Moringa oleifera Lam. (family Moringaceae) leaf extract attenuates high-fat diet-induced dyslipidemia and vascular endothelium dysfunction in Wistar albino rats

Purpose: To investigate the protective effect of methanol extract of Moringa oleifera leaves (MEMO) in high-fat diet (HFD)-induced dyslipidemia and vascular endothelium dysfunction. Methods: Dose-dependent attenuating effect of MEMO was tested at doses of 200 and 400 mg/kg/day in an in vivo model of HFD-induced dyslipidemia using rats whereas vascular endothelial reactivity was assessed in isolated rat aorta using ex vivo organ bath setup. Results: MEMO administration in HFD-induced dyslipidemic rats for 3 consecutive weeks, resulted in significant decrease in rat body weight, LW/BW and RFPW/BW ratio when compared to rats treated with HFD only where an increase in body weight was observed. Decrease in the average daily feed intake and significant reductions in waist, Lee index and BMI was also observed after MEMO treatment in HFD-induced dyslipidemic rats. Lipid profile data indicate that HFD group showed significant increase in total cholesterol, triglyceride, LDL and VLDL levels while HDL levels decreased significantly. On the other hand, MEMO treatment improved lipid profile compared to HFD group. Ex-vivo isolated aorta results revealed that MEMO treatment reversed HFD-induced endothelium dysfunction when compared to SD group. Conclusion: MEMO treatment produces dose-dependent improvement in lipid profile and vascular endothelium protection, thereby rationalizing its traditional medicine use in the treatment of dyslipidemia and cardiovascular related endothelial disorders

First report of carbapenem-resistant Providencia stuartii in Saudi Arabia

We present the case of 31-year-old man who developed hospital-acquired pneumonia in the intensive care unit. Pathogens were identified to be carbapenem-resistant isolates of Providencia stuartii and Klebsiella pneumoniae. The patient was treated with an extended infusion of double-dose meropenem (targeting the carbapenem-resistant P. stuartii) and colistin (targeting the carbapenem-resistant K. pneumoniae) for 2 weeks. The patient's disease responded well to the prescribed regimen; his chest X-ray became normal, and all other signs of infection subsided. To our knowledge, this is the first description of the emergence of carbapenem-resistant P. stuartii due to AmpC hyperproduction in Saudi Arabia. Keywords: Carbapenem resistant, extended infusion, meropenem, Providencia stuarti

Cymbopogon Proximus Essential Oil Protects Rats against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis

Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Several cardiovascular protective properties of Cymbopogon proximus have been reported. However, no reports investigating the direct effect of C. proximus essential oil on the heart are available. The goal of this study was to explore the cardioprotective effect of C. proximus on cardiac hypertrophy and fibrosis. Male albino rats were administered C. proximus essential oil in the presence or absence of hypertrophic agonist isoproterenol. Cardiac hypertrophy and fibrosis were assessed using real-time polymerase chain reaction (PCR) and histological examination. Pre- treatment of rats with C. proximus decreased the ratio of heart weight to body weight and gene expression of hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), which were induced by isoproterenol. Moreover, C. proximus prevented the increase in gene expression of fibrosis markers procollagen I and procollagen III and alleviated the collagen volume fraction caused by isoproterenol. The pre- treatment with C. proximus essential oil conferred cardio-protection against isoproterenol- induced cardiac hypertrophy and fibrosis

Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches

Tobacco/nicotine is one of the most toxic and addictive substances and continues to pose a significant threat to global public health. The harmful effects of smoking/nicotine affect every system in the human body. Nicotine has been associated with effects on endocrine homeostasis in humans such as the imbalance of gonadal steroid hormones, adrenal corticosteroid hormones, and thyroid hormones. The present study was conducted to characterize the structural binding interactions of nicotine and its three important metabolites, cotinine, trans-3′-hydroxycotinine, and 5′-hydroxycotinine, against circulatory hormone carrier proteins, i.e., sex-hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG). Nicotine and its metabolites formed nonbonded contacts and/or hydrogen bonds with amino acid residues of the carrier proteins. For SHBG, Phe-67 and Met-139 were the most important amino acid residues for nicotine ligand binding showing the maximum number of interactions and maximum loss in ASA. For CBG, Trp-371 and Asn-264 were the most important amino acid residues, and for TBG, Ser-23, Leu-269, Lys-270, Asn-273, and Arg-381 were the most important amino acid residues. Most of the amino acid residues of carrier proteins interacting with nicotine ligands showed a commonality with the interacting residues for the native ligands of the proteins. Taken together, the results suggested that nicotine and its three metabolites competed with native ligands for binding to their carrier proteins. Thus, nicotine and its three metabolites may potentially interfere with the binding of testosterone, estradiol, cortisol, progesterone, thyroxine, and triiodothyronine to their carrier proteins and result in the disbalance of their transport and homeostasis in the blood circulation

Europinidin Inhibits Rotenone-Activated Parkinson’s Disease in Rodents by Decreasing Lipid Peroxidation and Inflammatory Cytokines Pathways

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats

Synthesis of chromone-based thiosemicarbazone as selective chemosensor for cyanide ion and its DFT calculation studies

Chemosensors, for the recognition of anions have gained great attention in the field of supramolecular chemistry. Novel chromone-based colorimetric chemosensors, SN-1 and SN-2 are reported for the detection of F− and CN− ions. The structural characterization was done by1H-NMR, 13C-NMR, and UV-Vis spectroscopy. Colorimetric properties of the chemosensors were investigated in presence of different species (F−, AcO−, Br−, ClO−4, Cl−, HSO4−, I−, SCN−, and CN−). The chemosensors SN-1 and SN-2 displayed high selectivity towards CN− and F− ions. The limits of detection for SN-1 and SN-2 were found to be 5.5 × 10−8 and 3.3 × 10−8 for the CN− ion respectively. Chemosensor SN-2 showed greater response towards F− ion with low limit of detection 2.8 × 10−8 and its binding constant was assessed to be 2.5 × 104. The chemosensors could be used to detect the F− ion in real samples of toothpaste and in test strips. Density functional theory (DFT) study supported our experimental findings.</p

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L., known as “Abhal” in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-β) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR–induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-β and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke

Isolation, Characterization and Anticancer Activity of Two Bioactive Compounds from <i>Arisaema flavum</i> (Forssk.) Schott

Medicinal plants play important role in the public health sector worldwide. Natural products from medicinal plants are sources of unlimited opportunities for new drug leads because of their unique chemical diversity. Researchers have focused on exploring herbal products as potential sources for the treatment of cancer, cardiac and infectious diseases. Arisaema flavum (Forssk.) is an important medicinal plant found in the northwest Himalayan regions of Pakistan. It is a poisonous plant and is used as a remedy against snake bites and scorpion stings. In this study, two bioactive compounds were isolated from Arisaema flavum (Forssk.) and their anticancer activity was evaluated against human breast cancer cell line MCF-7 using an MTT assay. The crude extract of Arisaema flavum (Forssk.) was subjected to fractionation using different organic solvents in increasing order of polarity. The fraction indicating maximum activity was then taken for isolation of bioactive compounds using various chromatographic and spectroscopic techniques such as column chromatography, thin-layer chromatography (TLC), gas chromatography–mass spectrometry (GC-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Crude extract of Arisaema flavum (Forssk.), as well as various fractions extracted in different solvents such as n-hexane, chloroform and ethyl acetate, were tested against human breast cancer cell line MCF-7 using an MTT assay. The crude extract exhibited significant dose-dependent anticancer activity with a maximum activity of 78.6% at 500 µg/mL concentration. Two compounds, hexadecanoic acid ethyl ester with molecular formula C18H36O7 and molar mass 284 and 5-Oxo-19 propyl-docosanoic acid methyl ester with molecular formula C26H50O3 and molecular mass 410, were isolated from chloroform fraction. These compounds were tested against the MCF-7cell line for cytotoxic activity and exhibited a significant (p 50 of 25 µM after 48 h of treatment. Results indicated that Arisaema flavum (Forssk.) possesses compounds with cytotoxic activity that can further be exploited to develop anticancer formulations

Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity

Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p &lt; 0.0001), and lower in the IDA group compared to the ID group (p &lt; 0.0001). Ret-He was correlated with ferritin at ID level (&lt;30.0 mg/mL; r = 0.39) and severe IDA (&lt;13.0 ng/mL; p-value &lt; 0.01, r = 0.57). Cut-off values of &lt;28.25 pg for ID and &lt;21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p &lt; 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time

Patients’ enrollment flow diagram.

Patients’ enrollment flow diagram.</p