Indonesian Journal of Pharmacy
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    In Vitro Study: Effect of Cobalt(II) Chloride Against Dengue Virus Type 1 in Vero Cells

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    Dengue virus (DENV) serotypes DENV-1 to DENV-4 are enveloped viruses that belong to the genus Flavivirus of the Flaviviridae. Dengue vaccine or antiviral has not yet been clinically approved for humans, even though there have been great efforts toward this end. Antiviral activity against DENV is needed to develop to be an alternative drug for DENV virus. Cobalt(II) chloride have been used in the treatment and prevention of diseases of humans since ancient times. The aim of this study is to investigate the antiviral effects and Cytotoxicity of Cobalt(II) chloride. This compound was further investigated for its inhibitory effect on the replication of DENV-1 in Vero cells. Antiviral activity and Cytotoxicity measured by WST-1 assay. The IC50 value of the Cobalt(II) chloride for DENV-1 was 0.38 μg/ml. The cytotoxicity of Cobalt(II) chloride to Vero cell suggest that the CC50 value was 2.91 µg/ml The results of this study demonstrate the anti-dengue serotype 1 inhibitory activity of Cobalt(II) chloride was a high toxic compound

    Quality of Life of Patient with Hypertension in Primary Health Care in Bandar Lampung

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    The high prevalence of hypertension in Indonesia, encourages studies related to how the quality of life of patients with hypertension. The purpose of this study was to measure quality of life, identify and explain factors related to the quality of life of patients with hypertension.The study design was descriptive correlation using a cross sectional study approach. The study subjects were all outpatient hypertensive patients several health centers in Bandar Lampung. The instrument used in this study was the Indonesian SF-36. The data collected included the patient's demographic characteristics including gender, age, education, occupation, and marital status, and the fields related to the health history of the study subjects included the duration of hypertension, complications, and the number of antihypertensive drugs consumed. Data were analyzed using bivariate analysis to see the relationship between two variables with the level of significance used was 5% (α = 0.05) with the value of the confidence interval set was 95%. Multivariate analysis was conducted to study the relationship of several independent variables with one or several dependent variables.The results of univariate analysis showed that age, marital status, duration of illness, complications, and the number of drugs consumed had an effect on the quality of life of hypertensive patients (p <0.05). The results of multivariate analysis showed that the factors of age, marital status, and duration of hypertension are factors that influence the physical domain, while the factors of gender, marital status, duration of hypertension, complications, and the number of drugs are influential factors in the mental domain mental

    Application of Simplex Lattice Design on the Optimization of Andrographolide Self Nanoemulsifying Drug Delivery System (SNEDDS)

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    Background: Optimization of self-nanoemulsifying drug delivery system (SNEDDS) formulation is an important step to obtain optimal formulation with desired characteristics.Objective: This present study was aimed to utilize simplex lattice design in optimizing andrographolide SNEDDS.Method: Simplex lattice design was employed to optimize andrographolide SNEDDS in which component of SNEDDS was selected as the independent factor while the charactheristics of SNEDDS was used as the responses. Capryol-90, Kolliphor RH 40, and propylene glycol were selected as the oil, surfactant, and co-surfactant, respectively. Optimization of andrographolide SNEDDS formulation was based on their characteristics including emulsification time, droplet size, and drug content. The optimized SNEDDS formulation was evaluated for emulsification time, droplet size, drug content, and zeta potensial.Results: The emulsification time, droplet size, drug content, and zeta potensial of the optimized andrographolide SNEDDS was found to be 1.21±0.03 min, 44.02±0.67 nm, 6.69±0.08 mg/g, and -40.63±0.76 mV, respectively.Conclusion: This result suggested that simplex lattice design is a suitable for efficiently optimizing the formulation of andrographolide SNEDDS

    Design and Synthesis of Novel Derivatives of 4-(6-(4-Substituted Phenyl)-7H-[1,2,4] Triazolo[3,4-b][1,3,4]Thiadiazin-3- yl) Phenol as a Potent Inhibitor of Tubulin with Antitumor Activity

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    A new series of 4-(6-(4-substituted phenyl)-7H[1,2,4] triazolo[3,4b][1,3,4]thiadiazin-3-yl) phenol was synthesized and explored for anti-tubulin activity  using in silico and in vitro assay models. The starting nucleus, ethyl-4-hydroxybenzoate was treated with hydrazine hydrated, and converted to 4-hydroxybenzohydrazide (1). Then, (1) was stirred with CS2 and KOH in dry EtOH  to afford 2-(4-. hydroxyl benzoyl)hydrazine-1-carbodithioate, as a potassium salt (2). Compound (2) was used directly and refluxed with hydrazine hydrate to yield a parent nucleus, 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)phenol (3). The target compounds (4-7), were synthesized by refluxing compound (3) with various substituted phenacyl bromides  using  sodium acetate as  a abase, The new compounds (3-7) were characterized using different spectroscopic analysis  techniques including IR, and 1HNMR.  The anticipated  modes  of binding to α- tubulin were also investigated by means of a molecular docking experiment. The binding mode revealed good agreement with the in vitro work with binding energies of (-38.77 and  -37.50 kcal/ mol) for the most potent compounds 7 and 4, respectively. The effect of synthetic novel compounds on cancer cell lines proliferation was screened  by MTT assay. The ability of the synthetic compounds to induce apoptosis process was tested using acridine orange/ ethidium  bromide staining. The synthetic novel compounds exhibited potent inhibitory effects on the growth and viability of cancer cell lines SKOV-3 and AMJ-13 cells. They inhibited  the proliferation and growth  of cancer cell lines at low concentrations, with IC50 values ranging from10.44 to 19.67 µg/mL against SKOV-3 cells, and for AMJ-13 cells,  the IC50 values were11.35 to 20.52 µg/mL. The effect of  the synthetic compounds on  the cell growth, and proliferation of cancer cell lines was associated with increased apoptosis.Our results demonstrated that the target compounds inhibited cancer cell lines proliferation, with a mechanism of action parallel to that of other tubulin inhibitor

    The Effect of Brazilin from Caesalpinia sappan on Cell Cycle and Modulation and Cell Senescence in T47D cells

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    Ethanolic extract and brazilein-containing fraction of Caesalpinia sappan L., has been reported to inhibit cell proliferation in T47D (ER+ PR+/- cell, Luminal A subtype model). The Luminal A subtype is the most common subtype of breast cancer in Indonesian women. In this study, we explored the activity of the reduced form of brazilein, i.e. brazilin, in T47D cells proliferation and the mechanism that involved. The cytotoxicity activity of brazilin was observed using MTT assay. While the cell cycle modulation analysis was done by using flowcytometry, and the senescence assay was observed using S-A-β-galactosidase assay. The results showed that brazilin inhibited cell growth in a dose-dependent manner with an IC50 value of 50μM (or 14.3μg/mL). That was higher than a brazilein-containing fraction, which was reported previously by our group to have an IC50 value of 68μg/mL against the same cell. Cell cycle analysis showed that cells treated with brazilin were accumulated at the G2/M phase in a dose-dependent manner. Furthermore, cells treated with a combination of brazilin and doxorubicin was accumulated at the G2/M phase and sub G1 phase. Cells accumulation at sub G1 phase indicates that the cells undergo apoptosis. Our data of S-A-β-galactosidase assay showed that cells treated with 1/4IC50, 1/2IC50, and IC50 brazilin had lower senescent cells compared to the untreated cells. The morphology of cells treated with IC50 (50μM) brazilin changed. The cells shape became rounded, cells were shrinkage and detached from the well plate, indicating that cells may undergo apoptosis. These results suggested that brazilin was cytotoxic towards T47D cells and its combination with dox potentially induced apoptosis and decreased cell senescence. The ability of brazilin to decrease cell senescence provides new insight of utilization of C. sappan or its constituents, particularly brazilin, as anti-ageing

    In vitro Comparative Study for Anti-proliferative Activity of Some Plant Extracts, Fam. Apiaceae, on HeLa Cell Line

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    In this research, the biological activities of five plant extracts from family Apiaceae; Italian Parsley (Petroselinum neapolitanum), Fennel (Foeniculum vulgare), Celery (Apium graveolens), Cilantro (Coriandrum sativum) and Dill (Anethum graveolens), were studied. Antiproliferative effect of eleven ethanol crude extracts was tested in Human Cervical (Hela) cancer cells. Results clearly demonstrated that all plant extracts showed high significant difference when compared to the negative control (DMSO).Parsley leaves extract, cilantro leaves extract and cilantro stems extract showed no significant difference with the positive control (Actinomycin D). As for, fennel bulb extracts, fennel stalks extracts, celery stems gave better results than the positive control with no significant difference through the 24, 48 and 72 h treatment. There were no significant difference between Fennel extracts and the positive control, which showed high effect on the cancer cells survival. There were no significant difference between both extracts of Cilantro leaves and stems through each time but the best result was after 72 h of treatments. Regarding Dill leaves and stems, cell numbers recorded no significant difference between the both on time dependent manner. Further investigation for ethanolic extracts of parsley leaves, fennel bulb, fennel stalks, celery stems, cilantro leaves and cilantro stems which showed better results than using the commercial drug Actinomycin D (25ml/ml) for 24 h treatment or less depending on concentrations manner. Also, further investigation on different types of cancer cell lines to avoid the toxic effect of chemotherapy

    In Vitro Antiplasmodial Activity and Cytotoxicity of Active Subfractions of Harmsiopanax aculeatus Leaves

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    Harmsiopanax aculeatus leaves, a medicinal plant with locally named kapur, have been used traditionally to treat malaria in Maluku, Indonesia. However, the scientific information of this plant is still limited. In our previous study, the methanol extract of this plant leaves have been proven to possess in vitro antiplasmodial activity. This study was conducted to evaluate in vitro antiplasmodial activity and cytotoxicity of  subfractions of the plant leaves. Fractionation was performed using a column chromatography with Sephadex LH-20 as the  stationary phase and methanol as the mobile phase. The subfractions obtained were then tested for in vitro antiplasmodial activity on a chloroquine-resistant FCR3 strain of Plasmodium falciparum using a visual method. Cytotoxicity was evaluated by using MTT assay. The in vitro antiplasmodial activity and cytotoxicity were expressed as IC50, calculated using probit analysis with SPSS 16 for windows. The results showed that the four subfractions tested have a high antiplasmodial activity with IC50 values of 0.09; 0.18; 0.01; and 0.77 µg.mL-1, respectively. In addition, these subfractions had IC50 values of >400 µg.mL-1 against Vero cells indicating that they were non-toxic. In conclusion, the subfractions of H. aculeatus leaves are very active and selective against P. falciparum. Further study will be conducted to isolate the active compounds

    Inhibition of Cell Cycle and Induction of Apoptosis y Ethanol Leaves Extract of Chrysanthemum cinerariifolium (Trev.) In T47D Breast Cancer Cells

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    Chrysanthemum cinerariifolium (C.cinerariifolium) is a plant of the Asteraceae family, which has been applied by the community as an ornamental plant and traditional medicine. In this study, the effect of C. cinerariifolium leaves extract on inhibition of cell cycle and induction of apoptosis in T47D breast cancer cells was tested and compared to the standard chemotherapy agent. The citotoxic activity of C. cinerariifolium leaves extract against T47D cancer cells and Vero normal cells was tested by MTT method. Profile of apoptosis and cell cycle were observed by flow cytometry method. Based on chemical compounds profil which is tested used TLC showed that C.cinerariifolium leaves extracts contained flavonoid and terpenoid chemical compounds. The result of cytotoxic test showed that leaves extract of C. cinerariifolium was able to inhibit the growth of T47D cancer cell at IC50 418.8μg/mL. Doxorubicin, extracted from Streptomyces peucetius used as treatment in several cancers including breast cancer. Doxorubicin could inhibit the growth of T47D cancer cells in 115.1μg/mL. The results of cell cycle analysis showed that the C. cinerariifolium leaves extract inhibited cell cycle in G0-G1 and S phase, whereas doxorubicin was able to inhibit cell cycle in G0-G1 phase but experienced cell accumulation in G2-M phase. The percentage of apoptosis in cycle was showed in M1 (sub G1) and M5 (multinuclear) phase which treatment of C. cinerariifolium leaves extract was higher than doxorubicin. Therefore, C. cinerariifolium leaves extract has potential activity as anticancer agent causes inhibition of cell cycle and induction apoptosis.

    An Assessment of Cough Medicine Dispensing Practice to Children Under Two Years Old in Pharmacies in Ho Chi Minh City Using Simulated-Patient Method

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    Over-the-counter (OTC) cough and cold medications (CCMs) have been used to treat the symptoms of upper respiratory infection in children for decades. The safety of CCMs in children has been questioned. The data on knowledge of pharmacists in supplying cough medicines for children under two years have been limited. This study aimed to evaluate the pharmacists’ dispensing decisions to manage the cough in children under two years old. A descriptive cross-sectional was carried out in 300 pharmacies in 15 districts in Ho Chi Minh City, Vietnam. The pharmacists were interviewed by a simulated patient. The results showed that, information that pharmacists actively asked the client about the patient and disease symptoms was limited. Most pharmacists did not provide adequate instructions and counsel about using drugs for clients. Only 22/300 (7.33%) of pharmacists appropriately provided cough medicines for children under 2 years old. The main reason of inappropriateness was the deficiency of knowledge about updated contraindication of N-acetylcysteine (93.17%). Pharmacists in pharmacies located in districts 3, 11 and Binh Thanh had higher rate of rational provision than those in other districts. A good and full understanding of the patient symptom helped the pharmacists supply cough medicines more reasonably. The limited caution of pharmacists and the low proportion of pharmacists updating contraindication of N-acetylcysteine should be considered as a warning sign in pharmacy practice in Ho Chi Minh City, Vietnam

    Antidiabetic Activity of Okra Fruit (Abelmoschus esculentus (L) Moench) Extract and Fractions in Two Conditions of Diabetic Rats

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    Okra (Abelmoschus esculentus (L) Moench) fruit is empirically used in type 2 diabetes mellitus treatment. This research aims to know the antihyperglycemic activity of okra fruit extract and fractions in streptozotocin-nicotinamide (STZ-NA) induced as well as in insulin resistance diabetic rats, the effect on pancreatic cells regeneration, and the effect on immunohistochemical expression of glucose transporter-4. This study used a group of 35 male Wistar rats for STZ-NA induced diabetic model and another group of 35 rats for insulin resistance diabetic model. Gliclazide (0.72mg/kg BW) and metformin (45mg/kg BW) were used as drug control in STZ-NA induced and insulin resistance diabetes, respectively. Okra fruit ethanol extract, n-hexane, ethyl acetate, and water fraction were orally administered with dose of 200; 107; 6 and 86mg/kg BW, respectively, for 28 days after diabetic condition was obtained. Blood glucose level was measured every week. Hematoxylin-eosin staining was used to evaluate the pancreatic cells regeneration, while immunohistochemistry was used to evaluate the expression of glucose transporter-4 in muscle membrane cells, at the end of the treatment. The results revealed that ethyl acetate fraction was the most effective in lowering blood glucose level in both condition of diabetes. Ethyl acetate fraction decreased the necrosis of pancreatic cells in STZ-NA induced diabetic rats and increased the expression of glucose transporter-4 in muscle cell of insulin resistance diabetic rats

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