Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Antioxidant, antimicrobial, cytotoxic and protective effects of truffles.

Fungi can be used as a potent chemotherapeutic agent to treat various cancers. In current study acetone and methanol extracts of Terfezia claveryi, Terfezia boudieri, Terfezia olbiensis, Picoa lefebvrei, Picoa juniperi were used to assess total phenolic contents, antioxidant activity, ion-chelating impact, antimicrobial activity, the cytotoxic and protective effects. Both methanol and acetone extracts of T. boudieri had the highest FRAP and DPPH scavenging abilities. Dose-dependent increased ion-chelating impact of all tested truffles species was found. Extracts of T. boudieri, T. claveryi, and T. albiensis exhibited higher antimicrobial activities. T. claveryi and T. boudieri showed the highest protective effects against H2O2-induced genotoxicity (P < 0.05), in S. cerevisiae BY4741. The least protective effect was showed by the acetone extracts of T. olbiensis (144 ± 8); methanol extracts of P. lefebvrei (140 ± 8) and P. juniperi (140 ± 10). MCF 7 cells showed more sensitivity against to methanol extracts of T. boudieri at 10-100 µg/mL concentrations. HepG2 cells showed more sensitivity against the methanolic extracts of T. boudieri at both doses. Overall, P. lefebvrei and P. juniperi extracts had the least cytotoxic effects. The species of Terfezia exhibit significant protective effects against DNA damage and also have the potential of cytotoxicity effects.

Free radical scavenging activities of verbascoside and isoverbascoside from the leaves of Odontonema strictum (Acanthaceae).

The aqueous extract of the leaves of Odontonema strictum, a plant from tropical regions, is used by traditional physicians in Burkina Faso for its antihypertensive properties. Verbascoside and isoverbascoside, known phenylpropanoid glycosides with high solubility in water, have been isolated from the leaves. We evaluated their antioxidant properties in vitro by radical scavenging using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2). Verbascoside and isoverbascoside demonstrated high levels of DPPH radical scavenging activity, with IC50 values of 0.09 ± 0.03 µg/mL and 0.16 ± 0.07 µg/mL, respectively, compared to 0.05 ± 0.0 µg/mL for ascorbic acid as a control. These two phenylpropanoid glycosides were also more potent (2.6 ± 0.36 µg/mL and 3.0 ± 0.01 µg/mL) in scavenging H2O2 than the ascorbic acid control (4.1 ± 0.97 µg/mL). This is the first time that the antioxidant properties of verbascoside and isoverbascoside from O. strictum have been evaluated. These results can explain the use of this plant for hypertension in folk medicine.

Oat polyphenol avenanthramide-2c confers protection from oxidative stress by regulating the Nrf2-ARE signaling pathway in PC12 cells.

Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.

Inhibition of UVA Damage on Human Skin Dermis Fibroblasts by the Isoflavonoid Intermediate Deoxybenzoin-3A.

Ultraviolet rays are the main cause of skin aging. Isoflavone structures are good anti-ultraviolet natural compounds and have an especially strong anti-ultraviolet B (UVB) effect. However, the anti-ultraviolet A (UVA) effect of isoflavones is more controversial. Therefore, this study aims to discover which isoflavone analogue possesses a strong anti-ultraviolet A. We found the isoflavonoid intermediate deoxybenzoin-3A (DOB-3A) to be a similar isoflavone structural compound with strong anti-ultraviolet A effects. Ultraviolet rays with a wavelength of 350 nm are used to irradiate the fibroblasts of the human skin. Western blot, flow cytometry, and transmission electron microscope analyses were used to explore its anti-ultraviolet A mechanism. We established the results that DOB-3A (1) reduced the death of fibroblasts caused by ultraviolet A, (2) avoided the damage to the organelles and structures after UVA irradiation, (3) inhibited the generation of intracellular reactive oxygen species (ROS) and hydrogen peroxide-induced damage, and (4) decreased the phosphorylation of mitogen-activated protein kinases (MAPK) caused by UVA. Based on the above findings, DOB-3A is a very good anti-ultraviolet A isoflavone-related structure. Because it is simple to synthesize and has good effects, DOB-3A is a suitable anti-ultraviolet A product with an isoflavone structure. Moreover, DOB-3A's structure provides a reference for the synthesis of anti-UVA isoflavones.

Dicopper(II) Complexes of p-Cresol-2,6-Bis(dpa) Amide-Tether Ligands: Large Enhancement of Oxidative DNA Cleavage, Cytotoxicity, and Mechanistic Insight by Intracellular Visualization.

Dicopper complexes of a new p-cresol-2,6-bis(dpa) amide-tether ligand (HL1), [Cu2(µ-OH2)(µ-1,3-OAc)(L1)](ClO4)2 (1) and [Cu2(µ-1,1-OAc)(µ-1,3-OAc)(L1)]X (X = ClO4 (2a), OAc (2b)) were synthesized and structurally characterized. 2b rapidly cleaves supercoiled plasmid DNA by activating H2O2 at neutral pH to a linear DNA and shows remarkable cytotoxicity in comparison with related complexes. As 2b is more cytotoxic than HL1, the dicopper core is kept in the cell. A boron dipyrromethene (Bodipy)-modified complex of the p-cresol-2,6-bis(dpa) amide-tether ligand having a Bodipy pendant (HL2), [Cu2(µ-OAc)2(L2)](OAc) (3), was synthesized to visualize intracellular behavior, suggesting that 2b attacks the nucleolus and mitochondria. A comet assay clearly shows that 2b does not cleave nuclear DNA. The apoptotic cell death is evidenced from flow cytometry.

Selective targeting of cancer cells using a hydrogen peroxide-activated Hsp90 inhibitor.

Heat shock protein 90 (Hsp90) plays an important role in cancer cell proliferation, survival, and migration by regulating the maturation and stabilization of numerous oncoproteins. Despite significant efforts in developing Hsp90 inhibitors, none of these have been approved for clinical use, mostly due to toxicity, such as liver, cardiac, and retinal toxicity. To avoid undesirable toxicity, we herein report a hydrogen peroxide-activated Hsp90 inhibitor, Boro-BZide (3), which is capable of selectively targeting cancer cells over normal cells. Boro-BZide (3) can be activated by high levels of hydrogen peroxide, releasing its parent active Hsp90 inhibitor. The mechanism of action was determined by a series of experiments including fluorescence polarization assay, cell viability assay, western blotting, high-pressure liquid chromatography (HPLC), and fluorescence-activated cell sorting (FACS) analysis. These efforts ultimately led to the identification of a novel hydrogen peroxide-activated Hsp90 prodrug with improved therapeutic index, which was less prone to furnish unwanted adverse effects. This hydrogen peroxide-responsive prodrug strategy will be beneficial for overcoming the toxicity hurdles of Hsp90 inhibitors for clinical application.

Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt/Nrf2 signaling pathway.

Periodontal ligament stem cell (PDLSC)-based tissue engineering is an important method for regenerating lost bone in periodontitis. Maintaining or enhancing the osteogenic differentiation of PDLSCs, as well as enhancing the resistance of PDLSCs to oxidative stress, is necessary in this process. As a common hypoglycemic drug, metformin has been reported to have multiple effects on cell functions. This study found that low concentrations of metformin did not affect cell proliferation but did inhibit adipogenic differentiation and promote osteogenic differentiation of PDLSCs. This positive effect was associated with activation of Akt signaling by metformin. Moreover, applying metformin as either a pretreatment or co-treatment could reduce the amount of reactive oxygen species, enhance antioxidant capacity, and rescue the cell viability and osteogenic differentiation that were negatively affected by H2O2-induced oxidative stress in PDLSCs. In addition, metformin was found to activate the Nrf2 signaling pathway in PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin. Taken together, these results indicate that metformin not only promotes osteogenic differentiation of PDLSCs, but also protects PDLSCs against oxidative stress-induced damage, suggesting that metformin could be potentially useful in promoting PDLSC-based bone regeneration in the treatment of periodontitis.

Synergistic properties of bioavailable phenolic compounds from olive oil: electron transfer and neuroprotective properties.

Phenolic compounds from olive oil (ArOH-EVOO) are recognized for their antioxidant and neuroprotective capacities, but are often studied individually or through a natural extract. As their reactivity towards reactive oxygen species (ROS) depends on their structure and could implicate different complementary mechanisms, we hypothesized that their effects could be enhanced by an innovative combination of some of the most abundant ArOH-EVOO. Using electrochemical methods, we have compared their reactivity towards hydrogen peroxide and the superoxide anion radical. The mixture containing oleuropein, p-coumaric acid and tyrosol (Mix1), was more efficient than the mixture containing hydroxytyrosol, the oleuropein catechol moiety, and the two monophenols (Mix2). On neuronal SK-N-SH cells challenged with H2O2 or Paraquat, low concentrations (0.1 and 1 µM) of the Mix1 improved neuronal survival. These neuroprotective effects were supported by a decrease in intracellular ROS, in the protein carbonyl levels and the prevention of the redox-sensitive factors Nrf2 and NF-κB activation. These intracellular effects were supported by the demonstration of the internalization of these ArOH-EVOO into neuronal cells, evidenced by LC-HRMS. Our results demonstrated that this combination of ArOH-EVOO could be more efficient than individual ArOH usually studied for their neuroprotective properties. These data suggest that the Mix1 could delay neuronal death in neurodegenerative diseases related to oxidative stress such as Alzheimer's (AD) and Parkinson's diseases (PD).

Spermidine promotes melanin production through an MITF signalling pathway.

Melanin plays an important role in determining skin colour. Apoptosis of melanocytes and defect in melanin production cause vitiligo. Various studies have been conducted to treat the disease, but its treatment is still difficult. Therefore, this study aimed to investigate the effect of spermidine, which is known as an inhibitor of ageing-related oxidized proteins, on melanogenesis. Even though spermidine above 50 µM had no effect on antioxidant activity and DOPA oxidation, it displayed tyrosinase activity. However, spermidine at 2000 µM was cytotoxic in B16F1 cells using MTT assay. Spermidine above 125 µM decreased the amount of intracellular hydrogen peroxide in a concentration-dependent manner in DCFH-DA analysis. It was also found that spermidine above 2000 µM increased melanin synthesis in living cells. However, spermidine above 1000 µM increased melanin synthesis in a concentration-dependent manner in H2 O2 -treated B16F1 cells. Furthermore, spermidine enhanced the expression of tyrosine hydroxylase via MITF transcription factor involved in melanogenesis in H2 O2 -treated B16F1 cells. Therefore, these results suggest that spermidine could be applied as a potential stimulator of melanin synthesis for the prevention of hair greying.

Separation of constituents from Bergenia stracheyi (Hook. F. & Thoms.) Engl. by high-speed countercurrent chromatography with elution mode and its antidiabetic and antioxidant in vitro evaluation.

Diabetes, a metabolic disorder, is caused by a high blood sugar level. Diabetes is an increasing health issue and search for potent antidiabetic agents is desirable. Owing to its ethnomedicinal value, the Himalayan perennial herb Bergenia stracheyi (Hook. f. & Thoms.) Engl. (Saxifragaceae Juss) is used to treat diabetes. Herein, an efficient high-speed countercurrent chromatography with elution mode is reported for separation of active compounds from B. stracheyi. In current investigation, six main compounds including ß-arbutin (1), bergenin (2), 6-O-galloylarbutin (3), gallic acid (4), 11-O-galloylbergenin (5), and (-)-epicatechin 3-O-gallate (6) with above 95% purity were efficiently separated in a single run using biphasic tert-butyl methyl ether/n-butanol/methanol/water (1:3:1:5, v/v/v/v) solvent system. The structures of these compounds were characterized using spectral techniques and compared with the literature. Antidiabetic and antioxidant activities evaluation of the study samples showed that ß-arbutin (1) and 6-O-galloylarbutin (3) have a significant protective effect, especially at high dose against hydrogen peroxide induced oxidative injury. Our results might help further in-depth phytochemical and biological evaluation studies in search of potent antidiabetic compounds from B. stracheyi.

Ferrous hemoglobin and hemoglobin-based oxygen carriers acting as a peroxidase can inhibit oxidative damage to endothelial cells caused by hydrogen peroxide.

Oxidative damage caused by the ferryl hemoglobin is one of the major clinical adverse reactions of hemoglobin-based oxygen carriers (HBOCs), while the production of reactive oxygen species in a pathological state can oxidize hemoglobin (HbFe2+ ) to ferryl Hb, which can then enter the pseudoperoxidase cycle, making hemoglobin highly toxic. In this study, we found that ferrous hemoglobin and polymerized porcine hemoglobin (one of the HBOCs) have the peroxidase activity different from the pseudoperoxidase activity of ferric hemoglobin. Ferrous hemoglobin can catalyze the reaction of tyrosine (Tyr) with hydrogen peroxide. In addition, the results also indicated that ferrous hemoglobin and pPolyHb have a strong inhibitory effect on the pseudoperoxidase activity of ferric hemoglobin. Therefore, hydrogen peroxide was consumed in a large amount, which greatly prevented hemoglobin from becoming oxidized and entering the pseudoperoxidase cycle, thus inhibiting ferryl Hb toxicity. We further cultured human umbilical vein endothelial cells and monitored cell morphology, viability, cell cycle, apoptosis, lactate dehydrogenase (LDH) release, and malondialdehydes (MDAs) formation when incubated with H2 O2 , Tyr, and HbFe2+ . HbFe2+ and pPolyHb reduced cell cycle arrest, apoptosis, LDH release, and MDA formation. These results showed that reducing oxidative damage induced by H2 O2 and converted hemoglobin from a molecule that is toxic to one that inhibits oxidative damage, suggesting a new strategy for development of a safer HBOCs.

Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations.

Nine compounds (MO1-MO9) containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; MO1 most potently inhibited with an IC50 value of 0.030 µM, followed by MO7 (0.25 µM). MO5 most potently inhibited AChE (IC50 = 6.1 µM), followed by MO9 (IC50 = 12.01 µM) and MO7 most potently inhibited MAO-A (IC50 = 7.1 µM). MO1 was a reversible mixed-type inhibitor of MAO-B (Ki = 0.018 µM); MO5 reversibly competitively inhibited AChE (Ki = 2.52 µM); and MO9 reversibly noncompetitively inhibited AChE (Ki = 7.04 µM). MO1, MO5 and MO9 crossed the blood-brain barrier, and were non-toxic to normal VERO cells. These results show that MO1 is a selective inhibitor of MAO-B and that MO5 is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer's disease.

Design, Synthesis, and Molecular Docking of Some Novel Tacrine Based Cyclopentapyranopyridine- and Tetrahydropyranoquinoline-Kojic Acid Derivatives as Anti-Acetylcholinesterase Agents.

A novel series of tacrine based cyclopentapyranopyridine- and tetrahydropyranoquinoline-kojic acid derivatives were designed, synthesized, and evaluated as anti-cholinesterase agents. The chemical structures of all target compounds were characterized by 1 H-NMR, 13 C-NMR, and elemental analyses. The synthesized compounds mostly inhibited acetylcholinesterase enzyme (AChE) with IC50 values of 4.18-48.71 µM rather than butyrylcholinesterase enzyme (BChE) with IC50 values of >100 µM. Among them, cyclopentapyranopyridine-kojic acid derivatives showed slightly better AChE inhibitory activity compared to tetrahydropyranoquinoline-kojic acid. The compound 10-amino-2-(hydroxymethyl)-11-(4-isopropylphenyl)-7,8,9,11-tetrahydro-4H-cyclopenta[b]pyrano[2',3' : 5,6]pyrano[3,2-e]pyridin-4-one (6f) bearing 4-isopropylphenyl moiety and cyclopentane ring exhibited the highest anti-AChE activity with IC50 value of 4.18 µM. The kinetic study indicated that the compound 6f acts as a mixed inhibitor and the molecular docking studies also illustrated that the compound 6f binds to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE. The compound 6f showed moderate neuroprotective properties against H2 O2 -induced cytotoxicity in PC12 cells. The theoretical ADME study also predicted good drug-likeness for the compound 6f. Based on these results, the compound 6f seems to be a very promising AChE inhibitor for the treatment of Alzheimer's disease.

An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2.

Cyclooxygenases 2 (COX2) is a therapeutic target for many inflammation and oxidative stress associated diseases. A high-throughput technique, biolayer interferometry, was performed to primarily screen the potential COX2 binding activities of twelve newly synthesized double hydroxide-based benzophenone derivatives. Binding confirmation was achieved by molecular docking and multi-spectroscopy studies. Such a combined method provided a comprehensive understanding of binding mechanism and conformational changes. Compounds DB2, SC2 and YB2 showed effective COX2 binding activity and underlined the benefits of three phenolic hydroxyl groups adjacent to each other on the B ring. The twelve tested derivatives were further evaluated for antioxidant activity, wherein compound SC2 showed the highest activity. Its concentration for the 50% of maximal effect (EC50) value was approximately 1000 times greater than that of the positive controls. SC2 treatment effectively improved biochemical indicators caused by oxidative stress. Overall, compound SC2 could serve as a promising candidate for further development of a new potent COX2 inhibitor.

Antioxidative Effects of Chrysoeriol via Activation of the Nrf2 Signaling Pathway and Modulation of Mitochondrial Function.

Retinal pigment epithelium (RPE) cell dysfunction caused by excessive oxidative damage is partly involved in age-related macular degeneration, which is among the leading causes of visual impairment in elderly people. Here, we investigated the protective role of chrysoeriol against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. The cellular viability, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were monitored under oxidative stress or pre-treatment with chrysoeriol. The expression levels of mitochondrial-related genes and associated transcription factors were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Moreover, the protein expression of antioxidant signal molecules was characterized by Western blot analysis. Chrysoeriol significantly increased cell viability, reduced ROS generation, and increased the occurrence of antioxidant molecules in H2O2-treated ARPE-19 cells. Additionally, mitochondrial dysfunction caused by H2O2-induced oxidative stress was also considerably diminished by chrysoeriol treatment, which reduced the mitochondrial membrane potential (MMP) and upregulated mitochondrial-associated genes and proteins. Chrysoeriol also markedly enhanced key transcription factors (Nrf2) and antioxidant-associated genes (particularly HO-1 and NQO-1). Therefore, our study confirms the protective effect of chrysoeriol against H2O2-induced oxidative stress in RPE cells, thus confirming that it may prevent mitochondrial dysfunction by upregulating antioxidant-related molecules.

Curcumin-Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders.

Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin-coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11-18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.

Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch (Betula pendula Roth) and Black Birch (Betula obscura Kotula) Barks by FT-IR and HPLC-PDA.

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.

Neurotrophic Effect of Magnesium Comenate in Normal and under Conditions of Oxidative Stress in Culture of Chicken Spinal Ganglia.

The neurotrophic properties of magnesium comenate were studied under standard conditions and under conditions of oxidative stress. It was found that magnesium comenate has a stimulating effect on the neurotrophic processes of the spinal ganglia under normal conditions and under conditions of oxidative stress. Under standard conditions, magnesium comenate exhibits neurotrophic activity at a concentration of 0.0001 mM, under conditions of oxidative stress, magnesium comenate exhibits neurotrophic activity at concentration 0.1 mM.

Dual Ratiometric SERS and Photoacoustic Core-Satellite Nanoprobe for Quantitatively Visualizing Hydrogen Peroxide in Inflammation and Cancer.

Excessive production of oxidative species alters the normal redox balance and leads to diseases, such as chronic inflammation and cancer. Oxidative species are short-lived species, which makes direct, precise, and real-time measurements difficult. Herein, we report a novel core-satellite gold nanostructure for dual, ratiometric surface-enhanced Raman scattering (SERS) and photoacoustic (PA) imaging to enable the precise detection of inflammation/cancer-related H2 O2 . The combination of H2 O2 -activated second near-infrared (NIR-II) PA imaging and SERS imaging enables the differentiation between the inflamed region and normal tissue with high accuracy. The mesoporous silica shell of the nanoprobe could be used to deliver drugs to the target area to precisely treat disease. Therefore, this core-satellite nanostructure can not only quantitatively and precisely monitor H2 O2 produced in inflammation, tumor, and osteoarthritis in rabbits in real-time, but can also be used to track the progress of the anti-inflammatory treatment in real-time.