Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. Conclusion. 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.
Objective: The objective of this study is to investigate the effect of light-roasted green coffee bean extract (GCE) administration for 7 weeks on the improvement of metabolic profile, adiponectin level, homeostatic model assessment insulin resistance (HOMA-IR) index in metabolic syndrome (MS) rat model. Methods:Adult male Sprague-Dawley rats were induced by a combination of high sucrose and high-fat diet for 8 weeks and streptozotocin injection in the 2 nd week. The MS was confirmed by NCEP-ATP III criteria. They were divided into six weight-matched groups (n=5), normal control, MS, metformin and simvastatin-treated group (DMS), 100 and 200/body weight (bw) GCE (GCE 100 and GCE 200, respectively). The extracts were given through oral gavage daily for 7 weeks. The effect of GCE on body weight, serum glucose, triglyceride, (TG) and high-density lipoprotein (HDL) level was analyzed by colorimetric method. HOMA-IR index and adiponectin were analyzed by enzyme-linked immunosorbent assay methods.Result: Fasting blood glucose, TG, and systolic blood pressure decreased significantly (p<0.05) in both GCE groups. Moreover, after 7 weeks, those parameters were significantly lower (p<0.05) compared to that of MS group. Only GCE 100 group that showed a significant decrease in HDL level. GCE 100 mg/bw and 200 mg/bw group showed significantly higher adiponectin level compared to that of MS and DMS group. Furthermore, GCE 100, GCE 200, and DMS group showed a significant lower HOMA-IR index compared to that of MS group. Conclusion: 7 weeks GCE administration could decrease fasting blood glucose, profile lipid, blood pressure, and improved adiponectin level and HOMA-IR index.
The study was designed to establish an experimental models of metabolic syndrome that adequately mimic metabolic syndrome criteria as determined by NCEP ATP III.Eighteen Male Sprague dawley rats, 2 -3 months old were used in the study. Combination of high fat and high sucrose (HFHS) diet for eight weeks and streptozotocin (STZ) injection in the second week was administered to induce metabolic syndrome. The body weight and biochemical parameters (blood glucose, triglyceride, HDL-cholesterol) were measured every 2 weeks. The rats with blood glucose (>126mg/dL), triglyceride (TG) (>150mg/dL), high systolic blood pressure (≥140 mmHg), and reduced HDL levels (<40 mg/dL) confirmed presence NCEP-ATP III criteria of metabolic syndrome. The adiponectin level was analyzed by ELISA methods.Fasting blood glucose, triglyceride, and systolic blood pressure increased significantly (p<0.05) in HFHS group compared to that of NC group. Moreover, after 8 week a significant lower HDL level was observed in HFHS group compared to that of NC group. In addition, HFHS group showed a significantly lower adiponectin level compared to that of NC group.The combination of low doses of STZ (30mg/kg) and HFHS administration for 8 weeks could induce metabolic syndrome mimicking human criteria of metabolic syndrome.
BACKGROUND: The development of an oral typhoid fever vaccine need more effective and having high-efficacy in preventing typhoid fever. The use of liposomes as a vaccine vehicle can be formulated to target a specific location or trigger the release of antigens on its target. β-Glucan derived from Candida albicans cell wall as immunoadjuvant can strengthen the immune response and increases the protection against Salmonella Typhi bacterial invasion. AIM: This study aimed to determine the immune response in typhoid fever mice by administering a combination of AdhO36 S. Typhi liposome vaccine with β-Glucan and determine the protectivity to inhibit bacterial colonization in typhoid fever. METHODS: Mice were divided into five groups include negative and positive control also treatment group. IL-12 was evaluated after 4-h immunization while the other (was IL-12, IL-10, Th1 (IL-2), Th2 (IL-4), and the protective test against bacterial invasion) evaluated after 96-h. RESULTS: IL-12 level in the combination of β-Glucan and AdhO36 groups showed significantly lower than infected groups (p = 0.034), whereas IL-10 level significantly increase (p = 0.0009). The percentage of Th-1 (IL-2) cells significantly lower than infected groups (p = 0.000), this also happened on the percentage of Th-2 (IL-4) cells that significantly lower than infected groups (p = 0.018). The protective test toward bacterial invasion showed no bacterial colonization in all tissues intestine, liver, spleen, and mesenteric lymph node. CONCLUSION: The administration of a combination of liposome containing β-Glucan from C. albicans and AdhO36 S. Typhi has a potential effect on cellular and humoral immune response.
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