JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA

The Effect of Quercetin on Coenzyme HMG-CoAR, ABCA1 Transporter, Dyslipidemia Profile and Hepatic Function in Rats Dyslipidemia Model

Fri, 13 Dec 2024 00:00:00 +0700

Background: Dyslipidemia is a lipid metabolic disorder that increases the risk of cardiovascular disease, typically marked abnormality of triglycerides (TG), low-density lipoprotein (LDL) and total cholesterol (TC), along with decreased high-density lipoprotein (HDL). This research explored the potential of quercetin, a natural substance, as a preventive for dyslipidemia induced by a high-fat diet (HFD) in a rat model. Simvastatin, a standard cholesterol-lowering drug, was used for comparison. Objective: The main principle of this research was evaluating quercetin's potential in lipid metabolism for dyslipidemia caused by HFD and comparing its effects with first-line drug therapy simvastatin, which had a similar mechanism. Methods: Rats given an HFD were treated with quercetin and simvastatin, and their lipid profiles, liver enzyme activities, and molecular markers related to cholesterol metabolism were analyzed. Results: Quercetin markedly decreased cholesterol by inhibiting the enzyme 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG CoAR). It also prevented liver damage by cellular observation and showed a protective effect on liver enzyme activity. Quercetin enhanced expression of the Adenosine Triphosphate Binding Cassette subfamily A member 1 (ABCA1) protein, showing a protective effect against dyslipidemia akin to simvastatin, yet with a reduced likelihood of liver toxicity. Conclusion: Quercetin may serve as an effective and safer alternative to simvastatin for treating dyslipidemia, offering cholesterol-lowering benefits without the hepatotoxic risks associated with long-term statin therapy.

In Silico Analgesic and Toxicity Analysis of Modified Paracetamol on COX-2 Receptor (PDB ID: 3LN1)

Nurul Hidayah, Lina Permatasari, Agriana Rosmalina Hidayati, Handa Muliasari — Fri, 13 Dec 2024 00:00:00 +0700

Background: Paracetamol is still often used in Indonesia as the main analgesic. Use above 4 gram per day or a single dose above 10 gram can cause hepatotoxicity. This can be overcome by modifying the structure through a CADD (computer aided drug design) approach, especially molecular docking, aims to produce compounds with greater potency and fewer side effects. Objective: This study aimed to determine the analgesic activity and toxicity of paracetamol derivative compounds modified by the Topliss method. Methods: Analgesic activity was tested by molecular docking on COX-2 receptor (PDB ID 3LN1) using AutoDock Tool 4.2, and toxicity testing using pkCSM and Protox Online Tool. Results: The results of docking show that the free binding energy values for test compounds 1 to 5 are -10.59 kcal/mol, -10.17 kcal/mol, -8.79 kcal/mol, -10.01 kcal/mol, and -9.32 kcal/mol, respectively, with corresponding inhibition constants of 17.29 nM, 35.21 nM, 360.88 nM, 46.36 nM, and 146.65 nM. These values are lower than paracetamol which has a free binding energy of -6.21 kcal/mol and an inhibition constant of 28,043 nM. The results show that the test compound is more stable in ligand-receptor binding. Toxicity tests showed that all test compounds and paracetamol belonged to toxicity class IV. The test compound had an LD₅₀ value of 1551 mg/kg, higher than paracetamol (338 mg/kg), thus indicating better effectiveness. Conclusion: Compound 2 is predicted to have the best biological activity and potential as an alternative to paracetamol.

A Case Report of Lurasidone-Induced Tardive Dyskinesia: Therapeutic Role of Valbenazine

Ambika Nand Jha, Varsha Ratan Gaikwad — Fri, 13 Dec 2024 00:00:00 +0700

Introduction: Tardive dyskinesia (TD) is a complex, potentially irreversible movement disorder primarily associated with the long-term use of antipsychotic medications, particularly typical neuroleptic drugs. TD can develop during treatment and persist long after thediscontinuation of the culprit medication. The etiology of this condition involves dysregulation of dopaminergic signalling, especially within the striatum, leading to the activation of D2 dopamine receptors. This imbalance affects the homeostasis of neurotransmitters, including GABA and glutamate. Chronic dopamine receptor antagonism incites neuroadaptive alterations that may linger post-therapy, resulting in abnormal involuntary movements affecting the orofacial regions, limbs, and trunk, which profoundly diminishes patient quality of life. Case: A 29-year-old female with a known history of schizophrenia presented with sudden-onset neurological symptoms, notably persistent orofacial dyskinesias such as lip smacking and grimacing, which had developed over a 24-hour period. A thorough review of her medication indicated that lurasidone classified as an atypical antipsychotic, was likely responsible for the onset of these dyskinetic movement features. Consequently, the physician opted to discontinue lurasidone and initiate valbenazine at 40 mg once daily, with the intent of managing the dyskinetic symptoms while considering the overall psychiatric and medical treatment plan for the patient. Conclusion: The emergence of orofacial dyskinesias in this patient suggests a possible adverse reaction to lurasidone, necessitating re-evaluation of her psychopharmacological regimen. Valbenazine, a selective vesicular monoamine transporter 2 inhibitor, may provide a tailored approach to mitigate dyskinetic movements while maintaining therapeutic efficacy in psychiatric care.

Antidiarrhea Activity of Ethanol Extract of Rambutan Leaves ( Nephelium lappaceum L.) in Capsule Form on Male Mice

Thu, 19 Dec 2024 00:00:00 +0700

Background: Diarrhea characterized by changes in stool form to soft or liquid with an intensity of bowel movements more than three times a day. One of the plants used as an alternative treatment for diarrhea is rambutan, especially its leaves. Rambutan leaf extract in previous studies has shown that it can treat diarrhea. Objective: The purpose of this study was to determine the antidiarrhea activity in capsules of ethanol extract of rambutan leaves containing tannins and flavonoids as antidiarrhea that inhibiting intestinal motility. Methods: The study was conducted experimentally using the intestinal transit method, which measures the length of the intestine passed through by the marker. The smaller the ratio between the length of the intestine and the marker, the more it indicates a decrease in intestinal motility in mice. Group 1 loperamide HCl with a dose of 4 mg/kg BW, Group 2 used placebo, Group 3 used FI, FII, FIII capsules with a dose of 50 mg, 100 mg, and 150 mg. Results : The test results showed that formulation 1, 2, 3 had an activity of 23.3%, 26.8%, and 32.3%. The capsule with the best results was formulation 3 with a dose of 150 mg. Compared to the positive control, the effectiveness of this capsule was 22% higher than loperamide. Conclusion: The results of the study showed that rambutan leaves extract in capsule form effectively treat diarrhea. The One Way Anova test showed a significant value between groups FI, FII, and FIII (ρ<0.05).

Solubilization Inclusion Bodies from Synthetic Recombinant PGA Gene Expressed in E. coli BL21(DE3) by Denaturing and Non-denaturing Agents

Fri, 13 Dec 2024 00:00:00 +0700

Background: With the rise of green chemistry, synthesis of antibiotic compounds through enzymatic process is a preferred option. Penicillin-G acylase (PGA) is an important enzyme for producing important antibiotics, such as penicillin and its derivatives. For this reason, studies on PGA have been widely carried out worldwide. In penicillin biosynthetic pathway, PGA catalyzes conversion of penicillin-G into 6-amino penicillanic acid (6-APA), a precursor for enzymatic synthesis of penicillin derivatives. Unfortunately, bacteria naturally produce the PGA enzyme in very small quantities. Objective: One strategy to produce this enzyme in larger quantities is DNA recombination, expressed in Escherichia coli. A common obstacle of protein overexpression in E. coli is the formation of inclusion bodies (IBs). In this study, we would like to discuss IBs solubilization methods of recombinant PGA derived from E. coli (rPGAEc) expressed in E. coli BL21 (DE3). Methods: Recombinant E. coli BL21 (DE3) harboring rPGAEc was induced by IPTG for enzyme expression. Induction was performed at 16^oC for 4 h and 24 h. The PGA enzyme expressed in IBs form, was then incubated in two solutions containing 8 M urea and 0.2% sarcosine to get a soluble enzyme. Results: Based on protein analysis by SDS PAGE, a solution containing 8 M urea solubilized the PGA enzyme more abundantly than 0,2% sarcosine. Conclusion: The solubilization technique of the PGA enzyme expressed by E. coli proposed by this research became an alternative solution that can be considered for this purpose.