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Background: Onion waste was reported to be a valuable source of bioactive constituents with potential health-promoting benefits. This sparked a surge of interest among scientists for its valorization. This study aims to investigate the chemical profiles of peel and root extracts of four onion cultivars (red, copper-yellow, golden yellow and white onions) and evaluate their erectogenic and anti-inflammatory potentials., Methods: UPLC-QqQ-MS/MS analysis and chemometric tools were utilized to determine the chemical profiles of onion peel and root extracts. The erectogenic potential of the extracts was evaluated using the PDE-5 inhibitory assay, while their anti-inflammatory activity was determined by identifying their downregulating effect on the gene expression of IL-6, IL-1β, IFN-γ, and TNF-α in LPS-stimulated WBCs., Results: A total of 103 metabolites of diverse chemical classes were identified, with the most abundant being flavonoids. The organ's influence on the chemical profiles of the samples outweighed the influence of the cultivar, as evidenced by the close clustering of samples from the same organ compared to the distinct separation of root and peel samples from the same cultivar. Furthermore, the tested extracts demonstrated promising PDE-5 and anti-inflammatory potentials and effectively suppressed the upregulation of pro-inflammatory markers in LPS-stimulated WBCs. The anti-inflammatory activities exerted by peel samples surpassed those of root samples, highlighting the importance of selecting the appropriate organ to maximize activity. The main metabolites correlated with PDE-5 inhibition were cyanidin 3-O-(malonyl-acetyl)-glucoside and quercetin dimer hexoside, while those correlated with IL-1β inhibition were γ-glutamyl-methionine sulfoxide, γ-glutamyl glutamine, sativanone, and stearic acid. Taxifolin, 3'-hydroxymelanettin, and oleic acid were highly correlated with IL-6 downregulation, while quercetin 4'-O-glucoside, isorhamnetin 4'-O-glucoside, and p-coumaroyl glycolic acid showed the highest correlation to IFN-γ and TNF-α inhibition., Conclusion: This study provides a fresh perspective on onion waste as a valuable source of bioactive constituents that could serve as the cornerstone for developing new, effective anti-PDE-5 and anti-inflammatory drug candidates., (© 2024. The Author(s).)

Objectives: To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent., Methods: Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics., Key Findings: Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively., Conclusions: Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Ethnopharmacological Relevance: Onion (Allium cepa L.) is one of the most widely distributed species within the Allium genus of family Amaryllidaceae. Onion has been esteemed for its medicinal properties since antiquity. It has been consumed for centuries in various indigenous cultures for the management of several ailments including microbial infections, respiratory, gastrointestinal, skin and cardio-vascular disorders, diabetes, renal colic, rheumatism, sexual impotence, menstrual pain, and headache. However, so far, there is a scarcity of recent data that compiles the plant chemistry, traditional practices, biological features, and toxicity., Aim of the Work: The aim of this review is to provide a comprehensive and analytical overview of ethnopharmacological uses, phytochemistry, pharmacology, industrial applications, quality control, and toxicology of onion, to offer new perspectives and broad scopes for future studies., Materials and Methods: The information gathered in this review was obtained from various sources including books, scientific databases such as Science Direct, Wiley, PubMed, Google Scholar, and other domestic and foreign literature., Results: Onion has a long history of use as a traditional medicine for management of various conditions including infectious, inflammatory, respiratory, cardiovascular diseases, diabetes, and erectile dysfunction. More than 400 compounds have been identified in onion including flavonoids, phenolic acids, amino acids, peptides, saponins and fatty acids. The plant extracts and compounds showed various pharmacological activities such as antimicrobial, antidiabetic, anti-inflammatory, anti-hyperlipidemic, anticancer, aphrodisiac, cardioprotective, and neuroprotective activities. In addition to its predominant medicinal uses, onion has found various applications in the functional food industry., Conclusion: Extensive literature analysis reveals that onion extracts and bioactive constituents possess diverse pharmacological activities that can be beneficial for treating various diseases. However, the current research primarily revolves around the documentation of ethnic pharmacology and predominantly consists of in vitro studies, with relatively limited in vivo and clinical studies. Consequently, it is imperative for future investigations to prioritize and expand the scope of in vivo and clinical research. Additionally, it is strongly recommended to direct further research efforts towards toxicity studies and quality control of the plant. These studies will help bridge the current knowledge gaps and establish a solid basis for exploring the plant's potential uses in a clinical setting., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Roasting, honey-roasting and fermentation are the most common pre-processing procedures of licorice roots. They were shown to noticeably change the composition of extracts. In this work, the common alterations in licorice secondary metabolites by processing were interpreted. Comprehensive metabolic profiling of different studied samples was undergone., Methods: UPLC-QqQ-MS/MS analysis coupled to various chemometric analysis models was implemented to unravel the effect of different pre-processing procedures on the chemical profile of licorice samples., Results: UPLC-QqQ-MS/MS analysis designated 133 chromatographic peaks with saponins, flavonoids, chalcones and pterocarpans being the most abundant groups. Triterpene saponins dominated the secondary metabolites in the aqueous extracts, with fermented samples showing the highest relative amounts. Meanwhile the ethanol extracts showed significant amounts of chalcones. Melanoidins were only detected in roasted and honey roasted samples. Multivariate models indicated that roasting of samples induced a greater effect on the polar metabolites rather than nonpolar ones. Variable of importance (VIP) plot indicated that glycyrrhizin and its hydrolysis product glycyrrhetinic acid, trihdroxychalcone diglycoside, glabrone and glabridin are the main chemical features responsible for the discrimination of samples., Conclusion: Coupling UPLC-MS/MS to multivariate analysis was a successful tool that unveiled the significant effect of different pre-processing methods on the chemical profile of processed and unprocessed licorice samples. Moreover, such coupling unraveled the discriminatory chemical compounds among tested samples that can be employed as markers for the processing procedure of licorice., (© 2023. The Author(s).)

Platycladus orientalis L. Franco has many folk uses as it is mainly used to treat inflammatory ailments. UPLC-MS/MS was used for the chemical profiling of P. orientalis leaves. Identified metabolites were forwarded to network pharmacology analysis. Networks were constructed based on STITCH, SEA, DAVID, KEGG and STRING databases and using Cytoscape. The identified hit compounds were afzelin, myricetin, apigenin-7-O-hexoside, quercetrin and hyperoside. IL2, VEGFA, AKT1, AKT2, CREB1, IL5, RPS6KB1 and TNF were the main inflammation-related targets identified. Quercetrin and hyperoside were tested for their anti-inflammatory activity. it can be concluded that, the identified hit compounds exhibited strong synergistic interactions with the inflammation and immunity-related targets and pathways.

Lantana camara L. is widely used in folk medicine for alleviation of inflammatory disorders, but studies that proved this folk use and that revealed the molecular mechanism of action in inflammation mitigation are not enough. Therefore, this study aimed to identify L. camara phytoconstituents using UPLC-MS/MS and explain their multi-level mechanism of action in inflammation alleviation using network pharmacology analysis together with molecular docking and in vitro testing. Fifty-seven phytoconstituents were identified in L. camara extract, from which the top hit compounds related to inflammation were ferulic acid, catechin gallate, myricetin and iso-ferulic acid. Whereas the most enriched inflammation related genes were PRKCA, RELA, IL2, MAPK 14 and FOS. Furthermore, the most enriched inflammation-related pathways were PI3K-Akt and MAPK signaling pathways. Molecular docking revealed that catechin gallate possessed the lowest binding energy against PRKCA, RELA and IL2, while myricetin had the most stabilized interaction against MAPK14 and FOS. In vitro cytotoxicity and anti-inflammatory testing indicated that L. camara extract is safer than piroxicam and has a strong anti-inflammatory activity comparable to it. This study is a first step in proving the folk uses of L. camara in palliating inflammatory ailments and institutes the groundwork for future clinical studies., (© 2022. The Author(s).)

Ethnopharmacological Relevance: Red sage (Lantana camara L.) (Verbenaceae) is a widely spread plant that was traditionally used in Brazil, India, Kenya, Thailand, Mexico, Nigeria, Australia and Southeast Asia for treating several ailments including rheumatism and leprosy. Despite its historical role in relieving respiratory diseases, limited studies progressed to the plant's probable inhibition to respiratory viruses especially after the striking spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections., Aim of the Study: This study aimed to investigate the inhibitory activity of different L. camara cultivars to SARS-CoV-2, that was not previously inspected, and clarify their mechanisms of action in the metabolomics viewpoint, and to determine the biomarkers that are related to such activity using UPLC-MS/MS coupled to in vitro-studies and chemometric analysis., Materials and Methods: Chemical profiling of different cultivars was accomplished via UPLC-MS/MS. Principle component analysis (PCA) and orthogonal projection to latent structures (OPLS) models were built using SIMCA® (multivariate data analysis software). Cytotoxicity and COVID-19 inhibitory activity testing were done followed by TaqMan Real-time RT-PCR (Reverse transcription polymerase chain reaction) assay that aimed to study extracts' effects on RNA-dependent RNA polymerase (RdRp) and E-genes expression levels. Detected biomarkers from OPLS analysis were docked into potential targets pockets to investigate their possible interaction patterns using Schrodinger® suite., Results: UPLC-MS/MS analysis of different cultivars yielded 47 metabolites, most of them are triterpenoids and flavonoids. PCA plots revealed that inter-cultivar factor has no pronounced effect on the chemical profiles of extracts except for L. camara, cultivar Drap d'or flowers and leaves extracts as well as for L. camara cv Chelsea gem leaves extract. Among the tested extracts, flowers and leaves extracts of L. camara cv Chelsea gem, flowers extracts of L. camara cv Spreading sunset and L. camara cv Drap d'or showed the highest selectivity indices scoring 12.3, 10.1, 8.6 and 7.8, respectively, indicating their relative high safety and efficacy. Leaves and flowers extracts of L. camara cv Chelsea gem, flowers extracts of L. camara cv Spreading sunset and L. camara cv Drap d'or were the most promising inhibitors to viral plaques exhibiting IC 50 values of 3.18, 3.67, 4.18 and 5.01 μg/mL, respectively. This was incremented by OPLS analysis that related their promising COVID-19 inhibitory activities to the presence of twelve biomarkers. Inhibiting the expression of RdRp gene is the major mechanism behind the antiviral activity of most extracts at almost all concentration levels. Molecular docking of the active biomarkers against RdRp revealed that isoverbascoside, luteolin-7,4'-O-diglucoside, camarolic acid and lantoic acid exhibited higher docking scores of -11.378, -10.64, -6.72 and -6.07 kcal/mol, respectively, when compared to remdesivir (-5.75 kcal/mol), thus these four compounds can serve as promising anti-COVID-19 candidates., Conclusion: Flowers and leaves extracts of four L. camara cultivars were recognized as rich sources of phytoconstituents possessing anti-COVID-19 activity. Combination of UPLC-MS/MS and chemometrics is a promising approach to detect chemical composition differences among the cultivars and correlate them to COVID-19 inhibitory activities allowing to pinpoint possible biomarkers. Further in-vitro and in-vivo studies are required to verify their activity., (Copyright © 2022. Published by Elsevier B.V.)

Colocynth has a long history of use in traditional medicine for treatment of various inflammatory diseases where it is commonly roasted before being applied for medical purposes to reduce its toxicity. This study aims at tracking the effect of heat processing on the metabolic profile of the peels, pulps and seeds of colocynth fruit using UPLC-QqQ-MS-based metabolomics. The analysis resulted in tentative identification of 72 compounds belonging to different chemical classes. With roasting, a decline was observed in the relative amounts of chemical constituents where 42, 25 and 29 compounds were down-regulated in the peels, pulps and seeds, respectively. EC 100 values resulting in 100% cell viability were all higher in roasted samples compared to their relevant raw ones. Correlation analysis indicated that the main cytotoxic chemical markers were cucurbitacin glycosides and their genins. Further, ex vivo anti-inflammatory activity testing multivariate models revealed that unprocessed samples correlated with inhibition of TNF-α, IL-1β and IFN-γ where quercetrin, calodendroside A, and hexanoic acid methyl ester were the most significant chemical markers, while processed samples showed correlation with IL-6 pro-inflammatory marker inhibition with protocatechuic and protocatechuic acid glycoside being the main correlated chemical markers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The application of a newly developed HPTLC-bioautography assay for detecting peroxidase enzyme inhibitors in plant extracts in addition to bioautography methods for detecting antioxidant compounds resulted in the isolation of a new biflavonoid 3'-methoxy sahranflavone along with two known biflavonoids and three flavonoids from the leaves and cones of Juniperus communis, J. horizontalis and J. chinensis . The structures of all compounds were elucidated by means of 1 D and 2 D NMR and MALDI-TOF MS technique in addition to comparison to literature data. Quantitative estimation of antiperoxidase and antioxidative capacity based on DPPH free radical scavenging activity and β-carotene bleaching of extracts, active fraction and constituents was achieved by applying validated high resolution image analyses techniques. 3'-methoxy sahranflavone and quercetrin possessed high mutual antiperoxidase and antioxidant activities. Molecular docking simulations were performed to reveal the interaction of isolated compounds with human myeloperoxidase enzyme on the molecular level indicating the potential anti-inflammatory activity of 3'-methoxy sahranflavone and quercetrin.

In this study, the seasonal dynamics of the flavonoids in the cones and leaves of oriental Thuja ( Platycladus orientalis L. Franco) as well as the in vitro anti-inflammatory activity of their extracts were investigated. The important chemical markers of the studied extracts were determined using untargeted HPTLC profiling, which was further utilized to assess the seasonality effect on the composition of these metabolites over three seasonal cycles. A quantitative HPTLC method was developed and validated for the identified chemical markers of oriental Thuja : hyperoside, quercetrin, isoscutellarein-7- O -β-xyloside, cupressuflavone, hinokiflavone, sotetsuflavone and isoscutellarein-8-methyl ether. The highest amounts of flavonoids were observed during the summer and winter seasons, where the leaves possessed higher contents of flavonoids compared to cones. Flavone glycosides are a major class of flavones encountered in leaves, while the cones mainly accumulated biflavones. The results showed that the effect of seasonal variation on the accumulation of flavonoids within the cones was less pronounced than in the leaves. The summer leaves showed a remarkable reduction in the levels of INF-γ, where the value decreased to 80.7 ± 1.25 pg mL -1 , a significantly lower level than that obtained with piroxicam (180 ± 1.47 pg mL -1 ); this suggests a noteworthy anti-inflammatory potential. OPLS (orthogonal projection to latent structures) models showed that flavonoidal glycosides, quercetrin, hyperoside and isoscutellarein-7- O -β-xyloside were the most contributing biomarkers to the reduction in pro-inflammatory mediators in LPS-stimulated WBCs. The results obtained in the study can thus be exploited to establish the best organs as well as the optimal periods of the year for collecting and obtaining certain biomarkers at high concentrations to guarantee the efficacy of the obtained extracts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ethnopharmacological Relevance: Juniperus plants are considered important sources of cedar-wood oil which is used widely in folk medicine as antiseptic and in treatment of inflammatory disorders such as, rheumatoid arthritis but there is not enough scientific evidence to support the claimed uses and there is no specification of a certain Juniperus species as the most active., Aim of the Study: The aim of this study is volatiles profiling of three Juniperus species; J. communis, J. horizontalis and J. chinensis in addition to efficacy-directed discrimination of the three studied essential oils based on their antimicrobial, and anti-inflammatory activities in LPS (lipopolysaccharide)-stimulated WBCs (White blood cells) to investigate the inter-specific variability effect on the biological activities of each oil., Materials and Methods: Volatile components profiling of the three studied plants volatile oils was achieved using GC-FID (Gas chromatography - flame ionization detector) and GC-MS (Gas chromatography - mass spectrometry). The antimicrobial activity of the studied essential oils was investigated and the minimum inhibitory concentration (MIC) was determined for oils. The production of the pro-inflammatory cytokines was evaluated by ELISA (Enzyme linked immunosorbent assay). Identification of the biomarkers responsible for each activity was attempted through construction of orthogonal projection to latent structures model using multivariate statistical analysis., Results: Forty five components were identified in the volatile oils of the three studied plants. J. horizontalis oil displayed the highest activity against E. coli while J. communis showed the highest activity against S. aureus. OPLS model biplot showed the in-between class discrimination of J. chinensis oil sample from J. communis and J. horizontalis. The three oils were found to significantly decrease the production of the pro-inflammatory cytokines tumour necrosis factor (TNF)- α, interleukin (IL)-1β, and gamma interferon (INF- γ) in lipopolysaccharide-activated white blood cells. All studied oils were similar in reduction of TNF-α, and INF-γ, while J. chinensis oil possessed the highest potency against IL-1β. The coefficient plots of TNF-α and INF-γ pro-inflammatory mediators showed that 1-terpineol, 4-terpineol, bornyl acetate, dl-limonene and α-pinene positive contributors to both activities while β-thujone, 3-carene and γ-muurolene were the positive contributors to IL-1β inhibitory activity., Conclusion: The differences observed in the volatile profiles among the three studied oils demonstrate the effect of inter-specific variability on the biological activities of the tested oils. It was shown that the tested oils possessed good antibacterial activities against E.coli and S. aureus justifying its folk use as an a topical antiseptic while the observed anti-inflammatory effects in human WBCs is due at least in part to their inhibitory effect on the production of pro-inflammatory cytokines., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Elevated intracranial intravenous pressure is not routinely measured in clinical practice. Indirect evidence of increased venous pressure is reflected in the size change of the cerebral sinuses and the presence of venous infarctions. The purpose of this study is to evaluate the role of brain perfusion venous time-density curves in the diagnosis of cerebral venous hypertension. A retrospective review of four cases in which increased cerebral intravenous pressure was reflected in abnormal time-density curves on CT brain perfusion studies was completed. The abnormal venous time-density curves correlated with clinically increased intravenous pressure and normalized after treating the underlying pathology. Abnormal venous outflow affects brain perfusion. This could be identified on a CT brain-perfusion study based on characteristic venous time-density curves. These curves may appear quite similar even when the underlying etiologies are different. Normalization of the venous time-density curves may be observed after the underlying pathology was treated.

Background: The intrinsic pathway of apoptosis has been proposed as one mechanism of cell death after traumatic brain injury (TBI). This study tested the hypothesis that cytochrome c and activated caspase-9 are released into the cerebrospinal fluid (CSF) after severe TBI and that their presence correlates with mitochondrial injury and severity of neurologic outcome., Methods: Nine adult patients with severe TBI (GCS < or = 8) underwent placement of intraventricular catheters for monitoring and management of intracranial pressure. CSF was sampled at catheter insertion (2-26 h after injury) and at intervals of 24, 48, and 72 h thereafter. Control samples were obtained from patients undergoing spinal anesthesia (ASA1). CSF levels of cytochrome c and activated caspase-9 were measured using ELISA., Results: Cytochrome c was detected in 18 (51.4%) samples, in the range of 0.08-5 ng/ml; mean value for cytochrome c was 0.44 ng/ml (SD +/- 0.632). Activated caspase-9 was detected in 10 samples (28.6%); mean value was 0.28 ng/ml (SD +/- 0.39). R (s) between cytochrome c and Glasgow outcome score (GOS) was -0.25 (P = 0.14), and between GOS and activated caspase-9 was -0.35 (P = 0.04). R calculated based on linear regression of activated caspase-9 and cytochrome c concentrations was 0.18. Control CSF samples had no detectable levels of either marker (detection level for cytochrome c was 0.08 ng/ml and 0.20 for activated caspase-9)., Conclusions: We concluded that activated caspase-9 and cytochrome c are present in the CSF of patients with severe TBI. Activated caspase-9 shows weak correlation with poor neurologic outcome.

This study was undertaken to evaluate the role of transcranial Doppler ultrasonography in arterial blood pressure management during hypervolemia/hypertension/ hemodilution therapy in patients with vasospasm from subarachnoid hemorrhage and correlate this data with neurologic outcome. The study included 18 adult patients, Hunt and Hess grades III-IV. Complete neurologic assessment was performed. Transcranial Doppler indices were calculated by standard formulas. On the basis of our results, resistance area product can be used to estimate the optimal arterial blood pressure in hypervolemia/hypertension/hemodilution therapy. An increase in the cerebral blood flow index was associated with better performance on neurologic examination. Estimated cerebral perfusion pressure from transcranial Doppler data analysis showed poor correlation with cerebral perfusion pressure derived from direct measurement of intracranial pressure in patients with cerebral vasospasm (rho = 0.15; 95% CI, 0.11-0.39; P = .2590).

Background: Oxidative stress has been indicated as a mechanism of secondary neuronal injury in traumatic brain injury (TBI). Nitrotyrosine in the cerebrospinal fluid (CSF) may be an in vivo marker of oxidative nitric oxide damage. We tested the hypothesis that increased levels of nitrotyrosine correlate with poor neurologic outcomes in patients with TBI and attempted to identify the source of increased CSF nitrotyrosine., Methods: This institutional-review-board-approved study included 10 adults with severe closed TBI (Glasgow Coma Scale score <8) and no documented hypoxic brain injury. These patients underwent routine evaluation and, when indicated, placement of an intraventricular catheter. CSF samples (n = 27) were collected 2 to 72 hours after TBI and were also obtained from four healthy individuals. Nitrotyrosine levels were measured, and immunohistochemistry was performed. Neurologic follow-up extended to 1 month after injury., Results: Nitrotyrosine was not detected in the control samples but was detected in 13 CSF samples from 7 TBI patients (range, 22.4-97.6 nM/mL). Seven patients had poor outcomes, and, in each, nitrotyrosine was detected. Nitrotyrosine immunoreactivity was detected in neurons and glia and confirmed in brain homogenate., Conclusion: Oxidative stress contributes to secondary brain injury in patients with TBI. Poor neurologic outcome is associated with increased levels of nitrotyrosine in the CSF. Identifying patients or the stage at which oxidative stress is more active using CSF markers of oxidative injury may help in the development of more targeted treatments.