New neuroprotective derivatives of cinnamic acid by biotransformation.

Microbial transformation is extensively utilized to generate new metabolites in bulk amounts with more specificity and improved activity. As cinnamic acid was reported to exhibit several important pharmacological properties, microbial transformation was used to obtain its new derivatives with enhanced biological activities. By manipulating the 2-stage fermentation protocol of biotransformation, five metabolites were produced from cinnamic acid. Two of them were new derivatives; N-propyl cinnamamide 2̲ and 2-methyl heptyl benzoate 3̲ produced by Alternaria alternata. The other 3 metabolites, p-hydroxy benzoic acid 4̲, cinnamyl alcohol 5̲ and methyl cinnamate 6̲, were produced by Rhodotorula rubra, Rhizopus species and Penicillium chrysogeneum, respectively. Cinnamic acid and its metabolites were evaluated for their cyclooxygenase (COX) and acetylcholinesterase (AChE) inhibitory activities. Protection against H2O2 and Aß1-42 induced-neurotoxicity in human neuroblastoma (SH-SY5Y) cells was also monitored. Metabolite 4̲ was more potent as a COX-2 inhibitor than the parent compound with an IC50 value of 1.85 ± 0.07 µM. Out of the tested compounds, only metabolite 2̲ showed AChE inhibitory activity with an IC50 value of 8.27 µM. These results were further correlated with an in silico study of the binding interactions of the active metabolites with the active sites of the studied enzymes. Metabolite 3̲ was more potent as a neuroprotective agent against H2O2 and Aß1-42 induced-neurotoxicity than catechin and epigallocatechin-3-gallate as positive controls. This study suggested the two new metabolites 2̲ and 3̲ along with metabolite 4̲ as potential leads for neurodegenerative diseases associated with cholinergic deficiency, neurotoxicity or neuroinflammation.

Stagnation point flow of hybrid nanofluid flow passing over a rotating sphere subjected to thermophoretic diffusion and thermal radiation.

The effects of thermal radiation and thermophoretic particles deposition (TPD) on the hybrid nanofluid (HNF) flow across a circling sphere have momentous roles in research and engineering. Such as electrical devices, projectiles, thermal conveyance, sheet production, renewable energy, and nuclear-powered plants. Therefore, the current study presents the stagnation point flow of HNF flows about an orbiting sphere. The HNF is organized with the accumulation of aluminum alloys (AA70772 and AA7075) nanoparticles in the water. The HNF flow model equations are changed into the non-dimensional form of ODEs through the similarity variables and then numerically solved through the parametric simulation. It has been perceived that the significance of the rotation factor boosts the velocity curve, while the flow motion drops with the increasing numbers of AA7072 and AA7075 nanoparticles. Furthermore, the addition of AA7072 and AA70775 nano particulates in water lessens with the temperature profile. The energy distribution rate in case of hybrid nanoliquid enhances from 3.87 to 13.79%, whereas the mass dissemination rate enhances from 4.35 to 11.24% as the nanoparticles concentration varies from 0.01 to 0.03.

Araucaria heterophylla oleogum resin essential oil is a novel aldose reductase and butyryl choline esterase enzymes inhibitor: in vitro and in silico evidence.

The essential oil isolated by hydrodistillation of the oleogum resin of Araucaria heterophylla has been analyzed by GC-MS. Twenty-four components accounting to 99.89% of the total detected constituents of this essential oil were identified. The major ones were: caryophyllene oxide (14.8%), ( +)-sabinene (12.07%), D-limonene (11.22%), caryophyllene (10.36%), α-copaene (8.00%), ß-pinene (6.44%), trans-verbenol (5.88%) and α-pinene oxide (5.18%). The in vitro inhibitory activities of this oil against aldose reductase, BuCHE, COX-2 and SARS-CoV-2 Mpro enzymes were evaluated. This revealed promising inhibitory activity of the essential oil against both aldose reductase and BuCHE enzymes. The molecular docking study of the major components of the Araucaria heterophylla essential oil was carried out to correlate their binding modes and affinities for aldose reductase and BuCHE enzymes with the in vitro results. In conclusion, the in vitro inhibitory activity of the essential oil attributed to the synergistic effect between its components and the in silico study suggested that compounds containing epoxide and hydroxyl groups may be responsible for this activity. This study is preliminary screening for the oil to be used as antidiabetic cataract and Alzheimer's disease therapeutics and further investigations may be required.

Microbial Transformation of the Sesquiterpene Lactone, Vulgarin, by Aspergillus niger.

The biotransformation of vulgarin (1), an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica, by the microorganism, Aspergillus niger, was carried out to give three more polar metabolites; 1-epi-tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11ßH-eudesman-6,12-olide (2), 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11ßH-6,12-olide (3a), 10% yield, and C-1 epimeric mixture (3a, b), 4% yield, in a ratio of 4:1, 3a/3b. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that (1) exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite (3a) retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, ß unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

Design, biological evaluation, and molecular modelling insights of cupressic acid derivatives as promising anti-inflammatory agents.

The major labdanes in the oleogum resin of Araucaria heterophylla (Salisb.) Franco, 13-epi-cupressic acid (1) and acetyl-13-epi-cupressic acid (2) were used to prepare seven new (3-9), along with one known (10) derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (1-10) via measuring the level of COX-2 expression and IL-6. Pre-treated RAW264.7 cells with 1-10 (except for derivative 7) at 25 µM for 24h exhibited downregulation of COX-2 expression in response to LPS stimulation. Moreover, pre-treatment with compounds 1, 2, or 3 significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells (p < 0.05). A docking study was conducted against phospholipase A2 (PLA2), a crucial enzyme in initiating the inflammatory cascade. The significant structural features of compounds (1-10) as PLA2 inhibitors included the carbonyl group at C-4 (free or substituted) and the hydrophobic diterpenoid skeleton. This study suggested 13-epi-cupressic acid as a scaffold for new anti-inflammatory agents.

Impact of an effective Prandtl number model on the flow of nanofluids past an oblique stagnation point on a convective surface.

The stretched surface's convective heat transfer capability can be improved by using nanoparticles. There is a significant role of the Prandtl number in determining the thermal and momentum stretching layer surfaces. It is proposed in this study that an effective Prandtl number model be used to explore the two-dimensional oblique stagnation point flow of γ A l 2 O 3 - H 2 O and γ A l 2 O 3 - C 2 H 6 O 2 nanofluids moving over a convective stretching surface. The fluid in question is subjected to a thorough investigation. It is necessary to apply non-linear ordinary differential equations in order to connect the controlling partial differential equations with the boundary conditions. To solve these equations, an efficient and reliable numerical technique is used. Shooting Method with Runge Kutta-IV in Mathematica software. Visual representations of normal and tangential velocity and temperature as well as streamlines as a function of many physical parameters are shown. The results show that as the volume fraction of nanoparticles increases, the fluid flow f ( y ) , h ( y ) and velocity f ' ( y ) , h ' ( y ) all increase, whereas the flow f ( y ) and velocity f ' ( y ) both increase against the stretching ratio parameter, while the flow h ( y ) and velocity h ' ( y ) both decrease. When the volume percentage of nanoparticles and the Biot number are both increased, the temperature rises. However, when the stretching ratio parameter is increased, the temperature falls. Physical attributes like the local skin friction coefficient and the heat flow may be characterized in many ways. A nanofluid comprised of γ A l 2 O 3 - C 2 H 6 O 2 outperformed a γ A l 2 O 3 - H 2 O nanofluid in terms of heat transfer rate. The source of zero skin friction may be observed to move to the left or right depending on the balance of obliqueness and straining motion at point x s . The computed numerical results of the current research correspond well with those accessible in the literature for the limiting scenario.

In Vitro Antidiabetic, Antioxidant, and Prebiotic Activities of the Chemical Compounds Isolated from Guizotia abyssinica.

India and Ethiopia employ Guizotia abyssinica (niger plant) as a source of edible vegetable oil. Previous studies have documented the niger plant's antioxidant properties and dietary benefits. Here, G. abyssinica extract was obtained and ten known bioactive components (1-10) were isolated. The antioxidant, antidiabetic, and prebiotic properties of whole extract and isolated components of niger and the plant's ability to cooperate symbiotically with probiotic strains were examined. Compound 10, myricetin-3-O-L-rhamnoside, had the highest antioxidant capacity measured in the 2,2-diphenylpicrylhydrazyl (DPPH, 4629.76 ± 6.02 µmol Trolox equivalent/g compound) and ferric-reducing antioxidant power (FRAP, 2667.62 ± 7.5 mol Trolox equivalent/g compound) assays. The lowest α-amylase and glycogen phosphorylase activities and glucose diffusion were obtained with whole G. abyssinica extracts, whereas compounds 8-10 had moderate inhibitory effects. G. abyssinica extract also induced the highest glucose absorption by yeast cells in the presence of 5 mM of glucose. Moreover, Lactobacillus plantarum and L. rhamnosus incubated with ß-sitosterol 3-O-D-glucoside (compound 7) showed the highest prebiotic activity score. The levels of L-(+)-lactic acid isomer in the probiotic strains were the highest in presence of the whole extract and decreased progressively in the presence of flavonoid glycosides (compounds 8-10) and ß-sitosterol 3-O-D-glucoside. The enzymatic profile of the probiotic strains was unaffected by the niger extract and compounds 7-10. The findings revealed that the biological activities of G. abyssinica extract are mediated by the compounds 1-10, and it may be considered as a promising plant for the treatment of diabetes mellitus.

Effect of some plant extracts from Egyptian herbal plants against Toxoplasma gondii tachyzoites in vitro.

Nowadays, herbal extracts are considered to be a potential source for developing new drugs that will overcome resistance to conventional chemotherapeutic agents. This study was aimed to explore the efficacy of several Egyptian plant extracts against Toxoplasma gondii infection in vitro for future development of a new, safe, and effective compound for T. gondii. Methanol extracts from Matricaria chamomilla (German chamomile), Laurus nobilis, Citrullus colocynthis, Cinnamum camphora, Boswellia scara, and Melissa officionalis plants and oil extracts (either essential or fixed oils) of some plants such as: lemon grass (Cymbopogon citratus), marjoram (Origanum majorana), watercress (Nasturtium officionale), wheat germ (Triticum aestivum), sesame (Sesamum indicum), rosemary (Salvia rosmarinus), citronella (Cymbopogon nardus), clove (Syzygum aromaticum), jojoba (Simmondsia chinesis), and basil (Ocimum basilicum) were investigated for their anti-Toxoplasma activities. The methanol extracts from C. colocynthis and L. nobilis and the oil extracts from lemon grass and marjoram were active against T. gondii with half maximal inhibitory concentrations (IC50) of 22.86 µg/ml, 31.35 µg/ml, 4.6 µg/ml, and 26.24 µg/ml, respectively. Their selectivity index (SI) values were <10. Interestingly, the methanol extract from M. chamomilla and oil from citronella had the lowest IC50 values for T. gondii (3.56 µg/ml and 2.54 µg/ml, respectively) and the highest SI values (130.33 and 15.02, respectively). In conclusion, methanol extract from M. chamomilla and oil from citronella might be potential sources of novel therapies for treating toxoplasmosis.

Could Araucaria heterophylla resin extract be used as a new treatment for toxoplasmosis?

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC50 = 3.90) and CUP (EC50 = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC50 = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis.

Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life.

Significance of Anti-C1q Antibodies in Patients with Systemic Lupus Erythematosus as A Marker of Disease Activity and Lupus Nephritis.

Anti-C1q autoantibodies have been proposed as a useful marker in SLE. This study aimed at measuring serum levels of anti-C1q antibodies in patients with SLE and investigates correlations of this level with the histopathological classes of renal biopsies and disease activity. The anti-C1q antibody level was measured in 30 females SLE patients and 20 controls. The activity of SLE disease was calculated according to the SLE disease activity index. A renal biopsy from patients with clinical manifestations of renal disease was obtained. There was a significant increase in the level of anti-C1q antibodies in SLE patients than controls and in patients with active LN than inactive LN (P<0.05). There were significant positive correlations between anti-C1q antibody level and SLEDAI & rSLEDAI scores and activity index score of renal biopsies. Anti-C1q antibodies showed higher diagnostic sensitivity and specificity than anti-dsDNA antibodies. In conclusion, anti-C1q antibodies are useful and sensitive non-invasive biomarker with high specificity in combination with anti-dsDNA antibodies for the diagnosis of renal disease activity.