First-in-human study to evaluate the safety, tolerability, and population pharmacokinetic/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects.

FL058 is a novel diazabicyclooctane ß-lactamase inhibitor. This first-in-human study evaluated the safety, tolerability, and population pharmacokinetic (PK)/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects. The results showed that the maximum tolerated dose of FL058 was 3,000 mg after single-dose infusion. FL058 in combination with meropenem did not cause any grade 3 or higher adverse event when the dose was escalated up to 1,000 mg/2,000 mg. FL058 exposure PK parameters showed dose proportionality. FL058 was excreted primarily in urine. No significant PK interaction was found between FL058 and meropenem. Population PK model analysis indicated that the PK profiles of FL058 and meropenem were consistent with the two-compartment model. The impact of covariates, creatinine clearance, concomitant use of meropenem, body weight, sex, and FL058 dose, on FL058 exposure was less than 10%. FL058/meropenem combination was safe and well tolerated up to a 1,000-mg/2,000-mg dose in healthy adults. The recommended minimum dose of FL058/meropenem combination was 500 mg/1,000 mg by intravenous infusion over 2 h every 8 h based on target attainment analysis. The good safety, tolerability, and satisfactory PK profiles of FL058 alone and in combination with meropenem in this first-in-human study will support further clinical development of FL058 in combination with meropenem in patients with target infections (ClinicalTrials.gov identifiers: NCT05055687, NCT05058118, and NCT05058105).

Specific and cumulative infection burden and mild cognitive impairment and dementia: A population-based study.

Infection by pathogenic microbes is widely hypothesized to be a risk factor for the development of neurocognitive disorders and dementia, but evidence remains limited. We analyzed the association of seropositivity to 11 common pathogens and cumulative infection burden with neurocognitive disorder (mild cognitive impairment and dementia) in a population-based cohort of 475 older individuals (mean age = 67.6 y) followed up over 3-5 years for the risk of MCI-dementia. Specific seropositivities showed a preponderance of positive trends of association with MCI-dementia, including for Plasmodium, H. pylori, and RSV (p < 0.05), as well as Chickungunya, HSV-2, CMV and EBV (p > 0.05), while HSV-1 and HHV-6 showed equivocal or no associations, and Dengue and VZV showed negative associations (p < 0.05) with MCI-dementia. High infection burden (5 + cumulated infections) was significantly associated with an increased MCI-dementia risk in comparison with low infection burden (1-3 cumulative infections), adjusted for age, sex, and education. Intriguingly, for a majority (8 of 11) of pathogens, levels of antibody titers were significantly lower in those with MCI-dementia compared to cognitive normal individuals. Based on our observations, we postulate that individuals who are unable to mount strong immunological responses to infection by diverse microorganisms, and therefore more vulnerable to infection by greater numbers of different microbial pathogens or repeated infections to the same pathogen in the course of their lifetime are more likely to develop MCI or dementia. This hypothesis should be tested in more studies.

Enhanced electrocatalytic degradation of tetracycline by ZIF-67@CNT coupled with a self-standing aligned carbon nanofiber anodic membrane.

Due to the misuse and overuse of the antibiotic tetracycline (TC), as well as its refractory degradability, it has become a stubborn environmental contaminant. In this study, a self-standing polyacrylonitrile-based ZIF-67@CNT/ACF aligned anodic membrane was fabricated by innovatively incorporating ZIF-67@CNT nanoparticles into an aligned carbon nanofiber (ACF) membrane to treat the TC. The flow-through nanoporous construction of the ZIF-67@CNT/ACF membrane reactor can compress the diffusion boundary layer on the electrode surface to enhance mass transfer under microscopic laminar flow, which can further enhance the degradation rate. In addition, the enhanced degradation performance also benefited from the significant electrooxidation capacity of the ZIF-67@CNT/ACF membrane. At the optimal electrocatalytic condition of 3.0 V applied potential and pH 6, the degradation rate reached 81% in 1 h for an initial TC concentration of 10 mg l-1. The refractory and highly toxic TC was electrochemically degraded into small non-toxic molecules. Our results indicate that electrocatalytic TC degradation can be enhanced by ZIF-67@CNT/ACF membrane.

Enhanced Indoor Positioning Using RSSI and Time-Distributed Auto Encoder-Gated Recurrent Unit Model.

This study presents a novel approach to indoor positioning leveraging radio frequency identification (RFID) technology based on received signal strength indication (RSSI). The proposed methodology integrates Gaussian Kalman filtering for effective signal preprocessing and a time-distributed auto encoder-gated recurrent unit (TAE-GRU) model for precise location prediction. Addressing the prevalent challenges of low accuracy and extended localization times in current systems, the proposed method significantly enhances the preprocessing of RSSI data and effectively captures the temporal relationships inherent in the data. Experimental validation demonstrates that the proposed approach achieves a 75.9% improvement in localization accuracy over simple neural network methods and markedly enhances the speed of localization, thereby proving its practical applicability in real-world indoor localization scenarios.

Baicalin Ameliorates Depression-like Behaviors via Inhibiting Neuroinflammation and Apoptosis in Mice.

Depression is a common neuropsychiatric disease which brings an increasing burden to all countries globally. Baicalin, a flavonoid extracted from the dried roots of Scutellaria, has been reported to exert anti-inflammatory, antioxidant, and neuroprotective effects in the treatment of depression. However, the potential biological mechanisms underlying its antidepressant effect are still unclear. In the present study, we conducted extensive research on the potential mechanisms of baicalin's antidepressant effect using the methods of network pharmacology, including overlapped terms-based analysis, protein-protein interaction (PPI) network topology analysis, and enrichment analysis. Moreover, these results were further verified through molecular docking, weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and subsequent animal experiments. We identified forty-one genes as the targets of baicalin in the treatment of depression, among which AKT1, IL6, TP53, IL1B, and CASP3 have higher centrality in the more core position. Meanwhile, the roles of peripheral genes derived from direct potential targets were also observed. Our study suggested that biological processes, such as inflammatory reaction, apoptosis, and oxidative stress, may be involved in the therapeutic process of baicalin on depression. These mechanisms were validated at the level of structure, gene, protein, and signaling pathway in the present study. Taken together, these findings propose a new perspective on the potential mechanisms underlying baicalin's antidepressant effect, and also provide a new basis and clarified perspective for its clinical application.

Preparation and Characterization of GX-50 and Vitamin C Co-encapsulated Microcapsules by a Water-in-Oil-in-Water (W1/O/W2) Double Emulsion-Complex Coacervation Method.

Co-encapsulated xanthoxylin (GX-50) and vitamin C (Vc) microcapsules (GX-50-Vc-M) were prepared by the combination of a water-in-oil-in-water (W1/O/W2) double emulsion with complex coacervation. The W1/O/W2 double emulsion was prepared by two-step emulsification, and it has a uniform particle size of 8.388 µm and high encapsulation efficiencies of GX-50 (85.95%) and Vc (67.35%) under optimized process conditions. Complex coacervation occurs at pHs 4.0-4.7, which has the highest encapsulation efficiency of GX-50 and Vc at pH 4.5. The complex coacervate with tannic acid solidifying (namely, wet microcapsules) has better mechanical properties and also enhances the ability of co-encapsulation of active ingredients. The resulting microcapsules by freeze-drying of wet microcapsules were characterized by UV-vis absorbance spectroscopy (UV-vis), Fourier infrared spectroscopy (FI-IR), confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), X-ray diffraction (XRD), 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging, and in vitro permeation measurements. Under optimal conditions, the encapsulation efficiency and drug loading of GX-50-Vc-M for GX-50 and Vc are, respectively, 78.38 ± 0.51 and 59.34 ± 0.56%, and 35.6 ± 0.68 and 29.8 ± 0.92%. A slight shift in the FTIR peak between single GX-50 or Vc and GX-50-Vc-M confirmed the successful co-encapsulation of GX-50 and Vc in microcapsules. GX-50-Vc-M has bridged irregular spherical aggregates, while GX-50 and Vc are, respectively, encapsulated in hydrophobic and hydrophilic cavities of microcapsules in an amorphous dissolved state. GX-50-Vc-M has the highest DPPH· radical scavenging rate of 62.51%, and the scavenging process of GX-50-Vc-M on DPPH· radicals is more in line with the pseudo-second-order kinetic equation model. Moreover, the in vitro permeation of GX-50 and Vc in GX-50-Vc-M can reach maximum values of 40 and 60%, respectively. This concludes that GX-50-Vc-M is a promising delivery system for the penetration of the antioxidant into the deeper layers of the skin for the antioxidant effect.

Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups.

Inflammation is the initial biological reaction of the immune system to various stimuli such as infection, injury, or irritation. Extensive research has demonstrated that a growing array of diseases are triggered by inflammatory mechanisms. Currently, anti-inflammatory drugs are widely utilized in clinical practice due to their therapeutic advantages; however, the potential side effects cannot be ignored by us. In our work, a series of amide compounds with chromones as the parent nucleus were designed and synthesized using the principle of colligated drug design. The results of the biological evaluation indicated that four compounds exhibited lower EC50 values compared to the positive drug ibuprofen. Notably, compound 5-9 showed optimal inhibitory activity (EC50 = 5.33 ± 0.57 µM) against the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells. Structure-activity relationships (SAR) showed that the presence of electron-withdrawing groups at positions 5 and 8, or electron-donating groups at positions 6 and 7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound 5-9 exhibit potential as an anti-inflammatory drug that deserves further investigation.

[M8L4]8+-Type Squares Self-Assembled by Dipalladium Corners and Bridging Aromatic Dipyrazole Ligands for Iodine Capture.

Square-like metallamacrocyclic palladium(II) complexes [M8L4]8+ (1-7) were synthesized by reacting aromatic dipyrazole ligands (H2L1-H2L3 with pyromellitic arylimide-, 1,4,5,8-naphthalenetetracarboxylic arylimide-, and anthracene-based aromatic groups, respectively) with dipalladium corners ([(bpy)2Pd2(NO3)2](NO3)2, [(dmbpy)2Pd2(NO3)2](NO3)2, or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, and phen = 1,10-phenanthroline) in aqueous solutions via metal-directed self-assembly. Metallamacrocycles 1-7 were fully characterized by 1H and 13C nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry, and the square structure of 7·8NO3- was further confirmed via single crystal X-ray diffraction. These square-like metallamacrocycles exhibit effective performance for iodine adsorption.

Energy-efficient reuse of bio-treated textile wastewater by a porous-structure electrochemical PbO2 filter: Performance and mechanism.

In this work, a novel porous-structure electrochemical PbO2 filter (PEF-PbO2) was developed to achieve the reuse of bio-treated textile wastewater. The characterization of PEF-PbO2 confirmed that its coating has a variable pore size that increases with depth from the substrate, and the pores with a size of 5 µm account for the largest proportion. The study on the role of this unique structure illustrated that PEF-PbO2 possesses a larger electroactive area (4.09 times) than the conventional electrochemical PbO2 filter (EF-PbO2) and enhanced mass transfer (1.39 times) in flow mode. The investigation of operating parameters with a special discussion of electric energy consumption suggested that the optimal conditions were a current density of 3 mA cm-2, Na2SO4 concentration of 10 g L-1 and pH value of 3, which resulted in 99.07% and 53.3% removal of Rhodamine B and TOC, respectively, together with an MCETOC of 24.6%. A stable removal of 65.9% COD and 99.5% Rhodamine B with a low electric energy consumption of 5.19 kWh kg-1 COD under long-term reuse of bio-treated textile wastewater indicated that PEF-PbO2 was durable and energy-efficient in practical applications. Mechanism study by simulation calculation illustrated that the part of the pore of the PEF-PbO2's coating with small size (5 µm) plays an important role in this excellent performance which provides the advantage of rich ·OH concentration, short pollutant diffusion distance and high contact possibility.

The CmMYB3 transcription factors isolated from the Chrysanthemum morifolium regulate flavonol biosynthesis in Arabidopsis thaliana.

KEY MESSAGE: Chrysanthemum morifolium MYB3 factors are transcriptional activators for the regulation of flavonol biosynthesis. Flavonol was not only the critical secondary metabolite participating in the growth and development of plants but also the main active ingredient in medicinal chrysanthemum. However, few pieces of research revealed the transcriptional regulation of flavonol biosynthesis in Chrysanthemum morifolium. Here, we isolated two CmMYB3 transcription factors (CmMYB3a and CmMYB3b) from the capitulum of Chrysanthemum morifolium cv 'Hangju'. According to the sequence characteristics, the CmMYB3a and CmMYB3b belonged to the R2R3-MYB subgroup 7, whose members were often reported to regulate flavonol biosynthesis positively. CmMYB3a and CmMYB3b factors were identified to localize in the nucleus by subcellular localization assay. Besides, both of them have obvious transcriptional self-activation activity in their C-terminal. After the overexpression of CmMYB3 genes in Nicotiana benthamiana and Arabidopsis thaliana, the flavonol contents in plants were increased, and the expression of AtCHS, AtCHI, AtF3H, and AtFLS genes in A. thaliana was also improved. Interestingly, the CmMYB3a factor had stronger functions in improving flavonol contents and related gene expression levels than CmMYB3b. The interaction analysis between transcription factors and promoters suggested that CmMYB3 could bind and activate the promoters of CmCHI and CmFLS genes in C. morifolium, and CmMYB3a also functioned more powerfully. Overall, these results indicated that CmMYB3a and CmMYB3b work as transcriptional activators in controlling flavonol biosynthesis.

N-acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin-induced diabetic mice by inhibiting oxidative stress.

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus erectile dysfunction (DMED). This study aimed to investigate the effect of N-acetylcysteine (NAC) on DMED in streptozotocin-induced diabetic mice and to explore potential mechanisms. In the present study, we show that an erectile dysfunction is present in the streptozotocin-induced mouse model of diabetes as indicated by decreases in intracavernous pressure responses to electro-stimulation as well as from results of the apomorphine test of erectile function. After treatment of NAC, the intracavernous pressure was increased. In these DMED mice, oxidative stress and inflammatory responses were significantly reduced within the cavernous microenvironment, while activity of antioxidant enzymes in this cavernous tissue was enhanced after NAC treatment. These changes protected mitochondrial stress damage and a significant decreased in apoptosis within the cavernous tissue of DMED mice. This appears to involve activation of the nuclear factor erythroid 2-like-2 (Nrf2) signalling pathway, as well as suppression of the mitogen-activated protein kinase (MAPK) p38/ NF-κB pathway within cavernous tissue. In conclusion, NAC can improve erectile function through inhibiting oxidative stress via activating Nrf2 pathways and reducing apoptosis in streptozotocin-induced diabetic mice. NAC might provide a promising therapeutic strategy for individuals with DMED.

Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study.

OBJECTIVE: To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. MATERIALS AND METHODS: An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. RESULTS: Cmax were 3.58 ± 2.74 ng/mL and 6.01 ± 3.93 ng/mL, and AUC0-∞ were 35.71 ± 18.68 h×ng/mL and 52.15 ± 31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00 hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00 - 125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. CONCLUSION: Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.

Supramolecular Hydrogen Bonding Assembly from Non-Coplanar Aromatic Tetra-1H-Pyrazoles with Crystallization-Induced Emission (CIE).

Here, we report a design strategy for constructing supramolecular organic frameworks by introducing 1H-pyrazole groups to aromatic cores as non-coplanar molecules to form diverse supramolecular assemblies through multiple 1H-pyrazole [N-H···N] hydrogen bonds as well as other weak interactions. The new supramolecular organic frameworks displayed interesting crystallization-induced emission (CIE) behavior.

Lipin1 mediates cognitive impairment in fld mice via PKD-ERK pathway.

Lipin1 is important in lipid synthesis because of its phosphatidate phosphatase activity, and it also functions as transcriptional coactivators to regulate the expression of genes involved in lipid metabolism. We found that fld mice exhibit cognitive impairment, and it is related to the DAG-PKD-ERK pathway. We used fld mice to explore the relationship between lipin1 and cognitive function. Our results confirmed the presence of cognitive impairment in the hippocampus of lipin1-deficient mice. As shown in behavioral test, the spatial learning and memory ability of fld mice was much worse than that of wild-type mice. Electron microscopy results showed that the number of synapses in hippocampus of fld mice was significantly reduced. BDNF,SYP, PSD95 were significantly reduced. These results suggest that lipin1 impairs synaptic plasticity. Hence,a deficiency of lipin1 leads to decreased DAG levels and inhibits PKD activation, thereby affecting the phosphorylation of ERK and the CREB.

Protective effect of acacetin in human periodontal ligament cells via regulation of autophagy and inflammation.

Our study investigated the effects of acacetin, a natural flavonoid compound, on the survival and expression of inflammatory related cytokines in lipopolysaccharide (LPS)-stimulated human periodontal ligament (PDL) cells. Treatment with acacetin significantly promoted survival and suppressed apoptosis in LPS-stimulated PDL cells in a dose-dependent manner, as shown by CCK-8 and flow cytometry assays, respectively. Moreover, ELISA assay showed that acacetin dose-dependently attenuated LPS-induced increases of TNF-α, IL-6 and IL-1ß in PDL cells. Western blot analysis showed that administration of acacetin dose-dependently increased the ratio of LC3II/LC3I, as well as the expression of beclin-1, as compared to LPS-stimulated PDL cells. Inhibition of autophagy by rapamycin, an autophagy inhibitor, increased the production of pro-inflammatory cytokines and decreased survival, abolishing the beneficial role of acacetin in LPS-stimulated PDL cells. In addition, the expression of GSK-3ß, a regulator of autophagy, was suppressed by administration with acacetin in a dose-dependent manner. Acacetin treatment promotes survival and suppresses inflammation in LPS-stimulated PDL cells via regulating autophagy and GSK-3ß signal in PDL cells, suggesting that acacetin may be a potential novel agent for the treatment of chronic periodontitis.

Photodegradation of soluble microbial products (SMPs) from membrane bioreactor by GO-COOH/TiO2/Ag.

This study aimed to explore a new degradation method - photocatalysis technology to polish membrane bioreactor (MBR) effluent, using 2,6-di-tert-butylphenol (2,6-DTBP) as a model soluble microbial product (SMP). 2,6-DTBP is one of the predominant SMPs in MBR effluent, which is refractory and difficult to biodegrade. This study developed a novel carboxylated graphene oxide/titanium dioxide/silver (GO-COOH/TiO2/Ag) nanocomposite to photodegrade 2,6-DTBP. GO-COOH/TiO2/Ag was successfully synthesized, using l-cysteine as the linker bonding TiO2/Ag to GO-COOH. The structural, morphological and optical properties of the GO-COOH/TiO2/Ag nanocomposite were characterized using various techniques. Owing to synergistic effects, the GO-COOH/TiO2/Ag nanocomposite exhibited enhanced photocatalytic degradation performance under solar light irradiation when compared to TiO2, Ag and GO-COOH. To remove 25 mg/L 2,6-DTBP, the reaction time for GO-COOH/TiO2/Ag was only 30 min, faster than the 90 min required for pure TiO2 or Ag. In addition, the 200 mg/L GO-COOH/TiO2/Ag nanocomposite aqueous solution showed the best performance under solar light, with 99% removal of 2,6-DTBP. This enhanced capability is likely due to the surface plasmon resonance (SPR) effect contributed by Ag nanoparticles (NPs) doped onto the TiO2. In addition, GO-COOH had a high effective surface area, which assisted in degrading the 2,6-DTBP through improved adsorption. The stability study showed that the photocatalytic activity of the GO-COOH/TiO2/Ag was stable enough for recycling multiple times. The effective degradation performance and excellent stability demonstrates that the GO-COOH/TiO2/Ag nanocomposite can be a promising photocatalyst in the field of effluent SMP photodegradation, which solves the problem of the difficult biodegradation of highly toxic 2,6-DTBP.

Gold and Carbene Relay Catalytic Enantioselective Cycloisomerization/Cyclization Reactions of Ynamides and Enals.

The combined use of gold as transition metal catalyst and N-heterocyclic carbene (NHC) as organic catalyst in the same solution for relay catalytic reactions was disclosed. The ynamide substrate was activated by gold catalyst to form unsaturated ketimine intermediate that subsequently reacted with the enals (via azolium enolate intermediate generated with NHC) effectively to form bicyclic lactam products with excellent diastereo- and enantio-selectivities. The gold and NHC coordination and dissociation can be dynamic and tunable events, and thus allow the co-existence of both active metal and carbene organic catalysts in appreciable concentrations, for the dual catalytic reaction to proceed.

Unusual Photoelectrochemical Properties of Electropolymerized Films of a Triphenylamine-Containing Organic Small Molecule.

The electropolymerized films of poly(L)n on an indium-tin oxide (ITO) electrode was prepared by anodic electrooxidation of a dichloromethane solution of a triphenylamine-carrying organic molecule L and were characterized/studied by ultraviolet-visible absorption spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, electrochemical impedance spectroscopy, cyclic voltammetry, and photoelectrochemical measurements. Poly(L)n films were found to show surface-controlled TPA•+1/0 associated quasi-reversible redox and exceptionally high photocurrent generation properties. At a zero external bias potential and under 100 mW/cm2 white light irradiation, a photoelectrochemical device composed of a poly(L)1-modified ITO as the working electode, a platinum disk counter electrode, and saturated calomel electrode reference electrode in a 0.1 M Na2SO4 aqueous solution exhibited a significant cathode photocurrent density of 2.2 µA/cm2, which could be switched to be anodic and outperform most previously reported molecule-based modified ITO electrodes under similar experimental conditions. The results indicate that poly(L)n films offer a number of future perspectives ranging from organic photovoltaic to photoelectrochemical catalysis and sensing.

Access to Imidazolidines via 1,3-Dipolar Cycloadditions of 1,3,5-Triazinanes with Aziridines.

The unprecedented 1,3-dipolar cycloaddition of 1,3,5-triazinanes and aziridines has been described. With readily available starting material, this method offers efficient access to a wide range of functionalized imidazolidine derivatives in moderate to good yields (up to 92%) under mild conditions. Preliminary mechanistic investigations show that the ring opened zwitterionic pathway product dominated over the second-order nucleophilic substitution-like product. This protocol is very promising because the reaction is scalable, and gives versatile transformation of the products into other functionalized imidazolidines.

Ginsenoside Rg1 Prevents Chronic Stress-Induced Depression-Like Behaviors and Neuronal Structural Plasticity in Rats.

BACKGROUND/AIMS: Ginsenoside Rg1 has been demonstrated to exhibit neuroprotective effects in various studies. This study aimed to investigate the neuronal mechanisms underlying the neuroprotective and antidepressant-like effects of ginsenoside Rg1 in a rat model of depression. METHODS: Chronic unpredictable mild stress was used to induce depression-like behaviors in rats. Transmission electron microscopy was used to observe neuronal synapses within the basolateral amygdala (BLA). The expression of microRNA (miR)-134 in the BLA was verified by real-time quantitative PCR. Finally, the synaptic plasticity-associated proteins CAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were detected by immunoblotting. RESULTS: Results showed that chronic stress effectively induced depression-like behaviors in rats, which were associated with significant ultrastructural changes within BLA neurons. Moreover, chronic stress decreased the expression of miR-134 in the BLA, which was accompanied by decreased phosphorylation of CREB and decreased expression of BDNF. Remarkably, chronic administration of ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) significantly ameliorated the neuronal structural abnormalities and biochemical changes induced by chronic stress, as well as preventing depression-like behaviors in these rats. CONCLUSION: Results suggested that ginsenoside Rg1 may exhibit neuroprotection and antidepressant-like effects by activating the CREB-BDNF system within the BLA in this rat model of depression. Amelioration of depression-like behaviors by ginsenoside Rg1 appears to involve modulation of the synapse-associated factor miR-134 within the BLA. Therefore, these findings demonstrate some of the neuronal mechanisms associated with depression and the therapeutic potential of ginsenoside Rg1 for use in the treatment of depression in clinical trials.