Network pharmacology, molecular docking, and dynamics analyses to predict the antiviral activity of ginger constituents against coronavirus infection.

COVID-19 is a global pandemic that caused a dramatic loss of human life worldwide, leading to accelerated research for antiviral drug discovery. Herbal medicine is one of the most commonly used alternative medicine for the prevention and treatment of many conditions including respiratory system diseases. In this study, a computational pipeline was employed, including network pharmacology, molecular docking simulations, and molecular dynamics simulations, to analyze the common phytochemicals of ginger rhizomes and identify candidate constituents as viral inhibitors. Furthermore, experimental assays were performed to analyze the volatile and non-volatile compounds of ginger and to assess the antiviral activity of ginger oil and hydroalcoholic extract. Network pharmacology analysis showed that ginger compounds target human genes that are involved in related cellular processes to the viral infection. Docking analysis highlighted five pungent compounds and zingiberenol as potential inhibitors for the main protease (Mpro), spike receptor-binding domain (RBD), and human angiotensin-converting enzyme 2 (ACE2). Then, (6)-gingerdiacetate was selected for molecular dynamics (MD) simulations as it exhibited the best binding interactions and free energies over the three target proteins. Trajectories analysis of the three complexes showed that RBD and ACE2 complexes with the ligand preserved similar patterns of root mean square deviation (RMSD) and radius of gyration (Rg) values to their respective native structures. Finally, experimental validation of the ginger hydroalcoholic extract confirmed the existence of (6)-gingerdiacetate and revealed the strong antiviral activity of the hydroalcoholic extract with IC 50 of 2.727 µ g / ml . Our study provides insights into the potential antiviral activity of (6)-gingerdiacetate that may enhance the host immune response and block RBD binding to ACE2, thereby, inhibiting SARS-CoV-2 infection.

Metabolomic Profiling and DNA-Fingerprinting of Newly Recorded White-Flowered Populations of Salvia lanigera Poir. in Egypt.

Salvia lanigera Poir. is a small herbaceous perennial species with violet flowers that grows in low-altitude deserts, and sandy loam. During the collection of S. lanigera, unusual populations with white flowers were found. Therefore, the two populations (violet- and white-flowered) were subjected to comparative investigations, including DNA fingerprinting, chemical composition, and biological evaluation. The two populations showed DNA variations, with 6.66 % polymorphism in ISSR and 25 % in SCoT markers. GC/MS and UHPLC/HRMS of aqueous methanol extracts, led to the tentative identification of 43 and 50 compounds in both populations. In addition, the structures of nine compounds, including four first-time reported compounds in the species, were confirmed by NMR. Furthermore, the total extracts exhibited weak radical scavenging activity against DPPH and a lower inhibitory effect towards acetylcholinesterase. In conclusion, the obtained data suggested that the white-colored flower could be an additional important character record for the Egyptian S. lanigera.

Discriminative Metabolomics Analysis and Cytotoxic Evaluation of Flowers, Leaves, and Roots Extracts of Matthiola longipetala subsp. livida.

Matthiola longipetala subsp. livida is an annual herb in Brassicaceae that has received little attention despite the family's high reputation for health benefits, particularly cancer prevention. In this study, UPLC-HRMS-MS analysis was used for mapping the chemical constituents of different plant parts (i.e., flowers, leaves, and roots). Also, spectral similarity networks via the Global Natural Products Social Molecular Networking (GNPS) were employed to visualize their chemical differences and similarities. Additionally, the cytotoxic activity on HCT-116, HeLa, and HepG2 cell lines was evaluated. Throughout the current analysis, 154 compounds were annotated, with the prevalence of phenolic acids, glucosinolates, flavonol glucosides, lipids, peptides, and others. Predictably, secondary metabolites (phenolic acids, flavonoids, and glucosinolates) were predominant in flowers and leaves, while the roots were characterized by primary metabolites (peptides and fatty acids). Four diacetyl derivatives tentatively assigned as O-acetyl O-malonyl glucoside of quercetin (103), kaempferol (108 and 112), and isorhamnetin (114) were detected for the first time in nature. The flowers and leaves extracts showed significant inhibition of HeLa cell line propagation with LC50 values of 18.1 ± 0.42 and 29.6 ± 0.35 µg/mL, respectively, whereas the flowers extract inhibited HCT-116 with LC50 24.8 ± 0.45 µg/mL, compared to those of Doxorubicin (26.1 ± 0.27 and 37.6 ± 0.21 µg/mL), respectively. In conclusion, the flowers of M. longipetala are responsible for the abundance of bioactive compounds with cytotoxic properties.

Artemisia spp.: An Update on Its Chemical Composition, Pharmacological and Toxicological Profiles.

Artemisia plants are traditional and ethnopharmacologically used to treat several diseases and in addition in food, spices, and beverages. The genus is widely distributed in all continents except the Antarctica, and traditional medicine has been used as antimalarial, antioxidant, anticancer, antinociceptive, anti-inflammatory, and antiviral agents. This review is aimed at systematizing scientific data on the geographical distribution, chemical composition, and pharmacological and toxicological profiles of the Artemisia genus. Data from the literature on Artemisia plants were taken using electronic databases such as PubMed/MEDLINE, Scopus, and Web of Science. Selected papers for this updated study included data about phytochemicals, preclinical pharmacological experimental studies with molecular mechanisms included, clinical studies, and toxicological and safety data. In addition, ancient texts and books were consulted. The essential oils and phytochemicals of the Artemisia genus have reported important biological activities, among them the artemisinin, a sesquiterpene lactone, with antimalarial activity. Artemisia absinthium L. is one of the most famous Artemisia spp. due to its use in the production of the absinthe drink which is restricted in most countries because of neurotoxicity. The analyzed studies confirmed that Artemisia plants have many traditional and pharmacological applications. However, scientific data are limited to clinical and toxicological research. Therefore, further research is needed on these aspects to understand the full therapeutic potential and molecular pharmacological mechanisms of this medicinal species.

Chemical compositions of Commiphora opobalsamum stem bark to alleviate liver complications in streptozotocin-induced diabetes in rats: Role of oxidative stress and DNA damage.

CONTEXT: Hyperglycaemia plays an important role in the development of non-alcoholic fatty liver disease, which is a common complication in diabetics. OBJECTIVE: The present study aimed to investigate the chemical composition and the efficacy of Commiphora opobalsamum stem bark butanol fraction in ameliorating liver injury associated with diabetes induced by streptozotocin (STZ) in rats. MATERIALS AND METHODS: The butanol fraction was applied to high-performance liquid chromatography-mass spectrometry (HPLC/MSn) to identify the most bioactive metabolites. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), while treatment with the plant extract was performed (100 mg/kg body weight) for three weeks after diabetic induction for one month. RESULTS: Thirty eight metabolites were tentatively identified from the butanol fraction of C. opobalsamum stem bark. Insulin, glutathione, superoxide dismutase, and high density lipoprotein levels in diabetic rats were significantly low (p < 0.05), while glucose, α-amylase, malondialdehyde, aspartate and alanine aminotransferases, cholesterol, triglycerides, low density lipoprotein, tumour necrosis factor-α, interleukin-6, and DNA fragmentation levels were significantly high. Treatment with the plant extract showed improvements in the seleced parameters by variable degrees. Conclusion: The plant extract is considered as a promising natural therapeutic agent against liver injury, hyperglycemia, oxidative stress, inflammation, hyperlipidaemia, and DNA damage.

Purchasing health services under the Egypt's new Universal Health Insurance law: What are the implications for universal health coverage?

BACKGROUND: Egypt's Universal Health Insurance (UHI) Law of 2018 implies major transformation to the health financing system. This commentary provides an assessment of the purchasing arrangements as stipulated by the UHI Law and Bylaw, their implications and contribution to progress towards universal health coverage (UHC). The purpose of this assessment is to inform the multi-year implementation process of the Law and propose options for progress towards UHC. METHODS: Guided by an analytical framework on purchasing, the qualitative analysis was based on the review of the legal provisions and structured discussions with key stakeholders. RESULTS: The Law foresees important changes, such as a purchaser-provider split, stricter referral rules and regulated cost-sharing. However, several purchasing aspects were not sufficiently specified in the legal provisions, for example benefit design and provider payment methods. It remains unclear for decision-makers how to proceed, hindering the Law's effective implementation. There are also concerns about the mixed provider payment system creating incoherent provider incentives. CONCLUSION: In view of the remaining legal unclarities on purchasing, progress towards UHC is restrained. Benefits design and the provider payment system should be further specified with a clearer governance structure around the purchasing decision-making processes. Additional technical options for strategic purchasing are suggested.

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2.

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

Genetic diversity and volatile oil components variation in Achillea fragrantissima wild accessions and their regenerated genotypes.

BACKGROUND: Wild medicinal plants are suffering natural environmental stresses and habitat destruction. The genetic diversity evaluation of wild accessions and their in vitro raised genotypes using molecular markers, as well as the estimation of substances of pharmaceutical value in wild plants and their regenerated genotypes are convenient approaches to test the genetic fidelity of regenerated plants as a source of substances of pharmaceutical value. In this study, the genetic diversity of 12 accessions of the medicinal plant Achillea fragrantissima, representing five sites in the mountains of South Sinai, Egypt, were estimated by the inter simple sequence repeats (ISSR) fingerprinting and their volatile oil components were identified using gas chromatography-mass spectrometry (GC-MS) analysis. The same accessions were regenerated in vitro and the genetic diversity and volatile oil components of propagated genotypes were determined and compared to their wild parents. RESULTS: Clustering and principal component analyses indicated that the wild accessions and their regenerated genotypes were genetically differentiated, but the regenerated plants are relatively more diverse compared to their wild parents. However, genetic variation between wild accessions is inherited to their in vitro propagated genotypes indicating genotypic differentiation of the examined accessions. The number of volatile oil compounds in the wild A. fragrantissima accessions was 31 compounds while in the in vitro propagated plants only 24 compounds were detected. Four major compounds are common to both wild and regenerated plants; these are artemisia ketone, alpha-thujone, dodecane, and piperitone. CONCLUSIONS: Genome profiling and essential oil components analysis showed variations in A. fragrantissima accessions from different populations. Genetic differences between wild and regenerated genotypes were analyzed and validated with the final conclusion that in vitro conditions elicited higher genetic variation that is associated with reduced amount and diversity in the essential oil components.

Trigonelline recovers memory function in Alzheimer's disease model mice: evidence of brain penetration and target molecule.

Trigonelline (TGN; 1-methylpyridin-1-ium-3-carboxylate) is a widely distributed alkaloid derived from plants. Since we previously found a neurite outgrowth effect of TGN, we hypothesised that TGN might help to improve memory deficits. Here, the efficacy of TGN in restoring amyloid ß (Aß)-induced axonal degeneration and in improving memory function was investigated in Alzheimer's disease 5XFAD model mice that overexpress mutated APP and PS1 genes. Exposure of Aß25-35 for 3 days induced atrophy of axons and dendrites. Post treatment of TGN recovered the lengths of axons and dendrites. Following oral administration of TGN in mice, TGN itself was detected in the plasma and cerebral cortex. Oral administration of TGN to 5XFAD mice for 14 days showed significant improvement in object recognition memory (P < 0.001) and object location memory (P < 0.01). TGN administration also normalised neurofilament light levels in the cerebral cortex (P < 0.05), which is an axonal damage-associated biomarker. Analysis of target proteins of TGN in neurons by a drug affinity responsive target stability (DARTS) method identified that creatine kinase B-type (CKB) is a direct binding protein of TGN. Treatment with a CKB inhibitor cancelled the TGN-induced axonal and dendritic growth. In conclusion, we found for the first time that TGN penetrates the brain and may activate CKB, leading to axonal formation. This study shows the potential of TGN as a new drug candidate, and a new target molecule, CKB, in memory recovery signalling.