Propylene Glycol Caprylate-Based Nanoemulsion Formulation of Plumbagin: Development and Characterization of Anticancer Activity

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.

Corchorus olitorius L. Leaf Extract Protects Rats from Acrylamide-Induced Hepatic Injury

Acrylamide is a water-soluble compound that forms during the high-temperature cooking of starchy foods and has carcinogenic, neurotoxic, and genotoxic properties. Also, short-term exposure to acrylamide has been shown to cause significant hepatic injury in laboratory animals, along with disruption of antioxidant defense mechanisms due to excessive ROS production. Therefore, dietary antioxidants are believed to be useful in combating the negative effects of acrylamide. Corchorus olitoris L., also known as molokhia in Arabic, is a leafy vegetable which is shown to possess potent antioxidant and organoprotective properties. In this study, rats were administered with an aqueous extract of molokhia leaves to see if it could protect them against acrylamide-induced hepatic damage. Hepatic injury markers included serum total protein, total bilirubin, ALT, AST, and ALP, while oxidative stress markers included MDA, GSH, CAT, and SOD after dosing with three levels of extract (100, 250, and 500 mg/kg) for 21 days. Results indicated that the extracts substantially reduced elevated levels of bilirubin, ALT, AST, ALP, and MDA to normal levels at all doses. The extracts also brought serum protein, GSH, CAT, and SOD levels back to normal. Although the restoration of serum hepatic enzyme levels was dose dependent, no specific dose dependent relationship was found for serum proteins, MDA, GSH, CAT, or SOD activities. The study's findings show that molokhia leaves extract protects against acrylamide-induced hepatic damage by virtue of its good radical scavenging and anti-lipiperoxidative properties conferred by phenolics, flavonoids, and alkaloids.

Synthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivativessynthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivatives

A series of water-soluble fluoroquinolones based upon DOTA modification were synthesized and characterized by NMR and HRMS spectra. All the newly prepared quinolones compounds exhibited potent antimicrobial activities against MRSA, P. aeruginosa and E. coli. Molecular docking study indicated they could form stable complex with DNA gyrase and topoisomerase IV-DNA respectively, ADMET prediction showed they were low toxicity to the mice as whole. Among them, water-soluble quinolone 4c exhibited promising antibacterial potency, its MIC, MBC value for MRSA and P. aeruginosa was (1.56, 6.25) µg/mL, (3.1, 12.5) µg/mL respectively. Atomic Force Microscope (AFM) imaging revealed 4c could effectively destroy MRSA bacterial membrane and wall, causing its contents to leak out. Cytotoxicity assay showed 4c had low toxicity to L-02, A549 and MCF-7, over 80% cell viability even at 100 µmol/L. These results showed that water-soluble compound 4c was a promising antibacterial candidate.

Characterisation of Preformulation Parameters to Design, Develop and Formulate Silymarin loaded PLGA Nanoparticles for Liver Targeted Drug Delivery

Silymarin, a flavonolignan,derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. It inhibits the binding of hepatotoxins to receptor sites, protects hepatocyte membranes, enhances liver parenchyma regeneration and increases glutathione levels. The pharmacokinetic studies of past three decades revealed that Silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Typical oral adult dose of Silymarin is 240-800mg /day .It is a non-lipophilic and poorly water soluble compound with water solubility of 0.04mg/ml. Only 20-30% of oral Silymarin is absorbed from gastrointestinal tract where it undergoes extensive entero-hepatic circulation. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin to hepatocytes. A controlled release PNP of Silymarin was prepared by solvent evaporation method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer. Prior to the development of this novel dosage form, it is very important to identify fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder. This data helps in many of the subsequent events and approaches towards the development of a better formulation. Preformulation studies included determination of solubility, moisture content, partition coefficient, melting point , powder properties like tapped density, bulk density, compressibility index, flow properties like angle of repose, excipient compatibility, entrapment efficiency, release profile of nanoparticles like dissolution, stability studies like effect of temperature and humidity and analysis by scanning Electron Microscopy.

Effect of Alternative Preservation Steps and Storage on Vitamin C Stability in Fruit and Vegetable Products: Critical Review and Kinetic Modelling Approaches

Vitamin C, a water-soluble compound, is a natural antioxidant in many plant-based products, possessing important nutritional benefits for human health. During fruit and vegetable processing, this bioactive compound is prone to various modes of degradation, with temperature and oxygen being recognised as the main factors responsible for this nutritional loss. Consequently, Vitamin C is frequently used as an index of the overall quality deterioration of such products during processing and post-processing storage and handling. Traditional preservation methods, such as thermal processing, drying and freezing, are often linked to a substantial Vitamin C loss. As an alternative, novel techniques or a combination of various preservation steps (“hurdles”) have been extensively investigated in the recent literature aiming at maximising Vitamin C retention throughout the whole product lifecycle, from farm to fork. In such an integrated approach, it is important to separately study the effect of each preservation step and mathematically describe the impact of the prevailing factors on Vitamin C stability, so as to be able to optimise the processing/storage phase. In this context, alternative mathematical approaches have been applied, including more sophisticated ones that incorporate parameter uncertainties, with the ultimate goal of providing more realistic predictions.

Identification of binding interaction between Curcumin derivative and PERK13 Proline rich receptor like protein kinase protein using In silico docking techniques – to help plants tackle salt water

Introduction: Arabidopsis thaliana, mouse ear cress or thale cress are small flowering plants included in the cruciferae family. They comprise of various characteristics such as diploid genetics, small genome size, rapid growth cycle, and relatively low repetitive DNA content, making it a perfect model for plant genome projects. Objective: The aim of this present Insilico research study is to carry out molecular drug docking studies between PERK13 Proline rich receptor like protein kinase and De O Acetylated Curcumin Di Galactose or digalactosylated curcumin, a derivative of curcumin. PERK13 protein is considered to play a significant role in helping plants tackle salinity levels in water. Methods: In this study, protein modelling tools and servers are used to model the 3D structure and the same is validated using Protein structure validation tools. Automated drug docking servers were used to dock the modelled protein with the chemical compound to analyse the electrostatic (H bond) interaction between PERK13 and De O Acetylated Curcumin Di Galactose, a better water soluble compound than curcumin. The docked structure was visualized using an advanced molecular visualization tool. Results and Discussion: The overall results obtained from this study on De O Acetylated Curcumin Di Galactose and PERK13 protein shows that De O Acetylated Curcumin Di Galactose, directly binds with the active site and other potentially binding regions of PERK13. Hence, it is concluded that De O Acetylated Curcumin Di Galactose could potentially play a vital role in future research related to the problem of helping the plants tackle increased saline levels in water. Keywords: A. thaliana, De O Acetylated Curcumin Di Galactose, Drug Docking, Insilico, PERK13, Protein Modelling.

Standardization of Mango (Mangifera Indica L.) Peel Simplisia of Gadung Variety

Mango peel (Mangfera indica L.) has many pharmacological effects as a traditional medicine. Therefore, standardization of mango peel simplisia needs to be done as a preparation of phytopharmaca raw material. This research aimed to obtain standardization of mango peel simplisia include specific and non-specific parameter. The research procedures include plant determination, simplisia preparation as well as specific standardization test (includes organoleptic, water-soluble compound concentration, and ethanol solution compound concentration) and nonspecific standardization test (includes moisture content, dried shrinkage, total ash content and acid insoluble ash content). The specific organoleptic parameters of dried mango peel simplisia have a distinctive sweet aroma, bitter taste, and brownish yellow colour. Water-soluble and ethanol-soluble concentrations are 22,36% ± 1,17% and 9,56% ± 0,07%. Moisture content is 9,09% ± 1,44%. Dried shrinkage rate is 0,19% ± 0,04%. Total ash and acid insoluble ash contents are 4,11% ± 0,10% and 0,14% ± 0,03%. The mango peel simplisia has met the quality standard of the raw material.

Identification of Local Rice Genotypes from Deli Serdang, North Sumatera, Indonesia to Drought Stress Condition

Regency of Deli Serdang in the Province of Sumatera Utara has high diversity of landrace rice that has adapted to various climatic and edaphic condition including drought. Studies on various local rice genotypes tolerant to drought is of important to be carried out. This will help plant breeders with germplasms for future breeding program. Polyethylene glycol (PEG) is a water-soluble compound with high osmotic pressure and unlikely to have specific interaction with biological chemicals. With these properties, PEG is often be used in studies of plant response to drought stress. The experiment reported here was aimed at determining rice genotypes, local to Regency of Deli Serdang, tolerant to drought. The experiment was carried out at Laboratory of Physiology and Glass House of Faculty of Agriculture, Universitas Islam Sumatera Utara, Medan from February to April 2020. A two-way factorial experiment was assigned in a completely randomized design (CRD) with 3 replicates. The first factor was 23 local rice genotypes plus 4 genotypes tolerant to drought and the second factor was the concentration of PEG 6000 i. e 0 and 20% (w/v). Observations included percent of germination, plant height, length and number of roots protruding from paraffin-wax layer, leaf chlorophyll content, seedling fresh and dry weight, index of tolerance, probability of resistance, and proline content. Data were analyzed with analysis of variance and mean separation of DNMRT at 5%. Results demonstrated that 6 local rice genotypes, Gemuruh, Ramos Merah, Arias, Sialus, Silayur, and Sirabut were resistant to drought stress under the experimental condition.

Bioassay-Guided Isolation of 2-[P-(2-Carboxyhydrazino)Phenoxy]-6-(Hydroxymethyl)Tetrahydro-2h-Pyran-3,4,5-Triol From Oroxylum Indicum and Investigation of Its Molecular Mechanism Action of Apoptosis Induction

Leaf crude extract (aqueous) of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and inhibition of cell proliferation in prostate cancer cell line, PC3 as assessed by agarose gel electrophoresis, comet assay, and MTT assay respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT as-say. The brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), fourier transform infrared (FT-IR) and electrospray ionization (ESI) mass spectrometry, and the compound was iden-tified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from oroxylum indicum in this current study is named as oroxyquinone. The half-maximal inhibitory concentration (IC50) of oroxyquinone on PC3 cells was 19.44 µg/ml (95% CI = 17.97 to 21.04). Oroxyquinone induced cell cycle arrest at S phases and inhibition of cell migration on PC3 as assessed by flow cytome-try and wound healing assay respectively. On investigating the molecular mechanism of inducing apoptosis, the results indicated that the oroxyquinone induced apoptosis through the p38 pathway and cell cycle arrest, however, not through caspase-3 and PARP pathways. The present study identifies a novel an-ticancer molecule and provides scientific evidence supporting the therapeutic potency of OI for ethnomedicinal uses.