Open Access Original Research Article

Pre-clinical Evaluation of the Hypotensive and Anti Atherogenic Activity of Hydroethanolic Extract of Eribroma oblongum (Malvaceae) Stem Bark on Wistar Rats Models

M. V. Tsague, C. N. Fokunang, B. Ngameni, E. A. Tembe-Fokunang, N. M. Guedje, E. Ngo Lemba Tom, F. M. Mecthi Dongmo, J. Ngoupayo, S. Sokeng, Dzeufiet Djomeni, J. E. Oben, T. Dimo, J. Ze Minkande, B. Ngadjui Tchaleu

Journal of Pharmaceutical Research International, Page 1-14
DOI: 10.9734//BJPR/2015/12782

Aims: The stem bark of Eribroma oblongum (Malvaceae) is used in traditional Cameroonian medicine to treat various metabolic illnesses including the management of hypertension without scientific evidence to how relief is brought about. The present study was to evaluate the effect of the dried stem bark of hydroethanolic extract of E. oblongum on arterial blood pressure and heart rate in normotensive rat (NTR) and in atherogenic diet induced - hypertensive rats.
Study Design: This was a prospective cross-sectional analytical study.
Place and Duration of Study: Study was conducted in the Laboratories of Animal Physiology, Organic Chemistry and Natural Product of the Faculty of Sciences, and the Preclinical Animal Toxicology laboratory of the Faculty of Medicine and Biomedical Sciences of the University of Yaoundé 1-Cameroon, during the period August 2013 to April 2014. Fresh stem bark of Eribroma oblongum were collected at Eseka, Centre Region of Cameroon, in August 2013. The plant material was identified at the National Herbarium (HNC) of Yaoundé-Cameroon where a voucher specimen N°27489SRFCam has been deposited.
Methodology: The effects of a hydroethanolic extract of Eribroma oblongum (HEEO; 10, 20, 30 mg/kg; i.v) was tested on systolic blood pressure (SBP) and heart rate (HR) of normotensive rat. The mechanism of HEEO (10 mg/kg) was studied in the presence of atropine, yohimbine, propranolol, L-NAME or reserpine. Preventive effects were studied after feeding atherogenic diet (AD) with oral administration of HEEO (100 mg/kg/day) in rats for 45 days. Body weight and food intake were measured every five days during the 45 days of study At the end of the experiment, SBP and HR were recorded. Aorta, heart, liver and kidneys were weighted, and biochemical assays of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), nitrites (NO2-) and lipid profile, transaminases and creatinine were done.
Results: HEEO (10-20 mg/kg) induced a significant hypotensive effect of SBP. The hypotensive effects of HEEO (10 mg/kg) were inhibited by pre-treatment of rats with atropine, reserpine, yohimbine and L-NAME. The AD significantly elevated SBP (P<0.01). Treatment with HEEO (100 mg/kg) reduced blood pressure and significantly decreased HR (P<0.01). HEEO significantly improved the plasma of triglycerides 35.08%, cholesterol total 33.71%, LDL-Cholesterol 73.73% with a significant low atherogenic index 1.73.HEEO significantly increased NO2-and SOD in aorta, CAT in heart P<0.01 and ASAT P<0.05.
Conclusion: This study demonstrates the hypotensive and antihypertensive potential of the crude hydroethanolic extract of the stem bark of Eribroma oblongum. Our data validate the use of the extract traditional medicine against hypertension in Cameroon. The effect on blood pressure is, at least in part, due to a modulation of the orthosympathetic nervous system and to the improvement of the antioxidant status. Further studies are now needed to identify the bioactive compounds responsible for the cardiovascular effects of Eribroma oblongum.

Open Access Original Research Article

Human Skin Penetration and Distribution via Different Vesicular Systems

Khaled Shalaby, Ming Chen, Mohammed Elmowafy, Alfred Fahr

Journal of Pharmaceutical Research International, Page 15-28
DOI: 10.9734/BJPR/2015/14344

Aims: This Study was performed to evaluate the quantitative distribution of mannitol (model hydrophilic molecule) and corticosterone (model lipophilic molecule) in human skin following the application of different vesicular systems (liposome, ethosome and invasome).
Methodology: Vesicular systems were prepared by thin film hydration method and particle size, particles distribution, zeta potential and in vitro human skin penetration and skin deposition were evaluated.
Results and Discussion: Results showed that all of the investigated vesicular systems had almost nanometric size ranging from 67.46±0.25nm and 108.3±0.95nm with low polydispersity (PDI <0.2). All vesicular systems exhibited negative zeta potential. In vitro skin deposition of corticosterone showed that invasome had significant lower accumulation than ethosome and liposome in SC (by ~ 5 and 4 folds respectively) while showed only lower accumulation than liposome in epidermis. Ethosome showed insignificant higher accumulation than CL-CS in both SC and epidermis. Mannitol data revealed that ethosome and liposome showed significant higher accumulation than invasome (by ~ 15 and 4.5 folds respectively) while showed liposome slight insignificant higher accumulation than liposome in SC. Going deeper into epidermis and dermis, vesicular systems and ethanolic solution improved accumulation when compared with buffered solution.
Conclusion: In sum, drug deposition in and penetration through skin is not only influenced by formula in which the drug is incorporated (though it is important factor) but also affected by another factors such as partition coefficient of the drug.

Open Access Original Research Article

In vitro Antisalmonellal and Antioxidant Properties of Mangifera indica L. Stem Bark Crude Extracts and Fractions

Landric Romeo Noghogne, Donatien Gatsing, Fotso ., Norbert Kodjio, Jean Baptiste Sokoudjou, Jules Roger Kuiate

Journal of Pharmaceutical Research International, Page 29-41
DOI: 10.9734/BJPR/2015/13390

Aims: Typhoid fever is still a major public health problem in developing countries, where it remains endemic. In view of searching for new antityphoid substances, the antisalmonellal and antioxidant properties of extracts and fractions of Mangifera indica L. stem bark were assessed.
Study Design: Extraction, fractionation, antibacterial and antioxidant evaluation, phytochemical screening.
Place and Duration of Study: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon, between October 2013 and May 2014.
Methodology: Different fractions, i.e. hexane, ethyl acetate and residual fractions, were obtained from methanol/methylene chloride (MeOH/CH2Cl2) (1:1) extract of Mangifera indica L. stem bark by partitioning. Various aqueous extracts were also prepared by decoction, infusion and maceration. All these extracts and fractions were subjected to antibacterial evaluation against Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B and Salmonella Typhimurium isolates, and a strain of Salmonella Typhi ATCC 6539, using the microdilution method. The evaluation of antioxidant properties, quantitative determination of total phenols and flavonoids, and phytochemical screening of these extracts and fractions were also performed.
Results: The antimicrobial results showed that Mangifera indica L. extracts and fractions exhibited minimum inhibitory concentrations (MICs) ranging from 64 to 1024 µg/mL. The extracts and fractions exhibited antioxidant properties, e.g. IC50 = 10.00 µg/mL for the MeOH/CH2Cl2 extract and fractions, and 11.99 µg/mL for the infused extract. Significant amounts of total phenols and flavonoids were detected. Phytochemical screening showed the presence of alkaloids, flavonoids, tannins, anthraquinones, triterpenes and steroids in all the extracts and fractions.
Conclusion: In the light of the foregoing, it was obvious that Mangifera indica L. stem bark contain antisalmonellal and antioxidant principles which could be developed for the treatment of enteric fevers (typhoid and paratyphoid fevers) and the management of oxidative stress induced by the infection. These findings support the claim of the local community about the use of this plant for the treatment of typhoid fever.

Open Access Original Research Article

Evaluation of Anti-ulcer Activity of Hydro Alcoholic Extracts of Abutilon indicum, Helianthus annuus and Combination of Both against Ethanol and Pyloric Ligation Induced Gastric Ulcer in Albino Wistar Rats

Kambham Venkateswarlu, K. Vijayabhaskar, O. Sreenivasa Krishna, N. Devanna, K. B. Chandra Sekhar

Journal of Pharmaceutical Research International, Page 42-51
DOI: 10.9734/BJPR/2015/14386

Background: Abutilon indicum and Helianthus annuus consists of various compounds which have different therapeutic activities.
Objective: The main aim of the present study was to compare the anti-ulcer activity of hydroalcoholic extracts of A. indicum, H. annuus and combination of both against Ethanol induced gastric ulcer and pyloric ligation induced gastric ulcer in Albino Wistar Rats.
Methodology: The method used was OECD 423 (Acute Toxic Class Method), which allowed evaluating the toxic dose of the crude drugs. Furthermore, the method adopted, provided the selection of proper dose regime to investigate the activity against both types of stomach ulcers in animal models. The omeprazole was used as standard drug for comparison.
Results: Three different extracts were prepared for evaluation namely: HAEAI, HAEHA and C-HAEAIHA which showed a statistically significant anti-ulcer activity. The protective effect was found to be in the following order: C-HAEAIHA > HAEHA > HAEAI.
Conclusion: Among the tested extracts, the combined mixture of hydroalcoholic extract of A. indicum and H. annuus (C-HAEAIHA) showed better anti-ulcer activity.

Open Access Original Research Article

Acute Toxicity and Hepatocurative Effect of Aqueous Leaf Extract of Jatropha curcas in Rats

M. A. Dangambo, H. T. Kabara, A. J. Alhassan, M. S. Sule, M. K. Atiku, A. M. Wudil, J. A. Mashi

Journal of Pharmaceutical Research International, Page 52-57
DOI: 10.9734/BJPR/2015/13105

Acute toxicity and effect of aqueous leaf extract of Jatropha curcas (ALEOJC) on carbon tetrachloride (CCl4) induced hepatotoxicity in albino rats was evaluated. The rats (60) were divided into five groups designated as; I, II, III, IV and Vof which groups I and II has 15 rats each while, group III, IV and V have 10 rats each. Groups II to V were induced with hepato-toxicity using 150 mg/kg body weight CCl4 intramuscularly. Serum liver marker enzymes were assayed 48hrs after induction of liver injury followed by 2nd and 4th weeksof treatment with ALEOJC and Livolin. Oral LD50 of ALEOJC was found to be 2,792.85 mg/kg. Serum levels of alanine amino transferase (ALT), Aspartate amino transferase (AST), Alkaline Phosphatase (ALP) and bilirubin level were significantly (P<0.05) increased in group II (untreated rats) compared to group I (normal control). Following treatment with ALEOJC {10 mg/kg (Group III) and 1000 mg/kg (Group IV)} orally, once daily for 4 weeks, a significant hepatocurative effect was observed as evident by decreased level of the serum liver marker enzymes, total bilirubin and direct bilirubin and increase in serum albumin. The hepatocurative effect of ALEOJC is comparable to the standard drug livolin (Group V receiving livolin at 10 mg/kg/day orally for 4 weeks). This finding suggested that ALEOJC may possess hepatocurative effect against CCl4 – induced liver damage in rats. The curative effects may be associated with the phytochemical content of the plant.

Open Access Original Research Article

Solid State Characterization of Two Tropical Starches Modified by Pregelatinization and Acetylation: Potential as Excipients in Pharmaceutical Formulations

Adenike Okunlola, Sarafadeen Amusa Adebayo, Moji Christianah Adeyeye

Journal of Pharmaceutical Research International, Page 58-71
DOI: 10.9734/BJPR/2015/13445

Aims: To pre-gelatinize, acetylate and characterize Dioscorea dumetorum (bitter yam) and Dioscorea oppositifolia (Chinese yam) starches using solid-state parameters such as differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscope (1H-NMR) and scanning electron microscopy (SEM). The pH, swelling, density, flow and rheological properties of the starches were also determined. Commercial native corn and pre-gelatinized potato starches were used as standards.
Methodology: Pregelatinization and acetylation were conducted by thermal and chemical modification respectively. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. The presence of acetyl groups was confirmed by FT-IR, 1H NMR spectroscopy, SEM, DSC and PXRD.
Results: The DSC endotherms revealed that pre-gelatinized bitter and Chinese starches had higher gelatinization temperatures than the native forms (111.56 to 123.52°C and 101.14 to 108.88°C respectively), whereas the acetylated starches had lower gelatinization temperatures (84.69°C and 69.85°C respectively). The modified starches showed lower enthalpies (ΔH values 154.0 to 91.91 J/g and 263.57 to 120.70 J/g for the respective pre-gelatinized starches; 8.09 J/g and 7.02 J/g for the respective acetylated starches). Acetylation was confirmed by FT-IR and NMR spectroscopy. The PXRD spectra showed characteristic semi-crystalline structures of the native starches (2θ between 13°C and 23°C) were disrupted by acetylation and pregelatinization, forming amorphous structures. Viscosity of 5% slurry of the starches decreased with increasing shear rate; flow curves were typical of non-Newtonian shear thinning fluids. Bitter and Chinese yam starches had lower bulk density (0.33±0.02 and 0.38±0.01 gcm-3 respectively) and better compressibility (40±2.00 and 27.17±2.18% respectively) relative to commercial native corn, suggesting their potential effectiveness as binders in tablets. Pre-gelatinized yam starches had higher (p<0.01) swelling than their native forms and standards, suggesting their potential as disintegrants. Acetylation altered the nature of the starches from hydrophilic to hydrophobic and reduced swellability, suggesting their suitability for controlled release application.
Conclusion: Bitter and Chinese yam starches in their native, pre-gelatinized and acetylated forms could find applications as cheaper alternative excipients in various pharmaceutical formulations.

Open Access Original Research Article

Bioactive Secondary Metabolites from Terrestrial Streptomyces baarnensis MH4

Hamdi Nasr, Mohamed S. Abdel-Aziz, Mohamed O. Radwan, Mohamed Shaaban

Journal of Pharmaceutical Research International, Page 72-81
DOI: 10.9734/BJPR/2015/14074

Aims: Isolation, screening and identification of potent bioactive compounds producing Streptomyces sp. from the terrestrial soil of Egypt. Fermentation study, product recovery, purification and its characterization was also taken into consideration.
Study Design: Cultivation in lab fermenter, solvent extraction and purification of the compounds by column chromatography, identification of the compounds by mass spectrometry and NMR spectroscopy, determination of the antimicrobial activity.
Place and Duration of Study: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Germany; Department of Microbial Chemistry, National Research Centre, Egypt and Chemistry of Natural Compounds Department, National Research Centre, Egypt, between January, 2009 and December, 2010.
Methodology: The strain was cultivated at 25-liter shaker culture and the fermented broth was filtered and the filtrate was extracted by XAD-16 resin and then by methanol-water, and the concentrated water residue was extracted by ethyl acetate followed by evaporation till dryness. The resultant crude extract was fractionated on silica gel and the components were purified by column chromatography (silica gel, Sephadex column and preparative TLC). The pure component was identified by mass spectrometry (ESI and HRESI-MS), NMR analysis (1H,13C NMR, and 2D NMR) and by comparison with reference data. The antimicrobial activity was determined by disc diffusion assay.
Results: The morphological, biochemical and physiological characterization suggested that isolate MH4 belongs to the genus Streptomyces. Comparison the obtained data with literature data and showed 99% identity coverage towards Streptomyces baarnensis. The scale up fermentation of the isolate MH4 yielded eight known metabolites, nonactic acid (2), homononactic acid (3), 3-(3,3-Di-indolyl)propane-1,2-diol (4), turbomycin A (5), indolyl-3-acetic acid, indolyl-3-carbaldehyde, indolyl-3-carboxylic acid and 2'–deoxyadenosine. Structures of the isolated compounds were assigned by intensive studies of nuclear magnetic resonance (NMR) and mass spectrometry and comparison with corresponding literatures. The taxonomical characterization, fermentation, and biological activity of the Streptomyces baarnensis MH4 were investigated.
Conclusion: The isolate Streptomyces baarnensis MH4 is a potent producer of several antibiotic compounds which can be exploited for their commercial production.