Molecular docking and prediction of ADME/drug-likeness properties of potentially active antidiabetic compounds isolated from aqueous-methanol extracts of Gymnema sylvestre and Combretum micranthum.

Gymnema sylvestre and Combretum micranthum are well known for their ethno-medicinal uses in the northwest of Nigeria. In our recent study, we demonstrated the antidiabetic and antioxidant activities of the aqueous-methanol extracts of the two plants and identified some potentially active compounds. The present study aimed to conduct molecular docking and ADME/drug-likeness screening of the identified potentially active candidate compounds from aqueous-methanol extracts of G. sylvestre and C. micranthum leaves by using in silico techniques. Molecular docking of compounds on target proteins (α-amylase, α-glucosidase, and phosphorylated insulin receptor tyrosine kinase) was performed using Molsoft ICM-pro 3.8-3. The physicochemical, ADME, and drug-likeness parameters were computed using the SwissADME online program. The result corroborated the antidiabetic activities of the plants with significant binding interactions between compounds A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethy-l2H-1-benzopyran-7-ol acetate), D (9,13-di-cis-retinoic acid), E (4-hydroxycinnamic acid), F ((-)-11-hydroxy-9,10-dihydrojasmonic acid), G (colnelenic acid), H (glyinflanin A), I (6,8a-seco-6,8a-deoxy-5-oxoavermectin "2a" aglycone), and J (3-deshydroxysappanol trimethyl ether) and at least one of the three target proteins. Four compounds, namely A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethyl-2H-1-benzopyran-7-ol acetate), E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether), yielded the best docking scores with respect to the target proteins, of which three (E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether)) were identified to have relatively optimal drug-likeness and medicinal chemistry characteristics. Thus, the present study concluded that these compounds may have contributed to the observed antidiabetic properties of these plants and can be investigated further as drugs or drug-like compound candidates.

Toxicological study of aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves.

Dacryodes edulis (G. Don) H.J. Lam) is the most popular species under the genus Dacryodes. It is well known for its nutritional and ethno-medicinal uses in South-eastern and South-western Nigeria. This study was aimed to evaluate the toxicity of the aqueous-methanol fraction of crude methanol extract of Dacryodes edulis leaves (AMDE). The test rats were randomized to groups of single oral treatment of AMDE (10-5000 mg/kgbw) for the acute toxicity study. They were monitored for obvious signs of behavioural change and mortality. For the subacute toxicity study, the rats were randomized to three daily treatment groups (of 200, 400 and 600 mg/kgbw of AMDE) for 28 days. The fourth group (control) received 2.5 %v/v DMSO. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. The histopathology of the livers and kidneys were assessed using the excised organs. The cytotoxicity and genotoxicity of AMDE were also evaluated using Allium cepa model. The result showed that acute administration of AMDE, up to a dose of 5000 mg/kgbw did not result in mortality of the test rats. The observed median lethal dose (LD50) was greater than 5000 mg/kgbw. The subacute oral administration of AMDE for 28 days showed no significant (p > 0.05) effect on liver function, kidney function indices, organ - body weight ratio, but significantly (p < 0.05) decreased erythrocytic indices: red blood cells, haematocrit, and haemoglobin at 600 mg/kgbw. The Allium cepa assay revealed a non-significant reduction in mitotic index and low chromosomal aberrations of the treated groups. In conclusion, the aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves, AMDE is relatively safe. However, there are strong indications that it may contain compounds that are cytotoxic and reduces erythrocytic indices including red blood cells at high doses. Thus, adequate care should be taken in dosing and administering the extract to avert anaemic condition.

Investigation of cytotoxicity potential of different extracts of Ziziphus mauritiana (Lam) leaf Allium cepa model.

Previous studies showed that Ziziphus mauritiana is ethnomedicinally beneficial against various diseases, however the cytotoxic and genotoxic effects of this plant have not been well investigated. Therefore this study was undertaken to investigate cytotoxic and genotoxic effects of four different solvents extracts of Ziziphus mauritiana (Lam) leaf at different concentrations (20, 40, 60, 80, and 100 mg/L) using Allium cepa model. The cytotoxicity and genotoxicity parameters evaluated were mitotic index, root tip growth length and chromosomal aberration respectively. The result revealed a decrease in mitotic index percentage (%MI) and a dose dependent decrease in root tip length with increase in extracts concentration for all the extracts studied - with the ethanol extract showing the most significant effect in mitotic index. Furthermore, the effective concentrations (EC50) obtained were 81.30, 52.01, 90.68 and 112.30 mg/l for aqueous, ethanol, ethyl acetate and hexane extract respectively. Finally chromosomal aberrations such as vagrant chromosome, c-mitosis, bridged anaphase, sticky telophase were also observed in all four extracts and the percentage chromosomal aberration were observed to decrease with increased concentrations of extracts. Therefore based on the result obtained in this study it may be concluded that the plant (Ziziphus mauritiana (Lam)) extracts are cytotoxic and genotoxic in nature and the observed decrease in percentage chromosomal aberration may be as a result of antimutagenic bioactive principles present in the plant extracts. Hence care must be taken in its consumption and use in folk medicine.

Evaluation of the biosafety potentials of methanol extracts/fractions of Tapinanthus bangwensis and Moringa oleifera leaves using Allium cepa model.

Medicinal plants are considered two-edged swords. They are pharmacologically beneficial and sometimes toxic when abused. The health benefit of medicinal plant is due to their abundant phytochemical endowment. The present study is aimed at evaluating the biosafety potentials of methanol extracts/fractions of Tapinanthus bangwensis (T. bangwensis) and Moringa oleifera (M. oleifera) leaves using Allium cepa (A. cepa) model. Cytotoxicity assay was carried out by A. epa model. The cytotoxicity parameters studied were number of dividing cells, percentage mitotic index (% MI), root tip growth length and chromosomal aberrations. The phytochemistry was determined by UV-spectrophotometry while 2,2-diphenyl-1-picrylhydrazine (DPPH) and nitric oxide (NO) were used to assay antioxidant activity. The A. cepa assay result showed that the inhibitory effect of M. oleifera on root tip growth length was higher compared to T. bangwensis at 60-100mg/100ml concentrations. Decreased number of dividing cells and percentage mitotic index as concentrations increased observed indicate cytotoxicity however the acetone fractions were most cytotoxic. The frequently occurring chromosomal aberrations observed were vagrant, bridged, attached and sticky chromosomes while C-mitosis and binuclear chromosomes were not observed. Therefore cytotoxic effect was significant at 100mg/100ml. The phytochemical screening of methanol extracts/fractions of T. bangwensis and M. oleifera leaves revealed the presence of alkaloids, flavonoids, phenolics, saponins and tannins however saponins were significantly abundant in both plants compared to others. Alkaloid content was found to be low but was not detected in the acetone fractions of the plants. Methanol extracts/fractions of the plants' leaves exhibited antioxidant activities but was more prominent in the ethylacetate fraction of T. bangwensis and acetone fraction of M. oleifera. In conclusion, administration at 100mg/100ml could be unsafe for the biological system.

Insecticide Resistance Profile of Anopheles gambiae Mosquitoes: A Study of a Residential and Industrial Breeding Sites in Kano Metropolis, Nigeria.

Monitoring and understanding the trend and dynamics of insecticide resistance is very key to devising efficient control strategies. This study was carried out to characterize the mosquito population, its insecticide resistance profile, and the physicochemical properties of their breeding sites in Sharada and Wailari of Kano State, Nigeria. Six breeding sites from the 2 study areas were sampled and their physicochemical parameters determined. Mosquito larvae were sampled from the sites and reared to adult. The emergent adults were morphologically and molecularly identified to species level. The World Health Organization (WHO) susceptibility assay was carried out on the adult mosquitoes using different classes of insecticides in WHO discriminating concentrations. kdr-mutation was detected by polymerase chain reaction (PCR)-based method using the permethrin (pyrethroid) resistant and susceptible adult mosquitoes. Most of the determined physicochemical parameters were significantly higher in the industrial area, Sharada. Morphologically, the mosquitoes from the 2 sites were identified as Anopheles gambiae and 100% of the randomly sampled population were found to be Anopheles coluzzii by PCR-based molecular technique. The WHO susceptible assay revealed a graded level of resistance to bendiocarb, dichlorodiphenyltrichloroethane (DDT), and permethrin with mortalities of 78.36%, 75.74%; 43.44%, 56.96%; and 37.50%, 37.50% in both Sharada and Wailari, respectively. Pre-exposure to piperonyl butoxide (PBO) resulted in a significant but minor recovery of susceptibility to permethrin. The kdr mutation frequency was higher in Sharada (45.71%) relative to Wailari (31.43%). Higher kdr mutation frequency was also observed in the resistant population (48.56%) relative to the susceptible (28.54%). The kdr mutation frequency was weakly associated with the resistance status (odds ratio [OR]: 5.9, χ2:3.58, P = .058) and the breeding sites (OR: 3.46, χ2:2.90, P = .088). In conclusion, the study revealed a highly pyrethroid-resistant A coluzzii population with low PBO recovery rate. Furthermore, the data suggested the involvement of kdr mutation, detoxification enzyme, and possibly abiotic factors of the breeding sites.

In vitro and in vivo anti-diabetic and anti-oxidant activities of methanolic leaf extracts of Ocimum canum.

BACKGROUND: Diabetes is a metabolic disorder with a highly complex, multifaceted and intricate etiologies and thus may require management options that proffers multimodal mechanism of action. This present study evaluated the antidiabetic and antioxidant potential of the methanolic extract/fractions of leaves of Ocimum canum. METHODS: The antidiabetic potential was evaluated and using STZ-induced diabetic Wistar rat model (in vivo) and inhibition of α-amylase and α-glucosidase activity (in vitro). Antioxidant activity was assessed in vitro by free radical scavenging and reducing power assays and in vivo via monitoring SOD and CAT activities; GSH and MDA levels. RESULTS: The total phenolic content (221.0±3.0 mg catechol/g of sample) and tannins (146.0±4.0 mg tannic acid/g of sample) of the crude extract; and flavonoid of the aqueous-methanol fraction (216.0.0±1.0 mg of rutin/g of sample) were found to be significantly higher relative to others. The crude extract and the aqueous-methanol fraction exhibited a significantly (p<0.05) higher percentage reduction in fasting blood glucose and a concomitant increase in serum insulin level relative to the diabetic control group. The highest radical scavenging activity and reducing power were observed in the aqueous-methanol fraction. The aqueous-methanol solvent fraction also significantly reversed the alterations in oxidative stress markers occasioned by the diabetic condition. CONCLUSION: In conclusion, the result of the present study has demonstrated evidently that extracts of Ocimum canum leaves ameliorates hyperglycemia and the associated oxidative stress in STZ-induced rats.

Methanol-Extract/Fractions of Dacryodes edulis Leaves Ameliorate Hyperglycemia and Associated Oxidative Stress in Streptozotocin-Induced Diabetic Wistar Rats.

The present study evaluated the antidiabetic and antioxidant potential of the methanolic extract/solvent fractions of the leaves of Dacryodes edulis using a streptozotocin (STZ)-induced diabetic Albino Wistar rat model. The fasting blood glucose/insulin levels and inhibition of α-amylase and α-glucosidase were determined. Antioxidant activity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide scavenging, reducing power, and total antioxidant capacity assays and in vivo by monitoring catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and reduced glutathione (GSH) and malondialdehyde (MDA) levels. The aqueous-methanol fraction exhibited the highest and significant ( P < .05) reduction in fasting blood glucose (FBG; 54.03%) with a concomitant inhibition of α-amylase and α-glucosidase activities. The ethyl acetate fraction also exhibited a significant ( P < .05) reduction in FBG and an increase in insulin levels in the treated diabetic Wistar rats. A significantly ( P < .05) higher reducing power and radical scavenging activity was observed in the aqueous-methanol and ethyl acetate fractions. The aqueous-methanol and ethyl acetate fractions also significantly ( P < .05) reversed the alterations in oxidative stress markers (GSH, MDA, CAT, and SOD) observed in the diabetic control group. In conclusion, the study demonstrated that the methanol extract of Dacryodes edulis ameliorates hyperglycemia and the associated oxidative stress in STZ-induced diabetic Wistar rats. These observed activities are largely due to the compounds that partitions into the aqueous-methanol (55:45) solvent fraction. This provides scientific evidence for the use of this plant extract in folk medicine and also a baseline data for its further characterization. Further work should be carried out to characterize the aqueous-methanol solvent fractions for the active compounds.

Cytotoxic and Hepatocurative Effect of Aqueous Fraction of Tapinanthus bangwensis Against Paracetamol-Induced Hepatotoxicity.

Medicinal plants over time have proven to have potential to manage a huge number of diseases and disorders and thus have become a great source of pharmaceutical drugs. One of such plants is Tapinanthus bangwensis (African mistletoe). It is a semiparasitic and epiphytic plant growing on citrus tree, obtaining its food photosynthetically while its nutrient and water is got from the host plant. The aim of this study was to determine the cytotoxicological and hepatocurative effect of aqueous fraction of T bangwensis in acetaminophen (paracetamol)-induced Wistar rats. The antioxidant potential of the plant was determined by 2,2-diphenyl-1-picrylhydrazine scavenging and ferric reducing power assays. The cytotoxic effect was determined using Allium cepa test while the liver biochemical indices were determined by standard protocols. Data obtained were analyzed by 2-way analysis of variance at 95% confidence level and reported as mean ± standard deviation. The concentrated aqueous fraction of T bangwensis was found to be 23.3 g (58.25%). Quantitative determination of some vital phytochemicals revealed the following: flavonoid (84.6 ± 0.41 mg/100 g), phenol (147.5 ± 1.07 mg/100 g), tannin (31 ± 0.85 mg/ 100 g), alkaloid (23.45 ± 0.09 mg/100 g), and saponin (0.146 ± 0.0 mg/100 g). Treatment of rats with the aqueous extract of T bangwensis significantly decreased paracetamol-induced elevation of activities of liver function indices, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol level and increased the albumin, total protein, and high-density lipoprotein levels. The plant extract also attenuated the paracetamol elevated lipid peroxidation product, malondialdehyde. The research findings suggest that aqueous extract of T bangwensis is slightly cytotoxic, possesses appreciable antioxidant property and exhibited hepatocurative effect against paracetamol-induced hepatoxicity.