Journal of Biochemistry International

NOVEL ACTIVE SITE INHIBITION OF O-LINKED N-ACETYL GLUCOSAMINE TRANSFERASE (OGT) FROM ALKALOID LIBRARY

Mon, 23 Jan 2023 00:00:00 +0000

O-linked-N- acetyl glucosaminetransferase (OGT) is an important enzyme which regulates many important cellular processes through posttranscriptional modification of the nuclear and cytosolic proteins. OGT catalyzes the attachment of N- acetylglucosamine portion of uridine diphosphate N- acetyl glucosamine (UDP- GlcNac) to the serine and threonine residues of nuclear and cytoplasmic proteins of multicellular eukaryote in protein O-GlcNacylation process. Hyperglycemia increases GlcNacylation of proteins. GlcNacylation has been linked to some human diseases, such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and cancer. Several inhibitors of the enzyme have been explored in the treatment of the diseases associated with it. In this study, alkaloids were mined from online database and screened computationally using molecular docking approach. 290 alkaloids were retrieved and docked against OGT, using OGT complexed with a thio – linked substrate as the control, and the docking approach predicted 14-norpseurotinA (14-NSA), Protoveratrine B (PB) and 3-(4-methoxyphenyl)-3-[[2-(4-methoxyphenyl)-1-oxoethyl] amino] propanoic acid (MPOAPA) to be suitable inhibitors of OGT, through their interaction and binding pose with the amino acid residues at the substrate-binding site of the protein, with a docking score of -11.106, -9.176 and -8.269 respectively. Additionally, the hit compounds were then subjected to ADMETox screening to predict their drug – likeness. The ADMETox analysis predicted that 14-NSA, and MPOAPA shows more drug-like characteristics compared to PB and the co crystallised ligand by obeying the rule of five for drug development. However, natural bioactive compounds 14-NSA, and MPOAPA could be a potential active site inhibitor of OGT in the treatment of cancer, diabetes, neurodegenerative diseases and cardiovascular diseases caused by aberrant O- GlcNacylation.

Some Bioactive Nutrient Chemical Composition and Effect of Datura stramonium Leaf Extract on Body Weight Using Wistar Albino Rats

Tue, 11 Apr 2023 00:00:00 +0000

Some bioactive nutrient chemical composition and effect of Datura stramonium leaf extract on body weight using Wistar albino rats were investigated using standard methods. D. stramonium leaves were procured from Rhema University school farm and processed for further studies. Some amino acids observed in the sample were lysine (3.16±0.12 g/100g protein), threonine (2.27±0.14 g/100g protein), glutamic acid (10.94±0.15 g/100g protein), and proline (1.62±0.13 g/100g protein). The amino acid groups of the leaf sample showed a Total Acidic Amino Acid (TAAA) of 18.04 g/100g protein (32.19%), Total Neutral Amino Acid (TNAA) of 14.38 g/100g protein (25.66%) and Total Basic Amino Acid (TBAA) of 11.00 g/100g protein (19.63%). Lauric acid, stearic acid and linolenic acids were among the fatty acids observed in D. stramonium in this study. The leaf extract showed significantly (p<0.05) reduced effects on weight and some visceral organs in Wistar albino rats. These effects could be due to the presence of these bioactive compounds observed in the plant. This study has shown some bioactive nutrient chemical composition and effect of D. stramonium leaf extract on body weight using Wistar albino rats.

Hypoglycemic and Antimicrobial Properties of Parkia biglobosa, Lannea humilis Stem Bark and KO-888 Methanol Extracts as a Target for Treatment of Diabetic Wounds

F. E. Abem , M. Z. Zaruwa , C. C. Nweze , B. Y. Muhammad , B. A. Ashikaa — Thu, 04 May 2023 00:00:00 +0000

Diabetes is characterized by insulin deficiency or insulin resistance leading to hyperglycemia and a lowered immune response when the individual is exposed to infection, increasing the risk of a delay in wound healing. The aim of the study was to evaluate the hypoglycemic and antimicrobial properties of Parkia biglobosa, Lannea humilis stem bark methanol extracts, and KO-888 (Jigsimur). These plants’ stem barks were extracted with methanol using soxhlet extraction. The phytochemical screening of the extracts and KO-888 was carried out using standard procedures. Hypoglycemia was induced in 45 male albino rats divided into 9 groups of 5 each, and extracts were administered orally with 2.5 mg/kg of glucose and treated with various doses of the extracts and KO-888. The antibacterial properties of the extracts and KO-888 were tested against pure isolates of Escherichia coli, Staphylococcus spp., and Pseudomonas spp. The formulated extracts and KO-888 were tested on 25 male rats grouped into 5 groups of 5 rats each and applied topically to the excised wound for 20 days. The results of the phytochemical analysis showed the presence of tannins, saponins, flavonoids, steroids, hydrogen cyanides, glycosides, alkaloids, phenols, and terpenoids with copious concentrations of glycosides, alkaloids, and terpenoids in the plant extracts. While, steroids, hydrogen cyanides, alkaloids, and terpenoids were absent in K0-888 compared to the plant extracts. The hypoglycemic effect of the extracts and KO-888 showed a significant (p=.05) decrease in blood glucose levels at all doses, similar to glibenclamide. The antimicrobial activity of the extracts showed a similar effect as compared to penicillin on the bacterial isolates. However, KO-888 was effective against Staphylococcus spp., and Pseudomonas spp. with a significant (p=.001) antibacterial activity at 25 mg/ml. The extracts and KO-888 were more potent than penicillin at a significant (p=.001) level of wound closure. Hence, these extracts may be formulated and used as herbal remedies, especially for diabetes, since the effect is similar to that of KO-888, which is a known commercial herbal remedy.

Antibacterial Activity of Selected Medicinal Plants and Therapeutic Potential of Bridelia micrantha on Excision Wound Infected with Pseudomonas aeruginosa in Rat

Jean-De-Dieu Tamokou , Steve Brice Nana Bakop , Sylvie Carolle Meffo Dongmo — Fri, 02 Jun 2023 00:00:00 +0000

Bridelia micrantha (Hochst.) Baill (Euphorbiaceae) and Smilax krausiana Meisn. (Smilaceae) are traditionally used in tropical Africa to treat various diseases including infectious diseases, stomach pains, skin diseases and wounds. The study aimed to evaluate the antibacterial activity of Bridelia micrantha (Hochst.) Baill (Euphorbiaceae) and Smilax krausiana Meisn. (Smilaceae) extracts and the healing potential of the most active extract in a rat excision wound model infected by Pseudomanas aeruginosa. The crude extracts were prepared by maceration in ethanol. Phytochemical analysis was performed using standard methods. Antibacterial activities of extracts alone and the combinations of extracts with amoxicillin as well as the effect of osmotic stress on their activities were determined by the broth microdilution method against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. The therapeutic effect of the B. micrantha extract ointment was evaluated in a rat excision wound model infected by P. aeruginosa. Skin and eye toxicity tests were performed using the Draize method. The ethanol extract of B. micrantha (MIC = 512 - 1024 µg/ml) displayed the largest antibacterial activity compared with that of S. krausiana (MIC = 512 - 2048 µg/ml). The antibacterial activities of plant extracts and amoxicillin increased under osmotic stress conditions ((2.5% and 5% NaCl). B. micrantha extract showed indifference and antagonism effects with amoxicillin against the tested bacteria. The B. micrantha extract ointment yielded the shortest epithelization times, highest wound contraction rates and lowest numbers of colony forming units of P. aeruginosa at the infection site as compared with the standard drug (Baneocin) and blank (palm kernel oil). The antibacterial and wound healing effects observed may be attributed to the presence of polyphenols, flavonoids, anthocyanins, alkaloids, triterpenes, saponines and tannins found in the test plants. The results of this study clearly demonstrate the antibacterial activity of B. micrantha and S. krausiana as well as the wound healing potential of B. micrantha.