Exploring Sorbus torminalis Leaves: Unveiling a Promising Natural Resource for Diverse Chemical and Biological Applications.

Sorbus torminalis (L.) Crantz has a rich history of versatile applications spanning the fields of medicine and nutrition. It is noteworthy that the decoction obtained from S. torminalis leaves is a traditional treatment method against both diabetes and stomach disorders. Phytochemical profiling determined by HPLC/MS-MS. The effects of the extracts on cell viability were investigated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method against MDA-MB-231 cell line (human breast adenocarcinoma).The ethanol/water extract contained more concentration of total phenolic (91.41 mg gallic acid (GAE) equivalent /gr) and flavanoid (29.10 mg rutin (RE) equivalent/gr) in the tested extract (p<0.05). Resulting of HPLC analysis, the chemical constituents varied depending on the solvents and chlorogenic acid, hyperoside, isoquercetin, delphindin-3,5-diglucoside, procyanidin B2, epicatechin, neochlorogenic acid, 3,5-dicaffeoylquinic acid were identified in all extracts. Overall, ethanol, n-hexane and ethyl acetate extracts showed the highest inhibition for the tyrosinase enzyme. The effect of leaf extracts of S. torminalis on antimicrobial, biofilm inhibitory, and anticancer activities was examined. Based on outcomes of our study recognize this plant as a critical source of medically active chemicals for feasible phytopharmaceutical and nutraceutical applications, providing the first scientific insight into the detailed biological and chemical profiles of S. torminalis.

Cardiac Assessment in Children with MIS-C: Late Magnetic Resonance Imaging Features.

Multisystem Inflammatory Syndrome (MIS-C) is a new entity that emerges 2-4 weeks after the SARS-CoV-2 infection in children. MIS-C can affect all systems, the most severe of which is cardiac involvement. The duration of the cardiac symptoms is still uncertain and may be persistent or prolonged. The American College of Rheumatology Clinical Guidelines recommends cardiac magnetic resonance imaging (MRI) 2-6 months after the diagnosis of MIS-C in patients presenting with significant transient left ventricular (LV) dysfunction in the acute phase of illness (LV ejection fraction 50%) or persistent LV dysfunction. There are a few studies investigating cardiac MRI findings in MIS-C patients. In this study, we aimed to evaluate cardiac MRI findings, at the earliest 3 months after diagnosis, and compare these findings with the echocardiograms in children with MIS-C. A retrospective study including 34 MIS-C patients was conducted at a tertiary-level University Hospital between June 2020 and July 2021. Centers for Disease Control and Prevention criteria were used in the diagnosis of MIS-C. Cardiac MRI was performed at least 3 months after MIS-C diagnosis. The study included 17 (50%) boys and 17 (50%) girls with a mean age of 9.31 ± 4.72 years. Initial echocardiographic evaluation revealed cardiac abnormality in 13 (38.2) patients; 4 (11.8%) pericardial effusion, 4 (11.8%) left ventricular ejection fraction (LVEF) < 55%, and 5 (14.7%) coronary artery dilatation. Echocardiography showed normal LV systolic function in all patients during follow-up; coronary dilatation persisted in 2 of 5 (40%) patients at the 6th-month visit. Cardiac MRI was performed in 31 (91.2%) patients, and myocardial hyperemia was not detected in any patients (T1 relaxation time was < 1044 ms in all children). However, 9 (29%) patients' MRI showed isolated elevated T2 levels, and 19 (61.3%) revealed at least one of the following findings: pericardial effusion, right ventricular dysfunction, or LVEF abnormality. In patients with MIS-C, a high rate of cardiac involvement, particularly pericardial effusion was determined by cardiac MRI performed at the earliest 2-6 months after diagnosis. Even if echocardiography does not reveal any abnormality in the initial phase, cardiac MRI should be suggested in MIS-C patients in the late period. This is the first study reporting cardiac MRI findings in the late period of MIS-C patients.

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches.

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.

Clinical and Laboratory Findings of SARS-CoV-2 Infection in Children Younger than 6 Months Old: Neutropenia is More Common Not Lymphopenia.

BACKGROUND: Studies on age-related differences in clinical and laboratory features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We aimed to evaluate the demographic, clinical, laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. METHODS: A single-center retrospective study, including 209 confirmed SARS-CoV-2 infection cases, was conducted between 11 March 2020 and 1 September 2021. The case group consisted of 47 patients younger than 6 months old, whereas the control group consisted of 162 patients older than 6 months old. RESULTS: The mean age of the case group was 2.77 ± 1.52 months, and the control group was 101.89 ± 65.77 months. Cough was statistically higher in the control group, and poor feeding was higher in the case group (p = 0.043, 0.010). The underlying disease rate was statistically higher in the control group; however, the hospitalization rate was higher in the case group (p = 0.036, 0.001). The case group had significantly lower median values of the absolute neutrophil count, hemoglobin and higher median values of white blood cell, absolute lymphocyte count and platelet than the control group (p < 0.05). C-reactive protein, fibrinogen values were significantly lower, and procalcitonin, D-dimer, troponin T, N-terminal pro-B-type natriuretic peptide significantly higher in the case group (p < 0.05). Lymphopenia was more common in the control group, whereas neutropenia was more common in the case group (p = 0.001, 0.011). CONCLUSIONS: We showed that most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher, and neutropenia was more common in older children. Lay summaryStudies on age-related differences in clinical and laboratory features on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients are limited. We aimed to evaluate the demographic, clinical and laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. A single-center retrospective study was conducted, including 209 SARS-CoV-2 infection cases. The case group consisted of 47 patients younger than 6 months old, and the control group consisted of 162 patients older than 6 months old. Most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher than older children. Neutropenia was more common in patients younger than 6 months than older children with SARS-CoV-2 infection, even if underlying diseases were excluded.

Phenolic Profile, Antioxidant and Enzyme Inhibitory Activities of Leaves from Two Cassia and Two Senna Species.

Several species within the genera Cassia or Senna have a treasure of traditional medicines worldwide and can be a promising source of bioactive molecules. The objective of the present study was to evaluate the phenolic content and antioxidant and enzyme inhibition activities of leaf methanolic extracts of C. fistula L., C. grandis L., S. alexandrina Mill., and S. italica Mill. The two Cassia spp. contained higher total polyphenolic content (42.23-49.75 mg GAE/g) than the two Senna spp., and C. fistula had significantly (p ˂ 0.05) the highest concentration. On the other hand, the Senna spp. showed higher total flavonoid content (41.47-59.24 mg rutin equivalent per g of extract) than that found in the two Cassia spp., and S. alexandrina significantly (p ˂ 0.05) accumulated the highest amount. HPLC-MS/MS analysis of 38 selected bioactive compounds showed that the majority of compounds were identified in the four species, but with sharp variations in their concentrations. C. fistula was dominated by epicatechin (8928.75 µg/g), C. grandis by kaempferol-3-glucoside (47,360.04 µg/g), while rutin was the major compound in S. italica (17,285.02 µg/g) and S. alexandrina (6381.85). The methanolic extracts of the two Cassia species exerted significantly (p ˂ 0.05) higher antiradical activity, metal reducing capacity, and total antioxidant activity than that recorded from the two Senna species' methanolic extracts, and C. fistula displayed significantly (p ˂ 0.05) the highest values. C. grandis significantly (p ˂ 0.05) exhibited the highest metal chelating power. The results of the enzyme inhibition activity showed that the four species possessed anti-AChE activity, and the highest value, but not significantly (p ≥ 0.05) different from those obtained by the two Cassia spp., was exerted by S. alexandrina. The Cassia spp. exhibited significantly (p ˂ 0.05) higher anti-BChE and anti-Tyr properties than the Senna spp., and C. grandise revealed significantly (p ˂ 0.05) the highest values. C. grandise revealed significantly (p ˂ 0.05) the highest α- amylase inhibition, while the four species had more or less the same effect against the α-glucosidase enzyme. Multivariate analysis and in silico studies showed that many of the identified phenols may play key roles as antioxidant and enzyme inhibitory properties. Thus, these Cassia and Senna species could be a promising source of natural bioactive agents with beneficial effects for human health.

New Biological and Chemical Evidences of Two Lamiaceae Species (Thymbra capitata and Thymus sipyleus subsp. rosulans): In Vitro, In Silico and Ex Vivo Approaches.

In this study, the methanolic and infusion extracts of two species, Thymbra capitata and Thymus sipyleus subsp. rosulans, were tested for their chemical composition and biological abilities (antioxidant, enzyme inhibitory and anti-inflammatory effects). The extracts yielded total phenolic and flavonoid contents in the range of 83.43-127.52 mg GAE/g and 9.41-46.34 mg RE/g, respectively. HPLC analysis revealed rosmarinic acid to be a major component of the studied extracts (15.85-26.43%). The best ABTS radical scavenging ability was observed in the methanol extract of T. capitata with 379.11 mg TE/g, followed by in the methanol extract of T. sipylus (360.93 mg TE/g). In the CUPRAC assay, the highest reducing ability was also found in the methanol extract of T. capitata with 802.22 mg TE/g. The phosphomolybdenum ability ranged from 2.39 to 3.61 mmol TE/g. In terms of tyrosinase inhibitory effects, the tested methanol extracts (83.18-89.66 mg KAE/g) were higher than the tested water extracts (18.74-19.11 mg KAE/g). Regarding the BChE inhibitory effects, the methanol extracts were active on the enzyme while the water extracts showed no inhibitory effect on it. Overall, the methanolic extracts showed better enzyme inhibition compared to the infusion extracts. Molecular docking also showed the selected exhibited potential binding affinities with all enzymes, with a preference for cholinesterases. Additionally, the extracts were effective in attenuating the LPS-induced increase in COX-2 and IL-6 gene expression in isolated colon, thus indicating promising anti-inflammatory effects. The preliminary results of this study suggest that these species are good natural sources of antioxidants and also provide some scope as enzyme inhibitors, most likely due to their bioactive contents such as phenolic acids, and thus can be exploited for different applications related to health promotion and disease prevention.

Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in pregnant women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with a higher risk of complications in pregnancy. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated in numerous inflammatory diseases. We evaluated the possible role of these markers in SLE pregnancies. Forty-six pregnant patients with an already established diagnosis of SLE were included in the study. Complete blood counts were obtained upon admission for delivery. Seven patients were diagnosed with a flare and managed with multiple medications, whereas rest of the patients were not on any treatment or managed with monotherapy. NLR and PLR values were also evaluated between two groups and no statistically significant difference was found (p=.44 and p=.80, respectively). This study is the first to evaluate the possible role of NLR and PLR in pregnant SLE patients in the literature. Further studies are warranted for an elaborate evaluation of NLR and PLR in lupus pregnancies.Impact StatementWhat is already known on this subject? Pregnancy in the setting of SLE is associated with a higher risk of complications. Active disease increases the risk of adverse outcomes further.What the results of this study add? This study is the first to evaluate NLR and PLR in pregnancies complicated by SLE. No significant association between the course of the disease in pregnancy and NLR/PLR was documented.What the implications are of these findings for clinical practice and/or further research? Further studies on the markers to predict prognosis of SLE in pregnancy are required to improve the maternal and neonatal outcomes in this exclusive group of high-risk patients.

Phytochemical profile, enzyme inhibition activity and molecular docking analysis of Feijoa sellowiana O. Berg.

Feijoa sellowiana leaves and fruits have been investigated as a source of diverse bioactive metabolites. Extract and eight metabolites isolated from F. sellowiana leaves were evaluated for their enzymatic inhibitory activity against α-glucosidase, amylase, tyrosinase, acetylcholinestrerase and butyrylcholinesterase both in vitro and in silico. Feijoa leaves' extract showed strong antioxidant activity and variable levels of inhibitions against target enzymes with a strong anti-tyrosinase activity (115.85 mg Kojic acid equivalent/g). Additionally, α-tocopherol emerged as a potent inhibitor of AChE and BChE (5.40 & 10.38 mmol galantamine equivalent/g, respectively). Which was further investigated through molecular docking and found to develop key enzymatic interactions in AChE and BChE active sites. Also, primetin showed good anti BChE (11.70 mmol galantamine equivalent/g) and anti-tyrosinase inhibition (90.06 mmol Kojic acid equivalent/g) which was also investigated by molecular docking studies. Highlights Isolation of eight bioactive constituents from Feijoa sellowiana leaves. In vitro assays using different enzymatic drug targets were investigated. In silico study was performed to define compound interactions with target proteins. Feijoa leaf is an excellent source of anti-AChE and antityrosinase bioactives.

Phytochemical Investigations and In Vitro Bioactivity Screening on Melia azedarach L. Leaves Extract from Nepal.

Melia azedarach is a common tree used in the traditional medicine of Nepal. In this work, leaves were considered as source of bioactive constituents and composition of methanol extract was evaluated and compared with starting plant material. Flavonoid glycosides and limonoids were identified and quantified by HPLC-DAD-MSn approaches in dried leaves and methanolic extract, while HPLC-APCI-MSn and GC/MS analysis were used to study phytosterol and lipid compositions. ß-Sitosterol and rutin were the most abundant constituents. HPLC-APCI-MSn and HPLC-DAD-MSn analysis revealed high levels of phytosterols and flavonoids in methanolic extract accounting 9.6 and 7.5 % on the dried weight, respectively. On the other hand, HPLC/MSn data revealed that limonoid constituents were in minor amount in the extract <0.1 %, compared with leaves (0.7 %) indicating that degradation occurred during extraction or concentration procedures. The methanol extract was subjected to different bioassays, and antioxidant activity was evaluated. Limited inhibitory activity on acetyl and butyryl cholinesterase, as well as on amylase were detected. Moreover, tyrosinase inhibition was significant resulting in 131.57±0.51 mg kojic acid equivalents/g of dried methanol extract, suggesting possible use of this M. azedarach extract in skin hyperpigmentation conditions. Moderate cytotoxic activity, with IC50 of 26.4 µg/mL was observed against human ovarian cancer cell lines (2008 cells). Our findings indicate that the Nepalese M. azedarach leaves can be considered as valuable starting material for the extraction of phenolics and phytosterols, yielding extracts with possible cosmetic and pharmaceutical applications.

Biological Insights and NMR Metabolic Profiling of Different Extracts of Spermacoce verticillata (L.) G. Mey.

Spermacoce verticillata (L.) G. Mey. is commonly used in the folk medicine by various cultures to manage common diseases. Herein, the chemical and biological profiles of S. verticillata were studied in order to provide a comprehensive characterization of bioactive compounds and also to highlight the therapeutic properties. The in vitro antioxidant activity using free-radical scavenging, phosphomolybdenum, ferrous-ion chelating and reducing power assays, and the inhibitory activity against key enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase of S. verticillata extracts (dichloromethane, ethyl acetate, methanol and water) were investigated. The highest total phenolic and flavonoid content were observed in the methanolic and aqueous extracts. Exhaustive 2DNMR investigation has revealed the presence of rutin, ursolic and oleanoic acids. The methanolic extract, followed by aqueous extract have showed remarkable free radical quenching and reducing ability, while the dichloromethane extract was the best source of metal chelators. The tested extracts showed notable inhibitory activity against cholinesterases (AChE: 1.63-4.99 mg GALAE/g extract and BChE: 12.40-15.48 mg GALAE/g extract) and tyrosinase (60.85-159.64 mg KAE/g extract). No inhibitory activity was displayed by ethyl acetate and aqueous extracts against BChE and tyrosinase, respectively. All the tested extracts showed modest α-amylase inhibitory activity, while only the ethyl acetate and aqueous extracts were potent against α-glycosidase. This study further validates the use of S. verticillata in the traditional medicine, while advocating for further investigation for phytomedicine development.

Chemical Composition and Pharmacological Evaluation and of Toddalia asiatica (Rutaceae) Extracts and Essential Oil by in Vitro and in Silico Approaches.

Toddalia asiatica (L.) Lam. is extensively used in traditional medicinal systems by various cultures. Despite its frequent use in traditional medicine, there is still a paucity of scientific information on T. asiatica growing on the tropical island of Mauritius. Therefore, the present study was designed to appraise the pharmacological and phytochemical profile of extracts (methanol, ethyl acetate and water) and essential oil obtained from aerial parts of T. asiatica. Biological investigation involved the evaluation of in vitro antioxidant and enzyme inhibitory potentials. The chemical profile of the EO was determined using gas chromatography coupled to mass spectrometry (GC/MS) analysis, while for the extracts, the total phenolic (TPC) and flavonoid content were quantified as well as their individual phenolic compounds by LC/MS/MS. Quinic acid, fumaric acid, chlorogenic acid, quercitrin and isoquercitrin were the main compounds in the extracts. Highest total phenolic (82.5±0.94 mg gallic acid equivalent (GAE/g)) and flavonoid (43.8±0.31 mg rutin equivalent (RE/g)) content were observed for the methanol extract. The GC/MS analysis has shown the presence of 26 compounds with linalool (30.9 %), linalyl acetate (20.9 %) and ß-phellandrene (7.9 %) being most abundant components in the EO. The extracts and EO showed notable antioxidant properties, with the methanol extract proved to be superior source of antioxidant compounds. Noteworthy anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BChE) effects were recorded for the tested samples, while only the methanol and ethyl acetate extracts were active against tyrosinase. With respect to antidiabetic effects, the extracts and EO were potent inhibitors of α-glucosidase, while modest activity was recorded against α-amylase. Docking results showed that linalyl acetate has the highest affinity to interact with the active site of BChE with docking score of -6.25 kcal/mol. The findings amassed herein act as a stimulus for further investigations of this plant as a potential source of bioactive compounds which can be exploited as phyto-therapeutics.

Two Medicinal Plants (Alkanna trichophila and Convolvulus galaticus) from Turkey: Chemical Characterization and Biological Perspectives.

The aim of the present study was to quantify selected phenolic compounds, determine antioxidant activity and enzyme inhibitory effects of the aerial parts of Alkanna trichophylla Hub.-Mor. (A. trichophylla) and Convolvulus galaticus Rost.ex Choisy (C. galaticus) extracts prepared by homogenizer-assisted extraction (HAE), maceration (MAC) and infusion techniques. This is the first time such study has been designed to validate the phytochemical composition and bioactivity of these plants. Multivariate analysis was conducted on collected data. Rutin and caffeoylquinic acid derivatives were the most significant compounds in A. trichophylla and C. galaticus, respectively. The highest antioxidant activity of A. trichophylla was mostly exhibited by HAE/methanolic extracts as determined by DPPH, ABTS, FRAP (51.39, 112.70 and 145.73 mg TE/g, respectively) and phosphomolybdenum (2.05 mmol TE/g) assays. However, significant antioxidant activities varied within the extracts of C. galaticus. HAE/methanolic extract of A. trichophylla significantly depressed AChE (2.70 mg GALAE/g), BChE (5.53 mg GALAE/g) and tyrosinase (26.34 mg KAE/g) activities and that of C. galaticus inhibited AChE (2.04 mg GALAE/g), tyrosinase (31.25 mg KAE/g) and α-amylase (0.53 mmol ACAE/g) activities significantly. We concluded that HAE was the most efficient extraction technique as high yield of compounds and promising bioactivities were recorded from extracts prepared. Multivariate analysis showed that types of solvents influenced recovery of compounds and biological activities. This research study can be used as one methodological starting point for further investigation on these plants as all results are clearly promising and open the door to further research challenges such as cytotoxicity evaluation, molecular docking analysis, and more screening of pharmacological actions.

Metabolomics and Physiological Insights into the Ability of Exogenously Applied Chlorogenic Acid and Hesperidin to Modulate Salt Stress in Lettuce Distinctively.

Recent studies in the agronomic field indicate that the exogenous application of polyphenols can provide tolerance against various stresses in plants. However, the molecular processes underlying stress mitigation remain unclear, and little is known about the impact of exogenously applied phenolics, especially in combination with salinity. In this work, the impacts of exogenously applied chlorogenic acid (CA), hesperidin (HES), and their combination (HES + CA) have been investigated in lettuce (Lactuca sativa L.) through untargeted metabolomics to evaluate mitigation effects against salinity. Growth parameters, physiological measurements, leaf relative water content, and osmotic potential as well as gas exchange parameters were also measured. As expected, salinity produced a significant decline in the physiological and biochemical parameters of lettuce. However, the treatments with exogenous phenolics, particularly HES and HES + CA, allowed lettuce to cope with salt stress condition. Interestingly, the treatments triggered a broad metabolic reprogramming that involved secondary metabolism and small molecules such as electron carriers, enzyme cofactors, and vitamins. Under salinity conditions, CA and HES + CA distinctively elicited secondary metabolism, nitrogen-containing compounds, osmoprotectants, and polyamines.

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes.

Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

Phytochemical Composition, Antioxidant Capacity, and Enzyme Inhibitory Activity in Callus, Somaclonal Variant, and Normal Green Shoot Tissues of Catharanthus roseus (L) G. Don.

This study aimed to investigate the impact of plant growth regulators, sucrose concentration, and the number of subcultures on axillary shoot multiplication, in vitro flowering, and somaclonal variation and to assess the phytochemical composition, antioxidant capacity, and enzyme inhibitory potential of in vitro-established callus, somaclonal variant, and normal green shoots of Catharanthus roseus. The highest shoot induction rate (95.8%) and highest number of shoots (23.6), with a mean length of 4.5 cm, were attained when the C. roseus nodal explants (0.6-1 cm in length) were cultivated in Murashige and Skoog (MS) medium with 2 µM thidiazuron, 1 µM 2-(1-naphthyl) acetic acid (NAA), and 4% sucrose. The in vitro flowering of C. roseus was affected by sucrose, and the number of subcultures had a significant effect on shoot multiplication and somaclonal variation. The highest levels of phenolics and flavonoids were found in normal green shoots, followed by those in somaclonal variant shoots and callus. The phytochemicals in C. roseus extracts were qualified using liquid chromatography-tandem mass spectrometry. A total of 39, 55, and 59 compounds were identified in the callus, somaclonal variant shoot, and normal green shoot tissues, respectively. The normal green shoot extracts exhibited the best free radical scavenging ability and reducing power activity. The strongest acetylcholinesterase inhibitory effects were found in the callus, with an IC50 of 0.65 mg/mL.

Phytocomplex Characterization and Biological Evaluation of Powdered Fruits and Leaves from Elaeagnus angustifolia.

Fully ripe fruits and mature leaves of Elaeagnus angustifolia were harvested and analyzed by means of analytical and biological tests to better comprehend the chemical composition and therapeutic/nutraceutical potential of this plant. Fruits and leaves were dried and the obtained powders were analyzed to study their color character and (via headspace gas chromatography) describe the chemical profile. Subsequently, they were submitted to a chloroform-methanol extraction, to a hydroalcoholic extraction procedure assisted or not by microwaves, and to an extraction with supercritical CO2, assisted or not by ethanol as the co-solvent, to detect the polyphenolic and the volatile content. The resulting extracts were evaluated in terms of chlorophyll and carotenoid content, polyphenolic content, volatile fraction, total phenolic content, total flavonoid content, antioxidant activity, radical scavenging activity, and enzymatic inhibition activity. The results confirmed the correlation between the chemical composition and the high antioxidant potential of leaf extracts compared to the fruit extracts in terms of the phenolic and pigment content. A promising effect against tyrosinase emerged for all the extracts, suggesting a therapeutic/nutraceutical use for this plant. Conversely, the volatile content from both natural matrices was similar.

Chromatographic Separation of Breynia retusa (Dennst.) Alston Bark, Fruit and Leaf Constituents from Bioactive Extracts.

Breynia retusa (Dennst.) Alston (also known as Cup Saucer plant) is a food plant with wide applications in traditional medicine, particularly in Ayurveda. Extracts obtained with four solvents (dichloromethane, methanol, ethyl acetate and water), from three plant parts, (fruit, leaf and bark) were obtained. Extracts were tested for total phenolic, flavonoid content and antioxidant activities using a battery of assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Results showed that the methanolic bark extract exhibited significant radical scavenging activity (DPPH: 202.09 ± 0.15; ABTS: 490.12 ± 0.18 mg Trolox equivalent (TE)/g), reducing potential (FRAP: 325.86 ± 4.36: CUPRAC: 661.82 ± 0.40 mg TE/g) and possessed the highest TAC (3.33 ± 0.13 mmol TE/g). The methanolic extracts were subjected to LC-DAD-MSn and NMR analysis. A two-column LC method was developed to separate constituents, allowing to identify and quantify forty-four and fifteen constituents in bark and fruits, respectively. Main compound in bark was epicatechin-3-O-sulphate and isolation of compound was performed to confirm its identity. Bark extract contained catechins, procyanidins, gallic acid derivatives and the sulfur containing spiroketal named breynins. Aerial parts mostly contained flavonoid glycosides. Considering the bioassays, the methanolic bark extract resulted a potent tyrosinase (152.79 ± 0.27 mg kojic acid equivalent/g), α-amylase (0.99 ± 0.01 mmol acarbose equivalent ACAE/g) and α-glucosidase (2.16 ± 0.01 mmol ACAE/g) inhibitor. In conclusion, methanol is able to extract the efficiently the phytoconstituents of B. retusa and the bark is the most valuable source of compounds.

Anti-Inflammatory and Neuromodulatory Effects Induced by Tanacetum parthenium Water Extract: Results from In Silico, In Vitro and Ex Vivo Studies.

Tanacetum parthenium (feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial T. parthenium water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K+ 60 mM Krebs-Ringer buffer and treated with T. parthenium water extract. The prostaglandin E2 (PGE2) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1ß gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE2 release and IL-1ß gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of T. parthenium water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.

Phytochemical Analysis, Network Pharmacology and in Silico Investigations on Anacamptis pyramidalis Tuber Extracts.

Anacamptis pyramidalis (L.) Rich. forms part of the Orchidaceae family that is highlyvalued for its horticultural as well as therapeutic benefits. The present study set out to investigatethe inhibitory activity of A. pyramidalis tubers against key biological targets for the management oftype 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidantpotential of the extracts was also assessed using multiple methods. The detailed phytochemicalprofiles of the extracts were determined using high-performance liquid chromatography. Based onqualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well.Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivativeswere present in the methanol extract. The methanol extract exhibited high inhibitory activityagainst tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarboseequivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, themethanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Troloxequivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC),and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results ofnetwork pharmacology analysis, besides corroborating traditional uses of plant extracts in themanagement of cold and flu, confirmed a direct involvement of identified phytochemicals in theobserved enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase.Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of A. pyramidalis extracts and identified phytocompounds on enzymesinvolved in type 2 diabetes, a docking study was conducted in order to investigate the putativeinteractions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldosereductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV,and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds againstthe aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxyoctadecenoic acid. Overall, the present findings supported the rationale for the use of A.pyramidalis as source of bioactive metabolites and highlight, today more than ever, for the strongnecessity of linkage strategy between wild resource valorization and conservation policy.

Experience with carnitine palmitoyltransferase II deficiency: diagnostic challenges in the myopathic form.

OBJECTIVES: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form of CPT II deficiency at Ege University Hospital. METHODS: A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. RESULTS: Ten patients were examined for rhabdomyolysis of unknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C>T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C>T (p.Ser113Leu). CONCLUSIONS: Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.