibition and zinc chelating ability of fermented black sesame seed hydrolysate (FBSSH) reached the highest of 60.78 ± 3.67 % and 2.93 ± 0.04 mg/mL at 48 h and 60 h of fermentation, respectively. Additionally, the antioxidant activities of FBSSH and surface hydrophobicity of FBSSP were increased noticeably by fermentation. The α-helix and ß-rotation of FBSSP tended to decrease and increase, respectively, during fermentation. Correlation analysis indicated strong positive relationships between ß-turn and ACE inhibition activity as well as zinc chelating ability with correlation coefficients r of 0.8976 and 0.8932. Importantly, novel ACE inhibitory peptides LLLPYY (IC50 = 12.20 µM) and ALIPSF (IC50 = 558.99 µM) were screened from FBSSH at 48 h using in silico method. Both peptides showed high antioxidant activities in vitro. Molecular docking analysis demonstrated that the hydrogen bond connected with zinc ions of ACE mainly attributed to the potent ACE inhibitory activity of LLLPYY. The findings indicated that fermentation by Lactobacillus Plantarum NCU116 is an effective method to enhance the antihypertensive potential of BSS.

Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats.

Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.