Indonesian Journal of Pharmacy
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Molecular Docking and ADMET Prediction Studies of Flavonoids as Multi-target Agents in COVID-19 Therapy: Anti-inflammatory and Antiviral Approaches
Get PDFRecent studies showed that hyper-inflammatory reactions including cytokines storm leads to acute respiratory distress syndrome and responsible for death toll in COVID-19. Thus, the pathways involved in inflammation and SARS-Cov-2 replication represent a promising therapeutic target. By employing a computational model, we investigated the effect of plant flavonoids on pro-inflammatory proteins (glucocorticoid receptor (GR), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (LOX) enzymes), and on proteins involved in virus replication (main protease (Mpro), and papain-like protease (PLpro)). This in silico study study aimed to identify promising flavonoids with anti-inflammatory and antiviral activities (multi-target) for combating COVID-19. Mpro (PDBID: 6LU7), PLpro (PDBID: 6WX4), COX-2 (PDBID: 6COX), LOX (PDBID: 6N2W), and GR (PDBID: 1P93) were selected as target proteins. The molecular docking experiment was done using PLANTS software. Parameters for Lipinski’s “Rule-of-Five'', and the prediction of pharmacokinetic and toxicity profiles were done using the online platform, pkCSM. We found that 2 flavonoids, diosmin and hesperidin demonstrated low binding score and stronger than that of the reference ligands for the target proteins of Mpro, PLpro, and LOX. These compounds interact with amino acid residues of the protein targets through hydrogen bonds and show similar binding pattern compared to the approved drugs and native ligands. The ADMET and drug-likeness profiles prediction indicated that they have low toxicity, and good pharmacokinetic properties with the exception of the absorption profile. Hesperidin and diosmin are the promising candidates to be further investigated as multi-target agent for the treatment of COVID-19 through simultaneous inhibition of inflammation and virus replication
Development of Bacterial Cocktail of Strains Staphylococcus hominis, Staphylococcus warneri, Bacillus subtilis, and Micrococcus luteus as active ingredients for Skin Care Formula
Get PDFThe microbial-based skin health care products that balance one's skin microbiome mimicking healthy skin are rapidly growing. Postbiotics gain more advantages in safety, shelf life, active peptides, and other active compounds such as GABA, which benefit human skin. We have isolated skin commensal bacteria, i.e., Staphylococcus hominis MBF12-19J, Staphylococcus warneri MBF02-19J, Micrococcus luteus MBF05-19J and Bacillus subtilis MBF10-19J in our previous study. This study aimed to make a formula of bacterial cocktail (BC) of those strains, elevate the BC formula into a ferment lysate (FL), and characterize the activities and test for skin sensitivity. The antibacterial activity was done by conducting a competition test using Propionibacterium acnes as an indicator bacterium, whereas the antioxidant activity assay was carried out using the DPPH method. The skin sensitivity was tested using the patch test method. The BC was lyzed by optimizing the enzymatic and ultrasonication methods, whereas sucrose was added as lyoprotectant to obtain a stable powder FL. Potential activity to inhibit P. acnes growth was achieved by a formula of FL consisting of M. luteus MBF05-19J: B. subtilis MBF10-19J: S. warneri MBF02-19J: S. hominis MBF12-19J in a ratio 1.5:1.5:0.5:0.5 or equivalent to DNA copy number/mL 1.01E+16: 1.14E+24: 1.96E+22: 1.50E+18. Skin sensitivity test results showed no sensitivity reaction, guaranteeing that CFS and FL are safe to use for the skin. Sucrose-FL at 12% sucrose formula showed higher physical stability than those without. However, the result of potential antioxidants showed mild and very mild activities compared to standard ascorbic acid
Neuroprotective Potential of Vitamin B-12 Against Cadmium–Induced Neuroinflammation Mediated Memory Dysfunctions in Adult Albino Mice
Get PDFCadmium induces neurotoxicity in brain and results in increased enzymatic functions, accumulation of Amyloid beta plaque and Neuo Fibrillary Tangles (NFTs) causing neurodegenerative diseases. The purpose of the present work was to investigate the anti-inflammatory or anti-oxidative potential of vitaminB12 against Cd -induced memory impairment and mechanism of signaling pathway of vitamin-B12 protection in Cd-induced neuroinflammatory in mice model. Male albino mice of BALB/C trait of age 7 to 8 weeks and weighing about (30-32±3g) were used as model animal in the study. All mice were divided in three groups. Control Group (CG) treated with 0.9% saline (1mL/Kg), Cd Cl2 administered Group (CD) (1mg/kg) and Cd +Vitamin administered group (CV) B-12 (500µg/kg). CD group was treated with Cd Cl2 for three weeks on alternate days while CV group was treated with Vitamin B12 and toxin CdCl2 for the next two weeks intraperitonealy. Behavior tests like Morris Water Maze (MWM) and Y-Maze (YM) tests were conducted on the experimental mice to study the neuro protective potential of Vitamin-B12 against CdCl2 induced memory dysfunctions. After completing the above procedures, mice were sacrificed and the brains of each group were collected for protein quantification step and western blotting. The Immuno blots of Iba-1, NF-kB, TNF-α, IL-1β, BACE1 and Aβ proteins in the brain homogenates of CD and CV mice confirm the anti-neuroinflammatory potential of vitamin-B12 against Cadmium –induced Neuroinflammation. Escape latency of CV group mice receiving Methylcobalamine was less and showed better performance in MWM test. The results of Y-maze test also showed that the spontaneous percentage alternation of CD group mice was less than CV and CG group of mice. Immuno blot of p-Akt confirm the signaling pathways of vitamin-B12 protection in Cd-induced neuroinflammatory mediated memory-impairment in the model mice. Our findings suggest that Vitamin-B12 could be a potent candidate drug for treating cognitive dysfunctions due to its anti-inflammatory and anti-oxidative potential. Our study also shows that Vitamin-B12 activates p-Akt signaling pathway along with decreasing the NF-Κb, TNF-α and IL-1β to protect the brain of mice against CdCl2 neurotoxicity
Clindamycin Peel-off Mask Film, an Effective Formulation for C. acnes Treatment: Characterization and Microbiological Activity
Get PDFClindamycin is the antibiotic of choice for treating Cutibacterium acnes (C. acnes) which was presented in various dosage forms such as topical solution, gel, and foam. In this current study, clindamycin was formulated as the peel-off mask gel, intending to form film, providing the drug release profile in a sustained manner leading to better antimicrobial efficacy and enabling peel-off after use. The peel-off mask gel was designed into many formulations with varying concentrations of film-forming agents. The major film-forming agent was 10 %w/w PVA that was combined with the additional film-forming agents PVP-K30 or SA. Clindamycin 1 %w/w was loaded in the selected formulations F18 (10 %w/w PVA and 20 %w/w PVP-K30) and F21 (10 %w/w PVA and 1.5 %w/w SA). The physical property evaluation of the peel-off mask gel showed that the types and concentrations of film-forming agents influenced the viscosity, spreadability, and film-forming ability. The film’s tensile strength indicating the preference of use was also determined. There was no interaction between the ingredients in the formulation evaluated by FT-IR, XRD, and DSC. The F18 and F21 formulations showed a good to very good spreadability and film-forming ability, a suitable tensile strength with a drying time of approximately 8 min, and pH 4-5. Both formulations provided the highest antimicrobial susceptibility for C. acnes compared to the blank film and the clindamycin solution indicating the potential to be developed as the new market formulation for acne treatment
An Integrated Authentication Analysis of Citrus aurantium L. Essential Oil Based on FTIR Spectroscopy and Chemometrics with Tuning Parameters
Get PDFCitrus aurantium L. essential oil or orange oil (OO) became more popular in recent years due to its benefit for human health. An “economically motivated adulteration” can be potentially occurred to achieve more profit in the market. On the other hand, a cheaper oil such as coconut oil (CO) was commonly used as adulterant. The objective of this study was to perform authentication analysis of OO by FTIR spectroscopy and chemometrics. Principal component analysis was applied in the exploratory data analysis at the initial stage of authentication analysis. Multivariate calibration of principal component regression (PCR) and partial least squares regression (PLSR) were constructed using five types of pre-processed FTIR spectral data. The PCR model using Standard Normal Variate (SNV) spectra was selected as the best prediction model for OO (Rcal2 = 0.999; RMSEC = 0.193; RCV2 = 0.998; RMSECV = 0.456; Rval2 = 0.992; RMSEP = 0.989), whereas the PLSR model using SNV spectra was selected as the best prediction model for CO (Rcal2 = 0.999; RMSEC = 0.174; RCV2 = 0.999; RMSECV = 0.476; Rval2 = 0.992; RMSEP = 0.991). SNV spectra of OO, CO, and binary mixture of OO+CO were used to generate sparse partial least squares-discriminant analysis (sPLS-DA) model. Tuning parameters of component numbers, the number of variables “keepX”, and the distance of prediction was executed. The component number of three with “keepX” for component 1, 2, and 3 were 1, 5, and 1, respectively, were selected along with the maximum distance approach to construct the discriminant model. The final sPLS-DA model explained the total variances of 94% with satisfaction separatibility of 100%, 97.8%, and 100% for OO, CO, and OO+CO, respectively
A Diabetes-Specific Questionnaires Validated in Indonesia: A Systematic Review
Get PDFDiabetes is a global problem that is increasingly higher from year to year. Diabetes-specific instruments so far can be well received by patients to evaluate specific aspects of their diabetic disease. This instrument is believed to be one of the best methods to evaluate certain characteristics in diabetic diseases. The purpose of the research is to identify and compare all validated diabetes-specific questionnaires. Researchers performed searches on three different electronic databases: PubMed, ScienceDirect, and Google Scholar. The study was selected covering cross-cultural adaptation and validation methodologies in Indonesia with type 1 and type 2 diabetes patients of all ages. After reviewing the full-text article, data related to psychometric characteristics are extracted from each selected study. Reliability is rated with Cronbach's (Cα). The initial search identified 1,576 studies. After the exception, 45 studies were put in for review. The questionnaires were grouped into 12 domains based on the focus of the study: adherence (n = 15), quality of life (n = 9), diabetes knowledge (n = 6), self-efficacy (n = 9), Attitude to diabetes (n = 2), emotional stress (n = 8), expectations (n = 1), perception of disease severity (n = 1), risk of developing diabetes (n = 1), family support (n = 3), diet (n = 1) and religiosity (n = 1)This study identifies and reviews all diabetes-specific questionnaires that have been validated for Indonesians to facilitate researchers to select the most appropriate instrument for each domain of interest in future research and clinical settings
Application of Hildebrand Solubility Parameter to Identify Ethanol-Free Co-Solvent for Pediatric Formulation
Get PDFFormulation of active pharmaceutical ingredients into liquid dosage form is frequently limited by solubility issues. Ethanol is commonly used as a cosolvent to improve the solubility of drugs. Due to the incomplete expression of ethanol metabolizing enzyme in children under 6 years, several drug authorities such as WHO, EMA, and FDA recommend avoiding the use of ethanol in pediatric formulation whenever possible. In addition to that Muslim consumers are regulated by the halal practice where excessive use of ethanol in pharmaceutical products should be avoided. Thus, it is necessary to explore an alternative co-solvent to reduce the use of ethanol in the pediatric formulation. This study is aimed to identify an alternative co-solvent to ethanol that is safe for the pediatric using Hildebrand Solubility Parameter approach.
In this study, the solubility parameter of the model drug, MH2011, was determined using Hildebrand Solubility Parameter (HSP). The solubility parameter (δ) of MH2011 was determined using two approaches. The first method is by measuring the maximum solubility of the model drugs in the binary mixture of water and 1,4 dioxane. The second approach is by calculating solubility parameters based on Fedor’s group substitution method.
Using binary solvent blend, the MH2011 solubility parameter was identified to be approximately 14.0 (cal/cm3 )½. This value is in agreement with the result of the second approach using Fedor’s Group substitution method which is 14. 4 (cal/cm3) ½. With this data, an alternate co-solvent to substitute ethanol was explored. The studies also suggested that propylene glycol 7% v/v may give solubility power as those of ethanol 7% (v/v). This study suggested that Hildebrand’s Solubility Parameter can be applied to identify an alternate co-solvent to ethanol. This cosolvent is important for the research area where the alcohol-free formulation is preferred such as in halal pharmaceuticals and pediatric liquid formulation
Nano-Perfumes As A Fragrance Carrier: Their Brief History, Essential Aspects, Development, Preparation Methods, Characteristics, And Future Perspectives
Get PDFNano-perfume is an alcohol-free perfume in the form of oil-in-water nanoemulsions containing fragrance. Due to its favorable properties, nano-perfume may appeal to a broader client base, including children and individuals with sensitive skin. This technology can provide an alternative solution to the low permanence of fragrances by eliminating ethanol and decreasing the amount of surfactant, co-surfactant, and solvents used in the formulation. However, relatively few researchers have studied and developed this technology to date. In this review, we examine several essential elements of nano-perfume, therefore it is hoped that relevant questions will be raised regarding the future of this technology. The discussion is focused on the definition and composition of perfume, the notion of "notes" in fragrances products, nanotechnology in the cosmetics industry, significant characteristics of nano-perfume, as well as problems and prospects
Revealing the Contribution of Phytochemicals in Syzygium cumini as Diabetics: A Systematic Review
Get PDFDiabetes mellitus (DM) is a chronic metabolic disorder characterized by increased blood glucose and abnormal carbohydrates, fats and proteins metabolism. Syzygium cumini (L.) Skeels (Myrtaceae) are widely used in anti-diabetic remedies and at the same time, rich in polyphenols. This study aims to provide a comprehensive review on the role of phytochemicals in Syzygium cumini to contribute in its anti-diabetic. The review covers related articles to antidiabetic AND Syzygium cumini AND phytochemicals OR bioactive which were published from 2012 to 2023. A systematic search was conducted by using databases Pubmed, Science Direct, Scopus, and Google The inclusion criteria include articles written in English as experimental research or clinical trials, randomized studies, and should contains phytochemical content profiling The exclusion criteria were other type of reports and or irrelevant to aforementioned topic. This review was written according to the reporting items guidelines for systematic payments and Meta-analysis (PRISMA), and SYRCLE's risk of bias (RoB) tool. By the systematic compensation used, 13 articles that meet the requirements were obtained and were further thoroughly reviewed. Seeds, leaves and bark of plant parts were reported to non-toxic in acute experiments on mice or rat. S. cumini contains flavonol glycosides, especially myricetin, myricitrin, quercetin, and kaempferol; phenolics, such as ellagic acid, tannins, gallic acid; alkaloids and saponins. These compounds contribution to the overall anti-diabetic activity were discussed, i.e increase of insulin sensitivity, secretion and usage of glucose in tissues; reducing insulin resistance, oxidative stress, gluconeogenesisand absorption of carbohydrates and sucrose. The seeds and leaves of S. cumini exhibit high potential to be developed as herbal products for anti-diabetics. This review finds a gap in research to support the development of the herbs as herbal products for anti-diabetics, in form of established preclinical and clinical trials and a reliable analytical methods for the phytochemical profiling
Evaluation of Factors Associated with Beliefs About Antidiabetic Medicine in Outpatients with Type 2 Diabetes at Hue University Hospital
No full textPoor adherence to antidiabetic medication, which causes diabetes-related complications and increases medical burden, has been an important concern for both patients and physicians. Enhancing patients' beliefs about medicine can partially improve their non-adherence status to medications. To evaluate the factors associated with beliefs about antidiabetic medicine in outpatients with type 2 diabetes at Hue University Hospital. A cross-sectional study was conducted on 396 outpatients diagnosed with type 2 diabetes mellitus at the Endocrinology Clinic at Hue University Hospital. We interviewed the patients using a questionnaire based on the Vietnamese version of the Beliefs about Medicines Questionnaire (BMQ-V). The study was conducted on 396 patients with type 2 diabetes, with a median age of 66.9 ± 13.7 years. The prevalence of outpatients achieving HbA1C and glycemic targets was 18.7% and 20.7%, respectively. According to the BMQ-V questionnaire, the participants’ beliefs about medicine had a mean score of 50.3 ± 8.1. The mean value of the Specific-Concerns subscale was the highest (14.5 ± 3.8) and the Specific-Necessity subscale was the lowest (9.8 ± 3.9). Multivariate regression analysis revealed a statistically significant association between BMQ score and HbA1c control status, duration of diabetes, and home blood glucose monitoring (p < 0.05). Coordination between clinical pharmacists and physicians should be strengthened to improve their positive beliefs and gradually reduce their negative beliefs about medicines, thereby increasing medication adherence and improving treatment effectiveness