Synthesis, Characterization, Antibacterial and Anti-Inflammatory Activities of Enoxacin Metal Complexes

The present work comprises the synthesis of enoxacin (Heno) complexes with various transition metals. Two types of complexes [M(eno)2(H2O)2]3H2O(M = CuII, NiII or MnII) and [M(eno)(H2O)2]Cl · 4H2O (M = FeIII) were obtained. The complexes were characterized by different physicochemical, spectroscopic, and elemental analysis. Results suggest that enoxacin interacts with the metals as a monoanionic bidentate ligand. These complexes were also tested for their antibacterial activity against eleven (11) different microorganisms, and the results were compared with the parent drug. Moreover all the metal complexes were also tested for their ability to scavenge reactive oxygen species where by MnII and CuII complexes exhibited potential to mediate anti-inflammatory response

IMMUNOMODULATORY ACTIVITIES OF SOME COMMON LICHEN METABOLITES

Objective: To evaluate the immunomodulatory activities of some of the common lichen compounds by using chemiluminescence based cellular assays.Methods: Number of secondary lichen metabolites, representing a breadth of lichen substances, were investigated for their effects on the respiratory burst of human whole blood phagocytes, isolated human polymorphonuclear leukocytes (PMNs) and murine macrophages using luminol or lucigenin-based chemiluminescence probes. Results: This study identify a clear suppressive effect of some lichen metabolites on phagocytosis response upon activation with serum opsonized zymosan by several lichen substances. Amongst the compounds tested, orsellinic acid, methyl orsellinate, methyl haematomate, lecanoric acid and lobaric acid, showed a potent immunomodulatory activity as compared to the standards. The lobaric acid suppressed both the myloperoxidase dependent and myloperoxidase independent, Reactive Oxygen Species (ROS) production in the oxidative burst of polymorphonuclear neutrophils (PMN) at the lowest concentration tested (3.1 µg/ml). Whereas, lecanoric acid, suppressed only the myloperoxidase dependent ROS production with IC50< 3.1µg/ml when compared to the standard sodium diethyldithiocarbamate trihydrate (SDT) (IC50 = 1.3 ± 0.2 µg/ml). Orsellinic acid, methyl orsellinate and methyl haematomate showed a selective myloperoxidase independent pathway with IC50 values; < 3.1µg/ml; 6.1 ± 1.0 µg/ml;  3.3 ± 0.1 µg/ml, respectively, being lower as compared to standard SDT (IC50 = 8.2 ± 1.9 µg/ml). Conclusion: Based on the results obtained it is appropriate to conclude that lichen are not only a good source of antioxidants, but also potent immunomodulators, and thus deserve to be investigated further.Â

In Vivo Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity of Ziziphus Jujuba Fruit Extract

BACKGROUND: Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative).AIM: To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract.METHOD: The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat’s treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat’s paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin.RESULTS: EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group.CONCLUSION: EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin

Effects of Hibiscus sabdariffa on high blood pressure, lipid profile and C- reactive protein among adult hypertensive patients

BackgroundHypertension is a leading cause of mortality and morbidity worldwide. Hibiscus is a cheap readily available preparation.AimsWe aimed to assess the effect of Hibiscus sabdariffa on blood pressure, lipid profile, plasma sugar, and h-sensitive C-reactive protein.MethodsThis is a prospective cohort study conducted among 19 College staff members at the University of Tabuk, Saudi Arabia during January 2020. The participants signed written informed consent, then responded to a questionnaire to report their demographic data. At baseline,  the blood pressure was measured, anthropometric measures collected, and, and a blood sample was taken to measure fasting plasma sugar, serum cholesterol, triglycerides, high-density lipoproteins, and high-sensitive C-reactive protein. Participants thereafter took Hibiscus sabdariffa for four weeks, then the above measurements were repeated. The compliance of the participants was also assessed.Results No significant effects of Hibiscus sabdariffa consumption were observed on systolic and diastolic blood pressure, fasting plasma glucose, lipid profile, and high-sensitive C-reactive protein, P-value< 0.05.ConclusionNo significant effects were observed among Hibiscus sabdariffa users on blood pressure, plasma sugar, lipid profile, and C-reactive protein. Further larger multicenter studies are recommended

Cheiradone: a vascular endothelial cell growth factor receptor antagonist

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a <it>Euphorbia </it>species which inhibited <it>in vivo </it>and <it>in vitro </it>VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in <it>in vitro </it>(proliferation, wound healing, invasion in Matrigel and tube formation) and <it>in vivo </it>(the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC₅₀) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.</p> <p>Results</p> <p>Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC₅₀values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC₅₀values of 2.9 and 0.61 μM respectively.</p> <p>Conclusion</p> <p>Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.</p

IL-2 and IL-1β Patient Immune Responses Are Critical Factors in SARS-CoV-2 Infection Outcomes

Background: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. Aim: The aim of this study was to correlate cytokine and chemokine serum levels with COVID-19 disease severity and mortality. Subjects and Methods: A total of 60 hospitalized patients from the Tabuk region of Saudi Arabia with confirmed COVID-19 were included in the study. At hospital admission, the IL-1 β, IL-2, IL-8, IL-10, LT-B4, and CCL-2 serum levels were measured. The cytokine levels in COVID-19 patients were compared to the levels in 30 healthy matched control subjects. Results: The IL-1 β, IL-2, LTB-4, CCL-2, and IL-8 levels (but not IL-10) were significantly higher in all COVID-19 patients (47 survivors and 13 non-survivors) compared with the levels in the healthy control group. In the non-survivor COVID-19 patients, patients’ age, D-dimer, and creatinine kinase were significantly higher, and IL-1 β, IL-2, and IL-8 were significantly lower compared with the levels in the survivors. Conclusion: Mortality rates in COVID-19 patients are associated with increased age and a failure to mount an effective immune response rather than developing a cytokine storm. These results warrant the personalized treatment of COVID-19 patients based on cytokine profiling

Immunomodulatory activities of isolated compounds from the root-bark of Cussonia arborea

Context: Cussonia arborea Hochst. ex A. Rich (Araliaceae) is a folk medicine used to treat various diseases. However, there is no report of the root phytochemistry. Objective: This study isolates and identifies the immunomodulatory compounds from root-bark of C. arborea. Materials and methods: The methanol extract (18 g) was subjected to repeated column chromatography resulting in isolation of five compounds (1–5). Structure determination was achieved by analysis of their 1 D and 2 D NMR, and mass spectroscopy. The compounds (100–1.0 μg/mL) were examined immunomodulatory for effect on production of reactive oxygen species (ROS) from whole blood phagocytes and on proliferation of T-cells. The compounds cytotoxicity (100–1.0 μg/mL) was evaluated on NIH-3T3 normal fibroblast cells. Results: Three pentacyclic triterpenoids [3, 23-dihydroxy-12-oleanen-28-oic acid (1), 3β-hydroxylolean-12-en-28-oic (2) and 23-hydoxy-oxo-urs-12-en-28-oic acid (5)], two phytosterols: [stigmasterol (3)] and [3-O-β-d-glucopyranosyl stigmasterol (4)] were all isolated from the methanol soluble extract. All the tested compounds (1–4) were found to be nontoxic on NIH-3T3 cells. Compound 1 and 2 moderately inhibited the production of ROS (IC50 = 24.4 ± 4.3 and 37.5 ± 0.1 μg/mL, respectively) whereas compound 2 exhibited the highest inhibitory effect (IC50 = 12.6 ± 0.4 μg/mL) on proliferation of phytoheamagglutinin (PHA) activated T-cells. Conclusions: The isolated compounds (1–5) are reported for the first time from this species. In addition, compound 2 with suppressive potential on production of intracellular ROS and proliferation of T-cells could be of immense value in control of autoimmune diseases as well as in immune compromised patients