New Perspective on the Interaction Behavior Between Riboflavin and ß Lactoglobulin-ß Casein Complex by Biophysical Techniques.

Riboflavin (RF) is a vitamin that only exists in plants and microorganisms and must be procured externally by humans. On the other hand, there are two major allergic factors in cow's milk, including ß-lactoglobulin (ßLG) and ß-casein (ßCN), while their allergic properties can be eliminated by binding to micronutrients. In this regard, we examined the binding process of RF to ßLG and ßCN in the binary and ternary systems by different spectroscopies such as zeta potential, electric conductivity, and molecular modeling. According to the result of the fluorescence spectrum regarding the interaction of RF with ßLG and ßCN in binary and ternary systems, an increase in RF concentration declined the fluorescence intensity of three systems and also caused the quenching of proteins. Static quenching plays a pivotal role in the formation of stable interactions. The obtained thermodynamic parameters by Van't Hoff equation ascertained the predominance of hydrogen bonds and van der Waals interaction in all the systems. Considering how the negative value of ΔH0 resulted in the negative value of ΔG0, the systems were assumed to be enthalpy driven. The outcomes of circular dichroism (CD) disclosed that the attachment of RF to the targets of systems increased their a-helix content, which particularly included the binding of RF to ßLG that led to the conversion of ß-sheet to α-helix content. As indicated by the results of zeta potential, the low concentration of RF contained the dominance of hydrophobic forces in the interactions, whereas the enlargement of this concentration prevailed electrostatic forces. Moreover, conductometry measurements showed an extension in the rate of ionizable groups due to the addition of RF to the systems, which may increase the probability of an interaction between RF, ßCN, and ßLG in binary and ternary systems. In consistency with the outcomes of molecular dynamics simulation, the data of molecular docking approved the capability of RF in forming strong and stable interactions with ßCN and ßLG.

CB1 as a novel target for Ginkgo biloba's terpene trilactone for controlling chemotherapy-induced peripheral neuropathy (CIPN).

The application of antineoplastic chemotherapeutic agents causes a common side effect known as chemotherapy-induced peripheral neuropathy (CIPN) that leads to reducing the quality of patient's life. This research involves the performance of molecular docking and molecular dynamic (MD) simulation studies to explore the impact of terpenoids of Ginkgo biloba on the targets (CB-1, TLR4, FAAH-1, COX-1, COX-2) that can significantly affect the controlling of CIPN's symptoms. According to the in-vitro and in-vivo investigations, terpenoids, particularly ginkgolides B, A, and bilobalide, can cause significant effects on neuropathic pain. The molecular docking results disclosed the tendency of our ligands to interact with mainly CB1 and FAAH-1, as well as partly with TLR4, throughout their interactions with targets. Terpene trilactone can exhibit a lower rate of binding energy than CB1's inhibitor (7dy), while being precisely located in the CB1's active site and capable of inducing stable interactions by forming hydrogen bonds. The analyses of MD simulation proved that ginkgolide B was a more suitable activator and inhibitor for CB1 and TLR4, respectively, when compared to bilobalide and ginkgolide A. Moreover, bilobalide is capable of inhibiting FAAH-1 more effectively than the two other ligands. According to the analyses of ADME, every three ligands followed the Lipinski's rule of five. Considering these facts, the exertion of three ligands is recommended for their anti-inflammatory, neuroprotective, and anti-nociception influences caused by primarily activating CB1 and inhibiting FAAH-1 and TLR4; in this regard, these compounds can stand as potential candidates for the control and treatment of CIPN's symptoms.

1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2.

SARS-COV-2 stands as the source of the most catastrophic pandemic of this century, known as COVID-19. In this regard, we explored the effects of five Pistacia sp. active ingredients on the most crucial targets of SARS-COV-2, including 3CLpro, PLpro, RdRp, helicase, NSP15, and E protein. The results of molecular docking determined 1,2,3,4,6-pentagalloyl glucose (PG) as the most effective compound of Pistacia sp, which also confirmed its excellent binding affinities and stable interactions with helicase (-10.76 kcal/mol), RdRp (-10.19 kcal/mol), E protein (-9.51 kcal/mol), and 3CLpro (-9.47 kcal/mol). Furthermore, MD simulation was conducted to investigate the stability of all complexes throughout a 100 ns. In contrast to PLpro and NSP15, the analyses of Lennard-Jones potential, RMSDas, PCA, and SASA verified the ability of PG in forming stable and adequate interactions with RdRp, helicase, 3CLpro, and E protein due to standing as an effective inhibitor among the six targets, these data proposed the capability of PG, the most important compound of Pistacia sp., in inducing antiviral, anti-inflammatory, and antioxidant impacts on RdRp, helicase, 3CLpro, and E protein. Therefore, the possibility of inhibiting the replication and transcription processes and viral pathogenesis of SARS-COV-2 may be facilitated through the application of PG.