Open Access Original Research Article

Design, Synthesis, Biological Evaluation and Docking Studies of Some New Diclofenac Analogues

Hassan A. Osman, G. M. Nazeruddin

Journal of Pharmaceutical Research International, Page 770-777
DOI: 10.9734/BJPR/2014/5030

Aim: There is still a need for new, selective COX-2 inhibitors with an improved safety profile, therefore, a series of diclofenac analogues were designed and different physicochemical properties were calculated such as log P, hydrogen donor, hydrogen-acceptor, molecular weight and pKa etc and compared with diclofenac and study was aimed to design and calculate different physicochemical properties and attempt to introduce diclofenac derivatives with improved anti-inflammatory profile along with docking focusingon CO X-2.
Materials and Method: Carrageenan-induced paw edema to evaluate the anti-inflammatory activity of the conjugates 4 groups (n = 6) of Wistar rats (150–200 g) were examined. A first group of rats was used as a control without using the drug, group II received Diclofenac 20 mg kg–1, received PEG600-Diclo conjugate and PEG4000-Diclo conjugate (52.60 mg kg−1 and 214 mg kg−1 respectively), where the dose was molecularly equivalent to the diclofenac.
Results: Result showed a significant (p<0.05) dose dependent increase in reaction time in mice in the method at the doses of 150 and 200 mg/kg body weight. Also docking studies specifically on COX-2 exhibited promising anti-inflammatory effect as demonstrated by statistically significant (p<0.05) inhibition of paw volume at the dose of 150 mg/kg body weight and the dose of 500 mg/kg body weight at the three hours of study.
Conclusion: In this study molecular docking results, along with biological assay data, show that all compounds have a potential anti-inflammatory activity comparable to diclofenac.

Open Access Original Research Article

Antioxidant and Cytotoxic Activity of Crude Flavonoid Fraction from the Fruits of Hybrid Variety of Momordica charantia (Bitter Gourd)

Rashu Barua, Samsad Sultana, Md. Ehsan Uddin Talukder, Kanchan Chakma, Chowdhury Mohammad Monirul Hasan, Mohammad Sayedul Islam

Journal of Pharmaceutical Research International, Page 778-786
DOI: 10.9734/BJPR/2014/7288

Aims: The study was conducted to evaluate the antioxidant and cytotoxic properties of crude flavonoid fraction from hybrid variety of Momordica charantia (L.) (Bitter gourd) fruit.
Place and Duration of Study: The study was carried out in 2011 in the Department of Biochemistry and Molecular Biology, University of Chittagong, Bangladesh.
Methodology: In vitro assay for Antioxidant activity test was determined by means of 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, using ascorbic acid as standard. The Brine shrimp lethality test was used to assess the cytotoxicity of the extract with Gallic acid as positive control. Data were analysed by statistical software BIOSTAT 2009 and Excel.
Results: The fractionated crude flavonoid of Momordica charantia (L.) fruits showed moderate antioxidant activity with IC50 value of 75.21 µg/ml. Compared to Gallic acid (with LC50 of 4.40 µg/ ml), fractionated flavonoid demonstrated a significant cytotoxic activity (having LC50 of 12.38 µg/ml) which indicates that fractionated flavonoid is promisingly cytotoxic.
Conclusion: The study indicates the moderate antioxidant and potent cytotoxic activities of flavonoid fractionated from Momordica charantia (L.) fruits which can be used as a source of pharmacological references although specific flavonoids are responsible for such actions are unknown.

Open Access Original Research Article

Phytomedicines of Sickle Cell Crisis in Mezam Division, Cameroon: Preventive and Curative Cares

NOUMI Emmanuel, NFORBI Akonwi Ngwa Nebane

Journal of Pharmaceutical Research International, Page 787-805
DOI: 10.9734/BJPR/2014/4959

Background: The aim of this study was to survey the Mezam Division of Cameroon, with a view to documenting how the population of that area treat sickle cells disease using medicinal plants, and to determine the need for further information on sickle cell disease or sickle cell anaemia in that division.
Method: Two questionnaires (one to patients and the other to traditional healers) were designed to gather information on every day life of patients and their parents, and medicinal plants were collected during the field trips.
Results: Seventeen plants species belonging to 16 genera and 13 families were collected. They formed 12 recipes used to treat sickle cell by 5 traditional healers. With the help of these phytotherapists, we meet 92 former and new patients aged from 1 to 35 years old. The current symptoms of the disease were anaemia, hand and foot syndrome, splenomegaly and rheumatic pains. A rate of 52.2% of patients felt better after the treatment; 19.5% of patients with ongoing treatment, felt persistent symptoms; and 28.3% abandoned the treatment.
Conclusion: Two haemoglobin diseases rage in Mezam Division and present some standard clinic demonstrations of anaemia hemolytic: HbS/S and HbS/C. The therapeutic preparations with Zanthoxylum zanthoxyloides exert an influence over haematopoietic organs like the spleen, by a dedifferentiation of its cells, and the production of Hb(α2, Ò¯2) which is the foetal haemoglobin. Thus the patient haemoglobins are S/S and F. This was observed in a patient aged 26 years old in 1999. Since that year, she is still symptom-free up to 2011. The main limitation of this research, however, may be used as a direction for future research, which is, assessing the results from the field at the chemical level in laboratories.

Open Access Original Research Article

Densitometric and Spectrometric Determinations of Florfenicol and Buparvaquone

Fathalla F. Belal, Sawsan A. Abdel-Razeq, Manal M. Fouad, Fatma A. Fouad

Journal of Pharmaceutical Research International, Page 806-817
DOI: 10.9734/BJPR/2014/6495

Three new accurate and sensitive methods were developed for the determination of two veterinary drugs. Florfenicol was analyzed by a stability-indicating TLC/densitometric method in presence of its amine degradation product obtained via acid hydrolysis. It was based on the difference in Rf values of the drug and its degradation product at 254 nm on silica gel 60 GF254 plates using chloroform–methanol (7:3 v/v) as developing solvent (Method A). However, buparvaquone was analyzed through reduction with NaBH4 in methanolto yielda red colored product measured spectrophotometrically at 489 nm (Method B). This reduction product was also measured spectrofluorometrically at 450 nm after excitation at 334 nm (Method C). Good linearity was obtained in the range of 10-100 µg/spot for florfenicol in method A and 10-120 or 0.3-2.4 µg mL-1 for buparvaquone by methods B and C with mean accuracy of 99.94%±0.89, 99.99%±0.99 or 99.66%±1.80, respectively. The densitometric method A proved to be stability-indicating in presence of 10-90% of buparvaquone amine degradation product. The three proposed methods were validated according to ICH guidelines and successfully applied for the assay of the cited drugs in their pharmaceutical formulations.

Open Access Original Research Article

Prophylactic Effect of Clofibrate on Hyperbilirubinemia in Very Low Birth Weight Twins

Mohammadzadeh Ashraf, Farhat Ahmadshah, Esmaeli Habibullah, Javanrouh Niloofar

Journal of Pharmaceutical Research International, Page 818-825
DOI: 10.9734/BJPR/2014/5264

Aims: To determine the prophylactic effects of clofibrate on hyperbilirubinemia in very low birth weight twins.
Study Design: A randomized double blind clinical trial
Place and Duration of Study: Department of Neonatal Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, between Oct 2010- Sep 2011.
Methodology: Forty neonates with very low birth weight (20 pairs of twins) having same blood group and sex were elected. Infants with congenital anomalies, metabolic diseases, hemolytic disease, and infections were excluded. Case group received a single dose of clofibrate 100 mg/kg and control group received sterile water. Both clofibrate and sterile water were administrated through orogastric tube and were the same volume. Serum bilirubin levels were measured before administration, 24, 48, 72 and 96 hours after the administration. Data was analyzed using repeated measure ANOVA.
Results: Total serum bilirubin after clofibrate administration was lower than control group (F= 6.48, P=0.02); however, the duration of phototherapy and hospitalization were not significantly different between the two groups (P=0.39 and 0.91 respectively). No side effects of drug were observed based on the physical exam and liver function tests.
Conclusion: These findings suggest that clofibrate maintained total serum bilirubin lower in very low birth weight neonates but without effect on duration of phototherapy and hospitalization.

Open Access Original Research Article

Cytotoxicity of Enterolobium timbouva Plant Extract and Its Isolated Pure Compounds

Mariam I. Gamal El-Din, Omayma A. Eldahshan, Ashraf B. Abdel-Naim, Abdel-Nasser B. Singab, Nahla A. Ayoub

Journal of Pharmaceutical Research International, Page 826-836
DOI: 10.9734/BJPR/2014/5020

Aims: The present study aimed to evaluate the cytotoxic activities of the aqueous alcohol extract of Enterolobium timbouva leaves as well as its isolated pure compounds.
Place and Duration of Study: Department of Pharmacognosy, Faculty of pharmacy, Ain Shams University, between March 2010 and May 2012.
Methodology: In vitro Cytotoxic study was conducted for the aqueous methanol extract and the isolated pure single compounds to determine the IC50 by sulphorhodamine B (SRB) assay.
Results: Phytochemical investigation of the extract resulted in the isolation and structural determination of ten phenolic compounds isolated for the first time from entitled genus viz; 3,4-Dihydroxy-Cinnamic acid (Caffeic acid) (1); Quercetin-3-O-β-D-glucopyranoside (Isoquercitrin) (2); Quercetin-3-O-β-D-galacto-pyranoside (Hyperin) (3); Kaempferol-3-O-β-D–glucopyranoside (Astragalin) (4); Hesperetin-7-O-rutinoside (Hesperidin) (5); Quercetin 3-O-rutinoside (Rutin) (6); Quercetin (7); Kaempferol (8); 7-methoxycoumarin (Herniarin) (9); and Chrysin (10). The aqueous alcohol extract exhibited potent cytotoxic activity against diffferent cancer cell lines with IC50 values of 2.67 μg/mL against MCF-7 cell line, 3.89 μg/ml against HCT116 cells, 4 μg/mL against HEp2 cells, 4.5 μg/mL against HeLa cells, 1.7 μg/mL against PC-3 cells, and 5.7 μg/mL against Huh-7 cells. In vitro cytotoxic assay of the isolated pure compounds against Huh-7 cell Line showed that compounds 1, 9 and 10 are the only tested compounds exhibiting potent cytotoxic activity with IC50 of 3 μg/mL, 0.76 μg/mL, and 18.51 μg/mL respectively. The rest of tested compounds exhibited IC50 exceeding 1000 μg/mL which reflects their safety.
Conclusion: The current study indicated that the phenolic compounds isolated from Enterolobium timbouva leaves are promising molecules with potentially useful cytotoxic activity profiles. This confirms that this terrestrial plant has great value as a source of lead compounds with pharmaceutical applications.

Open Access Original Research Article

Impact of Highly Active Antiretroviral Therapy (HAART) on Organs of HIV Infected Children in Abia State, Nigeria

M. O. Ajulo, M. K. Omole, J. O. Moody

Journal of Pharmaceutical Research International, Page 837-848
DOI: 10.9734/BJPR/2014/4915

Aim: The aim of the study is to detect effect of zidovudine + lamivudine+nevirapine (AZT+3TC+NVP) on liver and kidney.
Study Design: Sixty-four children age 0 to 5 years attending FMC Umuahia were enrolled for the study in four groups.
Place of Study: Study was carried out in Antiretroviral Clinic and Pediatrics Clinic of Federal Medical Center, Umuahia in Abia State, Nigeria from February 2012 to December 2012.
Methodology: Fourteen asymptomatic immunocompromised HIV-infected children receiving HAART, AZT+3TC+NVP were in Group A. Thirty-five HIV-exposed children who initially received nevirapine for six weeks and later continued with co-trimoxazole were in Group B. Eight non-immunocompromised HIV-infected children who only received co-trimoxazole were in Group C. Group D had seven normal HIV-seronegative children who served as control for the study. A 2 ml blood was collected from the children, centrifuged to obtain serum which was analyzed in the laboratory for liver function test (AST, ALT) and kidney function test (creatinine, creatinine clearance).
Result: Thirty-three (51.6%) of the participants were male while thirty-one (48.4%) were female. ALT was highest in Group A (14.69 IU/L) followed by Group B (13.54 IU/L), Group D (7.77 IU/L) and Group C (6.12 IU/L) respectively. AST was highest in Group A (39.42 IU/L), followed by Group B (32.22 IU/L), Group C (18.66 IU/L) and Group D (14.46 IU/L) respectively. Creatinine was highest among children in Group A (57.17 µmol/l) followed by Group C (56.49 µmol/l), Group B (53.06 µmol/l) and Group D (35.42 µmol/l). Creatinine clearance was highest in Group A (100.58 ml/min/1.732m2), followed by Group D (84.48 ml/min/1.732m2), Group C (74.69 ml/min/1.732m2) and Group B (61.17 ml/min/1.732m2) respectively. The BMI was highest in Group A (32.89 kg/m2), followed by Group B (26.33 kg/m2), Group C (22.03 kg/m2) and Group D (17.34 kg/m2) respectively.
Conclusion: The study showed that HAART has significant effect on elevation of BMI and serum creatinine.

Open Access Original Research Article

Analgesic, Anti-inflammatory and CNS Depressant Activities of the Methanolic Extract of Abelmoschus esculentus Linn. Seed in Mice

Mst. Luthfun Nesa, Md. Monirul Islam, Md. Badrul Alam, Mst. Shirajum Munira, Shabnam Mollika, Mst. Nazmun Naher, Md. Rafiqul Islam

Journal of Pharmaceutical Research International, Page 849-860
DOI: 10.9734/BJPR/2014/7845

Aims: The study was carried out to assess the analgesic, anti-inflammatory and CNS depressant activity of the methanolic extract of Abelmoschus esculentus Linn. Seeds.
Study Design: The Present study was designed to observe pharmacological activities of the crude extract of the plant Abelmoschus esculentus seeds. The study consisted of hot extraction of the seeds of the A. esculantus with methanol. Afterwards, Methanolic crude extract was filtered and the filtrate was evaporated. Finally, screening of analgesic, anti-inflammatory and CNS depressant activity of crude extracts of A. esculantus on Swiss Albino mice.
Place and Duration of Study: Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka, Bangladesh. January, 2013- July 2013.
Methodology: The animals are divided into Four groups and each group consists of five mice. Analgesic activity was performed by acetic acid-induced writhing model and formalin induced licking and biting in mice. Anti-inflammatory effects of Abelmoschus esculentus seed extract were done by carrageenan induced anti-inflammatory method at the dose of 100 and 200 mg/kg b.wt., (p.o). The CNS depressant activity was evaluated by observing the reduction of locomotor and exploratory activities in the hole cross and opens field tests at the dose of 100 and 200 mg/kg body weight.
Results: In statistical analysis, the dose (200 mg/kg) was found to exhibit (significant p=0.05) better analgesic activity (65.16% and 54.38%) against both acetic acid and formalin induced pain in mice which is about similar to standard drug Indomethacin. The extract of A. esculentus (100 and 200mg/kg) also showed sustained inhibition (54.97% and 65.56%) of paw edema at the 4th hour compared to Indomethacin (74.17%). Besides this A. esculentus (significant p=0.05) seed extract (100 and 200mg/kg p.o.) also possesses depressant activity at 90min in both methods. Conclusion: this study recommends that the methanolic extract of the Abelmoschus esculentus seeds has significant CNS depressant, analgesic and anti-inflammatory properties.

Open Access Original Research Article

The Role of Coconut Oil on Pentylenetetrazole Induced Convulsion in Rats: An Electroencephalogram Study

Meraiyebu Ajibola, Olugbemi Olaniyan, Oshimakinde Abiola, A. Seriki Samuel, Okere Shekins

Journal of Pharmaceutical Research International, Page 861-869
DOI: 10.9734/BJPR/2014/4978

Aim: This study was carried out to investigate the role of coconut oil on pentylenetetrazole (PTZ) induced convulsant activity in Wistar rats using the laboratory model. Convulsant activity was achieved by injection of PTZ.
Study Design: The rats were divided into five groups. Group 1 served as control and received distilled water orally. Group2 was a reference group and received only PTZ. The remaining three groups (3, 4 and 5) were test groups and rats were given oral administration of coconut oil at doses of 2, 4 and 5.3 ml/kg for 21 days.
Methodology: 25 rats weighing between 125 and 200g were used. 30 minutes after the last administration of coconut oil after 21 days, a convulsive dose of PTZ was given intraperitoneally. Electroencephalogram (EEG) readings of the rats were then taken using an EEG machine and electrodes placed on the head of the rats recorded the waves produced on the scalp of the rats. The frequencies of the waves recorded were analyzed and compared for all groups.
Result: The frequency of EEG readings produced during convulsion that was caused by the PTZ in the rats were reduced for the rats that received coconut oil. There was a significant decrease in the mean frequency of EEG of rats that received 2, 4 and 5.3 ml/kg coconut oil ( which had frequencies of 13Hz, 14.6Hz and 14. 4Hz, respectively) when compared with the reference group that received only PTZ which had a mean frequency of 16Hz. Coconut oil significantly reduced the frequency produced by PTZ. The result also shows that the lower dose group had the most appreciable decline in convulsive activity returning the frequency of electroencephalogram waves recorded to 13Hz same as the control group.
Conclusion: The result suggests that coconut oil given at a moderate dose has anticonvulsant effect and will cause an increase in weight. These findings supports reports that ketogenic diet could help reduce convulsant activities and epileptic seizures.

Open Access Original Research Article

Possibilities of Developing New Formulations for Better Skin Protection from a Traditional Medicinal Plant Having Potent Practical Usage

A. Dasgupta, L. Jeyaseeli, A. Mukhopadhyay, S. Palchoudhuri, D. Sinha Roy, B. De, S. G. Dastidar

Journal of Pharmaceutical Research International, Page 870-879
DOI: 10.9734/BJPR/2014/7636

Aims: Natural products obtained from different types of plants have made an important impact since ancient times throughout Asia. Since wood of Hesperethusa crenulata (Roxb.) Roem has been used traditionally by women in Southeast Asia for protection against sunlight and other harmful environmental factors, present study was aimed to determine antioxidant and antimicrobial properties of water extract of H. crenulata wood.
Methodology: Wood was powdered, soaked in water, macerated, extracted fluid was lyophilized and tested for antioxidant and antimicrobial properties following standard techniques. The IC50 values were calculated from regression equations prepared from concentrations of extract and inhibition percent of free radical formation. The extract was screened for antimicrobial action following international guidelines against 44 organisms.
Results: In DPPH assay system IC50 value was 344.74 µg/ml, the same for superoxide scavenging assay was 326.13µg/ml, while in hydroxyl radical scavenging system it was 999.85 µg/ml. Among 32 strains of staphylococci 10 strains were inhibited at 25 -50 µg /ml level of the extract, 6 strains at 100 µg /ml, 4 at 200 µg /ml and the remaining 12 strains were resistant. Strains of Bacillus spp and Vibrio vulnificus were rather sensitive to the extract, while E. coli and Pseudomonas aeruginosa were resistant. Thus the extract was inhibitory for bacteria known to invade human skin.
Conclusions: The distinctly beneficial properties of the wood of H. crenulata indicate its usefulness as a highly active agent for the protection of skin against invasion by microorganisms and free radicals including those that may come from the sunlight.