Blood-brain barrier endothelial cells are the main targets of diabetes-related hyperglycemia that alters endothelial functions and brain homeostasis. Hyperglycemia-mediated oxidative stress may play a causal role. This study evaluated the protective effects of characterized polyphenol-rich medicinal plant extracts on redox, inflammatory and vasoactive markers on murine bEnd3 cerebral endothelial cells exposed to high glucose concentration. The results show that hyperglycemic condition promoted oxidative stress through increased reactive oxygen species (ROS) levels, deregulated antioxidant superoxide dismutase (SOD) activity, and altered expression of genes encoding Cu/ZnSOD, MnSOD, catalase, glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), NADPH oxidase 4 (Nox4), and nuclear factor erythroid 2-related factor 2 (Nrf2) redox factors. Cell preconditioning with inhibitors of signaling pathways highlights a causal role of nuclear factor kappa B (NFκB), while a protective action of AMP-activated protein kinase (AMPK) on redox changes. The hyperglycemic condition induced a pro-inflammatory response by elevating NFκB gene expression and interleukin-6 (IL-6) secretion, and deregulated the production of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) vasoactive markers. Importantly, polyphenolic extracts from Antirhea borbonica, Ayapana triplinervis, Dodonaea viscosa, and Terminalia bentzoe French medicinal plants, counteracted high glucose deleterious effects by exhibiting antioxidant and anti-inflammatory properties. In an innovative way, quercetin, caffeic, chlorogenic and gallic acids identified as predominant plant polyphenols, and six related circulating metabolites were found to exert similar benefits. Collectively, these findings demonstrate polyphenol protective action on cerebral endothelial cells during hyperglycemic condition.

Metabolic disorders related to obesity and type 2 diabetes are associated with aggravated cerebrovascular damages during stroke. In particular, hyperglycemia alters redox and inflammatory status, leading to cerebral endothelial cell dysfunction, blood–brain barrier (BBB) disruption and brain homeostasis loss. Polyphenols constitute the most abundant dietary antioxidants and exert anti-inflammatory effects that may improve cerebrovascular complications in stroke. This study evaluated the effects of the characterized polyphenol-rich extract of Antirhea borbonica medicinal plant and its major constituent caffeic acid on a high-fat diet (HFD)-induced obesity mouse model during ischemic stroke, and murine bEnd3 cerebral endothelial cells in high glucose condition. In vivo, polyphenols administered by oral gavage for 12 weeks attenuated insulin resistance, hyperglycemia, hyperinsulinemia and dyslipidemia caused by HFD-induced obesity. Polyphenols limited brain infarct, hemorrhagic transformation and BBB disruption aggravated by obesity during stroke. Polyphenols exhibited anti-inflammatory and antioxidant properties by reducing IL-1β, IL-6, MCP-1, TNF-α and Nrf2 overproduction as well as total SOD activity elevation at the cerebral or peripheral levels in obese mice. In vitro, polyphenols decreased MMP-2 activity that correlated with MCP-1 secretion and ROS intracellular levels in hyperglycemic condition. Protective effects of polyphenols were linked to their bioavailability with evidence for circulating metabolites including caffeic acid, quercetin and hippuric acid. Altogether, these findings show that antioxidant polyphenols reduced cerebrovascular, inflammatory and metabolic disorders aggravated by obesity in a mouse model of stroke. It will be relevant to assess polyphenol-based strategies to improve the clinical consequences of stroke in the context of obesity and diabetes.

Chemical study of the CH₂Cl₂-MeOH (1:1) extract of the sponge Fascaplysinopsis reticulata collected in Mayotte highlighted three new tryptophan derived alkaloids, 6,6′-bis-(debromo)-gelliusine F (1), 6-bromo-8,1′-dihydro-isoplysin A (2) and 5,6-dibromo-8,1′-dihydro-isoplysin A (3), along with the synthetically known 8-oxo-tryptamine (4) and the three known molecules from the same family, tryptamine (5), (E)-6-bromo-2′-demethyl-3′-N-methylaplysinopsin (6) and (Z)-6-bromo-2′-demethyl-3′-N-methylaplysinopsin (7). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their antimicrobial and their antiplasmodial activities. Regarding antimicrobial activities, the best compounds are (2) and (3), with minimum inhibitory concentration (MIC) of 0.01 and 1 µg/mL, respectively, towards Vibrio natrigens, and (5), with MIC values of 1 µg/mL towards Vibrio carchariae. In addition the known 8-oxo-tryptamine (4) and the mixture of the (E)-6-bromo-2′-demethyl-3′-N-methylaplysinopsin (6) and (Z)-6-bromo-2′-demethyl-3′-N-methylaplysinopsin (7) showed moderate antiplasmodial activity against Plasmodium falciparum with IC₅₀ values of 8.8 and 8.0 µg/mL, respectively.

Chemical study of the CH2Cl2−MeOH (1:1) extract from the sponge Haliclona sp. collected in Mayotte highlighted three new long-chain highly oxygenated polyacetylenes, osirisynes G-I (1–3) together with the known osirisynes A (4), B (5), and E (6). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS and MS/MS data. All compounds were evaluated on catalase and sirtuin 1 activation and on CDK7, proteasome, Fyn kinase, tyrosinase, and elastase inhibition. Five compounds (1; 3–6) inhibited proteasome kinase and two compounds (5–6) inhibited CDK7 and Fyn kinase. Osirisyne B (5) was the most active compound with IC₅₀ on FYNB kinase, CDK7 kinase, and proteasome inhibition of 18.44 µM, 9.13 µM, and 0.26 µM, respectively.

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer’s disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7–10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1–4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted.

A chemical study of the CH₂Cl₂−MeOH (1:1) extract from the sponge Ernsta naturalis collected in Rodrigues (Mauritius) based on a molecular networking dereplication strategy highlighted one novel aminopyrimidone alkaloid compound, ernstine A (1), seven new aminoimidazole alkaloid compounds, phorbatopsins D–E (2, 3), calcaridine C (4), naamines H–I (5, 7), naamidines J–K (6, 8), along with the known thymidine (9). Their structures were established by spectroscopic analysis (1D and 2D NMR spectra and HRESIMS data). To improve the investigation of this unstudied calcareous marine sponge, a metabolomic study by molecular networking was conducted. The isolated molecules are distributed in two clusters of interest. Naamine and naamidine derivatives are grouped together with ernstine in the first cluster of twenty-three molecules. Phorbatopsin derivatives and calcaridine C are grouped together in a cluster of twenty-one molecules. Interpretation of the MS/MS spectra of other compounds of these clusters with structural features close to the isolated ones allowed us to propose a structural hypothesis for 16 compounds, 5 known and 11 potentially new.