Approaches of marine compounds and relevant immune mediators in Autism Spectrum Disorder: Opportunities and challenges.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects social skills, language, communication, and behavioral skills, significantly impacting the individual's quality of life. Recently, numerous works have centered on the connections between the immune and central nervous systems and the influence of neuroinflammation on autism symptomatology. Marine natural products are considered as important alternative sources of different types of compounds, including polysaccharides, polyphenols, sterols, carotenoids, terpenoids and, alkaloids. These compounds present anti-inflammatory, neuroprotective and immunomodulatory activities, exhibiting a potential for the treatment of many diseases. Although many studies address the marine compounds in the modulation of inflammatory mediators, there is a gap regarding their use in the regulation of the immune system in ASD. Thus, this review aims to provide a better understanding regarding cytokines, chemokines, growth factors and immune responses in ASD, as well as the potential of bioactive marine compounds in the immune regulation in ASD. We expect that this review would contribute to the development of therapeutic alternatives for controlling immune mediators and inflammation in ASD.

Structural Elucidation of an Atropisomeric Entcassiflavan-(4ß→8)-Epicatechin Isolated from Dalbergia monetaria L.f. Based on NMR and ECD Calculations in Comparison to Experimental Data.

A rare dihydoxyflavan-epicatechin proanthocyanidin, entcassiflavan-(4ß→8)-epicatechin, was isolated from Dalbergia monetaria, a plant widely used by traditional people from the Amazon to treat urinary tract infections. The constitution and relative configuration of the compound were elucidated by HR-MS and detailed 1D- and 2D-NMR measurements. By comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD spectra of all 16 possible isomers, the absolute configuration, the interflavan linkage, and the atropisomers could be determined.

Antiinflammatory activity of natural triterpenes-An overview from 2006 to 2021.

Terpenes are one of the most abundant classes of secondary metabolites produced by plants and can be divided based on the number of isoprene units (C5 ) in monoterpenes (2 units-C10 ), sesquiterpenes (3 units-C15 ), diterpenes (4 units-C20 ), triterpenes (6 units-C30 ), etc. Chemically, triterpenes are classified based on their structural skeleton including lanostanes, euphanes, cycloartanes, ursanes, oleananes, lupanes, tirucallanes, cucurbitanes, dammaranes, baccharanes, friedelanes, hopanes, serratanes etc. Additionally, glycosylated (saponins) or highly oxidated/degraded (limonoids) triterpenes could be found in nature. The antiinflammatory effect and action as immunomodulators of these secondary metabolites have been demonstrated in different studies. This review reports an overview of articles published in the last 15 years (from 2006 to 2021 using PubMed and SciFinder database) describing the antiinflammatory effects of different triterpenes with their presumed mechanism of action, suggesting that triterpenes could be appointed as natural products with future pharmaceutical applicability.

Antioxidant capacity and fragmentation features of C-glycoside isoflavones by high-resolution electrospray ionization tandem mass spectrometry using collision-induced and high-energy collisional dissociation techniques.

The rapid annotation and identification by mass spectrometry techniques of flavonoids remains a challenge, due to their structural diversity and the limited availability of reference standards. This study applies a workflow to characterize two isoflavonoids, the orobol-C-glycosides analogs, using high-energy collisional dissociation (HCD)- and collision-induced dissociation (CID)-type fragmentation patterns, and also to evaluate the antioxidant effects of these compounds by ferric reducing antioxidant power (FRAP), 2,2'-azino-bis(3-ethylbenzothiazolin acid) 6-sulfonic acid (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. By the CID-type fragmentation, in positive mode and at all high-resolution mass spectrometry (HRMS) multiple stage, there were shown differences in the annotation of the compounds, mainly concerning some ratios of relative abundance. At CID-MS2 20 eV, the compounds could be efficiently characterized, because they present distinct base peaks [M + H]+ and [M + H-H2 O]+ for the orobol-8-C- and orobol-6-C-glycoside, respectively. Similarly, by the HCD-type fragmentation, in HRMS2 stage, differences between orobol analogs in both mode of ionization were observed. However, the HR HCD-MS2 at 80 eV, in positive mode, generated more ions and each isomer presented different base peaks ions, [0,2X]+ for the orobol-8-C-glycoside and [0,3X]+ for the orobol-6-C-glycoside. By the DPPH, the 8-C-derivative showed a very close value compared with the standard rutin and, in the ABTS method, a higher radical-scavenging activity. In both methods, the EC50 of orobol-8-C-glycoside was almost twice better compared with orobol-6-C-glycoside. In FRAP, both C-glycosides showed a good capacity as Fe+3 reducing agents. We could realize that combined MS techniques, highlighting the positive mode of ionization, can be used to evaluate the isoflavones analogs being useful to differentiate between the isomeric flavones; therefore, these data are important to mass spectrometry dereplication studies become more efficient. HIGHLIGHTS: The MS2, in positive mode of ionization, at low CID energies (15 and 20 eV) and at high HCD energies (50 eV), was suitable to characterize orobol 8 and 6-C-derivatives. Positive mode of ionization was effective to rapid annotation of each orobol C-glycoside. The orobol C-derivatives showed high radical scavenging effects. Orobol-8-C-glycoside showed higher antioxidant capacity.

Integrated analytical workflow for chromatographic profiling and metabolite annotation of a cytotoxic Phorbas amaranthus extract.

Phorbas is a widely studied genus of marine sponge and produce structurally rich cytotoxic metabolites. Still, only few studies have assessed metabolites present in Brazilian species. To circumvent redundancy, in this work, we applied and herein report the use of a scouting liquid chromatographic system associate to the design of experiment produced by the DryLab® software to obtain a fast and efficient chromatographic separation of the active hexane fraction, further enabling untargeted high-resolution mass spectrometry (HRMS) data. To this end, a crude hydroalcoholic extract of the sponge Phorbas amaranthus collected in Brazilian coast was prepared and partitioned. The cytotoxicity of the crude extract and the fractions was evaluated using tumor cell culture models. Fragmentation pathways assembled from HRMS data allowed the annotation of 18 known Phorbas metabolites, while 17 metabolites were inferred based on Global Natural Product Social Molecular Networking (GNPS), matching with a further 29 metabolites annotated through molecular subnetwork. The workflow employed demonstrates that chromatographic method development can be accelerated by the use of automated scouting systems and DryLab®, which is useful for profiling natural product libraries, as well as data curation by molecular clusters and should be incorporated to the tools of natural product chemists.

Characterization of Antibacterial Proanthocyanidins of Dalbergia monetaria, an Amazonian Medicinal Plant, by UHPLC-HRMS/MS.

Dalbergia monetaria is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of D. monetaria, in a search for metabolites active against human pathogenic bacteria. In vitro assays were performed against 10 bacterial strains, highlighting methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone C-glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by (epi)-cassiaflavan and (epi)-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by (ent)-cassiaflavan-(ent)-cassiaflavan-(epi)-catechin isomers, showed the lowest MIC against the S. aureus and P. aeruginosa with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in Cassia, and the traditional medicinal use of D. monetaria might be related to the antibacterial activity of proanthocyanidins characterized in the species.

Bioactive properties and phytochemical assessment of Bacupari-anão (Garcinia brasiliensis Mart.) leaves native to Rondônia, Brazil.

Leaf fractions of Garcinia brasiliensis were evaluated concerning their antioxidant, antimicrobial, anti-inflammatory and cytotoxic properties, and the most active fraction was then fully characterized regarding its phenolic composition using HPLC-DAD-ESI/MSn. The ethyl acetate fraction from partitioning of the methanolic leaf extract revealed a strong antioxidant activity that was comparable to Trolox, the positive control. This fraction was also able to show a significant antimicrobial activity against Gram-positive and Gram-negative bacteria and the fungus Candida albicans. However, the dichloromethane fraction was found to present the highest anti-inflammatory (83 ± 9 µg mL-1) and cytotoxic activities, thus presenting slight toxicity using a non-tumor cell line. Regarding the phenolic profile, the ethyl acetate fraction presented twelve flavonoids, with morelloflavone-7''-O-glucoside (52.1 ± 0.4 mg g-1) and gardinia biflavonoid 2a glucoside (27.5 ± 0.2 mg g-1) being the major compounds identified. These results indicate that leaves of G. brasiliensis might be a potential source of natural biomolecules for pharmaceutical and medicinal applications.