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    Satyrium nepalense: A RARE MEDICINAL ORCHID OF WESTERN HIMALAYA (INDIA); PHYTOCHEMICAL SCREENING, ANTIMICROBIAL EVALUATION AND CONSERVATION STUDIES

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    Satyrium  nepalense  is  an  endangered  medicinal  herb  found at  the higher altitude of 2400-5000m. Local inhabitant used tubers of  Satyrium  nepalense  as  an  energetic  tonic  and  as  an  important medicine  to  cure  different  type  of  fever  in  traditional  health  care system  of  Uttarakhand  (INDIA).  Present  study  was  carried  out  to evaluate  the  phytochemical,  antibacterial  screening  against  four (Streptococcus  mutans,  Pseudomonas  aeruginosa,  Staphylococcus aureus  and  Klebsiella  pneumoniae)  microorganisms  in  methanolic extracts  and  habitat  studies  for  conservation  of  S.  nepalense. Tubers  of  Satyrium  nepalense  were  extracted  separately  with methanol  by  hot  extraction  process  using  soxhlet  apparatus.  The extracts  were  subjected  to  Lyophilization  to  get  dry  extract  and preserved  in  aseptic  condition.  The  different  group  reagents  used for  phytochemical  screening  as  dragendorffs’s  for  alkaloid, molisch’s  test  for  carbohydrates,  shinoda  test  for  flavonoids  etc. Antibacterial  study  was  carried  out  by  disc  diffusion  method.  The highest  zone  of  inhibition  was  recorded  as  15.0±0.00  mm  against Klebsiella  pneumonia  and  15.0±0.82  mm  against  Staphylococcus aureus.  Phytochemical  screening  shows  the  presence  of  alkaloids, carbohydrates/glycosides,  flavonoids  and  unsaturated  sterols/triterpenes  in  Satyrium  nepalense.  The  result  indicates  that methanolic  extract  of  Satyrium  nepalense  shows  potent antibacterial activity against all four bacterial strains.Key  words:  Uttarakhand,  Satyrium  nepalense,  medicinal  orchid,  antibacterial, phytochemical

    PHYTOCHEMICAL SCREENING AND ANALYSIS POLYPHENOLIC ANTIOXIDANT ACTIVITY OF METHANOLIC EXTRACT OF WHITE DRAGON FRUIT (Hylocereus undatus)

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    White dragon fruit  is  a well  known  and  widely  used  herbal medicine,  especially  in  Asia,  which  contains  several  interesting bioactive constituents and possesses health promoting properties. The  aim  of  this  study  was  to  analyze  for  the  bioactive compounds,  evaluate  total  phenolic  contents  and  antioxidant capacities  of  methanolic  extract  of  white  dragon  fruit.  The antioxidant  activity  was  determined  by  the  1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity assay. Total phenolic  content  were  determined  by  Folin-Ciocalteu  method. Phytochemical  screening  of  the  white  dragon  fruit  showed the  presence  of  triterpenoid,  alkaloid,  flavonoid  and  saponin. The  extract  exhibited  strong  antioxidant  activity  with  IC50 of 193 μg/mL, and total phenolic content of 246 μg/mL in 1 Kg dry extract.Key words: antioxidant activity, total phenolic, DPPH, white dragon frui

    DEVELOPMENT THE VALIDATION OF INDONESIAN VERSION OF SF-36 QUESTIONNAIRE IN CANCER DISEASE

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    A  Cancer  patients  need  long  term  therapy  in  the  treatment of their disease. One of the outcome of cancer treatment in patients of  quality  of  life.  Because  of  the  limited  instrument  for  measuring cancer patients’ quality of life in Indonesian version, thus this study is  aimed  to  develop  the  validation  of  Indonesian  version  of  Short Form-36  questionnaire  in  cancer  patients.  The  observational  study was  carried  out  in  this  study.  Data  were  collected  from  cancer patients  in  the  Oncology  Department  of   Sardjito  Hospital, Yogyakarta,  Indonesia,  who  were  treated  with  cisplatin  at  the dosage  of  ≥  50mg/m2 as  monotherapy  or  in  combinations.  The validation  process  involved  known-group  validity,  discriminant validity, convergent validity and factor analysis. About 203 subjects who  were  diagnosed  with  cancer  were  recruited  in  this  study.  Theknown-group  validity  test  showed  that  there  were  no  significant differences  of  SF-36  domains  among  different  diagnosa.  All  of  the questions  met  the  criteria  of  convergent  validity  except  for  the questions  number  26,  28,  30  and  32.  Furthermore,  the  questions number 2  and  28  did  not meet  the  criteria  of discriminant  validity. This  study  presents  that  many  questions  are  needed  to  be reconstructed,  due  to  the  result  of  factor  analysis  which  showed that  those  questions  are  loaded  significantly  with  other  domain’s questions.  The  development  of  Indonesian  version  of  SF-36  scales in cancer disease is still less unstatisfactory. According to the result of this study, future study with new construction of questions in this version is still necessary.Key words: validation, SF-36, Indonesia, cancer

    SYNTHESIS AND ANALGESIC ACTIVITY OF 6-(MNITROPHENYL)-4-SUSTITUTED BENZYLIDENE-4,5-DIHYDROPYRIDAZIN-3(2H)-ONE DERIVATIVES

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    Many  research  groups  have  been  interested  in  3(2H)-pyridazinones  for  the  development  of  potential  analgesic  and  antiinflammatory  agents.  Stimulated  by  these  findings,  three  6-(mNitrophenyl)-4-sustituted  benzylidene-4,5-dihydropyridazin-3(2H)-ones (IVa-IVc) have been synthesized and evaluated for analgesic activity  against  hot  plate  method.  Compounds IVa-IVc were prepared from 6-m-nitrophenyl-4,5-pyridazin-3(2H)-one by condensation  with  respective  aldehydes.  All  compounds  (IVa-IVc)  having nitro  phenyl  and  benzylidene  groups  at  position  6  and  4  of  the pyridazinone  ring  receptively.  All  compounds  (IVa-IVc)  showed significant  analgesic  activity  when  compare  to  control  group  and were found less potent than reference drug aspirin.Key words:Pyridazinones, analgesic, benzylidene, nitrophenyl

    PREDICTORS OF THE USE OF GASTROPROTECTIVE AGENTS IN PATIENTS USING NSAID IN YOGYAKARTA INDONESIA

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    Non Steroid Anti-Inflammatory (NSAID) is one type of AntiInflammatory  drug  that  is  used  to  treat  pain  in  patients  of osteoarthritis  (OA)  and  rheumatoid  arthritis  (RA).  The  use  of NSAIDs can cause gastrointestinal side effects. To prevent the side effects,  NSAIDs  are  prescribed  in  combination  with gastroprotective  agent  (GPA).  The  aim  of  the  study  is  to determine  the  factors  considered  in  the  GPA  prescription  by  the doctors  in  patients  who  have risk  factors  for  gastric  disorder  due to  NSAIDs  use.  This  study was  performed using  a  cross-sectional observational  design.  The  data  were  collected  retrospectively during  a  period  of  January to December  2010.  The subjects were OA  and  RA  patients  considering  the  inclusion  and  exclusion criteria.  The  data  included  patient  characteristics  (gender,  age, occupation, payment  method, the primary diagnosis),  prescription of NSAID, prescription of GPA, history of gastrointestinal disease, NSAID  prescription  with  corticosteroids,  prescription  with antiplatelet.  The  data  were  processed  descriptively  and quantitatively, and analyzed statistically using chi-square and log. regression with 95% Confidence Interval. The results showed that there  were  correlation  between  some  predictor  factors  with prescription  of  gastroprotective agent.  These  factors  were  women patient,  patient  age of  ≥  65  years,  oxicam  prescribing, diclofenac sodium prescribing, prescribing >1 type of NSAIDs, prescription of NSAID  concomitant  with  corticosteroids,  prescription  of  NSAID concomitant  with  antiplatelet,  patients  with  history  of gastrointestinal, prescribing NSAIDs with duration of ≥ 3 months. Patient  with  a  history  of  gastrointestinal  disease  was  the  most predictor  influential  factor,  with  OR  (odds  ratio)  of  3.6  (95%  CI: 2.79  -  4.66).  Predictor  factor  of  patients  with  a  history  of dyspepsia  possessed  the  highest  OR  {OR=4,29  (CI  95%:  3.23–5.7)}.  It  means  that  patients  with  a  history  of  dyspepsia prescribed  NSAIDs  would  have  greater  risk  of  4.29  times  to  get GPA  prescription  than  patients  without  a  history  of  dyspepsia. Prescribing  NSAIDs  >  1  DDD  (defined  daily  dose)  had  p  value  of 0.777,  which  means  there  was  no  relationship  between  GPA prescription with NSAIDs > 1 DDD prescription.Key  words: Gastroprotective  Agent,  Non-steroid  anti-inflammatory, Osteoarthritis, Rheumatoid Arthriti

    ANTHELMINTIC ACTIVITY OF Cuminum cyminum, FOENICULUM VULGARE AND Eugenia caryophyllusAGAINST Pheritima posthuma

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    Ethanol  extract  of  fruit  of Cuminum  cyminum (EECC), aqueous  extract  of  fruit  of Cuminum  cyminum (AECC),  Ethanol extract  of  fruit  of  Foeniculum  vulgare (EEFV), aqueous  extract  of fruit of Foeniculum vulgare (AEFV) and Ethanol extract of flowering bud  of  Eugenia  caryophyllus(  EEEC),  aqueous  extract  of  flowering bud  of Eugenia  caryophyllus(  AEEC) were  taken  up  for  in  vitro studies  on  the  Anthelmintic  activity  against Pheritima  posthuma. Different  concentrations  (25,  50,  100,  200mg/mL)  were  used  for the activity is compared with the reference standard Albendazole at concentration 20mg/mL and normal saline( 0.9% NaCl) was used in control  treatment.  The  results  were  expressed  in  terms  of  time  in minutes  to  report  the  time  of  paralysis  and  time  of  death  of  the earth  worms.  The  results  obtained  from  study  indicate  towards anthelmintic  activity,  supporting  folk  used  of  all  three  plants compared with reference standard. The result established that EEEC and AEEC is more potent as compared with EECC, AECC and EEFV, AEFV.Key  words:  Anthelmintic  activity,  Cuminum  cyminum,  Eugenia caryophyllus, Foeniculum vulgare, Pheritima posthuma.

    ANTIOXIDANT ACTIVITY OF ETHYL ACETATE EXTRACT OF RED Psidium guajavaL. LEAVES GROWN IN MANOKO, LEMBANG - INDONESIA

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    Psidium  guajava L.  (Myrtaceae)  is  a  well  known  plant  in Malaysia  and  Indonesia.  Its  leaves  extract  was  found  to  possess antidiarrhea,  antimicrobial,  hepatoprotective  and  antioxidant activities.  Objective  of  this  research  is  to  isolate  an  antioxidant subtance   from  Red Psidium  guajava L.  leaves.  The  crude  leaves was extracted using Soxhlet apparatus by gradual polarity of three different  solvents,  n-hexane,  ethyl  acetate  and  methanol. Antioxidant  activity  of  each  extract  was  tested  by  using  DPPH (2,2-diphenyl-1-picrylhydrazyl)  radical  scavenging  method.  Total phenol,  total  flavonoid  and  total  tannin  content  of  the  extracts were  also  measured.  Ethyl  acetate extract  was fractionated  using vacuum  liquid  chromato-graphy  for  fractionation.  Purification  was performed using TLC  preparative. Isolate then characterized using specific  spray  reagent,  UV-Vis  spectrophotometry  and  infrared spectrophotometry.  Crude  drug  of  Psidiumguajava contained flavonoid,  tannin,  quinone,  saponin  and  steroid/  triterpenoid. Antioxidant  activity  of  ethyl  acetate  extract  is  65.63%  with  total phenol  4.25%,  total  flavonoid  0.53%  and  total  tannin  1.16%. Antioxidant  compound N was  isolated  from  ethyl  acetate  extract.Antioxidant  compound N was  supposed  to  be   aglycone  flavone that has OH at C -4’, C-5 and C-7.Key words: Psidium guajava L. , antioxidant activity, ethyl acetate extrac

    QSAR MODELING OF 2-[CH(OH)X]-5,8-(OY)2 -1,4-NAPHTHOQUININES AGAINST L1210 CELLS USING MULTIPLE LINEAR REGRESSION

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    Quinones are present in many drugs such as anthracyclines, daunorubicin,  doxorubicin,  mitomycin,  mitoxantrones  and saintopin, which are used clinically in the therapy of solid cancers. The  cytotoxic  effects  of  these  quinone  are  mainly  due  to  the inhibition  of  DNA  topoisomerase-II.  It  is  the  necessity  to  develop the  1,4-Naphthoquinone  analogues  with  Cytotoxic  effect.  Here  2-[CH(OH)X]-5,8-(OY)2-1,4-Naphthoquinines  analogues  have  been used  to  correlate  the  cytotoxic  activity  with  the  Eccentric Connectivity index (ECI), Fragment Complexity (FC) and McGowan Volumes  (MG)  for  studying  the  Quantitative  Structure  Activity Relationship  (QSAR).  Correlation  may  be  an  adequate  predictive model  which  can  help  to  provide  guidance  in  designing  and subsequently  yielding  greatly  specific  compounds  that  may  have reduced  side  effects  and  improved  pharmacological  activities.  We have  used  Multiple  Linear  Regression  (MLR),  one  of  the  best methods for developing the  QSAR model. Results from this QSAR study  have  suggested  that  ECI,  FC  and  MG  are  the  important descriptors for cytotoxic activities of 1,4-Naphthoquinones against L1210  cells.  For  the  validation  of  the  developed  QSAR  model, statistical  analysis  such  as  data  point-descriptor  ratio,  fraction  of variance,  cross  validation  test,  standard  deviation,  quality  factor, Fischer’s test; and internal validation such as Y-randomization test have been performed and all the tests validated this QSAR model.Key  words:  1,4-Naphthoquinones,  QSAR,  Eccentric  connectivity  index, Fragment  complexity,  McGowan  Volume,  Multiple  Linear Regression

    PASSIVE AND IONTOPHORETIC PERMEATION OF CAPTOPRIL GEL: AN IN VITRO AND IN VIVO STUDY

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    The  Objective  of  this  work  was  to  formulate  and evaluate  captopril  gel  to  assess  its  suitability  for  transdermal delivery  by  passive  and  iontophoresis.  A  polymer  gel  was prepared  using  hydroxypropyl  methyl  cellulose  and  in  vitro skin permeability was assessed in full thickness skin of rabbits and  pigs.  For  in  vivo  studies  New  Zealand  rabbits  were  used. In vitro  passive permeation was carried out in Franz diffusion cell but for iontophoresis, diffusion cell was modified according to  Glikfield  design.  Iontophoresis  was  performed  at  a  current density  of  0.5  mA/cm2via  silver  /silver  chloride  electrodes with passive controls but for in vivo  study current density wasreduced  to  0.1  mA/cm2.  Blood  samples  were  analyzed  for drug content by HPLC. Results of the  in vitro  study indicated that iontophoresis considerably increased  the permeation rate of  captopril  compared  to  passive  controls  in  both  the  skin types  (P<0.01).  The  plasma  concentration  of  captopril  was significantly  higher  (P<0.001)  than  that  obtained  in  the passive  controls.  Results  showed  that  the  target  permeation rates  for  captopril  could  be  achieved  with  the  aid  of iontophoresis by increasing the area in an appreciable range.Key words:   Captopril,  iontophoresis,  transdermal,  Rabbit,  Pigskin, in vitro, in vivo

    IN VIVO EVALUATION OF MISOPROSTOL FLOATING MICROSPHERES

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    Prostaglandin  (PG)  has  been  reported  to  be  an  important protective  and  acid  suppressive  factor  in  the  gastric  mucosa.  The objective  of  the  study  was  to  develop  and  evaluate  a  stomach specific  drug  delivery  system  for  controlled  release  of  Misoprostal  a PE analogue for gastric ulcer induced NSAIDs. Floating microspheres were  prepared  by  emulsification-solvent  evaporation  method  using ethyl  cellulose  as  a  polymer,  carbopol  as  mucoadhesive  polymer. Ulcers were induced by the oral administration of absolute ethanol (5 mL/kg)  to  24  h  fasted  Wistar  male  rats  (n=8),  weighing  200  g. Sodium  bicarbonate  solution,  misoprostal  solution  and  drug  loaded microspheres were tested. Formulations were administered orally 1h before the administration of ethanol. Prior to the oral administration, rats  were  anesthetized  with  ethylic  ether.  After  2  h  of  ethanol administration,  animals  were  sacrificed;  the  stomachs  were removed,  opened  along  he  greater  curvature  and  examined  for lesion measurements. Ulcer indexes (UI) were calculated. The in vivo evaluation showed that ulcer  index values were 0.61 ± 0.14 for the sodium  bicarbonate  solution,  0.58  ±0.18  for  the  misoprostal  and 0.11  ±  0.06  for  the  misoprostal-loaded  microspheres.  The  KruskalWallis  test  detected  statistical  differences  (p  =0.002)  between  the ulcer  indexes.  The  multiple  analyses  (Student-Newman-Keuls) showed  that  the  misoprostal  loaded  microspheres  presented  a gastric  ulcer  index  statistically  lower  than  that  of  the  sodium bicarbonate  solution  (p  =  0.001)  and  the  misoprostal  solution  (p  = 0.021).  The  percentages  of  ulceration  inhibition  were  31  and  75% after  the  administration  of  misoprostal  solution  and  microspheres, respectively.  In  conclusion,  the  in  vivo  evaluation  showed  that  the microspheres  presented  ulcer  index  lower  than  the  solutions, showing  that  misoprostal-loaded  microspheres  were  efficient  in protecting the stomach against ulcer formation.Key words: Misoprostal, microspheres, ulcer index,

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