Metabolite Profiling of Allium hookeri Leaves Using UHPLC-qTOF-MS/MS and the Senomorphic Activity of Phenolamides.

The plant Allium hookeri, a member of the Allium genus, has a rich history of culinary and medicinal use. Recent studies have unveiled its potent antioxidant and anti-inflammatory properties. While research on A. hookeri has demonstrated its neuroprotective and anti-neuroinflammatory effects, the specific bioactive compounds responsible for these effects remain unidentified in prior research. This study utilized an untargeted metabolomic approach, employing HRESI-qTOF MS/MS-based molecular networking, to comprehensively profile the chemical composition of metabolites in A. hookeri and identify new compounds within the plant. As a result, ten compounds, comprising one novel flavonoid (2) and nine known compounds (1 and 3-10), were isolated and identified through NMR analysis. The inhibitory effects of all isolated compounds on the senescent cell-associated secretory phenotype (SASP), which is pivotal in neuroprotective actions, were evaluated. Biological activity testing revealed N-trans-feruloyltyramine (7) to be the most potent compound, effectively inhibiting SASP markers and contributing to the senomorphic activities of A. hookeri. These findings underscore the potential of phenolamides from A. hookeri as a promising source of bioactive compounds for mitigating senescence-associated diseases.

Oxindole and Benzoxazinone Alkaloids from the Seeds of Persea americana (Avocado) and Their SIRT1 Stimulatory Activity.

Persea americana Mill. (Lauraceae), commonly known as avocado, is a well-known food because of its nutrition and health benefits. The seeds of avocado are major byproducts, and thus their phytochemicals and bioactivities have been of interest for study. The chemical components of avocado seeds were investigated by using UPLC-qTOF-MS/MS-based molecular networking, resulting in the isolation of seven new oxindole alkaloids (1-7) and two new benzoxazinone alkaloids (8 and 9). The chemical structures of the isolated compounds were identified by the analysis of NMR data in combination with computational approaches, including NMR and ECD calculations. Bioactivities of the isolated compounds toward silent information regulation 2 homologue-1 (SIRT1) in HEK293 cells were assessed. The results showed that compound 1 had the most potent effect on SIRT1 activation with an elevated NAD+/NADH ratio with potential for further investigation as an anti-aging agent.

Linderanidins A-F: Rare oligomeric flavonoids with an unusual C-3-C-4 linkage from the roots of Lindera erythrocarpa and their inhibitory activities on autophagy.

Autophagy is a crucial process for maintaining cellular homeostasis by degrading and recycling unnecessary or damaged cellular components. In the process of exploring autophagy regulators in plants, unique nine oligomeric flavonoids linked by the bonding of C-3 and C-4, consisting of three pairs of biflavonoids, linderanidins A-C [(+)-1/(-)-1, (+)-2/(-)-2, and (+)-3/(-)-3], and three trimeric A-type proanthocyanidins, linderanidins D-F (4-6), were isolated from the roots of Lindera erythrocarpa. The structures and absolute configurations of these compounds were determined using various techniques, such as 1D and 2D NMR, mass spectrometry, X-ray crystallography, and electronic circular dichroism. All isolates were evaluated for their ability to regulate autophagy, and compounds (±)-1-(±)-3, (-)-1-(-)-3, (+)-1-(+)-3 and 4 were found to inhibit autophagy by blocking the fusion process between autophagosome and lysosome in HEK293 cells. This study suggests that unique oligomeric flavonoids possessing a C-3-C-4 linkage derived from the roots of L. erythrocarpa are potent autophagy inhibitors.

Sesquiterpene lactone and its unique proaporphine hybrids from Magnolia grandiflora L. and their anti-inflammatory activity.

Two undescribed sesquiterpene lactone-proaporphine hybrid skeletons, two undescribed sesquiterpenes, and four known compounds were isolated from the aerial part of Magnolia grandiflora L. The structures of isolated compounds were unambiguously determined based on the interpretation of a combination of NMR spectroscopy, HRESIMS, DP4+ probability calculation of carbon data, X-ray crystallographic analyses, and ECD calculation. The isolated compounds were investigated for their anti-inflammatory activity against nitric oxide production and the protein expression of COX-2 in LPS-stimulated RAW 264.7 cells.

Drug prices and trends before and after requesting compulsory licenses: the Ecuadorian experience.

Introduction: The Ecuadorian Institute of Intellectual Property (IEPI) granted several compulsory licenses between 2011 and 2017. In 2009, the President of Ecuador signed a decree that was intended to facilitate the request of compulsory licenses (CL) in the country, not only for Enfarma EP but for any privately owned local company in order to produce more accessible medicines. Areas covered: The national and international regulatory framework of pharmaceutical patents and the local applicability of CL in Ecuador. The authors also analyzed the results of requesting unplanned and epidemiologically unnecessary CL at a national level. Finally, the authors reviewed the effects of requesting, granting or denying CL on price per unit in the last 7 years of available data. Expert opinion: The authors think that compulsory licenses are useful tools when negotiating drug prices or when the demand cannot be satisfied due to economic constrain within the local health system. However, the authors' experience suggests that Ecuador did not have an established and reliable production system neither an adequate plan before requesting CL, therefore the positive effects of this measure were not clearly established.

Rabies Epidemiology and Control in Ecuador.

OBJECTIVE: Describe the epidemiology and the control effort for rabies in Ecuador. METHODS: This observational study included data from the Ecuadorian National Institute of Census and Statistics (INEC), and mortality and morbidity data reported by the Ministry of Public Health and the National Institute for Social Security. We conducted a phylogeny analyses to compare the N gene from the Challenge Virus Standard (CVS) vaccine strain used in Ecuador with published Cosmopolitan, Asian and Sylvatic strains. Descriptive and inferential statistics were used to determine the significance of the data. RESULTS: In 1996 Ecuador suffered the highest rate of rabies per capita in the Americas, with an incidence rate of 0.56 cases per 100 000 people per year. Human and canine rabies showed a sharp decline until 2012. Between 1994 and 2014, we found a correlation of 0.925 (p<0.01) between annual cases of dog and human rabies. In 2011, there was an epidemic of sylvatic rabies transmitted to people by vampire bats (Desmodus rotundus) in the Amazon region, specifically in Morona Santiago, leading to 11 fatalities. Phylogenetic analyses of the CVS vaccine N gene showed an association with urban canine rabies strains (the Cosmopolitan lineage and Asian strains), whereas sylvatic rabies, like those reported in the Amazon region, were found to be grouped in a different clade represented mainly by bat-derived strains. CONCLUSIONS: This study presents the first compilation of epidemiological data on rabies in Ecuador. The incidence of human and canine rabies, also known as urban rabies, has clearly decreased due to massive canine vaccination campaigns. Phylogenetic analysis of the prevailing vaccine used in the country showed a clear separation from bat-derived rabies, the source of recent rabies outbreaks. Efforts are ongoing to develop rabies vaccines that are highly specific to the rabies virus genotype circulating in the region, including sylvatic rabies. These efforts include the implementation of reverse genetics to generate recombinant virus coding for the prevailing glycoprotein gene.