Indonesian Journal of Pharmacy

An overview of the role of Zingiber officinale as an antimicrobial resistance (AMR) solution and a source of antioxidants

Wed, 22 Feb 2023 00:00:00 +0700

In this review, we describe the known mechanisms of antimicrobial resistance which was increasing in this era, due to the misuse of antimicrobial agents such as antibiotics, or genetic and phenotypic mechanisms. In this review, the concerns, especially addressed by designated researchers in their study and WHO in their observations and reports, regarding the types or strains of bacteria with antimicrobial resistances were described. In addition, the predicted mechanisms that promote the development and occurrence of antimicrobial resistances, such as bacterial biofilm formation, horizontal gene transfer, genetic mutations, free DNA which contains antimicrobial resistance genes, plasmids transfer through transformation or conjugation from bacterial cell to cell were well described. In addition, we also tried to describe the use of Z. officinale. The antimicrobial capabilities of this herbal plant are attributed to its capacity to create many secondary metabolites with rather complicated structures that have antibacterial and antioxidant characteristics. Z. officinale had been used for many kinds of diseases treatment traditionally. And along the way, the advance techniques of research in chemistry and biology fields had found out the composition and bioactive compound. In this review, the common online databases such as PubMed, Semantic Scholar, Crossref, Medline, Scopus, and Web of Science (WoS) were utilized to conduct literature searches. According to recent progress of antimicrobial cases observed, the efforts to strengthen the surveillance, general health systems, tightened the antimicrobial medicine distribution rules, and education for public are indeed needed.

A bibliometric approach to preclinical studies of Tinospora crispa (L.) Hook. f. & Thomson as an antidiabetic

Fitriana Hayyu Arifah, Agung Endro Nugroho, Abdul Rohman, Wawan Sujarwo — Mon, 21 Nov 2022 00:00:00 +0700

The number of diabetes mellitus (DM) cases has increased, and Tinospora crispa (L.) Hook. f. & Thomson is recognized for treating DM. Despite publications on T. crispa as an antidiabetic, there were no bibliometric reports on this topic. Thus, this study aimed to conduct bibliometric studies of existing articles on the preclinical trials of T. crispa in DM management. We used Scopus to obtain a bibliographic database of primary research related to the topic. There were 24 selected publications between 1989 and 2019. Data were analyzed with VOSviewer 1.6.16. Malaysia, John Radcliffe Hospital (United Kingdom), Journal of Ethnopharmacology, Hamdan Noor, and Stephen J.H. Ashcroft (John Radcliffe Hospital, United Kingdom) were the most impactful country, institution, source, and author, respectively. The majority and diverse fields of this topic were phytochemistry and pharmacology. Our analysis’s findings strengthen research collaboration and identify research gaps required for herbal medicine applications.

Basil Extract (Ocimum basilicum L) Exhibits Antidiabetic and Hepatoprotective Effects via SIRT1 and Peroxisome Proliferator-Activated Receptors (PPARγ) on Gestational Diabetes Mellitus Rats Model

Liganda Endo Mahata, Hirowati Ali, Arina Widya Murni, Tofrizal Alimuddin — Fri, 02 Dec 2022 00:00:00 +0700

Gestational Diabetes Mellitus (GDM) is a disorder of carbohydrate metabolism that causes hyperglycemia and insulin resistance during pregnancy. Sirtuin 1 (SIRT1) and Peroxisome Proliferator-Activated Receptorγ (PPARγ) are genes that play a role in glucose metabolism. Dysregulation of SIRT 1 and PPARγ is associated with the GDM. Hyperglycemia in GDM induces inflammation and oxidative stress in hepatocytes causing liver damage. Basil extract (Ocimum basilicum L) is one of indonesia medicinal plant has been used as traditional medicice in diabetic disorder. This study aims to investigate the hypoglycemic activity of basil extract by evaluating the expression of SIRT 1 and PPARγ in GDM rats and investigate the potential hepatoprotective effect of basil extract by analyzing the rat’s liver histology. Twenty-four of pregnant rats were divided into four groups; negative control, positive group induced by streptozotocin 40 mg/kg BW intraperitoneally, and two groups of GDM rats treated with 100 mg/kg BW and 200 mg/kg BW of basil extract for 14 days. Blood glucose levels were examined with a blood glucose meter. The expression of SIRT 1 and PPARγ was assessed by the RT-PCR. Histological analysis of the rat`s liver was conducted to determine the percentage of cell damage and tissue edem The data were statistically processed using SPSS. The extract of basil at a dose of 200 mg/kg BW showed an anti-diabetic effect which decreased the glucose level concentration by about two times compared to the untreated rat. It enhanced the expression of SIRT-significantly with a value of p= 0.035 (p <0.05). Basil extract-treated group showed a trend of increasing PPARγ expression, but not statistically significant. In addition, HE staining on the liver showed a tendency to improve in the group given basil extract. This Study concluded that basil extract could increase SIRT 1 and potential to be an anti-hyperglycemic therapy with a hepatoprotective effect.

OPTIMIZATION POLYSORBATE 80 AND SORBITAN MONOOLEATE 80 AS EMULSIFIER IN COSMETIC FOUNDATION CONTAINING ETHYL CINNAMATE

Ungsari Rizki Eka Purwanto, Intan Martha Cahyani — Mon, 05 Dec 2022 00:00:00 +0700

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.

Network pharmacological analysis identifies the curcumin analog CCA-1.1 targets mitosis regulatory process in HER2-positive breast cancer

Dhania Novitasari, Riris Istighfari Jenie, Jun-ya Kato, Edy Meiyanto — Wed, 07 Dec 2022 00:00:00 +0700

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.

THE PHARMACOGNOSTIC STANDARDS, ANTIOXIDANT ACTIVITY, AND HEPATIC SAFETY PROFILE OF AN INDONESIAN ANTIDIABETIC POLYHERBAL FORMULATION

Dwi Hartanti — Tue, 20 Dec 2022 00:00:00 +0700

The excessive oxidative processes and the lack of cellular antioxidative mechanisms are significantly observed in diabetes. In addition, long-term medication required for the treatment might harm the hepatic tissues. This study evaluated the selected pharmacognostic characters, antioxidant activities, total phenolic content, and the hepatic safety of a polyherbal formulation containing seven plant constituents used by Klinik Wisata Kesehatan Jamu Kalibakung, Tegal, Indonesia, to treat diabetes patients. The pharmacognostic properties of the formulation were characterized according to the WHO quality control methods for herbal materials. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH RSA), ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) were evaluated as per the standard method. The effect of formulation on the hepatic HepG2 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The pharmacognostic properties of the formulation specified as follow: foreign matters (1.32±0.05%), loss on drying (11.50±0.07%), total ash (5.68±0.07%), acid-insoluble ash (0.94±0.04%), water-soluble extractable (18.22±0.60%), and ethanol-soluble extractable (16.90±0.77%). The ethanol extract showed a superior DPPH RSA (960.70±2.58 mM Trolox equivalent (TE)/ g dry weight (DW)), FRAP (1112.69±8.39 mM TE/g DW), and TPC (1768.40±32.40 mg gallic acid equivalent (GAE)/g DW) over its water counterpart. However, the water extract was safer for HepG2 cells than the ethanol one, with the IC₅₀values of 218.25±14.03 and 40.24±3.53 µg/ml, respectively. This study set the pharmacognostic standards for an antidiabetic polyherbal formulation with excellent antioxidant activities, in which its traditional use as a decoction was safe for the hepatic cells.

Optimization and Characterization of Extruded Partially Pregelatinized Cassava Starch as Filler-Binder

T N Saifullah Sulaiman, Gabriela Kasih Mawarni, Rumiyati Rumiyati — Thu, 22 Dec 2022 00:00:00 +0700

In order to use starch as a filler-binder, the pregelatinization method by extrusion can enhance the flow characteristics and compressibility of starch. This study aimed to find the optimum process parameter for producing partially pregelatinized cassava starch (PPCS) using twin screw extrusion and characterizing it as a filler-binder excipient. For arranging experimental trials, a three-level Box-Behnken design with three independent variables—starch moisture content (ranged from 20% to 40%), extrusion temperature (ranged from 50°C to 70°C), and screw speed (ranged from 10 rpm to 30 rpm)—was used to make PPCS. The response surface methodology approach was used for optimization. The desired filler-binder characteristic of PPCS was defined as having good flowability and compactibility properties. The most desirable process parameter was achieved by combining 39.9 percent starch moisture content, 70°C extrusion temperature, and 25.8 rpm screw speed. The results showed that optimized PPCS has good flow properties and also good water absorption capacity. The optimized PPCS had a polygonal shape and a size range of 149-400μm. PPCS showed birefringence characteristics under polarized light, indicating a large number of undamaged starch granules. The PPCS XRD pattern showed peaks at 15°, 17°, 18°, and 23°, and also a relative crystallinity of 27.3 percent. When analyzed with DSC, PPCS revealed glass transition curves and a gelatinization degree of 36.01 percent.

Synthesis and Antioxidant Actiivty of Some Dibenzylidene-Cyclohexanones

Thu, 29 Dec 2022 00:00:00 +0700

Dibenzylidene-cyclohexanone is a curcumin analog. Analog of curcumins showed activity as antioxidant. This research is aimed to synthesize and study the antioxidant activity of dibenzylidene-cyclohexanone compounds. The synthesis was carried out according to carbonyl condensation reaction and its antioxidant activity was tested by using DPPH radical scavenging activity and FRAP assay. Compound entry 1 (2,6-bis-(3’-Bromo-4’-methoxybenzylidene)-cyclohexanone) and entry 3 (2,6-bis-(2’-chloro-6’-fluorobenzylidene)- cyclohexanone) were obtained in 70 % yield. Compound entries 1 and 2 gave the same antioxidant activities according to the DPPH method and this result was not good enough compared to vitamin E. Compound entry 1 showed the best antioxidant activity among the series and also had a better antioxidant activity compared to vitamin E. From these results, it can be said that compound entry 1 was the best antioxidant agent in the series.

Tyrosinase Inhibitory and Antioxidant Activity of Paederia foetida L.

Wed, 21 Dec 2022 00:00:00 +0700

Paederia foetida L. is a tropical Asian plant containing bioactive compounds and often used as functional foods. The aim of this study was to determine the antioxidant capacity and inhibitory activity of P. foetida leaves extract on tyrosinase activity. In addition, the total phenolic content (TPC) and total flavonoid content (TFC) were determined. TPC and TFC was evaluated by the Folin-Ciocalteu and the aluminum chloride (AlCl₃) colorimetric method, respectively. The antioxidant capacity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) method. The antioxidant capacity was expressed as trolox equivalent antioxidant capacity (TEAC) dan ascorbic acid equivalent capacity (AAEC). The tyrosinase inhibitory activity was conducted by enzyme-linked immunosorbent assay (ELISA) using L-tyrosine as a substrate and measured at 490 nm by ELISA reader. TPC in the crude extract, fraction A, and fraction B was 173.18 ± 3.99, 553.95 ± 5.70 and 405.37 ± 33.90, respectively. TFC in the crude extract, fraction A, and fraction B was 12.79 ± 0,25, 143.16 ± 9.27, 143.50 ± 6.90, respectively. The best antioxidant capacity of the extract was shown in the DPPH method (15.71 ± 1.6 mg TEAC/g and 100.77 ± 8.5 mg AAEC/g). Meanwhile, fraction B showed the best antioxidant capacity by the FRAP (11.48 ± 1.5 TEAC/g and 8.39 ± 1.2 mg AAEC/g ) and CUPRAC (116.34 ± 1.9 mg TEAC/g and 66.11 ± 1.3 mg AAEC/g) methods. Tyrosinase inhibitory activity exhibited that the IC₅₀ of fraction A and B was 13.67 μg/mL and 13.37 μg/mL, respectively.

Optimization of Gelling Agent and Sunscreen Activity Test of 4-OH-chalcone Gel by In Vitro Method

Wed, 11 Jan 2023 00:00:00 +0700

ABSTRACT

The 4-OH-chalcone was suspected to absorb and reduce ultraviolet radiation intensity that exposed to the skin. The 4-OH-chalcone was formulated as gel dosage form using combination of carbopol in content of 0.50-1.00% w/w; propylene glycol in content of 19-20% w/w; and CMC-Na in content of 0.50-1.00% w/w. This study’s purpose was to optimize the three gel bases, evaluate physical properties, physical stability, and activity of 4-OH-chalcone gel as sunscreen by in vitro method. Simplex Lattice Design (SLD) method was used to optimize gel base with Design Expert software version 10.0. Activity of 4-OH-chalcone gel as sunscreen was determined spectrophotometrically by determining Sun Protecting Factor (SPF) value, percent transmission of erythema (% TE), and percent transmission of pigmentation (% TP). Data were analyzed statistically with SPSS Statistic software. Optimum formula of 4-OH-chalcone gel with 0.50% w/w carbopol content, 0.50% w/w carboxymethylcellulose sodium content, and 20,0% w/w propylene glycol content has pH of 5.59, viscosity of 37.4 dPa.s, spreadability of 28.8 cm², adhesive time of 1.28 seconds, SPF value of 28.65, %, TE value of 16.44%, %TP value of 0.24%, and relatively stable physical properties.

DEVELOPMENT AND VALIDATION OF HPLC–PHOTO DIODE ARRAY METHOD FOR DETECTING STEROIDS IN SKIN WHITENING PRODUCTS SIMULTANEOUSLY

Yustina Yustina — Thu, 19 Jan 2023 00:00:00 +0700

Since steroids are prohibited to be present in cosmetic products, thus an identification of these outlawed compounds intentionally incorporated in skin whitening product is enough for market surveillance purpose. Simultaneous method for detecting prednisone (PRN), triamcinolone acetonide (TCA), hydrocortisone acetate (HCA), clobetasole propionate (CBP), and mometasone furoate (MTF) has not been developed until now. The goals of this study were to develop and to validate for screening these five steroid compounds in cosmetic product by using reverse phase (RP) high-performance liquid chromatography (HPLC) equipped with photo diode array (PDA) detector. Validation method was applied including the system suitability test, determination of specificity and selectivity, and determination of detection limit. . In optimization step, we succeeded distinguish and identify five steroid compounds with different retention time.The retention times of PRN, TCA, HCA, CBP and MTF were detected at 3.267, 4.260, 4.910, 15.360, and 16.707 min, respectively. The method performed good selectivity with resolution more than 1.5. While for determination of limit of detection (LOD) was carried out by calibration curve approach over the range 0.5-5 µg/ml and resulted in LOD value for PRN, TCA, HCA, CBP and MTF were 7.20, 8.85, 8.17, 9.30, and 8.42 µg/g, respectively. The developed method can be applied for routine analysis of PRN, TCA, HCA, CBP and MTF in various type of cosmetic products.

Clindamycin peel-off mask film, an effective formulation for C. acnes treatment: characterization and microbiological activity

Boontida Morakul, Amaraporn Wongrakpanich, Veerawat Teeranachaideekul — Wed, 01 Feb 2023 00:00:00 +0700

Clindamycin 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.

Co-crystallization of sofosbuvir with sugars for enhanced dissolution rate

Taher Mohamed Yassen Mousa, Ahmed Atef Donia, Gamal Mohamed El Maghraby — Wed, 01 Feb 2023 00:00:00 +0700

Sofosbuvir is one of the direct acting antiviral agents which is approved in the treatment of chronic HCV in combination with other agents. The low aqueous solubility of sofosbuvir resulted in slow dissolution which is supposed to be responsible for its low and variable bioavailability after oral administration. Accordingly, the objective of this work was to investigate the effect of co-crystallization of sofosbuvir with hydrophilic sugars on its crystalline structure and dissolution rate. Mixtures of sofosbuvir with hydrophilic sugars at various molar ratios were prepared by ethanol assisted kneading followed by drying. The dry products were then characterized by attenuated total reflectance fourier transform infrared spectroscopy (ATR FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and in vitro dissolution studies. Combined instrumental analysis reflected development of new crystalline species of co-crystal type. This was evidenced by the existence of hydrogen bonding as shown from FTIR spectra, change in the thermal behaviour and appearance of new diffraction peaks in the diffractograms recorded by XRD. The co-crystallization was associated by weakening of intermolecular bonds which resulted in significant increase in the dissolution rate of sofosbuvir. The study introduced hydrophilic sugars as co-crystal co-formers for enhanced dissolution of sofosbuvir.

Steroidal Saponin Isolated from Dioscorea alata L. Extract Improve Digestive Tract Allergy in Balb/C Mice Induced by Ovalbumin

Sri Nabawiyati Nurul Makiyah — Tue, 14 Feb 2023 00:00:00 +0700

Steroidal saponin compound in Dioscorea species is one of the crucial substance because it has some biological functions, such as immunomodulatory and anti-allergic agent. This study aims to analyze the effect of steroidal saponin of Dioscorea alata L. on CD4 T cells activation, cytokines IL-4, IL-5 and TGF-β. This study used primary lymphocyte cell which isolated from BALB/c mice spleen. Mice lymphocyte were cultured in the complete medium with presence of various concentrations (50, 25 and 12.5 µg/mL) of three isolate of steroidal saponin of D. alata for 24 h. Diosgenin was used as positive control. After 24 h of treatment, the activation of lymphocyte, IL-4 and IL-5 production was determined by Flowcytometry analysis. Data were analyzed using student t-test with p < 0.05 and p < 0.01. The results showed that the low concentration of Isolate 1 (12.5 µg/mL) was found to be effective to stimulate the activation of CD4 T cells, reduce the production of IL4 and IL-5 by CD4 T cells and increase TGF-β production. These results showed that a low concentration of steroidal saponin of D. alata could be considered as immunomodulatory and anti-allergic agent. Purification and identification of each isolate isolated from DAE is in progress.

Influence of Polymer Combınatıon Concentratıon on The Characterıstıcs, In Vıtro Release And In Vıvo Lung Deposıtıon of Algınate-Carrageenan Mıcrospheres Encapsulatıng Cıprofloxacın HCl

Thu, 23 Feb 2023 00:00:00 +0700

Inhalation Ciprofloxacin HCl microspheres were formulated with combination of alginate and kappa carrageenan with a total of 1% (F1), 1.5% (F2), and 2% (F3). Aim of this research is to examine effect of polymer concentration on characteristics, release, and lung deposition of microspheres. Microspheres were characterized including loading, efficiency, yield, size, moisture content, mucoadhesivity, and release. Deposition was studied by fluorescence microscopy. Results showed spherical and smooth with size ofless than 2 µm. Loading showed about 18.55% to 29.65%. Entrapment efficiency was 52.86-76.29%. Yield was 49.83-70.72%. Swelling index was less than 10. For moisture content, all formulas demonstrated less than 6.5%. For mucoadhesivity, F1, F2, and F3 showed 0.0090 kg, 0.0217 kg, and 0.0329 kg respectively. It was found that increasing polymer concentration did not affect size, loading, efficiency, and yield of microspheres. Cumulative release at F1, F2, and F3 was 72.64%, 59.25%, and 47.66% respectively in 10 minutes at PBS pH 7.4 with burst release profile. In vivo showed that all formulas were able to deposit on rat lungs and it was found that the intensity were decreased at the 4th hour due to increase of polymer. Remaining intensity indicated that microspheres were able to maintain the drugs loaded.