Indonesian Journal of Pharmacy
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Optimization of Polysorbate 80 and Sorbitan Monooleate 80 aas Emulsifiers in Foundation Makeup Containing Ethyl Cinnamate
Cosmetic foundation is a type of decorative makeup and commonly include a sunscreen agent. Ethyl cinnamate is one of the potential organic essential oil sunscreens. Nevertheless, there is little study on ethyl cinnamate usage in cosmetics, particularly oil-in-water foundation cream. Using an emulsifier in oil-in-water foundation cream a higher concentration does not guarantee higher oil phase recovery. However, using two combinations of emulsifier such as polysorbate 80 and sorbitan monooleate 80 with the optimum combination can be the right solution. This study aims to optimize polysorbate 80 and sorbitan monooleate 80 in a cream foundation using ethyl cinnamate as an active ingredient designed to have an effective ability to protect facial skin from ultraviolet radiation and are safe to use. The optimization formulas design of the emulsifier combination in foundation cream was made using the Simplex Lattice Design method with help Design Expert version 10.0.1. Parameter optimization were the value of pH, viscosity, spreadability, adhesion, and Sun Protection Factor (SPF) value. The stability test and skin irritation test of optimum formula were also conducted. As a positive control, Revlon Colorstay Foundation as a brand cosmetic foundation was used (National Food and Drug Agency of Indonesia number : NA18140300519). The optimum ratio of polysorbate 80 and sorbitan monooleat 80 were 9.565 and 1.435 with the physical characteristics of pH 6.478+0.008; viscosity 5844.2+31.82 cPs; spreadability 6.16+0.11 cm; adhesion 3.346+0.14 seconds; SPF Value 22.385+0.48, and no irritation symptoms. The ethyl cinnamate foundation created was physically stable, had a pleasing look, and did not irritate the skin, making it safe to wear. It also provides efficient UV radiation protection
Geigeria Alata- a Potential Source for Anti-Alzheimer’s Constituents: In Vitro and Computational Investigations
Antioxidants and acetylcholinesterase inhibitors play a key role in the prevention and management of degenerative disorders including Alzheimer’s disease in particular. Identifying new anticholinesterases from natural sources may contribute to combating this class of diseases. The present study aimed to evaluate the potential anti-Alzheimer’s activity of Geigeria alata (DC), a plant used in Sudanese folkloric medicine. Accordingly, the whole DC plant extract including twenty phytoconstituents of phenolic, flavonoid, and tannin types was evaluated in vitro as antioxidants and acetylcholinesterase inhibitors. As well, their pharmacokinetics, drug likeliness, and toxicity profiles were assessed. Additionally, the virtual binding of the plant’s phytoconstituents with the cholinesterase target was investigated by docking against two AChE X-ray crystallographic structures. The best effective DPPH radical scavenging activity was demonstrated by both ethyl acetate and n-butanol fractions with percentages of inhibition of 91 ± 0.02% and 90 ± 0.02% (IC50 22 ± 0.01 and 66 ± 0.02 µg/mL), respectively. The ethyl acetate fraction showed statistically significant, and the highest AChE inhibitory activity (78% inhibition, IC50 0.246 ± 0.02 mg/mL). Furthermore, the ethyl acetate fraction exhibited the highest total phenolic, flavonoid, and tannin values. Among identified compounds, quercetin and hispidulin showed promising in silico anti-AChE activity and hence merit further studies for the isolation and characterization of these active constituents.
 
Traditional medicine and its impact on patient outcomes in type 2 diabetes mellitus therapy
The growing number of people with diabetes mellitus enhance the increasing number of antidiabetic medicine used and also the use of traditional medicine as a complementary medicine. The choice of treatment is depend on the patients’ perception and will have an effect on compliance and clinical outcome. This study aimed to determine the relationship between patients’ perception of consuming a combination of Traditional Medicine (TM) and Synthetic Medicine (SM) and their compliance with medication, as well as to examine its impact on the outcomes of type 2 DM treatment at three community health centers in Yogyakarta. This study is a cross-sectional study. Participants that met the inclusion criterias were 110 patients with type 2 diabetes mellitus who had been taking TM-SM combination at least one month at three community health centers in the City of Yogyakarta. The main outcome is the relationship between perception and compliance, as well as the outcome of therapy. Result showed that from 110 patients, only 40 (36.4%) had a good perception of the use of TM-SM combination, and 32 patients (29.1%) succeeded in adhering to the recommended administration of synthetic drugs. A total of 49 patients (44.5%) reported controlled blood sugar levels as the outcome of DM management. Patients' perception of drug combination was proven unrelated to patient compliance and treatment outcome (p> 0.05). For the conclusion, there is no relationship between patients’ perception of taking a combination medication with adherence and treatment outcomes.
Keywords: Compliance, Perception, Type 2 Diabetes Mellitus, Therapy Outcom
Ethnopharmacology, Biological evaluation and Chemical composition of Boswellia dalzielii Hutch: A Review
The Burseraceae family consists of 18 genera and 540 species. Boswellia dalzielii is a medicinal plant used in tropical and subtropical areas for the treatment and management of various ailments. Despite the medicinal value of B. dalzielii, there is no comprehensive documentation. The study aimed to review the ethnopharmacology, biological evaluation and chemical composition of B. dalzielii. Scopus, Web of Science, BioMed Central, Science Direct, PubMed, Springer Link, and Google Scholar were searched to find published articles. The results showed that the leaves, stem bark, and root of B. dalzielii have been traditionally used in Nigeria, Cameroon, Burkina Faso, Benin, Sudan, and Guinee for the treatment and management of antirheumatic, antispasmodic, analgesic, antiseptic, hypotensive, malarial mental illness, ulcer, pain, and fever. It is also found that leaves, stem bark, and root have antioxidant, antibacterial, antifungal, and antimalarial properties with stembark having the highest activity. Chemically, it was revealed the leaf has high contents of monoterpenes hydrocarbons with alpha-pinene as the major compound. The species were largely studied in vitro, according to the literature survey. A well-designed clinical experiment is required to obtain conclusive evidence on the efficacy of stembark. The standard dose and safety of the stembark should be established
Analgesic and Anti-inflammatory Activities of Urena lobata L. Leaf Extracts
Pulutan (Urena lobata) is a medicinal plant used to treat fever, infection and swelling traditionally, although the pre-clinical study about the herbs as analgesic and anti-inflammatory are still limited. The objective of this study is to measure analgesic and anti-inflammatory activity of U. lobata leaf extract through in vivo study and in silico. This study was performed using male wistar rats divided into eight groups (two control groups and six test groups) (n=5). U. lobata leaf was extracted by water and ethanol, each prepared in dose of 125, 250, 500 mg/kg body weight. Anti-inflammatory activity was evaluated by plethysmometer for 6 hours, meanwhile analgesic activity was examined by analgesymeter for 4 hours. The data was analyzed using one way ANOVA test continued with LSD test (p < 0.05). Following active compound identification using Liquid Chromatography-Mass Spectra (LC-MS/MS), several compounds were used in an in silico study using docking server. Both aqueous and ethanolic extract of U.lobata at 125 and 250 mg/kg bw inhibited paw edema with an Area Under Curve (AUC) volume about 10 % and 5%, respectively, compared to control group (p<0.05). For analgesic activity, aqueous extract of U. lobata were able to increase the AUC for pain threshold of about 30-100 % compared to control group (p<0.05), whereas the activity of ethanolic extract lower than aqueous extract. Stigmasterol and beta-sitosterol in U. lobata potentially inhibited Cycloxygenase-2 (COX-2) as a pro-inflammatory mediator and pain. Aqueous and ethanolic extract of U. lobata have analgesic activity and anti-inflammation, the mechanism was predicted through inhibitory activity of COX-2
Bioinformatics Analysis Uncovers the Importance of RTK-RAS-PI3K/Akt Regulation by Borneol in Overcoming Breast Cancer Resistance to Tamoxifen
Currently, tamoxifen-based hormonal treatment remains the first line for luminal A (estrogen receptor [ER]-positive) subtype breast cancer, with a response of more than 30%. Chemoresistance was induced by the long-term use of tamoxifen therapy. Therefore, to prevent resistance and improve the effectiveness of tamoxifen, combined therapy is required. This study used bioinformatics to identify possible borneol target genes and their mechanism for overcoming tamoxifen resistance in breast cancer cells. We used data from the gene expression omnibus (GEO) collection to find differentially expressed genes (DEGs). The Database for Annotation, Visualization, and Integrated Discovery (DAVID) site, version 6.8, was also used to undertake gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis of the DEGs. The STRING-DB site, version 11.0, was used to predict protein-protein interaction (PPI) study. The PPI analysis findings were visualized using the Cytoscape software, version 3.8.2. The hub gene was further calculated using the CytoHubba plugin. The genomic alterations from the hub gene were evaluated using cBioPortal, version 1.18.1. The potential target genes (PTGs) of borneol compounds are ESR1, FGFR2, STAT3, ERBB4, PRKCA, and RTK-RAS PI3K-Akt signaling as its prospective mechanism to overcome tamoxifen resistance in breast cancer cells. More studies are needed to confirm the potential of borneol to overcome tamoxifen resistance in breast cancer
Antibacterial Activity and GC–MS Based Metabolite Profiles of Indonesian Marine Bacillus
Investigating Indonesian marine bacteria producing active compounds is key to finding a cultivable source of marine drugs. Screening the potential strain as well as profiling the active compounds are important steps to identifying the targeted substances. Methods used in this study were isolated some Bacillus strains from several marine environments in Indonesia, evaluated the antibacterial activity, and characterized the secondary metabolite using GC-MS spectroscopy. Several active antimicrobial compounds derived from marine microorganisms were identified using GC-MS such as pyrrolo [1,2-a] pyrazine-1,4-dione, octatriacontyl pentafluoropropionate. We found that some marine bacillus showed antimicrobial activity, such as B. flexus, B. tequilensis, B subtilis, and Bacillus sp. Profiling of metabolites on GC-MS showed the presence of several bioactive compounds in the ethyl acetate extract, which were identified to be nitrogen compounds such as pyrrolo[1,2-a]pyrazine-1,4-dione, phthalates compounds (butyl isohexyl ester and 1,2 benzendicarboxilate bis (2-etilhexyl) ester), and dibutyl phthalate. Some phenolic compounds also were found, such as tris (2,4-di-ter-butilfenil) fosfat, phenol, 2,4-bis (1,1-dimethyl ethyl), and phenol 3,5-bis (1,1-dimethyl ethyl). Finally, fatty acid derivatives such as n-hexadecanoic acid, cis-vaccenic acid, 7-hexadecene, farnesol isomer A, and stigmastan-3,5-diene were also identified in several marine bacillus.  
Preparation and Characterization of Pregelatinized Sago Starch (PSS) from Native Sago Starch (NSS) (Metroxylon sp.) and its Evaluation as Tablet Disintegrant and Filler-Binder on Direct Compression Tablet
Starches are biodegradable and relatively inexpensive natural biopolymers which are widely used in the food and pharmaceutical industries. Sago starch is one of the starches which can be potentially used as the excipient in pharmaceutical formulation. The purpose of this study was to modify and to characterize the physical and chemical properties of native sago starch (Metroxylon sp) (NSS) and pregelatinized sago starch (PSS). NSS was evaluated to be confirmed with the requirement, including microscopic analyses, amylum identification, ash content, amylum acidity, loss on drying, solubility in water, solubility in ethanol, and chemical content of Pb, Cd, Hg. Physically evaluated for both types of sago starch were particle size, moisture content, flow rate, angle of repose, tapped density, compactibility, water absorption rate, and water absorption capacity. Fourier transform infrared spectroscopy (FT-IR) was used to characterize and evaluate PSS and NSS’s chemical properties. Chemical content (Pb, Cd, Hg) and microbial content (yeast mold figures, number of bacteria, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella sp., Shigella sp.) of PSS are also identified. The results of this study showed that PSS exhibited different values of those determined parameters compared to that of NSS on particle size, moisture content, flow rate, the angle of repose, tapped density, water absorption rate, and water absorption capacity. In conclusion, PSS has better flow properties because it has a larger particle size than the NSS. PSS also has a larger water absorption rate and water absorption capacity than the NSS because PSS can interact with water easier than NSS. There is no bacterial content in PSS which means PSS follows the regulatory requirement. PSS had a good effect on weight uniformity, hardness, and disintegration time of the tablets. It makes PSS can be potentially used as the excipient in solid dosage form formulation
Analysis of Enoxaparin Effectiveness Based on COVID-19 Severity: A Study in a Secondary Hospital in Bandung, Indonesia
Li Coagulopathy is a common predictor of mortality in COVID-19. Meanwhile, enoxaparin is an anticoagulant with anti-inflammatory, endothelial protection, and viral antagonist properties. Therefore, thromboprophylaxis with enoxaparin in COVID-19 is common in clinical settings. This study aims to assess enoxaparin's efficacy across different severity levels by examining its effect on primary outcomes comprising Length of stay (LOS), invasive mechanical ventilation, and mortality as well as secondary in the form of D-dimer, platelets, C-reactive protein (CRP), Neutrophil Lymphocyte Ratio (NLR), and Absolute Lymphocyte Count (ALC). During hospitalization, 269 patients received enoxaparin across varying severity levels comprising mild, moderate, and severe, while the Wilcoxon test was used to analyze the efficacy in each group. Additionally, the differences in patient characteristic profiles across the severity levels were determined using the Kruskal-Wallis test. The increase in mortality rate and the need for mechanical ventilation were directly proportional to the level of severity. D-dimer decreased from 1308.87 ng/ml to 979.83 ng/ml (p=<0,001) as well as from 1758.41 ng/ml to 1510.68 ng/ml (p=<0,001) in the mild and moderate levels respectively. The platelet increased from 225.65 to 369.39 x103/µl (p=<0,001) in mild and 256.77 to 398.97 x103/µl (p=<0,001) in moderate. Moreover, CRP improved in both mild 52.62 to 49.58 mg/l (p=0.031) and moderate 92.99 to 42.66 mg/l, (p=<0,001). Based on the results, enoxaparin effectively improves D-dimer, platelet, and CRP levels in mild and moderate but not in severe conditions, however, no effect was found on LOS, NLR, and ALC
Network Pharmacological Analysis Identifies the Curcumin Analog CCA-1.1 Targeting Mitosis Regulatory Process in HER2-Positive Breast Cancer
Recent studies present that the CCA-1.1 (a curcumin derivative) impedes the proliferation of breast cancer cells (luminal, HER2-overexpressed, and TNBC cells). Currently, we analyze the possible target of action of CCA-1.1, particularly in breast cancer cells with HER2 amplification using bioinformatics analysis. The differentially expressed genes (DEGs) of HER2-positive breast cancer were retrieved from TCGA-BRCA data (via UALCAN). We used three web-based tools (Swiss Target Prediction, BindingDB, and TargetNet) to predict the potential target of CCA-1.1 using the SMILE-similarity feature. The functional annotation and network enrichment were processed in WebGestalt. The alteration of selected genes was observed in CBioPortal. The protein-protein interaction (PPI) network was constructed in STRING, then ranked based on the degree score using Cytohubba feature in Cytoscape. The survival analysis from the hub-gene was collected in GEPIA2 with selection only for HER2-positive breast cancer cases. The correlation between the hub genes and tumor-infiltrating immune markers was determined using TIMER web tools. The pathway network analysis highlighted the cell cycle regulation in mitosis as affected signaling amid the putative CCA-1.1 targets. We denoted eight potential genes that could be responsible for inhibiting mitosis regulation upon CCA-1.1 treatment, including AURKA, AURKB, PLK1, TPX2, KIF11, MELK, CDK1, and CHEK1. Several of the potential markers (AURKB, AURKA, CDK1, and CHEK1) revealed to be correlated with the immune cells’ infiltration markers. CCA-1.1 might regulate mitosis to induce cell cycle arrest and lead to cell death. The predicted targets of CCA-1.11 gave insight into the potency of CCA-1.1 to be with immunotherapy. Further validation of the data presented in the study is essentially needed to develop CCA-1.1 for breast cancer