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.
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 β (Aβ)-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 Aβ25-35 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.
The Departmental Paper Series presents research by IMF staff on issues of broad regional or crosscountry interest. The views expressed in this paper are those of the author(s) and do not necessarily represent the views of the IMF, its Executive Board, or IMF management.This paper builds on a research project on macroeconomic policy in low-income countries (IATI Identifier: GB-1-202960) supported by the UK's Foreign, Commonwealth and Development Office (FCDO) and the partners in the IMF's COVID-19 Crisis Capacity Development Initiative (CCCDI)-
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.
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.
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