Structure-based molecular networking, molecular docking, dynamics simulation and pharmacokinetic studies of Olax subscorpioidea for identification of potential inhibitors against selected cancer targets.

The rationale at the basis of targeted approach in oncology is radically shifting-from development of highly specific agents aiming at a single target towards molecules interfering with multiple targets. This study was performed to isolate and characterize bioactive molecules from Olax subscorpioidea stem and investigate their potentials as multi-targeted inhibitors against selected non-small cell lung cancer, breast cancer and chronic myelogenous leukemia oncogenic targets. Three compounds: ß-sitosterol (1), α-amyrin (2) and stigmasterol (3) were isolated. The structures of 1 - 3 were elucidated by analysis of their spectroscopic data (NMR, MS and IR). To the best of our knowledge, this is the first time these compounds were isolated from O. subscorpioidea stems. Furthermore, integrated analysis of MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) workflow enabled dereplication and identification of 26 compounds, including alkaloids (remerine, boldine), terpenoids (3-hydroxy-11-ursen-28,13-olide, oleanolic acid), flavonoids (kaempferitrin, olax chalcone A) and saponins in O. subscorpioidea stem. Molecular docking studies revealed that some of the compounds, including olax chalcone A (-9.2 to -10.9 kcal/mol), 3-Hydroxy-11-ursen-28,13-olide (-6.6 to -10.2 kcal/mol), α-amyrin (-6.6 to -10.2 kcal/mol), stigmasterol (-7.7 to -10.1 kcal/mol), ß-Sitosterol (-7 to -9.9 kcal/mol) and kaempferitrin (-7.7 to -9 kcal/mol) possessed good inhibitory potentials against selected cancer targets, when compared with reference inhibitors (-8.4 to -13.7 kcal/mol). A few of these compounds were shown to have considerable to favorable pharmacokinetic and drug-likeness properties. This study provides some rationale for the use of O. subscorpioidea in ethnomedicinal management of cancer and identifies some potential anticancer agents.Communicated by Ramaswamy H. Sarma.

Antimalarial potentials of Stemonocoleus micranthus Harms (leguminoseae) stem bark in Plasmodium berghei infected mice.

BACKGROUND: Malaria is a leading cause of death in Nigeria. AIM: Antimalarial activity of Stemonocoleus micranthus stem bark was evaluated in mice with an objective to finding scientific evidence for its use as antimalarial remedy in South-east Nigeria. METHODS: Antiplasmodial activities of hydro-methanolic extract and solvent fractions (hexane, chloroform, ethyl acetate and aqueous) of S. micranthus stem bark against chloroquine-sensitive Plasmodium berghei infected mice were determined using suppressive and curative procedures. Chloroquine was used as positive control. In vitro models, DPPH (1, 1-diphenyl-2- picrylhydrazyl) radical scavenging, FRAP (ferric reducing antioxidant power) and TPC (total phenolic content) were used to assay antioxidant activity of the test samples. Phytoconstituents of the active fractions were analysed by GC-MS. RESULTS: Chemosuppressive effect exerted by extract (50, 100, 200, 400 mg kg-1) and fractions (20, 40, 80 mg kg-1) ranged between 54.14 - 67.73% and 59.41-94.51% respectively. Curative effects was also dose dependent. In both models, ethyl acetate was the active fraction. At low doses the animals lived longer but not protected (D0 - D29). At high doses, extract (400 mg kg-1), active fractions (80 mg kg-1) and chloroquine (5 mg kg-1) the animals were fully protected.The extract and fractions exhibited antioxidant potentials which could have contributed individually or synergistically to antimalarial activities reported in this study. Oral LD50 was estimated to be greater than 4000 mg kg-1, in mice. CONCLUSION: The results of this study may have provided support on traditional therapeutic use of the plant in treatment of malaria.

Chitosan-induced Synergy for Extended Antimicrobial Potency and Enhanced In Vitro Drug Release of Free Base Ciprofloxacin Nanoplexes.

BACKGROUND: Ciprofloxacin free base is practically insoluble in aqueous medium (0.0011 and 0.09 mg/mL at 25 and 37°C respectively). Its inorganic salt form (ciprofloxacin hydrochloride) is more soluble in water (1.35 mg/mL) however when administered orally, it exhibits decreased solubility in the stomach due to common ion effects. Ciprofloxacin free base was used in this study because of its greater hydrophobicity than its hydrochloride salt, which is required for effective permeability and potent antibacterial activity. OBJECTIVE: The purpose of this study is to enhance oral solubility and bacterial cell permeability of the free base ciprofloxacin (CPX) using a single step CPX-chitosan (CT) selfassembly to form nanoplexes with organic counterions. It was envisioned that this would allow the delivery of larger amounts of active drug into the microorganisms. METHODS: Ciprofloxacin-chitosan nanocomplex (nanoplex) was prepared using low energy electrostatic self-assembly technique previously described. Formation of eutectic nanoplex was confirmed using FTIR, DSC, TGA and SEM. The saturated solubility, in vitro release kinetics and mechanism of drug release were determined using mathematical models. Potency and synergism were determined from the inhibition zones, minimum inhibitory concentration (MIC) and Fractional Inhibitory Concentration (FIC) of the nanoplexes using Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. RESULTS: Formation of CPX-CT eutectic adduct polymeric nanoplexes was confirmed with FT-IR and DSC and SEM revealed the conversion of rod-like crystals of CPX (117 µm long) into spherical nanostructures (23-503 nm) dictated by pH, ionic strength and concentration of CT. The solubility of free base CPX increased to a maximum of 32.77 mg/mL compared to 0.0011-0.09 mg/mL reported in literature and dissolution efficiency increased to a maximum of 100% within 72 h. The synergistic effect of CT on antimicrobial activity of CPX was quantified, for the first time, using Fractional Inhibitory Concentration (FIC) of the nanoplexes. FIC was less than 0.5 in both Gram positive (0.031-0.250) and Gram negative (0.036-0.281) microorganisms used in this study, confirming synergistic enhancement of antimicrobial efficacy of CPX. CONCLUSION: It is evident that the design of drug-polymer nanocomplex formulation provides a platform for the synergistic enhancement of therapeutic potency of antibiotics.

Potential antimalarial activity of Coccinia barteri leaf extract and solvent fractions against Plasmodium berghei infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Coccinia barteri (Hook. F.) is traditional used in Southeast of Nigeria in management of fever. This study aimed to evaluate the antimalarial activities of hydro-methanol crude extract and solvent fractions of Coccinia barteri leaf. MATERIALS AND METHODS: Two animal models employed for the study were, 4-day suppressive and curative assays against chloroquine sensitive Plasmodium berghei NK65. Level of parasitaemia, mean survival time (MST), anal temperature and weight loss were measured to assess antimalarial efficacy of the extract/fractions. Chloroquine (10 mg kg-1) was used as positive control. Chemo-profile of extract was evaluated using GC-MS, HPLC techniques and standard phytochemical analysis. Preliminary toxicity test was done using modified Lorke's method. RESULTS: The crude extract (100-400 mg kg-1) and solvent fractions (20-80 mg kg-1) demonstrated antimalarial activity in both models compared to controls. Semi purified fractions of the extract produced stronger percentage chemosuppression and inhibition of parasite. The % inhibition of the fractions, hexane, chloroform, ethyl acetate and aqueous at 80 mg kg-1 were 96.0 0, 95.29, 89.86 and 96.00% respectively on day 8 (D8). While on D14, 100% parasite clearance, indicating cure was obtained for hexane, chloroform and aqueous fraction treatment groups, no death occurred in these groups. Ethyl acetate fraction treated groups lived longer but were not fully protected. Some marker compounds were identified. CONCLUSIONS: These results support the use of C. barteri as malaria remedy and potential source of antimalarial templates. Long acting parasitaemia reduction effect indicates its possible combination potential in poly-herbal combination therapy.

Protein Tyrosine Phosphatase 1B Inhibitory Iridoids from Psydrax subcordata.

Phytochemical investigation of the leaves and bark of Psydrax subcordata has led to the isolation of six new iridoids, subcordatanols I-V (1-4 and 6) and 1-O-methylcrescentin I (5), along with two known analogues (7 and 8). Among them, subcordatanol I (1) is the first example of a 3,8-monoepoxy-iridoid featuring a caged 2-oxa-bicyclo[3.2.1]octane core. The absolute stereochemistry at C-4 of 3, 4, and 6 was established through their acid-catalyzed reaction products subcordatalactones A (3a), B (4a), and C (6a), respectively. Subcordatanols I (1) and II (2), as well as subcordatalactones A (3a) and B (4a), displayed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Enzyme kinetic studies indicated that 3a and 4a are competitive inhibitors. A molecular docking study is also reported.

Occupational hazards and safety measures amongst the paint factory workers in lagos, Nigeria.

BACKGROUND: The manufacture of paint involves a variety of processes that present with medical hazards. Safety initiatives are hence introduced to limit hazard exposures and promote workplace safety. This aim of this study is to assess the use of available control measures/initiatives in selected paint factories in Lagos West Senatorial District, Nigeria. METHODS: A total of 400 randomly selected paint factory workers were involved in the study. A well-structured World Health Organization standard questionnaire was designed and distributed to the workers to elicit information on awareness to occupational hazards, use of personal protective devices, and commonly experienced adverse symptoms. Urine samples were obtained from 50 workers randomly selected from these 400 participants, and the concentrations of the heavy metals (lead, cadmium, arsenic, and chromium) were determined using atomic absorption spectroscopy. RESULTS: The results show that 72.5% of the respondents are aware of the hazards associated with their jobs; 30% have had formal training on hazards and safety measures; 40% do not use personal protective devices, and 90% of the respondents reported symptoms relating to hazard exposure. There was a statistically significant (p < 0.05) increase in the mean heavy metal concentrations in the urine samples obtained from paint factory workers as compared with nonfactory workers. CONCLUSION: The need to develop effective frameworks that will initiate the integration and ensure implementation of safety regulations in paint factories is evident. Where these exist, there is a need to promote adherence to these practice guidelines.

Trace elements and oxidative stress levels in the blood of painters in Lagos, Nigeria: occupational survey and health concern.

Adverse effects attributed to exposure to paints are currently a concern because of the continued widespread use of paint containing trace elements. Thus, occupational survey amongst painters in Lagos and determination of trace elements and oxidative stress parameters were carried out. Descriptive cross-sectional survey was done using a standardized questionnaire to obtain job safety-related information. Forty-eight percent of the painters were aware of hazards associated with painting and 52 % of these workers were aware of the necessary precautionary measures during painting. There were no significant differences (p ≥ 0.05) between the levels of trace elements in the blood of painters and the control subjects. However, there was a significance increase (p ≤ 0.0001) in the level of malondialdehyde and a decrease (p ≤ 0.001) in the levels of reduced glutathione, superoxide dismutase, and catalase of the painters compared to the control. An increase in oxidative stress parameters may not only be due to trace element concentrations, but also the painters' exposure to some petrochemical solvents during mixing of paints.

Antimicrobial activities of hexane extract and decussatin from stembark extract of Ficus congensis.

Ficus congensis (Moraceae) is used traditionally in the treatment of various diseases including infectious diseases, infertility, and gastrointestinal disorders. Investigation of hexane extract of the stem bark using chromatographic techniques led to isolation of a xanthone, 1-hydroxy-3,7,8-trimethoxyxanthone (Decussatin). The compound was elucidated based on spectroscopic methods such as nuclear magnetic resonance (NMR), UV, IR, and mass spectrometry (MS). Decussatin and the hexane extract were screened in vitro for antibacterial and antifungal activities using broth microdilution (MHB) and disc Agar diffusion (DAD) techniques against Escheichia coli, Bacilus substilis, Klebsiela pneumonia, Staphylococcus aureus, Aspergillus fumigatus, Trichophyton mentagrophytes, Trichophyton rubrum and Candida albicans. Hexane extracts showed potent antibacterial activity against E. coli and B. subtilis with minimum inhibitory concentrations (MIC) of 8 mg/mL and 5 mg/mL, respectively, while Decussatin of the highest concentration (8 mg/mL) used in this study showed no appreciable antimicrobial activity. Only hexane extract was active against C. albicans with a MIC of 1 mg/mL.

Modulatory activity of antioxidants against the toxicity of Rifampicin in vivo.

The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received 0.3 mL of distilled water, the Group 2 animals received the therapeutic dose of rifampicin, Group 3 animals received therapeutic doses of rifampicin plus vitamin E, while Group 4 received therapeutic doses of rifampicin and vitamin C. The administration was performed orally during three months; the animals were sacrificed by cervical dislocation at the end of that period. Blood samples were collected and liver function and lipid profile was analyzed using fully automated clinical chemistry device. The liver, brain and reproductive organs underwent histopathological examination. Sperm samples were collected from the epididymis to achieve count and motility and morphological analysis. Results showed rifampicin alone to raise (p < 0.05) liver function enzymes (Aspartate amino transferase [AST], Serum alanine amino transferase [ALT] and Total Bilirubin) when compared with controls. While the vitamin E treated group showed remarkable protection, the vitamin C treated group showed questionable protection against the rifampicin induced liver damage. Sperm count results showed an important (p < 0.05) increase in the sperm quality in vitamin E and C treated groups. However, the vitamin E plus Rifampicin treated group showed increased lipid peroxidation. The histopathological findings revealed structural damages by rifampicin in liver, brain and epididymis while some remarkable architectural integrity was observed in the antioxidant-treated groups. It can be concluded that vitamin E or C improved sperm quality and protected against the brain damage caused by rifampicin. Moreover, vitamin E demonstrated remarkable hepatoprotection against rifampicin induced damage while vitamin C shows a questionable hepatoprotection.

Modulatory activity of antioxidants against the toxicity of Rifampicin in vivo / Atividade modulatória de anti-oxidantes contra a toxicidade da rifampicina in vivo

The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received 0.3 mL of distilled water, the Group 2 animals received the therapeutic dose of rifampicin, Group 3 animals received therapeutic doses of rifampicin plus vitamin E, while Group 4 received therapeutic doses of rifampicin and vitamin C. The administration was performed orally during three months; the animals were sacrificed by cervical dislocation at the end of that period. Blood samples were collected and liver function and lipid profile was analyzed using fully automated clinical chemistry device. The liver, brain and reproductive organs underwent histopathological examination. Sperm samples were collected from the epididymis to achieve count and motility and morphological analysis. Results showed rifampicin alone to raise (p < 0.05) liver function enzymes (Aspartate amino transferase [AST], Serum alanine amino transferase [ALT] and Total Bilirubin) when compared with controls. While the vitamin E treated group showed remarkable protection, the vitamin C treated group showed questionable protection against the rifampicin induced liver damage. Sperm count results showed an important (p < 0.05) increase in the sperm quality in vitamin E and C treated groups. However, the vitamin E plus Rifampicin treated group showed increased lipid peroxidation. The histopathological findings revealed structural damages by rifampicin in liver, brain and epididymis while some remarkable architectural integrity was observed in the antioxidant-treated groups. It can be ...

A Organização Mundial da Saúde tem mostrado preocupação acerca da eclosão da tuberculose nos países em desenvolvimento. Embora a rifampicina seja droga efetiva para o controle da tuberculose têm sido documentados seus efeitos tóxicos em pacientes. Portanto este estudo tem a intenção de investigar o efeito modulador das vitaminas C e E na hepatotoxicidade, qualidade de esperma e a toxicidade cerebral da rifampicina. Quarenta ratos albinos da raça Wistar foram usados, 10 animais por grupo. O grupo 1 de animais recebeu 0,3 mL de água destilada. O grupo 2 recebeu a dose terapêutica de rifampicina. O grupo 3 recebeu doses terapêuticas de rifampicina mais vitamina E, enquanto o grupo 4 recebeu doses terapêuticas de rifampicina e vitamina C. A administração foi feita por via oral durante três meses; os animais foram sacrificados por deslocação cervical após este período. Amostras sanguíneas foram coletadas e função hepática e o perfil lipídico foram analisados usando aparelho automático de química clínica. O fígado, o cérebro e os órgãos reprodutivos foram submetidos a análise histopatológica. As amostras de esperma foram coletadas do epidídimo para contagem, motilidade e análise morfológica. Resultados revelaram que a rifampicina isoladamente aumenta (p < 0,05) os enzimas de função hepática (aspartato amino transferase {AST], alanino amino transferase sérica [ALT] e bilirrubina total) quando comparados com os controles. Embora o grupo tratado com vitamina E mostrasse marcada proteção, o grupo tratado com vitamina C mostrou proteção questionável contra a lesão hepática induzida pela rifampicina. Resultados da contagem espermática mostraram importante (p < 0,05) aumento na qualidade do esperma no grupo tratado com vitamina E e C. Entretanto, o grupo tratado com vitamina E e rifampicina mostrou aumento da peroxidação lipídica. Os achados histopatológicos revelaram danos estruturais pela rifampicina ao fígado, cérebro e epidídimo enquanto uma notável ...

Mutagenic screening of some commonly used medicinal plants in Nigeria.

The uses of medicinal plants have always been part of human culture. The World Health Organization estimates that up to 80% of the world's population relies on traditional medicinal system for some aspect of primary health care. However, there are few reports on the toxicological properties of most medicinal plants especially, their mutagenicity and carcinogenicity. Therefore, this research is to determine the mutagenic potentials of Morinda lucida [Oruwo (Root)], Azadirachta indica [Dongoyaro (Leaf)], Terapluera tetraptera [Aridan (Fruit)], Plumbago zeylanica [Inabiri (Root)], Xylopia aethiopica [Erunje (Fruit)], Newbouldia laevis [Akoko (Leaf)], Alstonia boonei [Ahun (Bark)], Enantia chlorantha [Awopa (Bark)], and Rauvolfia vomitoria [Asofeyeje (Root)] using the Allium cepa Linn. model and the modified Ames assay. Allium cepa model was used to determine the mean root length, mitotic index and chromosomal aberrations effects of these plants on onion bulbs using 0.1, 1, 5 and 10mg/ml concentration of the plant extracts. The modified Ames test which is a modification of the standard Ames test as described by Ames et al. [Ames, B.N., McCann, J., Yamasaki, E., 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Research 31, 347-364] was done using Escherichia coli (0157:H7) that has the phenotypic characteristics of glucose and lactose fermentation, motile, urease negative, indole positive and citrate negative. The results obtained from Allium cepa assay showed increasing root growth inhibition with increased concentration, decreasing mitotic index with increased concentration and chromosomal aberrations. The modified Ames test showed an alteration in the biochemical characteristics of Escherichia coli (0157:H7) for all plants except Rauvolfia vomitoria and Plumbago zeylanica. Three of the medicinal plants altered at least three of the normal biochemical characteristics thus demonstrating mutagenic potentials. The results of internationally accepted Allium cepa were comparable with the modified Ames test. However, a long term in vivo and dose dependent study should be carried out to validate these results and the findings should be communicated to drug and food regulatory body and also to the general public.

Vasorelaxant action of aqueous extract of the leaves of Persea americana on isolated thoracic rat aorta.

The present study investigated the vasorelaxant action of the aqueous leaves extract of Persea americana on isolated rat aorta. The results showed that the extract produced significant vasorelaxation and that the effect is dependent on the synthesis or release of endothelium-derived relaxing factors (EDRFs) as well as the release of prostanoid. The extract also reduced vasoconstriction probably by inhibiting Ca2+ influx through calcium channels.