Electrosprayed Nanoparticles Containing Mangiferin-Rich Extract from Mango Leaves for Cosmeceutical Application.

Mango (Mangifera indica L.) is one of the most economically important fruits in Thailand. Mango has been used as a traditional medicine because it possesses many biological activities, such as antioxidant properties, anti-inflammatory properties, microorganism-growth inhibition, etc. Among its natural pharmacologically active compounds, mangiferin is the main active component found in mango leaves. Mangiferin has the potential to treat a variety of diseases due to its multifunctional activities. This study aims to prepare a mangiferin-rich extract (MRE) from mango leaves and develop nanoparticles containing the MRE using an electrospraying technique to apply it in a cosmeceutical formulation. The potential cosmeceutical mechanisms of the MRE were investigated using proteomic analysis. The MRE is involved in actin-filament organization, the positive regulation of cytoskeleton organization, etc. Moreover, the related mechanism to its cosmeceutical activity is metalloenzyme-activity regulation. Nanoparticles were prepared from 0.8% w/v MRE and 2% w/v Eudragit® L100 solution using an electrospraying process. The mean size of the MRE-loaded nanoparticles (MNPs) received was 247.8 nm, with a PDI 0.271. The MRE entrapment by the process was quantified as 84.9%, indicating a high encapsulation efficiency. For the skin-retention study, the mangiferin content in the MNP-containing emulsion-gel membranes was examined and found to be greater than in the membranes of the MRE solution, illustrating that the MNPs produced by the electrospraying technique help transdermal delivery for cosmetic applications.

Depletion of ß-sitosterol and enrichment of quercetin and rutin in Cissus quadrangularis Linn fraction enhanced osteogenic but reduced osteoclastogenic marker expression.

BACKGROUND: Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine for healing bone fractures because of numerous active ingredients in CQ. It is still unclear which compounds are the active ingredients for bone formation. METHODS: The molecular docking technique, the ethanolic extraction along with hexane fractionation, and an in vitro experiment with a human osteoblast cell line (MG-63) were used to narrow down the active compounds, to prepare the CQ extract, and to test biological activities, respectively. RESULTS: The molecular docking technique revealed that quercetin and ß-sitosterol had highest and lowest potential to bind to estrogen receptors, respectively. Compared to the crude ethanol extract (P1), the ethanolic fraction (P2) was enriched with rutin and quercetin at 65.36 ± 0.75 and 1.06 ± 0.12 mg/g, respectively. Alkaline phosphatase (ALP) activity was significantly enhanced in osteoblasts exposed to the P2 in both tested concentrations. The amount of hydroxyproline was slightly increased in the P1 treatment, while osteocalcin was inhibited. Moreover, the P2 significantly activated osteoprotegerin (OPG) and inhibited receptor activator of nuclear factor κ ligand (RANKL) expression. CONCLUSIONS: Taken together, the enriched rutin and quercetin fraction of CQ triggered the molecules involved in bone formation and the molecules inhibiting bone resorption.

An integrated molecular modeling approach for the tryptase monomer-curcuminoid recognition analysis: conformational and bioenergetic features.

Human mast cell tryptase has been shown as an activating enzyme in matrix degradation process. The previous study suggest that tryptase either alone or in joining with activation of metalloproteinases, can associate in extra cellular matrix damage and the possible destruction of the basement membrane resulting in photoaging. Therefore the inhibition of tryptase activity is one of the most important therapeutic strategies against the photoaging. Curcumin has been shown to be a potential agent for preventing and/or treating the photoaging induced by UV radiation. However, the protective effect of curcumin against the photoaging through the tryptase inhibition is still inadequately understood. In this work, computational methods to characterize the structural framework and define the atomistic details of the determinants for the tryptase inhibition mechanism by curcuminoids were performed. By molecular docking, three putative binding models able to efficiently bind all curcuminoids were identified. Analysis of molecular dynamics simulations revealed that cyclocurcumin, curcumin glucuronide, and curcumin, the most effective inhibitors from the three models, modified significant tryptase monomer rigidity by binding in all the possible sites. The result of these binding events is the suppression of the functional enzymatic motions involving the binding of substrates to the catalytic site. On the basis of this finding may thus be beneficial for the development of new natural inhibitors for the therapeutic remedy of photoaging, targeting and modulating the activity of tryptase.

Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive.

Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit®L100 and Eudragit® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after 6 h; this would be expected to occur in the colorectal area. Therefore, this study demonstrates the potential of KGLP-NPRBO to prevent colorectal cancer via a specific colorectal dietary supplement delivery system.

A significant mechanism of molecular recognition between bioflavonoids and P-glycoprotein leading to herb-drug interactions.

Inhibition of P-glycoprotein (P-gp)'s function may conduct significant changes in the prescription drugs' pharmacokinetic profiles and escalate potential risks in taking place of drug/herb-drug interactions. Computational modeling was advanced to scrutinize some bioflavonoids which play roles in herb-drug interactions as P-gp inhibitors utilizing molecular docking and pharmacophore analyses. Twenty-five flavonoids were utilized as ligands for the modeling. The mouse P-gp (code: 4Q9H) was acquired from the PDB. The docking was operated utilizing AutoDock version 4.2.6 (Scripps Research Institute, La Jolla, CA) against the NBD2 of 4Q9H. The result illustrated the high correlation between the docking scores and observed activities of the flavonoids and the putative binding site of these flavonoids was proposed and compared with the site for ATP. To evaluate hotspot amino acid residues within the NBD2, Binding modes for the ligands were achieved using LigandScout to originate the NBD2-flavonoid pharmacophore models. The results asserted that these inhibitors competed with ATP for binding site in the NBD2 (as competitive inhibitors) including the hotspot residues which associated with electrostatic and van der Waals interactions with the flavonoids. In MD simulation of eight delegated complexes selected from the analyzed flavonoid subclasses, RMSD analysis of the trajectories indicated the residues were stable throughout the duration of simulations.

Insight into the molecular mechanism of P-glycoprotein mediated drug toxicity induced by bioflavonoids: an integrated computational approach.

In this work, molecular docking, pharmacophore modeling and molecular dynamics (MD) simulation were rendered for the mouse P-glycoprotein (P-gp) (code: 4Q9H) and bioflavonoids; amorphigenin, chrysin, epigallocatechin, formononetin and rotenone including a positive control; verapamil to identify protein-ligand interaction features including binding affinities, interaction characteristics, hot-spot amino acid residues and complex stabilities. These flavonoids occupied the same binding site with high binding affinities and shared the same key residues for their binding interactions and the binding region of the flavonoids was revealed that overlapped the ATP binding region with hydrophobic and hydrophilic interactions suggesting a competitive inhibition mechanism of the compounds. Root mean square deviations (RMSDs) analysis of MD trajectories of the protein-ligand complexes and NBD2 residues, and ligands pointed out these residues were stable throughout the duration of MD simulations. Thus, the applied preliminary structure-based molecular modeling approach of interactions between NBD2 and flavonoids may be gainful to realize the intimate inhibition mechanism of P-gp at NBD2 level and on the basis of the obtained data, it can be concluded that these bioflavonoids have the potential to cause herb-drug interactions or be used as lead molecules for the inhibition of P-gp (as anti-multidrug resistance agents) via the NBD2 blocking mechanism in future.