Ultrasensitive Plasmon-Free Surface-Enhanced Raman Spectroscopy with Femtomolar Detection Limit from 2D van der Waals Heterostructure.

Two-dimensional (2D) materials have been promoted as an ideal platform for surface-enhanced Raman spectroscopy (SERS), as they mitigate the drawbacks of noble metal-based SERS substrates. However, the inferior limit of detection has limited the practical applicability of 2D material-based SERS substrates. Here, we synthesize uniform large-area ReOxSy thin films via solution-phase deposition without post-treatments and demonstrate a graphene/ReOxSy vertical heterostructure as an ultrasensitive SERS platform. The electronic structure of ReOxSy can be modulated by changing the oxygen concentration in the lattice structure, obtaining efficient complementary resonance effects between ReOxSy and the probe molecule. In addition, the oxygen atoms in the ReOxSy lattice generate a dipole moment on the thin-film surface, which increases the electron transition probability. These synergistic effects outstandingly enhance the Raman effect in the ReOxSy thin film. When ReOxSy forms a vertical heterostructure on a graphene as the SERS substrate, the enhanced charge-transfer and exciton resonances improve the limit of detection to the femtomolar level, while achieving remarkable flexibility, reproducibility, and operational stability. Our results provide important insights into 2D material-based ultrasensitive SERS based on chemical mechanisms.

Suppressed Interdiffusion and Degradation in Flexible and Transparent Metal Electrode-Based Perovskite Solar Cells with a Graphene Interlayer.

Metal-based transparent conductive electrodes (TCEs) are attractive candidates for application in indium tin oxide (ITO)-free solar cells due to their excellent electrical conductivity and cost effectiveness. In perovskite solar cells (PSCs), metal-induced degradation with the perovskite layer leads to various detrimental effects, deteriorating the device performance and stability. Here, we introduce a novel flexible hybrid TCE consisting of a Cu grid-embedded polyimide film and a graphene capping layer, named GCEP, which exhibits excellent mechanical and chemical stability as well as desirable optoelectrical properties. We demonstrated the critical role of graphene as a protection layer to prevent metal-induced degradation and halide diffusion between the electrode and perovskite layer; the performance of the flexible PSCs fabricated with GCEP was comparable to that of their rigid ITO-based counterparts and also exhibited outstanding mechanical and chemical stability. This work provides an effective strategy to design mechanically and chemically robust ITO-free metal-assisted TCE platforms in PSCs.

Zwitterionic Conjugated Surfactant Functionalization of Graphene with pH-Independent Dispersibility: An Efficient Electron Mediator for the Oxygen Evolution Reaction in Acidic Media.

The functionalization of graphene has been extensively used as an effective route for modulating the surface property of graphene, and enhancing the dispersion stability of graphene in aqueous solutions via functionalization has been widely investigated to expand its use for various applications across a range of fields. Herein, an effective approach is described for enhancing the dispersibility of graphene in aqueous solutions at different pH levels via non-covalent zwitterion functionalization. The results show that a surfactant with electron-deficient carbon atoms in its backbone structure and large π-π interactive area enables strong interactions with graphene, and the zwitterionic side terminal groups of the molecule support the dispersibility of graphene in various pH conditions. Experimental and computational studies confirm that perylene diimide amino N-oxide (PDI-NO) allows efficient functionalization and pH-independent dispersion of graphene enabled by hydration repulsion effects induced by PDI-NO. The PDI-NO functionalized graphene is successfully used in the oxygen evolution reaction as an electron mediator for boosting the electrocatalytic activity of a Ru-based polyoxometalate catalyst in an acidic medium. The proposed strategy is expected to bring significant advances in producing highly dispersible graphene in aqueous medium with pH-independent stability, thus broadening the application range of graphene.

Site-Selective and van der Waals Epitaxial Growth of Rhenium Disulfide on Graphene.

The surface property of growth substrate imposes significant influence in the growth behaviors of 2D materials. Rhenium disulfide (ReS2 ) is a new family of 2D transition metal dichalcogenides with unique distorted 1T crystal structure and thickness-independent direct bandgap. The role of growth substrate is more critical for ReS2 owing to its weak interlayer coupling property, which leads to preferred growth along the out-of-plane direction while suppressing the uniform in-plane growth. Herein, graphene is introduced as the growth substrate for ReS2 and the synthesis of graphene/ReS2 vertical heterostructure is demonstrated via chemical vapor deposition. Compared with the rough surface of SiO2 /Si substrate with dangling bonds which hinders the uniform growth of ReS2 , the inert and smooth surface nature of graphene sheet provides a lower energy barrier for migration of the adatoms, thereby promoting the growth of ReS2 on the graphene surface along the in-plane direction. Furthermore, patterning of the graphene/ReS2 heterostructure is achieved by the selective growth of ReS2 , which is attributed to the strong binding energy between sulfur atoms and graphene surface. The fundamental studies in the role of graphene as the growth template in the formation of van der Waals heterostructures provide better insights into the synthesis of 2D heterostructures.

Development of Annealing-Free, Solution-Processable Inverted Organic Solar Cells with N-Doped Graphene Electrodes using Zinc Oxide Nanoparticles.

An annealing-free process is considered as a technological advancement for the development of flexible (or wearable) organic electronic devices, which can prevent the distortion of substrates and damage to the active components of the device and simplify the overall fabrication process to increase the industrial applications. Owing to its outstanding electrical, optical, and mechanical properties, graphene is seen as a promising material that could act as a transparent conductive electrode for flexible optoelectronic devices. Owing to their high transparency and electron mobility, zinc oxide nanoparticles (ZnO-NP) are attractive and promising for their application as charge transporting materials for low-temperature processes in organic solar cells (OSCs), particularly because most charge transporting materials require annealing treatments at elevated temperatures. In this study, graphene/annealing-free ZnO-NP hybrid materials were developed for inverted OSC by successfully integrating ZnO-NP on the hydrophobic surface of graphene, thus aiming to enhance the applicability of graphene as a transparent electrode in flexible OSC systems. Chemical, optical, electrical, and morphological analyses of ZnO-NPs showed that the annealing-free process generates similar results to those provided by the conventional annealing process. The approach was effectively applied to graphene-based inverted OSCs with notable power conversion efficiencies of 8.16% and 7.41% on the solid and flexible substrates, respectively, which promises the great feasibility of graphene for emerging optoelectronic device applications.

Mesoporous structured MoS2 as an electron transport layer for efficient and stable perovskite solar cells.

Mesoporous structured electron transport layers (ETLs) in perovskite solar cells (PSCs) have an increased surface contact with the perovskite layer, enabling effective charge separation and extraction, and high-efficiency devices. However, the most widely used ETL material in PSCs, TiO2, requires a sintering temperature of more than 500 °C and undergoes photocatalytic reaction under incident illumination that limits operational stability. Recent efforts have focused on finding alternative ETL materials, such as SnO2. Here we propose mesoporous MoS2 as an efficient and stable ETL material. The MoS2 interlayer increases the surface contact area with the adjacent perovskite layer, improving charge transfer dynamics between the two layers. In addition, the matching between the MoS2 and the perovskite lattices facilitates preferential growth of perovskite crystals with low residual strain, compared with TiO2. Using mesoporous structured MoS2 as ETL, we obtain PSCs with 25.7% (0.08 cm2, certified 25.4%) and 22.4% (1.00 cm2) efficiencies. Under continuous illumination, our cell remains stable for more than 2,000 h, demonstrating improved photostability with respect to TiO2.

Non hemolytic short peptidomimetics as a new class of potent and broad-spectrum antimicrobial agents.

Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics.

Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, two-way crossover study.

BACKGROUND: Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. OBJECTIVES: The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. METHODS: This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-∞) were within the predetermined bioequivalence range (80 - 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). RESULTS: A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-∞) with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference formulation, the values were 332.81 ng/ml, 0.44 hours, 726.46 ng×h/ml, and 769.46 ng×h/ ml, respectively. The 90% CIs for the logtransformed ratios of C(max) (92.74 - 111.24), AUC(0-12h) (104.31 - 113.67) and AUC(0-∞) (103.87 - 113.57) were within the predetermined range for the assumption of bioequivalence. No serious adverse events were reported. CONCLUSIONS: This single-dose (60 mg) study found that the test (capsule) and reference (syrup) formulations of levodropropizine met the regulatory criterion for assuming bioequivalence in these healthy, fasted, male Korean subjects. Both formulations were well tolerated in the population studied. Korea FDA registration number: BED-1784.

Rapid and sensitive LC-MS/MS method for determination of megestrol acetate in human plasma: application to a human pharmacokinetic study.

A rapid, simple and fully validated LC-MS/MS method was developed and validated for the determination of megestrol acetate in human plasma using tolbutamide as an internal standard (IS) after one-step liquid-liquid extraction with methyl-tert-butyl-ether. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 385.5 → 267.1 for megestrol acetate and m/z 271.4 → 155.1 for IS. Chromatographic separation was performed on a YMC Hydrosphere C18 column with an isocratic mobile phase, which consisted of 10 mm ammonium formate buffer (adjusted to pH 5.0 with formic acid)-methanol (60:40, v/v) at a flow rate of 0.4 mL/min. The achieved lower limit of quantitation (LLOQ) was 1 ng/mL (signal-to-noise ratio > 10) and the standard calibration curve for megestrol acetate was linear (r > 0.99) over the studied concentration range (1-2000 ng/mL). The proposed method was fully validated by determining its specificity, linearity, LLOQ, intra- and inter-day precision and accuracy, recovery, matrix effect and stability. The validated LC-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of megestrol acetate after oral administration of a single dose 800 mg of megestrol acetate (Megace™) to five healthy Korean male volunteers under fed conditions.

Engineering the Local Atomic Configuration in 2H TMDs for Efficient Electrocatalytic Hydrogen Evolution.

The introduction of heteroatoms is a widely employed strategy for electrocatalysis of transition metal dichalcogenides (TMDs). This approach activates the inactive basal plane, effectively boosting the intrinsic catalytic activity. However, the effect of atomic configurations incorporated within the TMDs' lattice on catalytic activity is not thoroughly understood owing to the lack of controllable synthetic approaches for highly doped TMDs. In this study, we demonstrate a facile approach to realizing heavily doped MoS2 with a high doping concentration above 16% via intermediate-reaction-mediated chemical vapor deposition. As the V doping concentration increased, the incorporated V atoms coalesced in a manner that enabled both the basal plane activation and electrical conductivity enhancement of MoS2. This accelerated the kinetics of the hydrogen evolution reaction (HER) through the reduced Gibbs free energy of hydrogen adsorption, as evidenced by experimental and theoretical analyses. Consequently, the coalesced V-doped MoS2 exhibited superior HER performance, with an overpotential of 100 mV at 10 mA cm-2, surpassing the pristine and single-atom-doped counterparts. This study provides an intriguing pathway for engineering the atomic doping configuration of TMDs to develop efficient 2D nanomaterial-based electrocatalysts.

Pharmacokinetic and Pharmacodynamic Characteristics of Pelubiprofen Tromethamine vs. Pelubiprofen in Healthy Subjects.

Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.

Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase-8, and the mitochondrial death pathway in HL-60 human leukemia cells.

Sulfuretin, a flavonoid isolated from heartwood of Rhus verniciflua, has been reported to have anti-cancer activities but the underlying molecular mechanism was not clear. In this study, sulfuretin induced apoptosis by activating caspases-8, -9, and -3 as well as cleavage of poly(ADP-ribose) polymerase. Furthermore, treatment with sulfuretin caused mitochondrial dysfunctions, including the loss of mitochondrial membrane potential (ΔΨ(m)), the release of cytochrome c to the cytosol, and the translocations of Bax and tBid. Sulfuretin also activated the extrinsic apoptosis pathway, that is, it increased the expressions of Fas and FasL, the activation of caspase-8, and the cleavage of Bid. Furthermore, blocking the FasL-Fas interaction with NOK-1 monoclonal antibody prevented the sulfuretin-induced apoptosis. The therapeutical effect of sulfuretin in leukemia is due to its potent apoptotic activity through the extrinsic pathway driven by a Fas-mediated caspase-8-dependent pathway.

In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor.

An extension of our previously reported 3,4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c(nu/nu) nude mice. The rate of tumor volume increment in mouse model with KYS05090-treated group was remarkably slower than that of control group. With respect to tumor weight, it exhibited 60% and 67% tumor growth inhibition through oral administration of 1 and 5mg/kg of bodyweight, respectively, compared to control and was more potent than paclitaxel (53%). In addition, KYS05090 (10 and 50mg/kg, po) was found to have a marked analgesic effect in acetic acid-induced writhing test, whereas it did not show any effect on hot plate test.

Graphene Antiadhesion Layer for the Effective Peel-and-Pick Transfer of Metallic Electrodes toward Flexible Electronics.

Owing to its exceptional physicochemical properties, graphene has demonstrated unprecedented potential in a wide array of scientific and industrial applications. By exploiting its chemically inert surface endowed with unique barrier functionalities, we herein demonstrate antiadhesive monolayer graphene films for realizing a peel-and-pick transfer process of target materials from the donor substrate. When the graphene antiadhesion layer (AAL) is inserted at the interface between the metal and the arbitrary donor substrate, the interfacial interactions can be effectively weakened by the weak interplanar van der Waals forces of graphene, enabling the effective release of the metallic electrode from the donor substrate. The flexible embedded metallic electrode with graphene AAL exhibited excellent electrical conductivity, mechanical durability, and chemical resistance, as well as excellent performance in flexible heater applications. This study afforded an effective strategy for fabricating high-performance and ultraflexible embedded metallic electrodes for applications in the field of highly functional flexible electronics.

Highly efficient and robust noble-metal free bifunctional water electrolysis catalyst achieved via complementary charge transfer.

The operating principle of conventional water electrolysis using heterogenous catalysts has been primarily focused on the unidirectional charge transfer within the heterostructure. Herein, multidirectional charge transfer concept has been adopted within heterostructured catalysts to develop an efficient and robust bifunctional water electrolysis catalyst, which comprises perovskite oxides (La0.5Sr0.5CoO3-δ, LSC) and potassium ion-bonded MoSe2 (K-MoSe2). The complementary charge transfer from LSC and K to MoSe2 endows MoSe2 with the electron-rich surface and increased electrical conductivity, which improves the hydrogen evolution reaction (HER) kinetics. Excellent oxygen evolution reaction (OER) kinetics of LSC/K-MoSe2 is also achieved, surpassing that of the noble metal (IrO2), attributed to the enhanced adsorption capability of surface-based oxygen intermediates of the heterostructure. Consequently, the water electrolysis efficiency of LSC/K-MoSe2 exceeds the performance of the state-of-the-art Pt/C||IrO2 couple. Furthermore, LSC/K-MoSe2 exhibits remarkable chronopotentiometric stability over 2,500 h under a high current density of 100 mA cm-2.

High-Crystalline Monolayer Transition Metal Dichalcogenides Films for Wafer-Scale Electronics.

Chemical vapor deposition (CVD) using liquid-phase precursors has emerged as a viable technique for synthesizing uniform large-area transition metal dichalcogenide (TMD) thin films. However, the liquid-phase precursor-assisted growth process typically suffers from small-sized grains and unreacted transition metal precursor remainders, resulting in lower-quality TMDs. Moreover, synthesizing large-area TMD films with a monolayer thickness is also quite challenging. Herein, we successfully synthesized high-quality large-area monolayer molybdenum diselenide (MoSe2) with good uniformity via promoter-assisted liquid-phase CVD process using the transition metal-containing precursor homogeneously modified with an alkali metal halide. The formation of a reactive transition metal oxyhalide and reduction of the energy barrier of chalcogenization by the alkali metal promoted the growth rate of the TMDs along the in-plane direction, enabling the full coverage of the monolayer MoSe2 film with negligible few-layer regions. Note that the fully selenized monolayer MoSe2 with high crystallinity exhibited superior electrical transport characteristics compared with those reported in previous works using liquid-phase precursors. We further synthesized various other monolayer TMD films, including molybdenum disulfide, tungsten disulfide, and tungsten diselenide, to demonstrate the broad applicability of the proposed approach.

Application of a rapid and selective method for the simultaneous determination of carebastine and pseudoephedrine in human plasma by liquid chromatography-electrospray mass spectrometry for bioequivalence study in Korean subjects.

We describe a simple, rapid and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometric method that was developed for the simultaneous determination of carebastine and pseudoephedrine in human plasma using cisapride as an internal standard. Acquisition was performed in multiple-reaction monitoring mode by monitoring the transitions: m/z 500.43 > 167.09 for carebastine and m/z 166.04 > 147.88 for pseudoephedrine. The devised method involves a simple single-step liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a C(18) reversed-phase chromatographic column at 0.2 mL/min by isocratic elution with 10 mM ammonium formate buffer-acetonitrile (30:70, v/v; adjusted to pH 3.3 with formic acid). The devised method was validated over 0.5-100 ng/mL of carebastine and 5-1000 ng/mL of pseudoephedrine with acceptable accuracy and precision, and was successfully applied to a bioequivalence study involving a single oral dose (10 mg of ebastine plus 120 mg of pseudoephedrine complex) to healthy Korean volunteers.

Phase Engineering of Transition Metal Dichalcogenides with Unprecedentedly High Phase Purity, Stability, and Scalability via Molten-Metal-Assisted Intercalation.

The crystalline phase of layered transition metal dichalcogenides (TMDs) directly determines their material property. The most thermodynamically stable phase structures in TMDs are the semiconducting 2H and metastable metallic 1T phases. To overcome the low phase purity and instability of 1T-TMDs, which limits the utilization of their intrinsic properties, various synthesis strategies for 1T-TMDs have been proposed in phase-engineering studies. Herein, a facile and scalable synthesis of 1T-phase molybdenum disulfide (MoS2 ) via the molten-metal-assisted intercalation (MMI) approach is introduced, which exploits the capillary action of molten potassium and the difference between the electron affinity of MoS2 and the ionization potential of potassium. Highly reactive molten potassium metal can readily intercalate into the MoS2 interlayers, inducing an efficient phase transition from the 2H to 1T crystal structure. The ionic bonding between the intercalated potassium and sulfur lowers the energy barrier of the 1T-phase transition, enhancing the phase stability of the 1T crystals. Owing to the high purity and stability of the 1T phase, the electrocatalytic performance for the hydrogen evolution reaction is significantly higher in 1T-MoS2 (MMI) than in 2H-MoS2 and even in 1T-MoS2 synthesized using n-butyllithium.

Defect-Induced in Situ Atomic Doping in Transition Metal Dichalcogenides via Liquid-Phase Synthesis toward Efficient Electrochemical Activity.

Transition metal dichalcogenides (TMDs), due to their fascinating properties, have emerged as potential next-generation semiconducting nanomaterials across diverse fields of applications. When combined with other material systems, precise control of the intrinsic properties of the TMDs plays a vital role in maximizing their performance. Defect-induced atomic doping through introduction of a chalcogen vacancy into the TMDs lattices is known to be a promising strategy for modulating their characteristic properties. As a result, there is a need to develop tunable and scalable synthesis routes to achieve vacancy-modulated TMDs. Herein, we propose a facile liquid-phase ligand exchange approach for scalable, uniform, and vacancy-tunable synthesis of TMDs films. Varying the relative molar ratio of the chalcogen to transition metal precursors enabled the in situ modulation of the chalcogen vacancy concentrations without necessitating additional post-treatments. When employed as the electrocatalyst in the hydrogen evolution reaction (HER), the vacancy-modulated TMDs, exhibiting a synergetic effect on the energy level matching to the reduction potential of water and optimized free energy differences in the HER pathways, showed a significant enhancement in the hydrogen production via the improved charge transfer kinetics and increased active sites. The proposed approach for synthesizing tunable vacancy-modulated TMDs with wafer-scale synthesis capability is, therefore, promising for better practical applications of TMDs.

Gluco-obtusifolin and its aglycon, obtusifolin, attenuate scopolamine-induced memory impairment.

In the present study, we assessed the effects of gluco-obtusifolin, isolated from the seeds of Cassia obtusifolia L., and its aglycone, obtusifolin, on the learning and memory impairments induced by scopolamine using the passive avoidance and the Morris water maze tasks in mice. Gluco-obtusifolin (1, 2, and 4 mg/kg, p.o.) and obtusifolin (0.25, 0.5, 1, and 2 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test (P<0.05). Moreover, gluco-obtusifolin (2 mg/kg, p.o.) and obtusifolin (0.5 mg/kg, p.o.) improved escape latencies, swimming times in the target quadrant, and crossing numbers in the zone where the platform previously existed in the Morris water maze test. In the acetylcholinesterase assay, gluco-obtusifolin and obtusifolin were found to inhibit acetylcholinesterase activity in vitro (IC(50) = 37.2 and 18.5 microM, respectively) and ex vivo. These results suggest that gluco-obtusifolin and its aglycone may be useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, by the enhancement of cholinergic signaling.