Effects of Cu2O nanoparticles on the kinetic characteristics of rapid chlorophyll fluorescence induction and related genes in wheat seedlings.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu2O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSⅡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Application of Multidimensional Quality Management Tools in the Management of Medical Adverse Events.

Purpose: This study aims to investigate the impact of multidimensional quality management tools in establishing a medical adverse event management system, with the aim of continuously improving medical quality and safety while ensuring patient well-being. Methods: This study introduces risk management theories, such as the "Gray Rhino Theory", and employs quality management tools like the Plan-Do-Check-Act (PDCA) cycle, Quality Control Circle (QCC), and Root Cause Analysis (RCA), to provide relevant quality management education and training to employees. This approach facilitates the establishment of a medical adverse event management system that encourages reporting and fosters a blame-free reporting culture, while simultaneously implementing quality management across the entire process. The regular utilization of the QCC facilitates ongoing quality improvement. Furthermore, for sentinel events and patient harm incidents with educational values, the study employs the Incident Decision Tree (IDT) to determine appropriate actions. Additionally, the hospital initiates RCA for system-wide improvements, focusing on areas such as management, institutional processes, and environmental aspects. Moreover, an internal medical quality improvement case competition is organized, with outstanding cases being selected to participate in the multidimensional quality management competition organized by the National Quality Management Alliance. Results: The study reveals a significant improvement in employees' awareness of adverse events, the percentage of employees reporting adverse events increased significantly from 39.15% in 2019 to 49.77% in 2022, P=0.002. Furthermore, the adverse event reporting rate has risen significantly from 2.78% (2019) to 5.96% (2022), P=0.002. Additionally, each department has been able to utilize QCC or RCA tools for quality improvement, thereby further reinforcing the development of a patient safety culture. Conclusion: Multidimensional quality management tools play a crucial role in establishing a hospital's adverse event management system, promoting continuous improvement in medical quality, ensuring patient safety, and effectively implementing a culture of patient safety.

Antibacterial Activity and the Mechanism of the Z-Scheme Bi2MoO6/Bi5O7I Heterojunction under Visible Light.

Z-scheme Bi2MoO6/Bi5O7I heterojunction was constructed by an in situ solvothermal method, which was composed of Bi2MoO6 nanosheets growing on the surface of Bi5O7I microrods. The antibacterial activities under illumination towards Escherichia coli (E. coli) were investigated. The Bi2MoO6/Bi5O7I composites exhibited more outstanding antibacterial performance than pure Bi2MoO6 and Bi5O7I, and the E. coli (108 cfu/mL) was completely inactivated by BM/BI-3 under 90 min irradiation. Additionally, the experiment of adding scavengers revealed that h+, •O2- and •OH played an important role in the E. coli inactivation process. The E. coli cell membrane was damaged by the oxidation of h+, •O2- and •OH, and the intracellular components (K+, DNA) subsequently released, which ultimately triggered the apoptosis of the E. coli cell. The enhanced antibacterial performance of Bi2MoO6/Bi5O7I heterojunction is due to the formation of Z-scheme heterojunction with the effective charge transfer via the well-contacted interface of Bi2MoO6 and Bi5O7I. This study provides useful guidance on how to construct Bi5O7I-based heterojunction for water disinfection with abundant solar energy.

Green synthesis of silver nanoparticles using Eucommia ulmoides leaf extract for inhibiting stem end bacteria in cut tree peony flowers.

Tree peony ( Paeonia suffruticosa Andr.) is a popular cut flower among ornamental plants. However, its short vase life severely hinders the production and application of cut tree peony flowers. To extend the postharvest longevity and improve the horticultural value, silver nanoparticles (Ag-NPs) was applied for reducing bacterial proliferation and xylem blockage in cut tree peony flowers in vitro and in vivo. Ag-NPs was synthesized with the leaf extract of Eucommia ulmoides and characterized. The Ag-NPs aqueous solution showed inhibitory activity against bacterial populations isolated from stem ends of cut tree peony 'Luoyang Hong' in vitro. The minimum inhibitory concentration (MIC) was 10 mg L-1. Compared with the control, pretreatments with Ag-NPs aqueous solution at 5 and 10 mg L-1 for 24 h increased flower diameter, relative fresh weight (RFW), and water balance of tree peony 'Luoyang Hong' flowers. Additionally, malondialdehyde (MDA) and H2O2 content in pretreated petals were lower than the control during the vase life. The activities of superoxide dismutase (SOD) and catalase (CAT) in pretreated petals were lower than that of the control at the early vase stage and higher at the late vase life. Furthermore, pretreatments with Ag-NPs aqueous solution at 10 mg L-1 for 24 h could reduce bacterial proliferation in the xylem vessels on the stem ends by confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM). Overall, pretreatments with green synthesized Ag-NPs aqueous solution effectively reduced bacteria-induced xylem blockage of cut tree peony, resulting in improved water uptake, extended vase life, and enhanced postharvest quality. Therefore, this technique can be used as a promising postharvest technology in the cut flower industry.

Liquid exfoliation of bulk g-C3N5 to nanosheets for improved photocatalytic antibacterial activity.

Liquid exfoliation of bulk g-C3N5 was applied to synthesize g-C3N5 nanosheets. In order to characterize the samples, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectra (XPS), UV-Vis absorption spectra (UV-Vis), and photoluminescence spectra (PL) were examined. g-C3N5 nanosheets exhibited enhanced performance in the inactivation of Escherichia coli (E. coli) with visible light irradiation relative to bulk g-C3N5 and promoted complete inactivation of E. coli within 120 min. h+ and •O2- were the principal reactive species in the antibacterial process. In the early stages, SOD and CAT played a defensive role in resisting oxidative damage of active species. With the prolonged light exposure time, the antioxidant protection system was overwhelmed leading to the destruction of the cell membrane. The leakage of cell contents such as K+, protein, and DNA caused bacterial apoptosis ultimately. The enhanced photocatalytic antibacterial performance of g-C3N5 nanosheets is ascribed to the stronger redox property by the upward shift of CB and downward shift of VB compared with bulk g-C3N5. On the other hand, larger specific surface area and better separation efficiency of photoinduced carriers are helpful to the improved photocatalytic performance. This study systematically revealed the inactivation process toward E. coli and expanded the application range of g-C3N5-based materials with abundant solar energy.

Construction of S-Scheme CuS/Bi5O7I Heterojunction for Boosted Photocatalytic Disinfection with Visible Light Exposure.

In this paper, a novel S-scheme CuS/Bi5O7I heterojunction was successfully constructed using a two-step approach comprising the alkaline hydrothermal method and the adsorption-deposition method, and it consisted of Bi5O7I microrods with CuS particles covering the surface. The photocatalytic antibacterial effects on Escherichia coli (E. coli) were systematically examined with visible light exposure. The results suggested that the 3%-CuS/Bi5O7I composite showed the optimal antibacterial activity, completely inactivating E. coli (5 × 108 cfu/mL) in 180 min of irradiation. Moreover, the bacterial inactivation process was scientifically described. •O2- and h+ were the major active species for the inactivation of the bacteria. In the early stages, SOD and CAT initiated the protection system to avoid the oxidative destruction of the active species. Unfortunately, the antioxidant protection system was overwhelmed thereafter, which led to the destruction of the cell membrane, as evidenced by the microstructure changes in E. coli cells. Subsequently, the leakage of intracellular components including K+, proteins, and DNA resulted in the unavoidable death of E. coli. Due to the construction of the S-scheme heterojunction, the CuS/Bi5O7I composite displayed the boosted visible light harvesting, the high-efficiency separation of photogenerated electrons and holes, and a great redox capacity, contributing to an outstanding photocatalytic disinfection performance. This work offers a new opportunity for S-scheme Bi5O7I-based heterojunctions with potential application in water disinfection.

A novel fluorescent probe for the detection of formaldehyde in real food samples, animal serum samples and gaseous formaldehyde.

Formaldehyde (FA) is widely used as an adhesion promoter and dyeing aid in industrial production. Ingestion of a certain amount of formaldehyde may cause corrosive burns in the mouth, throat, and digestive tract. Therefore, it is very necessary to use simple and effective detection methods to ensure human health and food safety. Herein, a novel fluorescent probe NFD based on naphthalimide for the detection of formaldehyde in food was designed and synthesized. The probe had a remarkable fluorescence response to formaldehyde at 554 nm. And it exhibited fascinating advantages of good selectivity, high sensitivity, and low detection limit. In addition, the solid sensor prepared by loading the probe on the filter paper was successfully realized the visual detection of liquid and gaseous formaldehyde. More importantly, the probe possessed excellent stability in the detection of formaldehyde in real food samples and animal serum samples.

Simultaneous Determination of Phenylethanoid Glycosides and Antioxidant Activity of Syringa pubescens Turcz. from Different Geographical Origin in China.

A high-performance liquid chromatograph with diode array detector was established for the simultaneous determination of five phenylethanoid glycosides in Syringa pubescens Turcz. The optimal chromatographic conditions were achieved on a Zorbax C18 column using gradient elution with 0.5% aqueous acetic acid and acetonitrile as the mobile phase at the flow rate of 1.0 mL/min. The detection wavelength was developed as follows: 0-10 min, 276 nm; 10-45 min, 332 nm. The validation of the method including linearity, precision, stability, accuracy, repeatability and recovery was tested. The chemometric analysis including hierarchical cluster analysis and principal component analysis was employed to investigate the similarity and difference of samples from different geographical origin. The results revealed that S. pubescens samples were divided into four clusters based on the phenylethanoid glycosides contents. Antioxidant activity of extract was measured using three different methods including α,α-diphenyl-ß-picrylhydrazyl and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging assays, and ferric reducing antioxidant power assay. Furthermore, different phenylethanoid glycosides exhibited different contribution to antioxidant capacities. This study provides a foundation for the quality evaluation and offers scientific data for the utilization of S. pubescens resources.

Efficient bacterial inactivation with S-doped g-C3N4 nanosheets under visible light irradiation.

The pathogenic bacteria in water that threatens the human health and photocatalytic disinfection have been proven to be a cost-effective and promising green technology. It is significant and necessary to develop efficient, safe, and visible light-driven photocatalysts. In this study, Escherichia coli was used as model bacterium and the disinfection performance of prepared S-doped g-C3N4 nanosheets (S-CNNs) under visible light was investigated. The results showed that the synergistic effects of S doping and the unique 2D structure of S-CNNs enhanced the visible light absorption, enlarged the specific surface area and reduced the recombination of photogenerated charge carriers which is beneficial for promoting the photocatalytic disinfection of the E. coli. Scavenger experiments indicated •O2- and h+ were the predominant reactive species in the photocatalytic disinfection process. In addition, the kinetics of disinfection activity were fitted by the modified Hom model and the k2 value of S-CNNs is 0.0219 min-1, which is much higher than that of the bulk g-C3N4 (CN). This work has demonstrated efficient bacterial inactivation with S-CNNs under visible light irradiation.

Impacts of cuprous oxide nanoparticles on wheat root morphology and genotoxicity.

To explore the ecotoxicity of Cu2O nanoparticles (NPs) on plant roots, the effects of Cu2O-NPs with different concentrations of 10, 50, 100 and 200 mg·L-1 on the seedling growth, root morphology, and cytogenetic toxicity of wheat 'Zhoumai 18' (Triticum aestivum Zhoumai 18) were examined in a hydroponic experiment. The results showed that Cu2O-NPs inhibited the growth of wheat seedlings. Cu2O-NPs reduced root and shoot lengths, fresh weights of shoot and root, root relative activity and ratio of root to shoot of wheat seedlings, but increased primary root number. Furthermore, with the increases of Cu2O-NPs concentrations, the root elongation zone shortened and the root became hard and brittle, while the average diameter of roots increased. Under the concentration of 100 mg·L-1 Cu2O-NPs, the mitotic index significantly decreased, and vacuolization, plasma membrane detachment, chromosomal abnormality occurred in the root tip cell. In conclusion, Cu2O-NPs are genotoxic to wheat seedlings, with consequences on the growth and development of wheat seedlings and root morphology.

A New Perspective on Ameliorating Depression-Like Behaviors: Suppressing Neuroinflammation by Upregulating PGC-1α.

Inflammation plays an important role in depression pathology, making it a promising target for ameliorating depression-like behaviors. The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional coactivator being able to constrain inflammatory events through NF-κB signaling. However, the role of PGC-1α in depression is not yet clear. This study was designed to investigate the role of PGC-1α in depression and explore the underlying mechanisms. Mice modeled with chronic unpredictable mild stimulation (CUMS) were explored for the relationship between depression-like behaviors and PGC-1α. Baicalin was used to evaluate the effect regulating PGC-1α. Furthermore, the anti-neuroinflammatory effect of baicalin was investigated both in BV2-SH-SY5Y co-culture system and in mice by LPS challenge. The role of PGC-1α in neuroinflammation was explored in cell co-culture systems under gene silencing conditions targeting NF-κB signaling. We found that the expression of PGC-1α was inhibited in the hippocampus of mice exposed to CUMS or LPS, while baicalin could increase the expression of PGC-1α and alleviate the depression-like behaviors. Furthermore, baicalin attenuated neuroinflammation in the hippocampus of mice and BV2-SH-SY5Y co-culture system by LPS challenge via regulating NF-κB signaling; however, knockdown of the PGC-1α could reverse the effect of baicalin on neuroinflammation and NF-κB signaling. Our results revealed a vital role for PGC-1α in attenuating neuroinflammation in depression, indicating that PGC-1α might be a therapeutic target for depression.

Saikosaponin-d impedes hippocampal neurogenesis and causes cognitive deficits by inhibiting the survival of neural stem/progenitor cells via neurotrophin receptor signaling in mice.

Neural stem/progenitor cells (NPCs) are multipotent stem cells in the central nervous system. Damage to NPCs has been demonstrated to cause adverse effects on neurogenesis and to contribute to neurological diseases. Our previous research suggested that saikosaponin-d (SSd), a cytostatic drug belonging to the bioactive triterpenoid saponins, exhibited neurotoxicity by inhibiting hippocampal neurogenesis, but the underlying mechanism remained elusive. This study was performed to clarify the role of SSd in cognitive function and the mechanism by which SSd induced damage to hippocampal neurogenesis and NPCs. Our results indicated that SSd caused hippocampus-dependent cognitive deficits and inhibited hippocampal neurogenesis by reducing the numbers of newborn neurons in mice. RNA sequencing analysis revealed that SSd-induced neurotoxicity in the hippocampus involved neurotrophin receptor-interacting MAGE (NRAGE)/neurotrophin receptor interacting factor (NRIF)/p75NTR -associated cell death executor (NADE) cell signaling activated by the p75 neurotrophin receptor (p75NTR ). Mechanistic studies showed that a short hairpin RNA targeting p75NTR intracellular domain reversed SSd-increased NRAGE/NRIF/NADE signaling and the c-Jun N-terminal kinase/caspase apoptotic pathway, subsequently contributing to the survival of NPCs, as well as cell proliferation and differentiation. The addition of recombinant brain-derived neurotrophic factor (BDNF) ameliorated the SSd-induced inhibition of BDNF/Tyrosine kinase receptor B (TrkB) neurotrophic signaling, but did not affect SSd-activated pro-BDNF/p75NTR signaling. Moreover, the SSd-induced elevation of cytosolic Ca2+ concentration was responsible for damage to NPCs. The extracellular Ca2+ chelator ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), rather than the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM), attenuated SSd-induced cytosolic Ca2+ dysfunction and SSd-disordered TrkB/p75NTR signaling. Overall, this study demonstrated a new mechanism for the neurotoxic effect of SSd, which has emerging implications for pharmacological research of SSd and provides a better understanding of neurotoxicity induced by cytostatic drugs.

Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice.

BACKGROUND: Alzheimer's disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer's disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-ß generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer's disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer's disease with Formononetin. OBJECTIVE: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. METHODS: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). RESULTS: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1ß and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. CONCLUSION: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy.

Mitochondrial dynamics regulate mitochondrial autophagy (mitophagy) and apoptosis, which are important events for the quality control of mitochondria and mitochondrial-associated diseases. Esculetin (ESC) is a natural coumarin that exhibits inspiring biological activities in a variety of animal models, but its neuroprotective effects on cerebral ischaemia have not been clearly elucidated. In this paper, we demonstrated the effects of ESC on transient cerebral ischaemia and reperfusion injury induced in a mouse model and examined the possible underlying mechanisms by investigating mitochondrial fragmentation-regulated mitochondrial autophagy and apoptosis. The experimental results showed that ESC treatment alleviated neurological defects and improved cognitive impairments in transient bilateral common carotid artery occlusion (tBCCAO)-treated mice. Further mechanism studies showed that tBCCAO induced mitochondrial oxidative stress injuries and triggered mitochondrial fragmentation, which were evident by the elevated levels of malondialdehyde and mitochondrial dynamin-related protein 1 (Drp1) and the downregulated activities of superoxide dismutase and nuclear transcription factor E2-related factor 2 (Nrf2). ESC treatment significantly alleviated tBCCAO-induced mitochondrial stress and mitochondrial fragmentation. Moreover, mitophagy and mitochondrial apoptosis were stimulated in response to the mitochondrial oxidative stress in the hippocampus of tBCCAO-treated mice, and ESC treatment regulated the expression of mitophagy-related factors, including Bnip3, Beclin1, Pink1, and parkin, the LC-3 II/I ratio, and apoptosis-related factors, including p53, Bax, and caspase 3. Taken together, our results suggest that ESC treatment regulated hippocampal mitophagy and mitochondrial apoptosis triggered by mitochondrial stress via the mediation of mitochondrial fragmentation during transient cerebral ischaemia and reperfusion injury, which provides insight into the potential of ESC for further therapeutic implications.

Modification of GSK3ß/ß-catenin signaling on saikosaponins-d-induced inhibition of neural progenitor cell proliferation and adult neurogenesis.

Saikosaponins-d (SSd) is a major bioactive compound isolated from Radix Bupleuri, an herb widely used in traditional Chinese medicine. Emerging studies demonstrate that SSd adversely affects adult neurogenesis and impairs learning and memory. However, the molecular mechanisms remain to be determined. The current study investigated the potential regulatory of GSK3ß/ß-catenin signaling on SSd-induced neurotoxicity. We demonstrated that SSd exposure inhibited the cell viability and proliferation of primary neuronal stem/progenitor cells (NPCs) from hippocampus in a concentration-dependent manner. Significantly, SSd exposure induced activation of GSK3ß and reduced the cellular ß-catenin in NPCs. Treatment with SB216763, a specific inhibitor for GSK3ß activation, we showed that inactivation GSK3ß improved the ß-catenin signaling by inhibiting degradation complex comprising Axin and APC and attenuated SSd-induced toxicity in NPCs. In addition, administration of SB216763 ameliorated SSd-induced inhibition of NPCs proliferation and enhanced radial glial cells in the hippocampus of mice. Moreover, inactivation GSK3ß promoted dendritic arborization and the survival of newborn neurons together with alleviated the impairment of SSd-induced cognitive function in mice. Overall, these data demonstrated that the significant inhibitory effects of SSd on NPCs proliferation and adult neurogenesis via GSK3ß/ß-catenin signaling pathway. Our results contribute to a better understanding of the molecular mechanisms of SSd-induced neurotoxicity.

Suppressing the Na+/H+ exchanger 1: a new sight to treat depression.

Na+/H+ exchanger 1 (NHE1), an important regulator of intracellular pH (pHi) and extracellular pH (pHe), plays a crucial role in various physiological and pathological processes. However, the role of NHE1 in depression has not yet been reported. This study was designed to investigate the role of NHE1 in the animal model of depression and explore the underlying mechanisms. Our results showed that inhibition of rho-associated kinase 2 (ROCK2) by fasudil (Fas) or baicalin (BA) significantly alleviated chronic unpredictable mild stress (CUMS) paradigm-induced depression-related behaviours in mice, as shown by decreased sucrose consumption in sucrose preference test (SPT), reduced locomotor activity in the open field test (OFT), and increased immobility time in the tail suspension test (TST) and forced swimming test (FST). Furthermore, ROCK2 inhibition inhibited the activation of NHE1, calpain1, and reduced neuronal apoptosis in the CUMS animal model of depression. Next, we used the lipopolysaccharide (LPS)-challenged animal model of depression to induce NHE1 activation. Our results revealed that mice subjected to 1 µl LPS (10 mg/ml) injection intracerebroventricularly (i.c.v.) showed depressive-like behaviours and NHE1 activation. Amiloride (Ami), an NHE1 inhibitor, significantly reversed the decrease in sucrose consumption and reduction in immobility time in the TST and FST induced by LPS challenge. Furthermore, Ami decreased the expression of ROCK2, NHE1, calpain1, and caspase-3 and increased the Bcl-1/Bax ratio in the hippocampus of LPS-challenged mice. Ami treatment also led to antidepressive effects in the CUMS-induced animal model of depression. Thus ROCK2 inhibition could be proposed as a neuroprotective strategy against neuronal apoptosis, and NHE1 might be a potential therapeutic target in depression.

Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway.

BACKGROUND: Baicalin, which is isolated from Radix Scutellariae, possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms. METHODS: A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression. RESULTS: The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia. CONCLUSION: Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.

Baicalin exerts antidepressant effects through Akt/FOXG1 pathway promoting neuronal differentiation and survival.

BACKGROUND AND AIMS: Impaired neurogenesis in hippocampus may contribute to a variety of neurological diseases, such as Alzheimer's disease and depression. Baicalin (BA), which is mainly isolated from the root Scutellaria baicalensis Georgi (traditional Chinese herb), which was reported to facilitate neurogenesis, but how to play the role and the underlying molecular mechanisms are still unknown. MAIN METHODS: In this study, we adopted the chronic unpredictable mild stress (CUMS)-induced mouse model of depression, and then explore antidepressant-like effects and possible molecular mechanisms. KEY FINDINGS: We found that BA significantly increased sucrose consumption in sucrose preference test, the number of crossing in open filed test and attenuated immobility time in tail suspension test. Additionally, BA administration notably promoted neuronal differentiation and the number of DCX+ cells. Moreover, BA facilitated immature neurons develop into mature neurons and their survival. FOXG1, a transcription factor gene, which is crucial for mammalian telencephalon development, specifically stimulates dendrite elongation. BA could reverse the decrease of p-Akt, FOXG1 and FGF2 caused by CUMS-induced. Additionally, the expression of FOXG1 and FGF2 significantly decreased when the Akt pathway were inhibited by LY294002 in SH-SY5Y cells. Interestingly, BA failed to counteract the decline. SIGNIFICANCE: These results suggest that BA could promote the differentiation of neurons, which transformation into mature neurons and their survival via the Akt/FOXG1 pathway to exert antidepressant effects.

Baicalin exerts neuroprotective effects via inhibiting activation of GSK3ß/NF-κB/NLRP3 signal pathway in a rat model of depression.

Chronic stress can provoke depressive-like behaviors through activation of inflammation and apoptosis, leading to a reduction of neurons. Antidepressant therapy may contribute to inhibiting inflammation responses and have neuroprotective effects. Baicalin (BA) has an antidepressant effect in the chronic unpredictable mild stress (CUMS) animal model and exerts anti-inflammation, anti-apoptosis, as well as neuroprotective effects in many central nervous system (CNS)-related diseases. But the effects of BA on neuroprotection, apoptosis, and neuroinflammation and the potential mechanisms in depression are unclear. Here, we focused on examining the therapeutic effects of BA in CUMS-induced depression rats and investigating the molecular mechanisms. Results showed that administration of BA improved depressive-like behaviors and significantly increased the levels of doublecortin (DCX), Neuron-specific enolase (NSE), and Brain-derived neurotrophic factor (BDNF) in hippocampus. Furthermore, administration of BA increased the cell survival by reducing the level of malondialdehyde (MDA) and increasing the level of superoxide dismutase (SOD). Finally, administration of BA significantly decreased CUMS-induced apoptosis and inflammatory cytokines (caspase-1 and IL-1ß) in hippocampus. These responses were mediated by Glycogen synthase kinase-3 (GSK3) ß/Nuclear factor-κB (NF-κB)/Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) signal pathway. Taken together, these results indicate that BA could promote neuronal maturation and rescue neurons from apoptosis via inhibiting activation of GSK3ß/NF-κB/NLRP3 signal pathway that is known to be associated with inflammation, thus exerting neuroprotective effects and preventing CUMS-induced depressive-like behaviors.

Radix Scutellariae Attenuates CUMS-Induced Depressive-Like Behavior by Promoting Neurogenesis via cAMP/PKA Pathway.

Chronic mild unpredictable stress (CUMS) causes neurogenesis damage in the hippocampus and depressive-like behaviors such as cognitive impairment. Radix Scutellariae from the dry root of Scutellaria baicalensis Georgi, with the common name Baikal skullcap. In this study, we demonstrated that Radix Scutellariae (RS 500, 1000 mg/kg) notably improved the behavior of the rat, such as shortened escape latency in morris maze test, reduced immobility time in tail suspension test and in forced swimming test, as well as increased sucrose consumption in sucrose preference test. In addition, RS alleviated the damage CUMS-induced neurogenesis and the reduced levels of BrdU; DCX and NeuN, the neurons hallmark of hippocampus neurogenesis. Moreover, associated proteins in cAMP/PKA pathway were up-regulated after RS treatment. By HPLC analysis, we found that RS decoction contains four main components, including baicalin, baicalein, wogonoside and wogonin, respectively. In conclusion, RS could exert a natural antidepressant with improving depressive-like behavior via regulation of cAMP/PKA neurogenesis pathway.