The phenotypic manifestation of lead toxicity includes cognitive, learning, and memory decline which is associated with neuronal injuries and death and been a major challenge in public health especially in developing countries. Thus, we explore the prophylactic potentials of luteolin in prefrontal Pb intoxication. Thirty-six (36) male Wistar Rats were used for this research and di-vided into six (6) groups of six animals each and were treated orally as follows: Group 1-Normal saline (0.5ml daily for 14 days); Group 2- PbCl3 (50mg/kg of PbCl3 daily for 14 days); Group 3- luteolin (100mg/kg of LUT daily for 14 days); Group 4- luteolin and PbCl3 (50mg/kg PbCl3 and 100mg/kg LUT daily for 14 days); Group 5- PbCl3 then luteolin (50mg/kg of PbCl3 daily for 14 days followed by 100mg/kg of LUT daily for 14 days); Group 6- luteolin then PbCl3 (100mg/kg of LUT daily for 14days followed by 50mg/kg of PbCl3 daily for 14 days). We measured cerebral oxidative redox parameters, G6PDH, IL-6, acetylcholinesterase levels, and total protein profiles using ELISA and biochemical assay kits. We also examined cerebral morphology and the Nissl profile with H&E and toluidine blue staining techniques, as well as astrocytic morphology and synaptic integrity with anti-GFAP and anti-synaptophysin antibodies. As a result of Pb perturba-tion, luteolin treatment inhibits MDA, IL-6, and AChE expression while increasing antioxidant enzyme activities (SOD, GPx) and G6PDH. Furthermore, luteolin has significant prophylactic po-tential against Pb-induced neuronal injuries and modulates astrocyte actions, preserving synap-tic integrity and thus improving cognition, learning, and memory. Taken together, our findings indicate that luteolin may be a promising candidate for managing and treating Pb neural intoxi-cation.

Trueperella pyogenes (T. pyogenes) can cause a variety of infections in animals and lead to economic loss in animal husbandry. TatD DNases are considered to be potential virulence factors in Plasmodium falciparum and Streptococcus pneumoniae. However, the function of TatD DNases in T. pyogenes is still unclear. Therefore, the aim of this study was to illustrate the function of TatD DNases of T. pyogenes (TpTatDs) and investigate whether luteolin is able to inhibit DNase function. The findings of our study are anticipated to be crucial to treating infections caused by T. pyogenes. Bioinformatic analysis has been used for the prediction of crucial functional residues of TpTatDs. The function of TpTatDs was investigated in the presence of divalent cations by hydrolyzing DNA with recombinant TatD proteins. Luteolin is a candidate nuclease inhibitor evaluated in our study. The interactions between luteolin and TpTatDs were tested using molecular docking analysis and surface plasmon resonance (SPR) assays. The inhibitory effect of luteolin on TpTatDs was analyzed by agarose gel electrophoresis. Two genes in the genome of T. pyogenes are suspected to encode TatD DNases. According to the length of their nucleotide sequences, they were named tatD960 and tatD825. Both of the TpTatDs, which are magnesium-dependent, were able to hydrolyze linear DNA and plasmids. In this study, we found through molecular docking analysis and SPR assays that luteolin can stably bind with TpTatDs. The gel assay revealed that luteolin can inhibit the DNase activity of TpTatDs. Our results indicated that TatD DNases from T. pyogenes are Mg2+-dependent DNases and exhibit DNA endonuclease activity. Moreover, luteolin reduced their DNA hydrolysis ability by decreasing the binding between TpTatDs and DNA.

To determine the mode of action of the effects of phytoalexins in soybeans, we analyzed enzyme inhibition kinetics using Michaelis–Menten plots and the Lineweaver–Burk plots. The results showed that glyceollin showed competitive inhibition, genistein showed noncompetitive, daidzein was uncompetitive, and luteolin showed a mixed mode of action. The Ki values were determined using a Dixon plot as: glyceollin, 18.99; genistein, 15.42; luteolin, 16.81; and daidzein, 9.99 μM, respectively. Furthermore, potential synergistic effects between glyceollin and the three designated polyphenols were investigated. A combination of glyceollin and luteolin (the ratio of 3:7 of glyceollin and luteolin) had synergistic effects on α-glucosidase inhibition according to combination index (CI)-isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit α-glucosidase activity via a synergistic mode of action.

Mast cells play a critical role in allergies and inflammation via secretion of numerous vasoactive, pro-inflammatory and neuro-sensitizing mediators. Secretion may utilize different modes that involve the cytoskeleton, but our understanding of the molecular mechanisms regulating secretion is still not well understood. We previously showed that the ability of the so called mast cell “stabilizer” disodium cromoglycate (cromolyn) to inhibit secretion from rat mast cells closely paralleled the phosphorylation of a 78 kDa protein, and subsequently showed this protein to be moesin, a member of the Ezrin/Radixin/Moesin (ERM) family of proteins, which are involved in linking cell surface-initiated signaling to the actin cytoskeleton. Unlike phosphorylation on the C-terminus Thr558 associated with activation of ERMs, including secretion from macrophages and platelets, we showed that phosphorylation of moesin during inhibition of secretion was on the N-terminal Ser56/74 and Thr66 residues. This phosphorylation pattern could lock moesin in its inactive state and remain inaccessible to bind to the Soluble NSF attachment protein receptors (SNAREs) and synaptosomal associated proteins (SNAPs). Using Confocal microscopic imaging, we showed moesin to colocalize with actin and cluster around secretory granules during inhibition of secretion, In conclusion, the phosphorylation pattern and localization of moesin may be important in the regulation of mast cell secretion and could be targeted for the development of effective inhibitors of secretion from mast cells.

Aflatoxin B1 (AFB1) is a mycotoxin considered as a potent carcinogenic for humans that contaminates a wide range of crops. Various strategies have been established to reduce or block the synthesis of AFB1 in food and feeds. The use of aqueous extracts derived from plants with high antioxidant activity has been a subject of study in recent years due to their efficacy in inhibiting AFB1. In this study, we assessed the effect of Aloysia citrodora aqueous extract on Aspergillus flavus growth and on AFB1 production. A bio-guided fractionation followed by High Performance Liquid Chromatography (HPLC) and Mass spectrometry analysis of active fraction were applied to identify the candidate molecules responsible for the dose-effect inhibition of AFB1 synthesis. Our results revealed that polyphenols are the molecules implicated in AFB1 inhibition, achieving almost a total inhibition of the toxin production (99%). We identified luteoline 7- diglucuronide as one of the main constituents in A. citrodora extract, and demonstrated that it is able to inhibit, by itself, AFB1 production by 57%. This is the first study demonstrating the anti-Aflatoxin B1 effect of this molecule, while other polyphenols surely intervene in A. citrodora anti-AFB1 activity.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

This study presents a detailed comparative analysis of Molecular Docking data, focusing on the binding interactions of conventional ligands and natural compounds, Apigenin and Luteolin, with TP-53, pRb, and APOBEC. Utilizing advanced bioinformatics techniques, coupled with Ar-tificial Intelligence software and High-Performance Computing (HPC), we measured and con-trasted the binding energies of these interactions. Additionally, we investigated protein-protein interactions between HPV-16 oncoprotein E6 and tumor suppressors TP-53 and pRb. Our findings demonstrate that the natural compounds Apigenin and Luteolin exhibit significantly higher binding affinities to TP-53, pRb, and APOBEC compared to conventional pharmacological ligands. The binding energies for Apigenin and Luteolin were approximately -6.9 kcal/mol and -6.6 kcal/mol, respectively, indicating their strong potential as therapeutic agents in inhibiting the oncogenic functions of HPV-16. In contrast, conventional ligands showed lower binding affinities, with energies around -4.5 to -5.5 kcal/mol. The study further revealed that the protein-protein interactions between E6 and TP-53, and E6 and pRb, exhibited considerably higher binding en-ergies, approximately -976.7 kcal/mol, due to the multiple interaction sites and the complex nature of protein interfaces. A conversion formula was developed to translate these high-energy inter-actions to a comparable scale for non-protein-protein interactions, highlighting the superior binding potential of natural compounds, which, through the same conversion formula, was shown to be higher than that of interaction between E6 with TP-53 and E6 with pRb. These results underscore the therapeutic promise of Apigenin and Luteolin in preventing HPV-16-related on-cogenesis. By demonstrating their higher binding affinities to crucial tumor suppressors, this study supports the development of natural compound-based therapies. The findings also em-phasize the necessity for further experimental validation to explore these compounds' efficacy in clinical settings. This comprehensive analysis provides a robust framework for understanding the comparative binding interactions and lays the groundwork for innovative therapeutic strategies against HPV-16.

This study investigates the use of artificial intelligence (AI) and ethnobotanical knowledge to identify natural compounds with potent antiviral activity against HPV-16. Through molecular docking simulations, we evaluated the binding affinities of various essential oil components, in-cluding Apigenin, against the key antigenic determinants of HPV-16 (E6, E7 oncoproteins, and L1 major capsid protein). Apigenin exhibited strong binding affinities, particularly to E6 Oncopro-tein. To further enhance these findings, we employed an AI-driven reverse engineering approach to predict a natural compound with superior efficacy. The AI identified Luteolin, a flavonoid with additional hydroxyl groups, as a promising candidate. Comparative docking studies demon-strated that Luteolin possesses significantly stronger binding affinities to all three HPV-16 targets, surpassing the efficacy of Apigenin. This work highlights the potential of AI in accelerating the discovery and optimization of natural antiviral agents, providing a powerful tool for pharmaco-logical and ethnopharmacological screenings. Our findings suggest that AI-guided identification of natural compounds can lead to the development of more effective antiviral therapies, warranting further experimental validation and potential synthesis in laboratory settings.