Antioxidant and Anti-Aging Phytoconstituents from Faucaria tuberculosa: In Vitro and In Silico Studies.

Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of Faucaria tuberculosa. Phytochemical investigation of F. tuberculosa extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2→1',4→2')-phloroglucinol (4). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2→1',4→2') phloroglucinol (4) and phloroglucinol (1) for their remarkable antioxidant activity, while isorhamnetin 3-O-rutinoside (3) and 3,5-dihydroxyphenyl ß-D-glucopyranoside (2) achieved the most potent inhibitory activity against tyrosinase (IC50 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC50 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC50 = 65.21 ± 0.47 µM) and luteolin, (IC50 = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds (3 and 2) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.

Clinical Association of a Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Patients with Systemic Lupus Erythematosus.

A triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily with an established role in innate and adaptive immune response. We aimed to determine the plasma concentrations and clinical association of sTREM-1 in Systemic Lupus Erythematosus (SLE) patients. Plasma from 79 SLE patients and 35 normal healthy subjects were assayed for sTREM-1 and IL-6 levels using Enzyme Linked Immunosorbant Assay (ELISA). The clinical disease characteristics and serological data were prospectively assessed. Disease activity was scored using the SLE disease activity index. We detected significantly higher levels of sTREM-1 in plasma of SLE patients than the healthy control group. We also detected high sTREM-1 levels in subgroups of patients with neuropsychiatric manifestations (NPLE) and patients with the total high disease activity and NPLE activity. In addition, sTREM-l levels were significantly correlated with parameters of disease activity, i.e. SLEDAI score, IL-6, hypoalbuminemia. On the other hand, we did not find significant differences in sTREM-1 levels in relation to age, disease duration, medications, ESR, other organ system involvement, or the presence of anti-dsDNA. Our preliminary data indicated that sTREM-1 levels may be an additional useful marker of disease activity in SLE. It also highlights its importance in patients with NPLE. An additional prospective longitudinal study should be carried out to support these findings.

Expression of concern: The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Expression of concern for 'The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches' by Abeer H. Elmaidomy et al., RSC Adv., 2022, 12, 11769-11785, https://doi.org/10.1039/D2RA01340A.

Phytochemical investigation and anti-inflammatory potential of Atriplex leucoclada Boiss.

BACKGROUND: The plant kingdom has long been considered a valuable source for therapeutic agents, however, some plant species still untapped and need to be phytochemically and biologically explored. Although several Atriplex species have been investigated in depth, A. leucoclada, a halophytic plant native to Saudi Arabian desert, remains to be explored for its phytochemical content and biological potentials. Herein, the current study investigated the metabolic content and the anti-inflammatory potential of A. leucoclada. METHODS: Powdered aerial parts of the plant were defatted with n-hexane then the defatted powder was extracted with 80% methanol. n-Hexane extract (ATH) was analyzed using GC-MS, while the defatted extract (ATD) was subjected to different chromatographic methods to isolate the major phytoconstituents. The structures of the purified compounds were elucidated using different spectroscopic methods including advanced NMR techniques. Anti-inflammatory activity of both extracts against COX-1 and COX-2 enzymes were examined in vitro. Molecular docking of the identified compounds into the active sites of COX-1 and COX-2 enzymes was conducted using pdb entries 6Y3C and 5IKV, respectively. RESULTS: Phytochemical investigation of ATD extract led to purification and identification of nine compounds. Interestingly, all the compounds, except for 20-hydroxy ecdysone (1), are reported for the first time from A. leucoclada, also luteolin (6) and pallidol (8) are isolated for the first time from genus Atriplex. Inhibitory activity of ATD and ATH extracts against COX-1 and COX-2 enzymes revealed concentration dependent activity of both fractions with IC50 41.22, 14.40 µg/ml for ATD and 16.74 and 5.96 µg/ml for ATH against COX-1 and COX-2, respectively. Both extracts displayed selectivity indices of 2.86 and 2.80, respectively as compared to 2.56 for Ibuprofen indicating a promising selectivity towards COX-2. Molecular docking study supported in vitro testing results, where purified metabolites showed binding affinity scores ranged from -9 to -6.4 and -8.5 to -6.6 kcal/mol for COX-1 and 2, respectively, in addition the binding energies of GC-MS detected compounds ranged from -8.9 to -5.5 and -8.3 to -5.1 kcal/mol for COX-1 and 2, respectively as compared to Ibuprofen (-6.9 and -7.5 kcal/mol, respectively), indicating high binding affinities of most of the compounds. Analysis of the binding orientations revealed variable binding patterns depending on the nature of the compounds. Our study suggested A. leucoclada as a generous source for anti-inflammatory agents.

Cardiac calcium score in systemic sclerosis.

Cardiac coronary Ca score (CCS), and extra coronary Ca score (ECCS) estimation in asymptomatic systemic sclerosis (SSc) patients and their relation to different disease and patients' variables. The CCS and ECCS were estimated in asymptomatic 20 SSc patients compared to 20 age and sex-matched healthy control using non-contrast cardiac computed tomography. All were applied for cardiac history taking, examination, echocardiography, body mass index (BMI), complete blood picture, erythrocyte sedimentation rate, and lipid profile estimation. The SSc patients were 11 females and 9 males with a mean age of (42.55 ± 9.145) and mean disease duration (12.9 ± 6.774). CCS was reported in 9 (45%) SSc cases and 2 (10%) of the control; (p = 0.013) and was significantly greater in SSc patients (58.4 ± 175.443) than in the control group (0.7 ± 2.25); (p = 0.01). The ECCS was significantly higher in SSc cases (194.45 ± 586.511) than control group (2.8 ± 7.8); (p = 0.001) and reported in 16 (80%) SSc cases and 3 (15%) of controls; (p = 0.000). Limited scleroderma cases had higher scores than diffuse type. Patients with total ca score (> 100) were older (p = 0.016), had longer disease duration (p = 0.001) and greater BMI (p = 0.002). Significant correlation was found between the log-transformed CCS and disease duration, age, BMI, left ventricular mass, and mass index. Systemic sclerosis patients are at increased risk of subclinical cardiovascular disease determined by cardiac Ca scoring as a noninvasive and reliable method. Extra coronary calcification may be an earlier indicator for this. Disease duration is a determinant risk factor for cardiac calcification in SSc. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • Systemic sclerosis patients are at high risk of accelerated atherosclerosis and cardiovascular diseases. Coronary atherosclerosis was previously estimated in SSc patients through coronary angiography. A novel method of assessing coronary artery disease is the coronary calcium score, as determined by multidetector computed tomography, it measures coronary artery calcification that occurs in atherosclerotic plaque. In this study, the cardiac coronary and extra coronary Ca score were evaluated in relation to disease characteristics in asymptomatic SSC patients for early detection of coronary artery disease.

The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Tamarindus indica Linn. (Tamarind, F. Fabaceae) is one of the most widely consumed fruits in the world. A crude extract and different fractions of T. indica (using n-hexane, dichloromethane, ethyl acetate, and n-butanol) were evaluated in vitro with respect to their DPPH scavenging and AchE inhibition activities. The results showed that the dichloromethane and ethyl acetate fractions showed the highest antioxidant activities, with 84.78 and 86.96% DPPH scavenging at 0.10 µg mL-1. The n-hexane, dichloromethane, and ethyl acetate fractions inhibited AchE activity in a dose-dependent manner, and the n-hexane fraction showed the highest inhibition at 20 µg mL-1. The results were confirmed by using n-hexane, dichloromethane, and ethyl acetate fractions in vivo to regress the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. Phytochemical investigations of those three fractions afforded two new diphenyl ether derivative compounds 1-2, along with five known ones (3-7). The structures of the isolated compounds were confirmed via 1D and 2D NMR and HRESIMS analyses. The isolated compounds were subjected to extensive in silico-based investigations to putatively highlight the most probable compounds responsible for the anti-Alzheimer activity of T. indica. Inverse docking studies followed by molecular dynamics simulation (MDS) and binding free energy (ΔG) investigations suggested that both compounds 1 and 2 could be promising AchE inhibitors. The results presented in this study may provide potential dietary supplements for the management of Alzheimer's disease.

Four new phenolics and antiparasitic secondary metabolites from Flacourtia rukam Zoll. & Mortizi.

Phytochemical investigation of Flacourtia rukam Zoll. & Mortizi (F. rukam) leaves and bark led to the isolation and characterization of seventeen compounds of which four phenolics were not previously described; 2-[(benzoyloxy)methyl]-phenyl-O-ß-xylosyl-(1→2)-ß-glucopyranoside (1), 2-[(benzoyloxy)methyl]-4-hydroxyphenyl-O-ß-xylosyl-(1→2)-ß-D-glucopyranoside (2), 2-hydroxy-5-(2-hydroxyphenoxy)phenoxy-ß-glucopyranoside (3) and biphenyl-1,1',2,2'-tetraol (5). Interestingly, the later compound is known as a synthetic but this is the first report for its isolation from nature. Chemical structures were established using extensive analysis of spectroscopic data (1 D and 2 D NMR and HRESIMS). Biphenyl-1,1,2,2'-tetrol (5) exhibited a good activity against Trypanosoma brucei trypomastigotes with IC50= 6.66 ug/mL. Compounds 2, 5, 9, 10, 11 and 12 showed a good in-vitro anti-inflammatory activity using proteinase inhibitory assay. On the contrary, all tested compounds were inactive as antileishmanial or antimalarial.

Clinical Features and Disease Damage Risk Factors in an Egyptian SLE Cohort: A Multicenter Study.

BACKGROUND: Systemic lupus erythematosus (SLE) has a variable natural history and clinical characteristics. OBJECTIVES: This study aims to evaluate the clinical and immunological characteristics, and assess the disease accrual of an Egyptian SLE cohort. METHODS: The study included 569 SLE patients who were collected from three different centers; demographic, laboratory data, cumulative manifestations, and comorbidities were assessed (characteristics at the time of diagnosis were recorded retrospectively, while current clinical data were recorded cross-sectionally). Evaluation of disease activity was done using Systemic Lupus Erythematosus Disease Activity Index score (SLEDAI) and damage by Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: The median age of patients at disease onset was 25.0±10.5 years, the median disease duration was 4.0 (6.5) years, the female to male ratio was (12.5:1), and the median SLEDAI was 12.0±14.0. Family history of SLE was noticed in 4%. Antinuclear antibody was positive in all patients and 86% had positive anti-double-stranded DNA. Arthritis/arthralgia was the most frequent presenting symptom (44%) followed by fever (39%). Along the disease course; alopecia was the most common clinical manifestation (76.1%), followed by constitutional symptoms (75.9%), and nephritis (65.7%). Three hundred and five patients encountered organ damage (SDI >1); kidney damage was the most frequent (32%), followed by cardiovascular damage (24.3%). Neutropenia, hypocomplementemia, arthritis, hypertension, longer disease duration, and higher disease activity were found to be independent risk factors for disease damage. CONCLUSIONS: There are some diversities and similarities in our findings compared to the previously reported data. Arthritis is the most common presenting symptom, while alopecia is the most frequent clinical finding, and a higher prevalence of nephritis was reported. Renal damage is the most frequent outcome.

Interleukin-17A biomarker as a predictor for detection of early axial spondyloarthritis changes in patients with psoriasis.

AIM: Although the pathogenic mechanisms of psoriatic arthritis (PsA) are not completely clarified, evidence suggests that interleukin 17A (IL-17A)-mediated immune responses play a pivotal role in the disease. This is best underscored by the important clinical effectiveness of IL-17A inhibitors in psoriasis treatment. We aim to investigate the predictive value of IL-17A in detecting the early axial spondyloarthropic (SpA) changes in psoriatic patients. METHODS: The study enrolled 100 patients with psoriasis, classified into group 1, included 62 patients with only psoriatic skin lesions (Ps), and group 2 included 38 patients with PsA, and 100 age and gender matched healthy volunteers. All participants were subjected to general and local clinical examination, laboratory assessment including IL-17A in the serum by means of enzyme-linked immunosorbent assay, and axial joint radiological assessment. RESULTS: Our study included 60 males (60%) and 40 females (40%).The positive radiological findings of early axial SpA changes were found among 30.6% of the Ps group and among 84.2% of the PsA group. There were significant differences between patients with positive magnetic resonance imaging (MRI) findings of early axial SpA and patients with negative MRI findings in both groups regarding IL-17A levels. There was a significant association between IL-17A level and early axial SpA changes in psoriatic patients with a clear cutoff point (222.5). CONCLUSION: Our study can imply that IL-17A is a valuable, useful and low-cost biomarker in detecting early axial SpA changes in asymptomatic and nonradiographic axial SpA (nr-axial SpA) psoriatic patients that helps early management and prevent progressive axial involvement and disabilities.

Value of Albumin-Fibrinogen Ratio and CRP-Albumin Ratio as Predictor Marker of Disease Activity in Egyptian RA Patients, Correlated with Musculoskeletal Sonography.

PURPOSE: To evaluate the albumin-fibrinogen ratio (AFR) and C-reactive protein-albumin ratio (CAR) as inflammatory markers in rheumatoid arthritis (RA) and to investigate their association with disease activity correlating with musculoskeletal ultrasonographic findings. PATIENTS AND METHODS: A total of 125 cases of RA patients were consecutively enrolled in a multicenter cross-sectional study compared to 100 healthy controls, all subjects were investigated for fibrinogen, albumin, CRP, erythrocyte sedimentation rate, AFR, and CAR measurements. Patients' disease activity was assessed by disease activity score (DAS28-ESR), and they were subjected to high-frequency ultrasound both in greyscale and power Doppler. RESULTS: RA patients had lower AFR and higher CAR than those in the control group (P < 0.001). A positive correlation was demonstrated between CAR and DAS score (r=0.589, P = 0.0001), whilst there was a precise negative correlation between AFR and DAS 28-ESR (r=-0.74, p<0.001). ROC curve analyses revealed fibrinogen showed the best sensitivity (92.1%) for the area under the curve of 0.928, at a criterion of 2.47, while AFR has an area under the curve of 0.826 with sensitivity and specificity (86.84% and 75%, respectively) at cut-off value 1.46. Actively diseased patients had elevated CAR than those in remission (P < 0.001). Patients with synovial thickening and bone erosions had lower AFR than those without, CAR was higher in patients with power doppler changes than those without (p=0.015). CONCLUSION: Higher CAR and lower AFR were expressed in active RA than those in remission. CAR and AFR could be useful markers of ongoing inflammation and joint affection detected by musculoskeletal ultrasonography.

Comparative DNA profiling, phytochemical investigation, and biological evaluation of two Ficus species growing in Egypt.

AIM AND BACKGROUND: A comparison between two Ficus species, cultivated in Egypt, was carried out in this study. Their DNA analysis revealed that they are not closely related. MATERIALS AND METHODS: The pharmacopoeial constants of the leaves showed higher total ash and acid insoluble ash in F. lyrata than in F. platypoda. The other parameters were close in both species. Preliminary phytochemical screening revealed the presence of carbohydrate and/or glycosides, tannins, flavonoids, sterols, and triterpenes in their leaves and was detected in traces in their stems. RESULTS: Saponification of n-hexane extract of the leaves yielded 46% and 74.8% for the unsaponifiable matters and 20% and 15% for the fatty acids for F. platypoda and F. lyrata, respectively. n-Docosane (21.69%) and n-heptacosane (33.77%) were the major hydrocarbons in F. platypoda and F. lyrata, respectively. b-Sitosterol was the main sterol, palmitic (22.07%) and carboceric (35.72%) acids were the major identified saturated fatty acids in both species, while linoleic acid was the main unsaturated fatty acid (18.66% and 16.7%) in both species, respectively. The acute toxicity study revealed that the two species were safe up to 2 g/kg. The antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and pyrogallol as the standard was more significant for F. platypoda (232.6 µg/ml) than for F. lyrata, (790.9 µg/ml). The oral antihyperglycemic activity in diabetic rats using alloxan revealed that the 80% ethanolic extract of the leaves of F. platypoda was more active than that of the leaves of F. lyrata in decreasing the blood glucose level at 200 mg/kg/day (107.9 ± 5.817, 127.2 ± 4.359) and 400 mg/kg/day (64.11 ± 4.358, 127.7 ± 6.889), respectively, when compared with the diabetic control gliclazide (172.3 ± 2.089). CONCLUSION: The results of this study provide evidence that the two Ficus species have antioxidant and antihyperglycemic activity, in the order F. platypoda and then F. lyrata.