International Journal of Anatomy and Physiology

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (9), pp. 001-005, September, 2018. © International Scholars Journals

Full Length Research Paper

Pharmacological studies of some pyrimidino derivatives

Saleh A. Bahashwan

College of Health Sciences, Pharmacy Department, Taibah University, Medina Munawarah, Saudi Arabia. E-mail: [email protected]. Tel: +966505308524. Fax: +9668450144.

Accepted 07 April, 2018

Abstract

Pyrimidine derivatives, in general, have received significant interest due to their purported biological activities the anti-inflammatory, analgesic, anti-Parkinsonism, and anti-microbial activities for five 2[(N-methyl indolyl)-methyl] pyrimidino derivatives 1-5 is reported. Pharmacological screenings showed that these compounds have good anti-inflammatory, analgesic, anti-Parkinsonism, and anti-microbial activities comparable with reference drugs. Compound 2 showed similar activity of diclofenac sodium as analgesic. Compound 1, 2, 4 and flurbiprofen exhibited essentially equipotent anti-inflammatory activities. Compounds 1 and 3 were the most potent anti-Parkinsonism agents compared with benztropine. In addition, compounds 1-5 showed antimicrobial activities comparable to streptomycin, erythromycin and fusidic acid as reference drugs. These pharmacological studies provide the activities for new pyrimidino derivatives and are expected to possess notable chemical and pharmacological activities for further pharmacological research.

Key words: Pyrimidino, pharmacological, analgesic, anti-inflammatory, anti-Parkinsonism.

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (8), pp. 001-009, August, 2018. © International Scholars Journals

Full Length Research Paper

Anti-oxidative effects of flavonoids enriched Corni fructus extract and the mechanism

Soo-Hwan Lim, Sung Ho Choi, Yun Im Oh and Sung-Jin Kim*

Department of Pharmacology and Toxicology, School of Dentistry, Kyung Hee University, Seoul, Korea 130-701, Korea.

Accepted 14 April, 2018

Abstract

We tested to determine if Corni fructus extract has antioxidant activities and explored its potential mechanism in terms of iNOS and COX-II involvement. Anti-oxidative actions were explored by measuring free radical (NO, DPPH) scavenging activity, and TBARS levels. The mechanism of anti-oxidative action of Corni fructus extract was determined by performing Western blot analysis for iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. 70% methanolic extract of Corni fructus exerted significant DPPH free radical scavenging activity in a dose-dependent manner. The DPPH-free radical scavenging activity was stronger than that of vitamin E. It also markedly inhibited TBARS formation. Strikingly, the Corni fructus extract has dramatic reducing power with maximal activity observed as 231-fold over control. Production of iNOS induced by LPS was significantly inhibited by the Corni fructus extract, suggesting it inhibits NO production by suppressing iNOS expression. However, COX-2 induced by LPS was not significantly altered by the Corni fructus extract. The Corni fructus extract contains anti-oxidant components including phenolics, flavonoids and anthocyanin at the concentration of 18.07, 2.31 and 7.83 mg/g, respectively. The subsequent chloroform fraction enriched with flavonoids almost completely blocked the iNOS induction and NO production caused by LPS in the Raw cells.

Key words: Corni fructus, free radical, iNOS, NO, COX-II, lipid peroxidation.

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (8), pp. 001-009, August, 2018. © International Scholars Journals

Full Length Research Paper

Preparation and characterization of crosslinked and non-crosslinked polycaprolactone fumarate (PCLF) NPs as carriers for doxorubicin HCl

Narges Shokri¹, Hamid Akbari Javar^1,5*, Shamileh Fouladdel², Ali Khalaj³, Rasoul Dinarvand^1,4 and Ebrahim Azizi²

¹Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar street, Engelab Sq, P. O. Box 14155-6451, Tehran, Iran.

²Department of Pharmacology and Toxicology, Molecular research lab, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

³Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

⁴Medical Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

⁵Department of Pharmacy, University of Malaya, Malaysia.

Accepted 14 April, 2018

Abstract

Polycaprolactone fumarate (PCLF) is a biocompatible and biodegradable polyester which has been evaluated for tissue engineering. Hydrophobic PCLF nanoparticles (NPs) may be uptaken by reticule endotelial system rich organs and useful for treatment of related tumors. NPs of three PCLFs were produced through nanoprecipitation method. Crosslinked (CR) NPs were prepared using Benzyl peroxide (BPO) and N-vinyl pyrrolidone (NVP) under heating. Doxorubicin HCl (Dox) loaded NPs of PCLF530, 1250 and 2000 showed size of 149, 238 and 274 nm, respectively and zeta potential of about - 40 mV, while their drug loadings (DL%) were 2.1, 6.0 and 6.8%, respectively. Dox was released from the NPs in 2 to 4 days in phosphate buffer saline, pH 7.4 at 37°C. Crosslinking of NPs could be completed at BPO/PCLF of 0.01 and NVP/PCLF of 0.1 at 40°C with no change in NP size. PCLF530 NPs possessed a higher CR% than two other NPs. The CR% was reduced in formulations without NVP and with NVP/PCLF of 0.8. Electron microscopic images revealed spherical (CR and not CR) NPs and core-shell structure. PCLF1250 NPs showed both more DL% and smaller size in relation to NPs of PCLF530 and 2000, respectively with a prolonged drug release profile and can be useful as a passive targeted drug delivery system. PCLF NPs could be CR (64.3%) through chemical crosslinking and consequently higher DL% (11.6%), longer drug release (6 days) and smaller size (188 nm) than not CR NPs.

Key words: Crosslinked PCLF NPs, doxorubicin HCl, nanoparticles.

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (7), pp. 001-006, July, 2018. © International Scholars Journals

Full Length Research Paper

Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

Fadhil G. Al-Amran*, Najah R. Hadi, Talib H. Kamoona and Zahraa J. Kadhum

Department of Surgery, Box C-320, 12700 E 19th Avenue, Aurora, CO80045, Iraq.

Accepted 21 September, 2017

Abstract

Nephrotoxicity is a major problem of Cyclosporine A (CsA) treatment, despite its beneficial role in organ transplantation and in a variety of immunologic disorders. This study was undertaken to investigate the potential renoprotective role of telmisartan in amelioration of chronic CsA induced nephrotoxicity. The rats were randomized into 4 equal groups. Group 1 received normal saline (control), group 2 received Cremophor EL and ethanol (CsA vehicle), group 3 received CsA 25 mg/kg/day s.c and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA. The rats were pair fed with a standard chow diet throughout the experiment period (8 weeks). CsA nephrotoxicity was assessed in terms of increased S.Cr (from 0.52± 0.16 to 1.29 ± 0.20 mg/ml), blood urea (from 24.69 ± 1.89 to 75.88± 2.33 mg/ml) and serum K (from 3.43 ± 0.18 to 5.23 ± 0.43 meq/l). CsA also caused significant increase (p<0.01) in MDA (from 0.74 ± 0.13 to 2.96 ± 0.43 nmol/mg protein) and significant decrease (p<0.01) in GSH and catalase in renal tissue. Telmisartan failed to restore the altered renal functions. On the other hand, it causes a significant improvement in the histological changes including the tubulointerstitial fibrosis and arteriolopathy (p<0.01). It also caused significant reduction (p<0.01) in CsA-induced oxidative stress. These findings suggested that telmisartan has a promising renoprotective effect against chronic CsA induced nephrotoxicity.

Key words: Cyclosporine A, nephrotoxicity, oxidative stress, telmisartan.

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (7), pp. 001-005, July, 2018. © International Scholars Journals

Full Length Research Paper

Effect of Urtica dioica leaf extract on activities of nucleoside diphosphate kinase and acetyl coenzyme, a carboxylase, in normal and hyperglycemic rats

Durdi Qujeq¹*, Saied Davary¹, Zoleika Moazzi² and Soleiman Mahjoub¹

¹Department of Biochemistry and Biophysics, Babol University of Medical Sciences, Babol, Iran.

²Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran.

Accepted 13 February, 2018

Abstract

Urtica dioica has been shown to have capability of reducing blood glucose through enhancing insulin secretion. The aim of this study was to assess in vivo and in vitro effects of aqueous and alcoholic extracts of U. dioica leaves on activities of Acetyl coenzyme A carboxylase (ACC), Nucleoside diphosphate kinase (NDPK) and insulin level and serum glucose concentration. The experimental animals were randomly distributed among 6 groups of 7 or 8 rats each. The treatment groups received 150 mg/kg of alloxan. Then rats were fed alcoholic and aqueous extracts of U. dioica at 50 mg/kg/day doses for a period of two weeks. Subsequently glucose, insulin levels, and ACC, NDPK activity were measured. Our studies showed significantly lower levels of glucose in the group of rats that were treated with ethanol extract of U. dioica leaves as compared with the control group (279.6 ± 24.3 vs. 393.6 ± 24.9 mg/dl), (p<0.01). Present results showed significantly elevated levels of insulin in the group of rats treated with ethanol extract of U. dioica leaves as compared with the control group (7.6 ± 0.3 vs. 3.6 ± 0.2, µg/l), (p<0.01). Also, results showed significantly elevated activity of ACC and NDPK in the group of rats treated with ethanol and aqueous extract of U. dioica leaves as compared with the control group. The results of the present study indicated that alcoholic extract of U. dioica leaves was found to reduce glucose level and increase insulin secretion, ACC and NDPK activity in the alloxan diabetic animals.

Key words: Urtica dioica, acetyl coenzyme A carboxylase, extract, nucleoside diphosphate kinase

International Journal of Anatomy and Physiology ISSN: 2326-7275 Vol. 7 (6), pp. 001-006, June, 2018. © International Scholars Journals

Full Length Research Paper

Experimental model for safe in vitro- and in vivo-influence of internal and external factors of cell differentiation

Iskra Ventseslavova Sainova¹*, Ilina Vavrek¹, Velichka Pavlova¹, Teodora Daneva², Ivan Iliev¹, Lilija Yossifova¹, Elena Gardeva¹ and Elena Nikolova¹

¹Department of Experimental Morphology, Institute of Experimental Morphology, Pathology and Anthropology with Museum – Bulgarian Academy of Sciences, “Acad. G. Bonchev“ Street, 1113 Sofia, Bulgaria.

²Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, “Acad. G. Bonchev “Street, 1113 Sofia, Bulgaria.

Accepted 13 January, 2018

Abstract

Gene transfer in laboratory-cultivated mouse embryonic stem cells (mESCs) was made by appropriate recombinant DNA-constructs. Electrophoretic profiles of genetic material from wild type on oncogene Dcn1 and “knock-down” on it inbred experimental mice differed not only in it, but also in tumor-suppressor gene HACE1 between both categories of laboratory rodents. The results obtained were compared with previous data, received from malignant rat insulinoma RIN-5F cells, transfected by recombinant gene constructs with inserted copy of “secretagogin” gene, by their in vitro-co-cultivation with malignant cell precursors, derived from populations of non-transfected laboratory- cultivated mESCs in the presence of Doxyciclin, probably by activation of tumor-suppressor genes of STAT-family. Furthermore, the so induced “secretagogin” over-expression could exert protective function on the transfected Rin-5F cells, which was confirmed by noticed differences in the degree of myeloid differentiation of derived precursor cells in their in vitro -co-cultivation with containing additional copy of “secretagogin” gene Rin-5F malignant rat insulinoma cells, in comparison with the results, obtained in their co-cultivation with human cervical carcinoma Hela cells in our laboratory. On the other hand, the derived normal cells with inserted additional copy of oncogene indicated good safety and immunogenity.

Key words: Oncogenes, tumor-suppressor genes, myeloid cell precursors, recombinant gene constructs, cell transfection.