![]() The interaction density function (IDF) method was applied to the fluorescence spectroscopy data in order to determine the binding constant, since the value of the binding constant is essential to comprehend the affinity of piperine toward RSA and therefore the efficiency of its transport in the blood stream. The present work aims to fill this information gap with respect to RSA using several experimental techniques with the help of computational simulations to elucidate models of the interaction of piperine into RSA. The lack of information on the tertiary structure of RSA together with the absence of multispectroscopic data analyses and the complete unavailability of computer simulation data were sufficient reasons to carry out this study. ![]() Various albumin structures of different species are available on the Protein Data Bank (PDB) and, according to structural characterization, serum albumins are composed mostly by α-helix and contain disulfide bridges, which confer to the protein a melting temperature of ~331 K. Rat serum albumin (RSA) contains 584 amino acids and just one tryptophan residue at position 214, which allows the use of fluorescence spectroscopy to evaluate the interaction of small molecules with it. This protein is synthesized in the liver and remains soluble in plasma. There is interest from the scientific community in the plasticity of albumin, since it can transport several different exogenous ligands. Although studies have shown the pharmacokinetics of piperine in rats, the molecular mechanism involved in the interaction of piperine toward rat serum albumin (RSA) is still unknown. As piperine is a lipophilic molecule (LogP = 3.69), its transport through the plasma depends on proteins capable of carrying lipophilic molecules, such as albumin. Studies in vivo with rats reported in the literature showed that after 6 h of oral administration, piperine presented the highest concentration in serum as well as in several organs, and its presence remained up to 96 h after its administration and was then excreted from the organism. Besides that, piperine plays a crucial role in enhancing the bioavailability of several drugs by inhibiting the drug metabolizing enzymes, which retards the clearance of those compounds. It presents a series of important pharmacological actions, such as anti-inflammatory, anti-carcinogenic, antimicrobial, and antiparasitic. Piperine is not only used as a seasoning but also in various preparations of traditional medicine in India it is also employed in the oldest medical science practiced since ancient time (Ayurveda). Piperine (1-piperoyl piperidine), whose molecular weight corresponds to 285 g/mol, is an alkaloid present in many types of plants, such as Piper nigrum linn (black pepper), Zingiber officinale (ginger), Piper longum L., Piper sarmentosum Roxb, and Dangzuo. The results of molecular docking and molecular dynamics matched appropriately made it possible to have detailed microenvironments of RSA accessed by piperine. This important set of experimental results served to parameterize the computational simulations. The Gibbs free energy, an important thermodynamic parameter, was determined (−25 kJ/mol), indicating that the interaction was spontaneous. From the spectroscopic results, it was possible to estimate the binding constant (3.9 × 10 4 M −1 at 288 K) using the Stern–Volmer model and the number of ligands (three) associated with the protein applying interaction density function model. ![]() In the present study, several spectroscopic techniques were employed to characterize rat serum albumin and, aided by computational techniques, the protein modeling was proposed. Although the first therapeutic trials relied on the use of rats, no proposal was mentioned either experimentally or computationally at the molecular level regarding the interaction between piperine and rat serum albumin (RSA). However, in all these assays, the molecular approach was absent. The tests used to validate these properties were performed in vitro or with small rats. The bioactive piperine (1-piperoyl piperidine) compound found in some pepper species ( Piper nigrum linn and Piper sarmentosum Roxb) has been shown to have therapeutic properties and to be useful for well-being.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |