Insights into the Role of Erythrina corallodendron L. in Alzheimer's Disease: in Vitro and in Silico Approach

Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100 μg mL⁻¹. AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.     

Synthesis,Cytotoxicity Evaluation,and Molecular Docking Studies of Novel Pyrrole Derivatives of Khellin and Visnagin via One-Pot Condensation Reaction with Curcumin

Russian Journal of Bioorganic Chemistry - Novel pyrrole derivatives were synthesized by one-pot four components condensation reaction of khellin and/or visnagin carbaldehyde; amine derivatives;...     

Sex differences impact the pancreatic response to chronic immobilization stress in rats

Chronic stress has been related to multiple diseases. Inflammation is proposed strongly to link stress to stress-related diseases in different organs, such as small intestine, colon, and brain. However, stress cellular effect on the pancreatic tissue, especially the exocrine one, had received relatively little attention. This work aimed to evaluate the cellular effect of chronic immobilization stress on the pancreatic tissue function and structure along with evaluating the sex role in this type of pancreatic injury. Thirty rats were equally divided into 5 groups: control male, control female, stressed male, stressed female, and stressed female with bilateral ovariectomy. Stressed rats were exposed to immobilization for 1 h/day, 6 days/week, for 3 weeks. Rats were then decapitated for further biochemical, histological, histo-morphometric, and immunohistochemical study. The results showed that, in male and female rats, chronic immobilization stress produced hypoinsulinemia and hyperglycemia, with increasing exocrine pancreatic injury markers by increasing oxidative and inflammatory status of the pancreatic tissue, and exhibited a degenerative effect on the pancreatic tissue. However, the stress-induced pancreatic effects were more obvious in male rats and female rats with bilateral ovariectomy than that in female rats. It could be concluded that male animals were more susceptible to stress-induced pancreatic damage than females. The ovarian hormones are responsible, at least partly, for pancreatic tissue protection since the stress-induced pancreatic injury in females was exacerbated by ovariectomy. In this study, inflammatory and oxidative stress differences in both sexes could provide a plausible explanation for sex differences.     

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

Molecular Biology Reports - Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19)....     

Urinary exosomal microRNA-96-5p and microRNA-183-5p expression as potential biomarkers of bladder cancer

Molecular Biology Reports - Because of low sensitivity and specificity of the currently available urine biomarkers of bladder cancer (BC) detection and painful cystoscopy procedure. Our study aimed...     

GABAA receptor subunit polypeptides increase in parallel but exhibit distinct distributions in the developing rat cerebellum

The GABA_A receptor, a multisubunit ligand-gated ion channel, plays a central role in cell–cell communication in the developing and adult nervous system. Although the developmental expression of mRNAs encoding many subunit isoforms has been extensively characterized throughout the central nervous system, little is known concerning the relationship between subunit mRNA and polypeptide expression. To address this issue, we examined the developmental expression of the α1, β2/3, and γ2 subunit polypeptides, subunits that are thought to coassemble in many brain regions. Western blot analysis using subunit-specific antibodies revealed that the levels of these polypeptides in both the cerebral cortex and cerebellum increased severalfold during the second postnatal week. Whereas polypeptide expression in the cerebellum paralleled that of the corresponding subunit mRNAs, increase in β2/3 and γ2 polypeptide expression in the cerebral cortex occurred in the absence of detectable changes in the mRNA levels. To determine whether the increases in subunit polypeptide expression in the cerebellum were accompanied by changes in distribution, immunohistochemistry was performed. These studies demonstrated that the subunits exhibited different but partially overlapping distributions that remained constant throughout postnatal development. Our findings suggest that although GABA_A receptor subunit polypeptide expression may be regulated primarily at the level of the mRNA, additional regulatory mechanisms may play role. Furthermore, the observation that subunit distribution remains constant in the cell bodies of cerebellar Purkinje neurons, which express the α1, β2, β3, and γ2 subunit mRNAs exclusively, suggests that GABA_A receptor subunit composition in this cell population does not change during postnatal maturation. 1994 John Wiley & Sons, Inc.     

Synthesis and biological evaluation of some nitrogen containing steroidal heterocycles

epi-Androsterone 1 was converted into its hydrazone derivative through the reaction with hydrazine hydrate 80%. Hydrazonoandrostane derivative 2b reacted with hydrazonoyl halides in the presence of K₂CO₃ forming the corresponding hydrazopyridazinoandrostane derivatives 6a–d. The 3β-acetyl-17-hydrazonoandrostane derivative 2b reacted with a halogen reagent, benzoyl chloride, to form the non-cyclic 16-benzoylated hydrazone 9.On the other hand, compound 2b produced the corresponding pyridazinoandrostane derivatives 11 and 12 via its reaction with phenacyl bromide and chloroacetone respectively. Reaction of the hydrazono derivative 2b with benzaldehyde in the presence of acetic acid drops led to the formation of the benzylidenehydrazonoandrostane derivative 13. The product 14, phosphinom-ethylenehydrazonoandrostane was obtained by the reaction of the derivative 13 with trisdimethylaminophosphine in the presence of dry benzene. The reaction of compound 2b with phenyl isothiocyanate followed by boiling in chloroacetic acid or thioglycolic acid produced the pyrazoloandrostane derivatives 17 and 18 respectively. The biological activity of compounds 6a, 6d, 11, 12, and 15 was evaluated as inhibitor of growth in a human liver carcinoma cell line and doxorubicine was used for comparison. Compounds 15 and 12 showed a higher potency than the other tested compounds.     

Natural occurrence of mycotoxins in different spices in Egypt

A total of 120 different samples belonging to 24 kinds of spices collected from different places atAssiut Governorate (Egypt) were examined for the natural occurrence of mycotoxins. TLC analysis of spice extracts revealed the presence of aflatoxins (8–35 μg/kg) in 16 samples of anise, black pepper, caraway, black cumin, fennel, peppermint, coriander and marjoram, sterigmatocystin (10–23 μg/kg) in ten samples of red pepper, caraway, cumin and marjoram and citrinin (8–12 ⧎g/kg) in two samples of black cumin, while ochratoxin A and zearalenone could not be detected.