IDENTIFICATION OF FLAVONOIDS FROM ACALYPHA INDICA L. (EUPHORBIACEAE) AS CASPASE-3 ACTIVATORS USING MOLECULAR DOCKING AND MOLECULAR DYNAMICS

Objective: The purpose of this study was to determine the structural-based molecular interactions between flavonoids contained in Acalypha indica L. and caspase-3 by molecular docking and molecular dynamics (MD) simulations. Methods: In a computer simulation, ten flavonoids contained in A. indica L. were evaluated for caspase-3 using the X-ray crystal structure of human caspase-3 (PDB ID 1NME). The AutoDock 4.2 software was used to study molecular docking, and MD simulations were done with GROMACS v2018. Results: The results of molecular docking identified the top four compounds, namely nicotiflorin, naringenin, hesperetin, and kaempferol, with docking scores of-6.81,-6.45,-6.33, and-6.10 kcal/mol, respectively. According to the MD simulation results, nicotiflorin was most effective in stabilizing the complex with caspase-3, with a total energy (ΔGbind, MM-PBSA) of-96.315 kcal/mol. Conclusion: This study showed that nicotiflorin was the flavonoid in A. indica L. that activated caspase-3 the best

Pharmaceutical Counseling Has a Positive Impact on Quality of Life of Hypertension Patients

Pharmacists play a major role in educating patients regarding drug therapy, in order to achieve optimal health outcomes. The aim of this study was to investigate the effect of pharmaceutical counseling on quality of life (QoL) of hypertensive patients with renal impairment at one of public hospital in Bandung, Indonesia. This study used a prospective experimental design with pretest-posttest design for 2 months. Inclusion criteria in this study were hypertensive patients with renal impairment who received antihypertensive drugs, aged >18 years, and signed the informed consent. Exclusion criteria were patients who were not able to fill in the questionnaire, patients with end stage renal diseases, diabetes, and pregnant or lactating patients. Pharmaceutical counseling was given during 2 months of the therapy. Pharmaceutical counseling consisted of education on the appropriate use of drugs and disease management. Schedule of their own medication and leaflet containing educational information were given to the subjects. QoL was assessed using a previously validated Mini-Questionnaire of QoL in Arterial Hypertension (MINICHAL). The questionnaire consisted of 16 two dimensions questions, i.e., mental health and somatic manifestation. We found that the mean increase in mental health status (49.5±5.3) was higher than that of somatic dimension (32.7±3.6). Both dimensions had statistically significant improvement (P value <0.05). In conclusion, pharmaceutical counseling is beneficial to improve QoL of hypertension patients. Keywords: hypertension, renal impairment, quality of lif

Efficacy and Side Effects of Deferasirox and Deferiprone for Thalasemia Major in Children

Thalassemia major (TM) is an inherited disease caused by defective or absent of hemoglobin chain synthesis. Regular chelation therapy is necessary to reduce excess iron in several organs of TM patients. The most commonly used chelating agents are deferasirox and deferiprone. However, information regarding their effectiveness and side effects in Indonesian children population with TM were limited. This study was conducted to assess the effectiveness and side effects of deferasirox and deferiprone in pediatric patients with TM. This was an observational study with prospective analysis which was conducted during April-August 2015. We included pediatric patients with TM who visited a hospital in Bandung, Indonesia, using consecutive sampling method. Thirty two subjects were divided into two groups, i.e., deferasirox and deferiprone group. Review of medical records and interview were performed for each participants. Effectiveness was defined as reduction in ferritin level. Side effects were assessed using Naranjo scale. Data were analyzed using Mann-Whitney test, Wiloxon test and Chi square test. P value < 0.05 defined statistical significance. We found that deferasirox was more effective than deferiprone for the treatment of TM in pediatric patiens, with less side effects. The use of deferasirox as iron chelating agent is recommended for patients with TM. Keywords: deferasirox, deferiprone, ferritin, thalassemia majo

HUBUNGAN MANFAAT PENGGUNAAN STATIN PADA PASIEN CORONAVIRUS DISEASE 2019 (COVID-19): SEBUAH REVIEW

Coronavirus Disease 2019 (Covid-19) merupakan penyakit sindrom pernafasan akut parah dengan tingkat morbiditas dan mortalitas yang tajam di seluruh dunia. Statin merupakan salah satu obat yang digunakan dalam pengobatan hiperkolesterol. Beberapa penelitian menyatakan bahwa statin dapat mengurangi tingkat keparahan penyakit infeksi COVID-19. Ulasan ini menguraikan manfaat penggunaan statin pada pasien COVID-19. Desain penulisan ini adalah study literature review. Beberapa hasil penelitian menyatakan bahwa penggunaan statin sebelum dan selama pengobatan di Rumah Sakit karena COVID-19 berkaitan dengan penurunan kematian. Karena selain menurunkan kadar serum lipid dengan menghambat HMG-CoA reduktase, statin juga memiliki efek lain seperti antiinflamasi.

MOLECULAR DOCKING AND MOLECULAR DYNAMICS STUDIES OF ACALYPHA INDICA L. PHYTOCHEMICAL CONSTITUENTS WITH CASPASE-3

Objective: This study investigated the structure-based molecular interactions between phytochemical constituents of Acalypha indica L. and caspase-3. Methods: Thirty-three phytochemical constituents of A. indica were screened against caspase-3. The X-ray crystal structure of human caspase-3 was retrieved from https://www.rcsb.org/structure/. The molecular interactions of the phytochemicals were studied using the AutoDock 4.2 software and followed by molecular dynamics (MD) simulations using the Amber18 software. Results: From this study, 25 screened phytochemicals were found to have a better binding mode than the native ligand. Moreover, the binding stability of the top four hits evaluated by MD indicated that the hydrogen bonds in MD were quite different from the molecular docking results due to the massive receptor and ligand movement in the MD simulations. However, with the exception of stigmasterol, all ligands were able to stabilize the protein. Conclusion: This study suggested that γ-sitosterol acetate, β-sitosterol acetate, and γ-sitosterol might be able to induce caspase-3, thereby activating apoptosis. These high-affinity compounds can bind to caspase-3 more efficiently and were able to stabilize the protein. Therefore, they have the potential to be used as lead compounds in the treatment of cancer

COMMUNITY HEALTH CENTRES AS THE PHARMACEUTICAL SERVICES SUPPORT SYSTEM IN HEALTHY INDONESIA PROGRAM: AN OBSERVATIONAL STUDY IN WEST JAVA INDONESIA

Objective: The Healthy Indonesia Programme with a family approach strategy was launched by the Indonesian government in 2015. Pharmaceutical service, including drug supply management and clinical pharmacy, is one of the essential components for the program implementation. This study was aimed to evaluate the pharmaceutical services support in the Healthy Indonesia Programme in West Java Indonesia. Methods: This was a cross-sectional study observed on pharmaceutical services under the family approach programme description. A self-completed questionnaire was distributed to 39 accredited community health centres (CHCs) in West Java, Indonesia. Several indicators of the Standard Pharmacy Services were assessed. Results: Thirty-nine CHCs were involved in this study. Most of the CHCs were accredited as intermediate (59%) and have applied good pharmaceuticals and consumables inventory management. The online system and more training will give room for improvement. A big gap was found in human resources number and competencies, impact on clinical pharmacy standard services including counselling services (23.1%) and home visit (7.7%). Conclusion: Applying an online system is needed to improve the inventory management system in CHCs. The quality of clinical pharmacy standard services in CHCs can be improved by fulfilling the minimum numbers and competencies of human resources

Stevia rebaudiana Bertoni Leaves Extract as a Nutraceutical with Hypoglycemic Activity in Diabetic Rats

BACKGROUND: The prevalence of diabetes mellitus is growing every year, including in Indonesia. Medicinal herbs were used empirically for lowering blood glucose. One of potential herb to have hypoglycemic activity is Stevia. Stevia rebaudiana Bertoni leaves contain stevoside, a natural, low-calorie sweetener that is 300 times sweeter than saccharose. In this study, we aimed to explore the hypoglycemic activity of S. rebaudiana Bertoni leaves extract in a rat model of type 2 diabetes mellitus (T2DM). METHODS: Male Wistar rats were feed high-fat, high-carbohydrate feed and sugar solution for 74 days to induce a diabetic rat model. The animals were then divided into five groups consisting of a negative control group treated with 2% Pulvis Gom Arabicum; a positive control group treated with Metformin 45 mg/kg body weight (BW); and three test groups treated with aqueous extract of S. rebaudiana Bertoni leaves at doses of 3.125, 6.25 and 12.5 mg/kg BW for 36 days. Blood glucose was measured on days 14, 28 and 36.RESULTS: The results showed that blood glucose levels over 36 days were significantly (p=0.043) lower in the group treated with S. rebaudiana Bertoni leaves extract. Further Newman-Keuls analysis suggested that the hypoglycemic activity of S. rebaudiana Bertoni leaves extract was dose-dependent. CONCLUSION: Our results indicate that S. rebaudiana Bertoni leaves extract has a potential role as a hypoglycemic agent in the treatment of T2DM.KEYWORDS: Stevia rebaudiana Bertoni, nutraceuticals, hypoglycemic, diabetic rat

Nutmeg extract modulates triglyceride levels and gene expressions of CD36,FATP1, and CPT1B in rat skeletal muscle

Obesity has become a global health problem. It affects all organs in the human body including skeletal muscle as fat deposits in skeletal muscle decrease skeletal muscle mass. Nutmeg, which is a native spice from Indonesia, has been known to be a herbal medicine to treat hyperlipidemia. Various In vivostudies have proven that nutmeg extract can reduce body weight and lipid deposition. However, there is limited information about the effects of nutmeg on lipid transport regulation particularly in muscle cells. Hence, in this study, we investigated the effects of nutmeg extract on blood lipid profile and lipid metabolism in skeletal muscles. Rats were divided into two groups: control and nutmeg extract-treated group. Treatment group was fed with nutmeg extract for 12 weeks. Blood samples of the rats were subjected to lipid profile examination. In addition, the soleus muscle of all groups were isolated and subjected for mRNA examination. Furthermore, expression of lipid transporter in cell membrane (CD36) and in mitochondrial membrane (FATP1 and CPT1B) were analyzed by semi-quantitative PCR. Although the daily food intake increased, no weight gain was observed in the nutmeg-treated group. Additionally, nutmeg extract has shown to decrease triglyceride blood levels in the treatment group. Interestingly, the CD36 FATP1 and CPT1B mRNA expressions in the soleus muscles increased with nutmeg treatment. The results of this study suggest that nutmeg extract modulates lipid utilization in skeletal muscle through CD36, FATP1, and CPT1B lipid transporter