Naturally occurring caffeic acid phenethyl ester from chestnut honey-based propolis and virtual screening towards DYRK1A.

Neurodegenerative diseases (NDDs) are disorders with dysfunction and ongoing loss of neurons, glial cells and the neural networks in the brain and spinal cord. DYRK1A protein was reported to modulate to the cytoskeletal fraction in human and mouse brain, and the remaining protein is located in the cytosolic and nuclear fractions. Caffeic acid phenethyl ester (CAPE) is a natural derivative of caffeic acid and found in propolis, a bee product. In this study, we focused on isolation and characterisation of CAPE from chestnut honey-based propolis by HPLC-MS/MS technique and virtual screening of CAPE towards DYRK1A by molecular docking methods. Results revealed that CAPE might be a beneficial option to treat Alzheimer disease (AD) by suppressing DYRK1A protein.

Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy.

One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal actin assembly, phenotypic signalling, and transcription process which affects a wide range of cellular processes such as cell motility, invasion, metastasis, cell growth, angiogenesis, and cell cycle progression. Most recently, PAK1 was shown to be involved in the progression of coronavirus-caused pulmonary inflammation (lung fibrosis), but clinical data is not currently available yet. This review highlights the naturally occurring compounds that inhibit the oncogenic, melanogenic, and ageing kinase PAK1. Additionally, the potent anti-inflammatory effects of natural products in an attempt to prevent pulmonary fibrosis in COVID-19 have also been discussed.

Na2SO4 and NaCl salts differentially modulate the antioxidant systems in the highly stress tolerant halophyte Prosopis strombulifera.

Prosopis strombulifera (Lam.) Benth. is a halophytic shrub abundant in high-salinity areas in central Argentina, with high tolerance against NaCl but strong growth inhibition by Na2SO4. In the present study, the modulation of the antioxidant systems (enzymatic and non-enzymatic components) was analyzed under different salt treatments (NaCl, Na2SO4 and the iso-osmotic mixture) in hydroponic cultivation. Na2SO4-treated plants showed strong indications of oxidative stress (H2O2 and O2-• increase). Modifications in antioxidant enzymes activities were observed mainly under Na2SO4 treatment, where CAT seems to play an important role in early detoxification of H2O2 in roots, whereas SOD and APX have a predominant role in leaves. As part of the non-enzymatic system, 21 compounds were identified in leaves, being polyphenols the most abundant. Control plants contained the major variety of detected phytochemicals (14). Na2SO4-treated plants contained 10 compounds and NaCl-treated plants nine compounds, but with a different profile. NaCl-treated plants showed the highest antioxidant capacity. Our findings confirm that different types of salt treatments provoke a differential modulation of the antioxidant systems. Polyphenols and other ROS-detoxifying compounds, in a joint action with the enzymatic antioxidant system, are proposed to have a fundamental role in the cellular protection of P. strombulifera plants under severe oxidative stress. Our findings also highlight the potential of this halophyte as a valuable source of bioactive compounds with high antioxidant activity and health benefits.

Associations between serum lipids and mannose levels in coronary artery disease among nondiabetic patients.

Aim: Nondiabetic patients have been studied to determine whether modest elevations in plasma mannose levels may be associated with a greater incidence of coronary artery disease (CAD). Materials & methods: The plasma mannose, lipids (triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein) and lactate dehydrogenase levels were successfully evaluated with respect to subsequent CAD using records of 120 nondiabetic patients and 120 healthy volunteers. CAD was identified from myocardial infarction and new diagnoses of angina. Results: Of 120 patients studied, the plasma mannose, triglyceride, lactate dehydrogenase and very low-density lipoprotein levels of patients were significantly higher than control groups. Conclusion: Our findings showed that elevated baseline mannose in plasma was associated with a progressive risk of CAD with time.

Saporin, a Polynucleotide-Adenosine Nucleosidase, May Be an Efficacious Therapeutic Agent for SARS-CoV-2 Infection.

Saporin, a type I ribosome-inactivating protein from soapwort plant, is a potent protein synthesis inhibitor. Catalytically, saporin is a characteristic N-glycosidase, and it depurinates a specific adenine residue from a universally conserved loop of the major ribosomal RNA (rRNA) of eukaryotic cells. It is well-known that saporin induces apoptosis through different pathways, including ribotoxic stress response, cell signal transduction, genomic DNA fragmentation and RNA abasic lyase (RAlyase) activity, and NAD+ depletion by poly-(ADP)-ribose polymerase hyperactivation. Saporin's high enzymatic activity, high stability, and resistance to conjugation procedures make it a well-suited tool for immunotherapy approaches.In the present study, we focus on saporin-based targeted toxins that may be efficacious therapeutic agents for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our discussed points suggest that saporin may be a strategic molecule for therapeutic knockout treatments and a powerful candidate for novel drugs in the struggle against coronavirus 2019 (COVID-19).

Molecular and Biochemical Parameters Related to Plasma Mannose Levels in Coronary Artery Disease Among Nondiabetic Patients.

Aims: Nondiabetic patients were studied to determine whether modest elevations in plasma mannose may be associated with a greater incidence of coronary artery disease (CAD). Materials and Methods: Plasma insulin, mannose, glucose, hexokinase 1-2, GLUT1-GLUT4 levels, and serum mannose phosphate isomerase enzyme levels were evaluated with respect to subsequent CAD using records from 120 nondiabetic CAD patients and 120 healthy volunteers. CAD was identified from myocardial infarction and new diagnoses of angina. Results: Of 120 nondiabetic CAD patients studied, their plasma GLUT4 and HK1 levels were significantly lower than those of the control group. In addition, a significant increase in plasma mannose levels was found in the patient group compared to the control group. Conclusion: Our findings showed that elevated baseline mannose levels in plasma are associated with an increased risk of CAD over time.

Comprehensive and quantitative profiling of lipid molecular species by LC-ESI-MS/MS of four native species from semiarid Patagonian Monte.

The maintenance of lipid and fatty acids unsaturated composition has been described as one of the mechanisms associated to drought tolerance, but research about the lipid profile in native plants of semiarid environment is still limited. The primary objective was to study whether lipid profiles correlates with drought resistance strategies (tolerant or avoidant) of two life forms (shrubs and grasses). The lipid classes and molecular species of green leaves of Larrea divaricata and Lycium chilense shrubs and Pappostipa speciosa and Poa ligularis grasses were determined using LC-ESI-MS/MS. The soil water content was very low during spring and leaf relative water content was between 47 and 74% in the four species. Lipid profiling was different between both life forms. The prevalent compounds were digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG) and phosphatidic acid (PA). The lipid signature shows that L. divaricata adjust its lipid composition to tolerate drought, increasing the content of: a) total lipids and total phospholipids, b) structural phospholipids (36:4 and 36:2-PC, phosphatidylcholine; 36:4-PE, phosphatidylethanolamine), c) chloroplast and mitochondria lipids (32:1 and 32:0-PG, phosphatidylglycerol; 34:3, 36:6 and 36:3-DGDG), d) signaling lipids (34:3, 34:2 and 36:5-PA and PI, phosphatidylinositol), and e) polyunsaturated fatty acids (PUFAs, 18:3 and 18:2) and long chain polyunsaturated fatty acids (LC-PUFAs, in 40:2 and 42:2-PS, phosphatidylserine). This membrane lipid composition contributes to membrane stabilization as metabolic-functional strategy for drought tolerance in the Patagonian Monte. In addition, the 18:3 present in lipids of both grasses could be incorporated to lamb fed based on pastures and result healthy for human dietary.

Biosynthetic Studies on Acetosellin and Structure Elucidation of a New Acetosellin Derivative.

Natural products from fungi, especially Ascomycota, play a major role in therapy and drug discovery. Fungal strains originating from marine habitats offer a new avenue for finding unusual molecular skeletons. Here, the marine-derived fungus Epicoccum nigrum (strain 749) was found to produce the azaphilonoid compounds acetosellin and 5',6'-dihydroxyacetosellin. The latter is a new natural product. The biosynthesis of these polyketide-type compounds is intriguing, since two polyketide chains are assembled to the final product. Here we performed 13C labeling studies on solid cultures to prove this hypothesis for acetosellin biosynthesis.

Phenolic compounds as indicators of drought resistance in shrubs from Patagonian shrublands (Argentina).

UNLABELLED: Plants exposed to drought stress, as usually occurs in Patagonian shrublands, have developed different strategies to avoid or tolerate the lack of water during their development. Production of phenolic compounds (or polyphenols) is one of the strategies used by some native species of adverse environments to avoid the oxidative damage caused by drought. In the present study the relationship between phenolic compounds content, water availability and oxidative damage were evaluated in two native shrubs: Larrea divaricata (evergreen) and Lycium chilense (deciduous) of Patagonian shrublands by their means and/or by multivariate analysis. Samples of both species were collected during the 4 seasons for the term of 1 year. Soil water content, relative water content, total phenols, flavonoids, flavonols, tartaric acid esters, flavan-3-ols, proanthocyanidins, antioxidant capacity and lipid peroxidation were measured. According to statistical univariate analysis, L. divaricata showed high production of polyphenols along the year, with a phenolic compound synthesis enhanced during autumn (season of greatest drought), while L. chilense has lower production of these compounds without variation between seasons. The variation in total phenols along the seasons is proportional to the antioxidant capacity and inversely proportional to lipid peroxidation. Multivariate analysis showed that, regardless their mechanism to face drought (avoidance or tolerance), both shrubs are well adapted to semi-arid regions and the phenolic compounds production is a strategy used by these species living in extreme environments. The identification of polyphenol compounds showed that L. divaricata produces different types of flavonoids, particularly bond with sugars, while L. chilense produces high amount of non-flavonoids compounds. SYNTHESIS: These results suggest that flavonoid production and accumulation could be a useful indicator of drought tolerance in native species.

GPR18 Inhibiting Amauromine and the Novel Triterpene Glycoside Auxarthonoside from the Sponge-Derived Fungus Auxarthron reticulatum.

The marine sponge-derived fungus Auxarthron reticulatum produces the cannabinoid receptor antagonist amauromine (1). Recultivation of the fungus to obtain further amounts for more detailed pharmacological evaluation of 1 additionally yielded the novel triterpene glycoside auxarthonoside (2), bearing, in nature, a rather rare sugar moiety, i.e., N-acetyl-6-methoxy-glucosamine. Amauromine (1), which inhibited cannabinoid CB1 receptors (Ki 0.178 µM) also showed antagonistic activity at the cannabinoid-like orphan receptor GPR18 (IC50 3.74 µM). The diketopiperazine 1 may thus serve as a lead structure for the development of more potent and selective GPR18 antagonists, which are required to study the orphan receptor's potential as a new drug target. Despite the execution of many biological assays, to date, no bioactivity could be found for auxarthonoside (2).

Simenoside A, a new triterpenoid saponin from Gypsophila simonii Hub.-Mor.

Saponins are amphiphilic glycoconjugates which give soap-like foams in H2 O. A new triterpenoid saponin, simenoside A (1), based on gypsogenin aglycone, and the known saponin 2 were isolated from Gypsophila simonii Hub.-Mor. The structure of the new saponin was elucidated as 3-O-ß-D-galactopyranosyl-(1→2)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucuronopyranosylgypsogenin 28-O-ß-D-glucopyranosyl-(1→3)-[ß-D-glucopyranosyl-(1→2)-ß-D-xylopyranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-ß-D-fucopyranosyl ester on the basis of extensive spectral analyses and chemical evidence. Saponins 1 and 2 were isolated from G. simonii for the first time.

Nebulosides A-B, novel triterpene saponins from under-ground parts of Gypsophila arrostii Guss. var. nebulosa.

A bioassay-guided phytochemical analysis of the triterpene saponins from under ground parts of Gypsophila arrostii var. nebulosa allowed the isolation of two triterpene saponins; nebuloside A, B based on gypsogenin and quillaic acid aglycone. Two new oleanane type triterpenoid saponins (nebuloside A, B) and three known saponins (1-3) were isolated from the root bark of Gypsophila arrostii var. nebulosa. The structures of the two new compounds were elucidated as 3-O-ß-D-galactopyranosyl-(1→2)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-glucopyranosyl-(1→3)-[ß-D-xylopyranosyl-(1→3)-ß-D-xylopyranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-ß-D-fucopyranosyl ester (nebuloside A) and 3-O-ß-D-xylopyranosyl-(1→3)-[ß-D-galactopyranosyl(1→3)-ß-D-galactopyranosyl-(1→2)]-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-glucopyranosyl-(1→3)-[ß-D-xylopyranosyl-(1→3)-ß-D-xylopyranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-ß-D-fucopyranosyl ester (nebuloside B), on the basis of extensive spectral analysis and chemical evidence. Nebuloside A and B showed toxicity enhancing properties on saporin a type-I RIP without causing toxicity by themselves at 15 µg/mL.

A cytotoxic triterpenoid saponin from under-ground parts of Gypsophila pilulifera Boiss.& Heldr.

A cytotoxic triterpenoid saponin was isolated from the under-ground parts of Gypsophila pilulifera Boiss.& Heldr. (Caryophyllaceae) naturally grow in the southwestern region of the Turkey. The structures of saponin was elucidated as 3-O-ß-D-galactopyranosyl-(1→2)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-glucopyranosyl-(1→3)-[ß-d-xylopyranosyl-(1→4]-α-l-rhamnopyranosyl-(1→2)-ß-D-fucopyranosyl ester on the basis of extensive spectral analysis and chemical evidence. The separated triterpenoid saponin was isolated from Gypsophila pilulifera for the first time. The saponin compound displayed significant cytotoxicity against A549 cell line with IC(50) values >16µM.

Phytochemical constituents and inhibitory activity towards methicillin-resistant Staphylococcus aureus strains of Eryngium species (Apiaceae).

The chemical composition of the essential oils of Eryngium campestre, E. thorifolium, and E. creticum (Apiaceae), growing in the Aegean region of Turkey (Mount Sandras, Denizli), was determined by direct thermal desorption (DTD)-GC/MS analyses. A total of 49 components were identified in the oils, α-pinene and hexanal being the major compounds. The three essential oils were also tested for their inhibitory activity of nine different methicillin-resistant Staphylococcus aureus (MRSA) strains by the agar disc diffusion method. The anti-MRSA activity of E. thorifolium oil, the most active of the three oils, was comparable with those of the reference antibiotic vancomycin and oregano oil, although somewhat lower.

Screening of the constituents, antimicrobial and antioxidant activity of endemic Origanum hypericifolium O. Schwartz & P.H. Davis.

The chemical compositions, total phenol content, antioxidant and antimicrobial activities with oxidant status of the essential oil from an endemic Turkish species, Origanum hypericifolium, were investigated. Steam distillation (SD) was used to isolate the essential oils, and the chemical analyses were performed by gas chromatography-mass spectrometry (GC-MS). The antimicrobial activity was tested by agar disc diffusion method against Morganella morganii (clinic isolate), Micrococcus flavus (clinic isolate), Micrococcus luteus NRLL B-4375, Proteus vulgaris RSKK 96026, Escherichia coli ATCC 11230, Escherichia coli ATCC 25922, Yersinia enterecolitica RSKK 1501, Staphylococcus aureus ATCC 25923, S. aureus ATCC 25933, S. aureus ATCC 12598, S. aureus (clinic isolate), MRSA 1 (clinic isolate), MRSA 2 (clinic isolate), MRSA 3 (clinic isolate) and MRSA 4 (clinic isolate). The major compounds found in volatiles of O. hypericifolium were p-cymene, carvacrol and γ-terpinene. Results showed that O. hypericifolium has the potential for being used in food and medicine because of its antioxidant and antibacterial activity.