Jalaluddin A. Khan

Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus

Both Alzheimers disease (AD) and Type 2 diabetes mellitus (T2DM) share the presence of systemic and neuro-inflammation, enhanced production and accumulation of β -amyloid peptide and abnormal levels of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Altered levels of AChE and BuChE both in AD as well as in T2DM imply that those two enzymes may be playing a pivotal role in the pathogenesis of the two disorders. AD and T2DM are both characterized by elevated levels of AChE and BuChE in the plasma. On the other hand, in AD the brain levels of AChE go down while those of BuChE go up, resulting in deregulation in balance between AChE and BuChE. This imbalance and change in the AChE/BuChE ratio causes cholinergic deficit in the brain, i.e. deficiency in the brain neurotransmitter acetylcholine. With better understanding of the inter-relationship of AChE and BuChE levels in normality as well as abnormality, AD and T2DM can be effectively treated. Thus, general cholinesterase inhibitors that inhibit both AChE and BuChE as well as highly selective BuChE inhibitors may have potential therapeutic benefits in the treatment of AD and other related dementias.

Utilization of Saudi date sugars in production of baker's yeast

Abstract Six different yeasts: Saccharomyces cerevisiae (I); S. dastorianus NRRL Y-12693; S. cerevisiae (II); S. dayanus NRRL Y-12624; S. cerevisiae NRRL Y-12632 and S. lodgwii were cultivated in different fermentation media. The results showed that S. cerevisiae (I) gave the highest biomass production. Sefry Beesha dates contained 60% total reducing sugars. When blackstrap molasses, the carbon source of the fermentation medium, was replaced by an equivalent amount of Sefry Beesha date sugars, they were as suitable as the molasses in the production of yeast. The best datesugar concentration was 50·0 mg/ml. Ammonium sulphate was a good nitrogen source, at a concentration of 2·0 mg/ml, for the production of yeast biomass. Biotin, at a concentration of 50 μg/l, was a good growth stimulator for S. cerevisiae (I). The ash of S. cerevisiae (I) contained Na, Mg, Ca, Fe, Zn and Cu. Cobalt and Ni were not detected. The concentrations of these metals in the bakers yeast are non-toxic.

Oxadiazoles and thiadiazoles: Novel α-glucosidase inhibitors

Oxadiazoles and thiadiazoles 1-37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1, 4, 5, 7, 8, 13, 17, 23, 25, 30, 32, 33, 35, 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1, 23 and 25, and thiadiazoles 35 and 37) were carried out to determine their mode of inhibition and dissociation constants Ki. The most potent compound of the oxadiazole series (compound 23) was found to be a non-competitive inhibitor (Ki=4.36±0.017 μM), while most potent thiadiazole 35 was identified as a competitive inhibitor (Ki=6.0±0.059 μM). The selectivity and toxicity of these compounds were also studied by evaluating their potential against other enzymes, such as carbonic anhydrase-II and phosphodiesterase-I. Cytotoxicity was evaluated against rat fibroblast 3T3 cell line. Interestingly, these compounds were found to be inactive against other enzymes, exhibiting their selectivity towards α-glucosidase. Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. α-Glucosidase inhibitors can also be used as anti-obesity and anti-viral drugs. Our study identifies two novel series of potent α-glucosidase inhibitors for further investigation.

Alzheimer’s disease and type 2 diabetes via chronic inflammatory mechanisms

Recent evidence has indicated that type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimers disease (AD). Therefore, it is crucial to investigate the potential common processes that could explain this relation between AD and T2DM. In the recent decades, an abundance of evidence has emerged demonstrating that chronic inflammatory processes may be the major factors contributing to the development and progression of T2DM and AD. In this article, we have discussed the molecular underpinnings of inflammatory process that contribute to the pathogenesis of T2DM and AD and how they are linked to these two diseases. In depth understanding of the inflammatory mechanisms through which AD and T2DM are associated to each other may help the researchers to develop novel and more effective strategies to treat together AD and T2DM. Several treatment options have been identified which spurn the inflammatory processes and discourage the production of inflammatory mediators, thereby preventing or slowing down the onset of T2DM and AD.

Antioxidant capacity of chewing stick miswak Salvadora persica

BackgroundChewing stick (miswak Salvadora persica L.) is an effective tool for oral hygiene. It possessed various biological properties including significant antibacterial and anti-fungal effects. In the present study, we evaluated the antioxidant compounds in miswak.MethodMiswak root was extracted with 80% methanol. Methanol extract as antioxidant was evaluated by using DPPH, ABTS and phosphomolybdenum complex assays and analysis by GC-MS. Peroxidase, catalase and polyphenoloxidase assays were performed for crude extract of miswak root.ResultsThe methanol extract of miswak contained the highest amount of crude extract among the various solvent extracts. The methanol extract showed a concentration dependent scavenging of DPPH and ABTS radicals with IC50 values 4.8 and 1.6 μg crude extract, respectively. The total antioxidant activities, based on the reduction of molybdenum (VI) to molybdenum (V), increased with increasing crude extract content. The correlation coefficients (R2) between total crude extract and DPPH, ABTS scavenging activities and the formation of phosphomolybdenum complex were 0.97, 0.99 and 0.95, respectively. The GC-MS analysis showed that the methanol extract doesn’t contain phenolic and flavonoid compounds or under detected limit. After silylation of methanol extract, three compounds namely 2-furancarboxaldehyde-5-(hydroxymethyl), furan-2-carboxylic acid-3-methyl- trimethylsilyl ester and D-erythro-pentofuranose-2-deoxy-1,3,5-tris-O-(trimethylsilyl) were identified by GC-MS analysis. These furan derivatives as they contain hydroxyl groups could be possessed antioxidant activities. The antioxidant enzymes were also detected in the miswak extract with high level of peroxidase and low level of catalase and polyphenoloxidase.ConclusionsThe synergistic actions of antioxidant compounds and antioxidant enzymes make miswak is a good chewing stick for oral hygiene and food purposes.

Solid state production of polygalacturonase and xylanase by Trichoderma species using cantaloupe and watermelon rinds

Different solid state fermentation (SSF) sources were tested such as cantaloupe and watermelon rinds, orange and banana peels, for the production of polygalacturonase (PG) and xylanase (Xyl) by Trichoderma harzianum and Trichoderma virens. The maximum production of both PG and Xyl were obtained by T. harzianum and T. virnes grown on cantaloupe and watermelon rinds, respectively. Time course, moisture content, temperature, pH, supplementation with carbon and nitrogen sources were optimized to achieve the maximum production of both PG and Xyl of T. harzianum and T. virens using cantaloupe and watermelon rinds, respectively. The maximum production of PG and Xyl of T. harzianum and T. virens was recorded at 4–5 days of incubation, 50–66% moisture, temperature 28–35°C and pH 6–7. The influence of supplementary carbon and nitrogen sources was studied. For T. harzianum, lactose enhanced PG activity from 87 to 120 units/g solid, where starch and maltose enhanced Xyl activity from 40 to 55–60 units/g solid for T. virnes. Among the nitrogen sources, ammonium sulphate, ammonium nitrate, yeast extract and urea increased PG activity from 90 to 110–113 units/g solid for T. harzianum. Similarly, ammonium chloride, ammonium sulphate and yeast extract increased Xyl activity from 45 to 55–70 units/g solid for T. virens.

Immobilization of Trichoderma harzianum α-Amylase on Treated Wool: Optimization and Characterization

α-Amylase from Trichoderma harzianum was covalently immobilized on activated wool by cyanuric chloride. Immobilized α-amylase exhibited 75% of its initial activity after 10 runs. The soluble and immobilized α-amylases exhibited maximum activity at pH values 6.0 and 6.5, respectively. The immobilized enzyme was more thermally stable than the soluble one. Various substrates were hydrolyzed by immobilized α-amylase with high efficiencies compared to those of soluble α-amylase. The inhibition of the immobilized α-amylase by metal ions was low as compared with soluble enzyme. On the basis of the results obtained, immobilized α-amylase could be employed in the saccharification of starch processing.

Biological mechanisms linking Alzheimer's disease and type-2 diabetes mellitus.

The emerging data suggest that type 2 diabetes mellitus (T2DM) can contribute significantly to the onset or progression of Alzheimers disease (AD) either directly or as a cofactor. Various in vitro and in vivo animal and human clinical studies have provided evidence that T2DM is a major risk factor in the pathology of AD and the two diseases share common biological mechanisms at the molecular level. The biological mechanisms that are common in the pathology of both T2DM and AD include insulin resistance, impaired glucose metabolism, β-amyloid formation, oxidative stress, and the presence of advanced glycation end products. With better understanding of the degree of association between AD and T2DM and the underlying molecular mechanisms explaining this relationship, it is hoped that researchers will be able to develop effective therapeutic interventions to treat or control T2DM and, as a consequence, delay the onset or progression of AD.

Properties of peroxidase from chewing stick miswak

Miswak is a chewing stick prepared from the roots, twigs or stems of Salvadora persica L. and widely used in Middle Eastern and Estern African cultures. Currently, its chemical components had antimicrobial and antioxidant activities. In the present study, peroxidase, as antioxidant and antibacterial enzyme, was screened in 4 parts of miswak and the level of peroxidase activity was recorded in the order of peel of stem > root without peel > peel of root > stem without peel. Generally, the people used the root without peel. By chromatography of miswak root without peel on DEAESpharose 3 peroxidases POI, POII and POIII were separated. Peroxidase POII with highest activity was reached to homogeneity by chromatography on Sephacryl S-200. The molecular weight of POII was found to be 70 kDa. o-Phenylenediamine was found to be the best substrate for the enzyme followed by guaiacol, o-dianisidine, pyrogallol and p-aminoantipyrine. The apparent Km for catalysis of H2O2 and guaiacol were 0.9 and 17.33 mM respectively. The enzyme had an optimum pH and temperature at 5.5 and 40°C respectively. POII was stable at 10 to 40°C and unstable above 50°C. Most of the examined metal ions had partially inhibitory effects on POII, while Co

Bone turnover biomarkers in obese postmenopausal Saudi women with type-II diabetes mellitus.

BACKGROUND There is a high prevalence of diabetes mellitus type-2 (T2DM) and osteoporosis are problems worldwide. In this study, we evaluated the correlation between T2DM and bone turnover in diabetic obese postmenopausal Saudi women. SUBJECTS AND METHODS The present study included total of 65 T2-DM obese postmenopausal Saudi women, (36 uncontrolled, 29 controlled). The following serum biochemical parameters were evaluated [fasting blood glucose (FBG), total calcium (Ca), phosphorus (Pi), parathyroid hormone (PTH), 1,25-(OH)2 Vitamin D3, osteocalcin (OC), procollagen (PICP) and cathepsin k (Cath K)]. RESULTS Serum OC levels were significantly decreased in diabetic obese postmenopausal group compared to their respective healthy group (P < 0.004). PICP and Cath K were significantly elevated in diabetic postmenopausal group compared to the healthy group (P < 0.024 & 0.001). A significant elevation in 1,25(OH)2 Vitamin D3, Ca and Pi levels in diabetic obese postmenopausal patients group compared to the healthy group. However, a non-significant changes was observed in serum PTH level between different groups. CONCLUSION In this study, the changes in the biochemical parameters and bone turnover markers in obese women are strong risk factors for diabetes development that may contribute to osteopenia and osteoporosis. The study showed the strong effect of T2DM on biochemical markers of bone turnover in obese postmenopausal Saudi women.