Peranan dan pengaturan ketergantungan psikis opioid oleh tipe reseptor opioid

ABSTRACT Arif Nurrochmad - Role and psychological dependenci arrangement of opioid by type of reseptor opioid Opioid receptor can be classified as p., 8, and K-opioid receptor that widely expressed in the CNS. The development of selective receptor agonist and cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. This review focuses on the functional interaction among these opioid receptor types that contribute to opioid dependence especially in psychological dependence. Several lines of evidence provide arguments to support substantial roles for p-opioid receptors and the possible involvement of 8-opioid receptors in the development of physical and psychological dependence on morphine. Many studies have pointed to the mesolimbic dopaminergic system projecting from the ventral tegmental area to the nucleus accumbens as a critical site for the initiation of psychological dependence on opioids. It is important to note as the broad existence of opposing interaction between p/8-, and K-receptors in the central nervous system. The activation of Kopioid receptors leads to the suppression of unpleasant p.- or 8-mediated side effects such as withdrawal and rewarding effect. Considering the functional interaction among opioid receptor types, the co-administration of morphine-like compounds with K-receptor agonists lead suppressing the side effects of p-opioid receptor agonist that benefit for the pain management. Key words: Opioid receptor â receptor types â psychological dependence â morphin

Anti cancer activity of rodent tuber (Thyphonium flagelliforme (lodd.)Blume on human breast cancer t47d cells

The incidence of breast cancer in developing countries showed an increase from year to year. The efforts of cancer prevention or treatment of the more important given the frequency of occurrence is quite high. Several studies have been focuses on natural products as agents of cancer chemoprevention and as co-chemotherapy agent against cancer. One of medicinal plant that is widely used as anticancer is rodent tuber (Thyphonium flagelliforme (Lodd.) Blume). In present study, we investigated the anticancer acitivty of rodent tuber extract (RTE) in vitro. Study of anti-proliferative conducted on human breast cancer primary T47D cells. Furthermore, the present study also investigated the molecular mechanisms of cell cycle arrest and induction of apoptosis. The study of rodent tuber as co-chemotherapy is determined by examining the effects on T47D and its combination with tamoxifen (TAM). The results showed the cytotoxic effects of RTE on T47D cells with IC50 value of 632 mg/mL. Low concentration RTE (below 250 ug/mL) are proliferative, while the concentration above 250 mg/mL indicated cytotoxic effect. Based on the calculation of Combination Index (CI), combination of RTE with TAM yielded a value above 10 indicated a strong antagonistic effect. In observation of apoptosis, low concentration of RTE (63 µg/mL) stimulate apoptosis better than high concentration of 250 mg/mL. However, the combination study with 5 nM TAM reduced the induction of apoptosis. Furthermore, the observation cell cycle arrest by flowcytometry, demonstrated that RTE 63 and 250 mg/mL increase the population of sub G1 phase respectively from 14.8% to 53.19 and 32.90%. These results suggest that RTE able to induce cell cycle to apoptosis, but low concentration of RTE more effective than high concentration. Similar to apoptosis observation, the combination of RTE and TAM also demonstrated the antagonistic effect by reducing the population of Sub-G1 RTE (63 mg/mL) and TAM 5 nM, respectively from 53.19% and 44.50% to 35.86%. All finding results of this study provide information that the use of rodent tuber extract (RTE) alone is better than the combination with TAM. In addition, the use of RTE together with TAM reduced the effectiveness of TAM in the treatment of breast cancer. Keywords: Rodent tuber (Thyphonium flagelliforme (Lodd.) Blume), anti cancer, chemoprevention, T47D cells

POLYMORPHISM OF CYTOCHROME P450 2A6 (CYP2A6*1 AND CYP2A6*4) AMONG JAVANESE INDONESIAN SMOKER AND NON SMOKER

Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. The present study was developed to investigate the genetic polymorphism of CYP2A6 in Javanese Indonesian subjects carrying the CYP2A6*1 allele and the CYP2A6*4. The whole gene deletion of CYP2A6 (CYP2A6*4) may inhibit smokers from giving up smoking, but appears to function as a protective factor against to some cancer. However, the investigation of these allele, a major functional polymorphisms common in Asian populations, have not been reported among Javanese Indonesian population. A single polymerase chain reaction-restriction fragment length polymorphism was used to resolve the genotypes into CYP2A6*1 (wild type) and CYP2A6*4 (CYP2A6del). The sample studied consisted of 100 healthy subject that consist of 50 non smokers and 50 smoker from Javanese Indonesian population. The allele frequencies of *1 (wild type) and *4, were 47.5 and 52.5%, respectively. When the two allel were considered simultaneously, among the non-smokers, 45% were genotyped for CYP2A6*1/*4 and 5% were genotyped for CYP2A6*4/*4; on the other hand all of the smoker were genotyped for CYP2A6*1/*4 and there was no homozygote of wild type. Based on the data collected, it could be concluded that the polymorphism of CYP2A6 were detected in among Javanese population sample study and the allele frequencies of CYP2A6*4 were high.Key word: Polymorphism, CYP2A6*1, CYP2A6*4, Javanese Indonesia

IN SILICO AND IN VITRO ASSAY OF HGV ANALOGUE AS ANTIBACTERIAL

Objective: The objective of this research was to design a new analogue compound, hexagamavunon (HGV). Methods: New design of analogue compound, HGV, was performed by QSAR study using BuildQSAR program. In this QSAR study, parameterized model (PM3) method using the Polak-Ribière algorithm was applied to calculate the optimal geometric structures of the used compounds. The new analogue compound, HGV had been synthesized using aldol condensation reaction. The assay of antibacterial activities was performed using the dilution method. Molecular operating environment (MOE) program was used for protocol docking. Results: The results of QSAR study reveal the good relationship of antibacterial activities. The in vitro antibacterial activities of 2,6-bis((E)-3,5-dibromo-4-hydroxybenzylidene) cyclohexan-1-one (A113) indicates the good potential to against S. aureus, B. subtilis and E. coli with IC50 27.3 μg/ml, 30.9 μg/ml, 32 μg/ml respectively. This is in accordance with the in silico evaluation showing that 2,6-bis((E)-3,5-dibromo-4-hydroxybenzylidene) cyclohexan-1-one has lower docking score than both amoxicillin and cefoxitin do as the native ligand of receptor 3MZE. Conclusion: Based on in silico and in vitro assay, 2,6-bis((E)-3,5-dibromo-4-hydroxybenzylidene) cyclohexan-1-one (A113) has good antibacterial activities against S. aureus, B. subtilis, and E. coli

Identification of active anti-inflammatory principles of betabeta wood (Lunasia amara Blanco) from Siawung Barru- South Sulawesi, Indonesia

Purpose: To identify the anti-inflammatory components of beta-beta (Lunasia amara Blanco.) wood.Methods: The wood material was extracted with 96 % ethanol and fractionated with dichloromethane using a liquid-liquid continuous extraction (LLCE). The fractions were subjected to silica gel column chromatography. Components of the extracts were identified by thin layer chromatography (TLC) scanner and UV-visible spectroscopy, using scopoletin as standard.Results: TLC results for Lunasia amara extract showed the same spot as standard scopoletin. UVvisible spectrum for scopoletin displayed maximum absorption at 213, 228, 255 and 344 nm, while betabeta wood extract showed characteristic bands at 344, 336, 299 and 255 nm. The results indicate that the main components of the extracts are scopoletin and its derivatives.Conclusion: The active anti-inflammatory compound in beta-beta (Lunasia amara) wood is scopoletin.Keywords: Beta-beta wood (Lunasia amara Blanco.), Scopoletin, Thin layer chromatograph

The advantages of fentanyl for the treatment of pain: Studies of pharmacological profiles and fentanyl relatedside effects

The understanding of the pharmacological profiles of fentanyl and fentanyl-related side effects seems to be critical for the management for control of pain. Therefore, the present study was designed to investigate the advantages for treatment with fentanyl and the side effects such as emesis and gastrointestinal transit inhibition. The results demonstrated that fentanyl produced a profound antinociception in ferrets and mice than that induced by morphine. These findings are consistent with the experiences in the clinic. Morphine with lower doses than antinociceptive doses, produced a significant increase in gastrointestinal transit inhibition. However, fentanyl produced no gastrointestinal transit inhibition unlike morphine. These findings are consistent with the clinical experiences in the use of fentanyl. The clinical studies in patients chronic cancer pain showed that transdermal therapeutic delivery system for fentanyl (TTS-fentanyl) produces less side effects such as constipation, nausea and vomiting than that induced by oral morphine. Morphine with lower doses than that used for antinociceptive assay also produced either in the number of retching or vomiting. However, fentanyl failed to produce emetic response in ferrets. These findings indicate that fentanyl produces much less emesis than that induced by morphine. Finally, we conclude that fentanyl produced potent antinociception in ferrets and mice. In addition, fentanyl produced much less side effects including emesis and constipation. These findings may provide evidence for benefit and usefulness of fentanyl for clinical frame on the management of pain treatment.Key word: fentanyl; antinociception; emesis; ferret

Total flavonoid contents and in silico study of flavonoid compounds from Meniran (Phyllanthus niruri L.) towards alpha-amylase and alpha-glucosidase enzyme

Meniran (Phyllanthus niruri L.) is a plant that is reported to contain flavonoids and shows the activity as a type 2 anti-diabetic by a mechanism of inhibiting the absorption of glucose. Flavonoid compounds such as rutin, quercetin and hesperidin shows anti-diabetic activity. This research aims to determine the levels of total flavonoids and docking studies of flavonoids from meniran against α-amylase and α-glucosidase. Analysis of content of total flavonoids utilizes colorimetric method using AlCl3 and routine standard, the docking study uses Autodock Vina (version 1.1.2) program with the assistance of AutoDockTools (ADT) and visualization of docking results using Discovery Study. The results of the determination of total flavonoids level was 12.32 ± 0.53 mgRE/g extract whereas in ethyl acetate fraction and water each were 19.33±0,68 and 20.07±1.23 mgRE/g respectively. Results of all flavonoids dicking study shows the potential to bind to both receptors, rutin has better binding energy towards α-amylase whereas against α-glucosidase is demonstrated by 3-O -β-D-glucopyranosyl-(2-1)-O-β-D-xylopyranoside quercetin

Phytoestrogens of Pachyrhizus erosus prevent Bone Loss in an Ovariectomized Rat Model of Osteoporosis

The effects of the etyl acetate extract of root of Pachyrhizus erosus (L) Urb (EPE) on bone loss and in ovariectomized (ovx) rats model of osteoporosis were investigated. Forty-two 6-weeks-old female Sprague–Dawley rats were randomly assigned to six groups as followed, sham-operated, OVX, OVX-Estradiol (2 μg/day), OVX-EPE 200 mg/kg BW, OVX-EPE 400 mg/kg BW, OVX-EPE 800 mg/kg BW for 4 weeks. The administration of EPE was given orally using a stomach tube. The results demonstrated that the administration EPE 200, 400, and 800 mg/kg BW significantly prevented bone loss in OVX rats which these effect equivalent to estradiol. These effects were described in increased length of femur and tibiae, bone density, and mineral content of calcium and phosphorous in bone ash. EPE also significantly prevented OVX-induced uterine atrophy and increased in body weight gain. The femur mechanical testing significantly increased the ultimate load and stiffness of femurs of ovariectomized-rats that its effect was greater than OVX or sham-operated rats. Increased bone density may lead to enhanced bone strength, reducing the risk of fracture, which is evident in the administration of EPE due to high content of mineral density and content and increase the ultimate load. This effect seems to be pro-estrogenic compound, which suppress bone resorption by directly acting on estrogen receptor in bone sites. This study suggest that phytoestrogen compound from Pachyrhizus erosus may offer a potential alternative therapy for the treatment of health problems such as osteoporosis in post-menopausal women.Keywords: phytoestrogen, Pachyrhizus erosus, ovariectomized-rat, osteoporosi

DEVELOPMENT AND VALIDATION METHOD FOR QUANTITATIVE DETERMINATION OF CIPROFLOXACIN IN HUMAN PLASMA AND ITS APPLICATION IN BIOEQUIVALENCE TEST

ABSTRACTObjective: This study aimed to develop and validate an high-performance liquid chromatography method coupled with an ultraviolet detection fordetermination of ciprofloxacin in spiked human plasma and subsequently used for bioequivalence (BE) study.Methods: The chromatographic separation was achieved on an RP-C18 column (Lachrom Hitachi, 250×4.6 mm, 5 μm), utilizing a mobile phase ofphosphate buffer/acetonitrile (87:13, v/v, pH 3.0±0.1) at a flow rate of 1.5 ml/minutes. Detection is carried out at 276.6 nm using a spectrophotometer.The developed method is statistically validated for the linearity, accuracy, limit of detection (LOD), limit of quantitation, precision, and specificity. Thespecificity of the method is ascertained by comparing chromatograms of blank plasma and plasma containing ciprofloxacin.Results: Plasma matrix and ciprofloxacin can be separated very well using the validated method. The LOD and limit of quantification (LOQ) were0.07 µg/ml and 0.26 µg/ml, respectively. The regression curve of the standard was linear (R>0.999) over a range concentration of 0.01-3.00 µg/ml.The mean recovery of the method ranged between 95.27% and 104.45%. Both intra- and inter-day precision data showed reproducibility (relativestandard deviation ≤8.0, n=9). The validated method is successfully applied in pharmacokinetic and BE study of ciprofloxacin tablet in a smallnumber of subjects. The mean values of Cmax, Tmax, area under curve (AUC)(0-12), and AUC for the test (generic) formulation of ciprofloxacin were2.25±0.29 µg/ml, 1.0 hr, 8.60±0.69 µg/ml/h, and 9.52±0.70 µg/ml/h, respectively. Meanwhile, for the reference formulation (ciproxin tablet), thevalues were 2.30±0.27 µg/ml, 1.0 hr, 8.54±0.85 µg/ml/h, and 9.38±0.89 µg/ml/h, respectively. From BE study, the 90% confidence intervals for thetest formulation/reference formulation ratio for the logarithmic transformations of Cmax(0-∞), AUC(0-12), and AUC were within the BE limit of 80-125%(96.08%, 101.00%, and 102.02%, respectively).(0-∞)Conclusion: According to the validation result, the method was rapid, simple, and reliable. It can be used for routine analysis of ciprofloxacin in humanplasma and BE study. The test formulation (tablet Xâ€) met the regulatory criteria for assuming BE in healthy subjects.Keywords: Validation, High-performance liquid chromatography, Ciprofloxacin, Plasma, Bioequivalence