Luteolin as a potent anti-leishmanial agent against intracellular Leishmania tropica parasite

Purpose: To examine the anti-leishmanial and cytotoxic effects of five naturally occurring phenolic compounds: luteolin (1), lalioside (2), luteolin-4’-O-β-D-glucopyranoside (3), apigenin 4-O-β-Dglucopyranoside (4) and apigenin (5) on Leishmania tropica KWH23 amastigotes .Methods: The compounds were isolated from the leaves of Lawsonia Inermis via hyphenated high performance liquid chromatography-high resolution mass spectrometry coupled with solid phase extraction-tube transfer nuclear magnetic resonance technique. The isolated compounds were given intraperitoneally to L. tropica KWH23 amastigotes-infected albino mice at a dose of ≥ 3 mg/kg for 5 days. Amphotericin-B was used as standard (reference) drug. Lymphocytes were used to analyze their cytotoxicity.Results: For compound 1, mean lesion size decreased from 0.82 ± 0.12 to 0.10 ± 0.01 after 120 days, with 97 % cure of intracellular L. tropica amastigotes at a dose of 15 mg/kg, compared to amphotericin B which produced 95 % cure at a dose of 30 mg/kg. Half-maximal concentration (IC50) for compound 1 was 4.15 μg/ml against lymphocytes.Conclusion: The results indicate that luteolin is a potent inhibitor of L. tropica  amastigotes, with a higher cytotoxic activity against lymphocytes, compared with luteolin-4’-O-β-D-glucopyranoside.Keywords: Leishmania tropica, Luteolin, Lalioside, Luteolin-4’-O-β-D-glucopyranoside, Apigenin 4-O- β-D-glucopyranoside, Apigeni

Anti-leishmanial and cytotoxic activities of extracts from three Pakistani plants

Purpose: To evaluate the in vitro and in vivo anti-leishmanial and cytotoxic activities of extracts of different parts of Lawsonia Inermis, Morus nigra and Ziziphus mauritiana.Methods: The methanol extracts of all three plant materials at concentrations of 10 - 100 μg/mL were tested for their in vitro anti-leishmanial effects on L. tropica KWH23 promastigotes for 24 - 48 h, relative to negative control and amphotericin-B (standard drug). For in vivo anti-leishmanial activity, the extracts were tested against L. tropica-infected albino mice, while cytotoxicity was investigated against mammalian cells (lymphocytes).Results: For Lawsonia Inermis leaves, mean inhibition of extracellular promastigotes at 10, 25, 50 and 100 μg/mL after 48 h were 98.2 ± 0.06, 98.75 ± 1.09, 99.31 ± 0.00 and 100.00 ± 0.00 %, respectively. After 8 weeks, mean lesion size decreased from 0.8 ± 0.2 mm to 0.3 ± 0.1 mm (p < 0.01), and cure at 150 mg/kg against intracellular amastigotes in albino mice was 97.02 % (95 % CI = 96.14 - 98.10). IC50 for Lawsonia inermis leaf extract was 12.22 μg/mL (95 % CI = 11.54 - 13.84) against lymphocytes.Conclusion: The results obtained in this study show that Lawsonia Inermis leaf is safe and possesses potent anti-leishmanial activity.Keywords: Leishmania tropica, Lawsonia inermis, Morus Nigra, Ziziphus Mauritiana, Anti-leishmania, Amastigotes, Lymphocyte

Synthesis of N-substituted acetamide derivatives of azinane-bearing 1,3,4-oxadiazole nucleus and screening for antibacterial activity

Purpose: To synthesize some acetamide derivatives bearing azinane and 1,3,4-oxadiazole heterocyclic cores and to evaluate their antibacterial potentials.Methods: Ethyl piperidin-4-carboxylate (2) was converted to ethyl 1-[(4-chlorophenyl)sulfonyl]piperidin- 4-carboxylate (3), 1-[(4-chlorophenyl)sulfonyl]piperidin-4-carbohydrazide (4) and 5-[1-(4-chlorophenylsulfonyl)-4-piperidinyl]-1,3,4-oxadiazol-2-thiol (5) using three consecutive steps. The target molecules, 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(substituted)-2-acetamoyl]thio]}-1,3,4- oxadiazole (8a-n) were synthesized by stirring 5 and N-aryl-2-bromoacetamides (7a-n) in an aprotic polar solvent. The structures were corroborated by infrared (IR), electron impact mass spectrometry (EIMS) and proton/carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopic techniques. The evaluation of antibacterial activity was based on the effect on the increase in absorbance of the broth medium due to log phase microbial growth.Results: Compound 8g bearing a 2-methylphenyl group was the most the active growth inhibitor of Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis bacterial strains with minimum  inhibitory concentrations (MIC) of 10.63±0.97, 10.31±1.00, 10.45 ± 0.94 and 11.77±5.00 μM, respectively. Ciprofloxacin was used as reference standard.Conclusion: All the synthesized compounds are moderate inhibitors but relatively more active against Gram-negative bacterial strains. 5-{1-[(4- Chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(2-methylphenyl)-2- acetamoyl]thio]}-1,3,4-oxadiazole (8g) is the most active growth inhibitor of all the strains except Staphylococcus aureus.Keywords: 1,3,4-Oxadiazole, Acetamides, Antibacterial activity, Piperidin

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels

<p>Abstract</p> <p>Background</p> <p><it>Morinda citrifolia </it>(Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders.</p> <p>Methods</p> <p>Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of <it>Morinda citrifolia </it>roots (Mc.Cr).</p> <p>Results</p> <p>The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K⁺induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca⁺⁺, similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 μM) in normal- Ca⁺⁺and Ca⁺⁺-free Kerb's solutions and by high K⁺, similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 μM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 μM) and removal of endothelium.</p> <p>Conclusions</p> <p>These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of <it>Morinda citrifolia </it>in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.</p

Characterization of Antileishmanial Compounds from Lawsonia inermis L. Leaves Using Semi-High Resolution Antileishmanial Profiling Combined with HPLC-HRMS-SPE-NMR

This work describes an analytical platform based on semi-high-resolution antileishmanial profiling combined with hyphenation of high-performance liquid chromatography – high-resolution mass spectrometry – solid-phase extraction – nuclear magnetic resonance spectroscopy, i.e., semiHR-antileishmanial assay/HPLC-HRMS-SPE-NMR. The platform enables fast pinpointing of HPLC peaks representing Leishmania tropica inhibitors in complex matrices, with subsequent structural identification of targeted inhibitors. Active analytes were cumulatively trapped on SPE cartridges and the structures elucidated by analysis of NMR spectra obtained in the HPLC-HRMS-SPE-NMR mode. This led to the identification of six known compounds 2,4,6-trihydroxyacetophenone-2-O-β-D-glucopyranoside (1), lalioside (2), luteolin-4′-O-β-D-glucopyranoside (3), apigenin-4′-O-β-D-glucopyranoside (4), luteolin (5), and apigenin (6). IC50 of the active compounds were determined with luteolin being the most potent inhibitor with an IC50 value of 4.15 μg/ml. The platform proved to be an efficient method for the identification of L. tropica inhibitors

Assessment of medication adherence among type 2 diabetic patients in Quetta city, Pakistan

Aims: Type 2 diabetes (T2DM) is a growing burden among all countries including Pakistan, with medication adherence very important. However, little is known about medication adherence in Pakistan and potential predictors among T2DM patients to provide future guidance. This needs to be addressed. Consequently, the present study sought to assess medication adherence among type 2 diabetic patients in Quetta city, Pakistan. Methods: Questionnaire based, descriptive study among 300 Pakistani patients attending public and private hospitals aged 18 years and above, having a confirmed diagnosis of T2DM, without additional co-morbidities were targeted. Descriptive statistics were used to describe demographic and disease characteristics. The association between socio-demographic data and study variables was compared through Man Whitney / Kruskal Wallis test (where applicable). The factors that were significantly associated with medication adherence were further assessed by logistic regression analysis. Results: 55.6% of patients had high adherence although overall patients reported moderate adherence. Age, gender, education, diabetes-related knowledge and treatment satisfaction were significantly associated with medication adherence. Older males with only primary education and with poor diabetes-related knowledge had the lowest adherence. Conclusions: This study presents a model that is associated with medication adherence among T2DM patients, with disease-related knowledge as a significant predictor of likely adherence. Results of the current study revealed that improved diabetes related knowledge plays a significant role in improving medication adherence. Healthcare practitioners and the system should formalize and acknowledge patient education as a key component to treat patients with T2DM. This should include a greater role for pharmacists and other professionals

Polymorphisms of the ABCB1 Gene in the Pakistani Population

Objective: To investigate the frequency of the single nucleotide polymorphism C1236T in exon 12 of the ABCB1 gene in Pakistani population and to compare it with published data on Asian and Caucasian populations