Novel insight into the therapeutical potential of flavonoids from traditional Chinese medicine against cerebral ischemia/reperfusion injury.

Cerebral ischemia/reperfusion injury (CIRI) is a major contributor to poor prognosis of ischemic stroke. Flavonoids are a broad family of plant polyphenols which are abundant in traditional Chinese medicine (TCM) and have beneficial effects on several diseases including ischemic stroke. Accumulating studies have indicated that flavonoids derived from herbal TCM are effective in alleviating CIRI after ischemic stroke in vitro or in vivo, and exhibit favourable therapeutical potential. Herein, we systematically review the classification, metabolic absorption, neuroprotective efficacy, and mechanisms of TCM flavonoids against CIRI. The literature suggest that flavonoids exert potential medicinal functions including suppressing excitotoxicity, Ca2+ overloading, oxidative stress, inflammation, thrombin's cellular toxicity, different types of programmed cell deaths, and protecting the blood-brain barrier, as well as promoting neurogenesis in the recovery stage following ischemic stroke. Furthermore, we identified certain matters that should be taken into account in future research, as well as proposed difficulties and opportunities in transforming TCM-derived flavonoids into medications or functional foods for the treatment or prevention of CIRI. Overall, in this review we aim to provide novel ideas for the identification of new prospective medication candidates for the therapeutic strategy against ischemic stroke.

Analogies between photochemical reactions and ground-state post-transition-state bifurcations shed light on dynamical origins of selectivity.

Revealing the origins of kinetic selectivity is one of the premier tasks of applied theoretical organic chemistry, and for many reactions, doing so involves comparing competing transition states. For some reactions, however, a single transition state leads directly to multiple products, in which case non-statistical dynamic effects influence selectivity control. The selectivity of photochemical reactions-where crossing between excited-state and ground-state surfaces occurs near ground-state transition structures that interconvert competing products-also should be controlled by the momentum of the reacting molecules as they return to the ground state in addition to the shape of the potential energy surfaces involved. Now, using machine-learning-assisted non-adiabatic molecular dynamics and multiconfiguration pair-density functional theory, these factors are examined for a classic photochemical reaction-the deazetization of 2,3-diazabicyclo[2.2.2]oct-2-ene-for which we demonstrate that momentum dominates the selectivity for hexadiene versus [2.2.2] bicyclohexane products.

Unified Synthesis of 2-Isocyanoallopupukeanane and 9-Isocyanopupukeanane through a "Contra-biosynthetic" Rearrangement.

Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2-isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd-mediated cyclization cascade. This subsequently facilitated an unprecedented bio-inspired "contra-biosynthetic" rearrangement, providing divergent access to 9-isocyanopupukeanane in 15 steps (formal synthesis). Computational studies provide insight into the nature of this rearrangement.

Reporting quality and risk of bias assessment of animal research on Chaihu-Shugan-San for depression: A systematic review.

Objective: Chaihu-Shugan-San (CSS) is a traditional Chinese medicine formula employed to treat depression. We aim to conduct a reporting quality assessment and risk of bias evaluation of animal research on CSS for depression. Methods: To acquire eligible studies, two reviewers searched plentiful databases from inception to October 23rd, 2021. Reporting quality assessment and risk of bias assessment of the included animal studies were evaluated by using Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines and the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, respectively. Results: The initial search identified 720 records, while only 30 studies were included. The result of the reporting quality assessment was inferior, items 17 and 19 were not reported at all. The details of five items (items 3, 6, 7, 10, and 18) were not reported. The outcome of the risk of bias assessment suggested that half of the entries (5/10) displayed an unclear risk of bias and a high risk of bias. Blinding with regard to performance bias and detection bias revealed an unclear risk of bias (100%), followed by baseline characteristics (76.67%) and sequence generation (60%). Random outcome assessment showed a high risk of bias (100%). Conclusion: The included animal studies exhibited methodological defects and imprecise reporting. Hence, the ARRIVE guidelines and SYRCLE's RoB tool should be disseminated among basic medical researchers examining CSS for depression to publish studies with low risk of bias and sufficient reporting so that the animal research can promptly be transformed into clinical research.

Through-Space, Lone-Pair Promoted Aromatic Substitution: A Relay Mechanism Can Beat Out Direct Activation.

We report a detailed experimental and theoretical analysis of through-space arene activation with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ-complex stabilization, our results suggest that these reactions proceed by a relay mechanism wherein the lone pair-containing activators form exothermic π-complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states. Noncovalent interactions (NCI) plots and Quantum Theory of Atoms in Molecules (QTAIM) analyses depict favorable interactions between the Lewis base (LB) and the nitronium ion in the precomplexes and the transition states, suggesting directing group participation throughout the mechanism. The regioselectivity of substitution also comports with a relay mechanism. In all, these data pave the way for an alternate platform of electrophilic aromatic substitution (EAS) reactions.

Handcuff-like metallo-pseudorotaxanes consisting of tiara[5]arene wheels and dimeric silver trifluoroacetate axles.

The complexation between tiara[5]arene (T[5]) and silver trifluoroacetate affords a binuclear metallo-pseudorotaxane on account of multiple endo-cavity AgI η2-arene interactions. Furthermore, two such enantiomeric [(CF3CO2Ag)2⊂T[5]] complexes are bridged by an extra (CF3CO2Ag)2 dimer through exo-wall AgI η2-arene coordination, resulting in a unique handcuff metallo-bis-pseudorotaxane structure in the solid state.

Benefit-risk assessment of traditional Chinese medicine preparations of sinomenine using multicriteria decision analysis (MCDA) for patients with rheumatoid arthritis.

OBJECTIVE: A multicriteria decision analysis (MCDA) model was used to evaluate the benefits and risks of traditional Chinese medicine preparations of sinomenine alone or in combination with conventional drugs in the treatment of rheumatoid arthritis (RA) and to provide a basis for the rational clinical application of sinomenine. METHODS: A study search was performed using six major databases, and Review Manager 5.3 was used for data analysis. Then, an MCDA model evaluation system was established for the treatment of RA with sinomenine preparations, and the benefit values, risk values, and total benefit-risk values of sinomenine preparations alone or in combination with conventional drugs were calculated using Hiview 3.2 software. Finally, Monte Carlo simulations were performed using Crystal Ball embedded in Excel software to calculate the 95% confidence intervals (95% CI), and the probability of the differences between the 2 drug regimens was determined to optimize the evaluation results. RESULTS: Forty-four randomized controlled trials (RCTs) were included. Quantitative assessment of the MCDA model showed that the sinomenine preparation alone offered less benefits than when combined with conventional drugs with a benefit difference of 20 (95% CI 3.06, 35.71). However, the risk of the combination was significantly lower with a risk difference of 13(95% CI -10.26, 27.52). The total value of the benefit-risk of sinomenine alone and in combination with conventional drugs was 46 and 53 at 60% and 40% of the benefit-risk ratio of the two dosing regimens, respectively, with a difference of 7 (95% CI -4.26, 22.12). The probability that the comprehensive score of the combined regimen is greater than that of sinomenine alone is 90.1%, and the evaluation was steady. CONCLUSION: The benefit-risk of the combined application regimen of sinomenine is greater than that of sinomenine alone.

Methodological and reporting quality evaluation of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury: a systematic review.

Buyang Huanwu decoction, a classic traditional Chinese prescription, has been used to prevent and treat stroke for hundreds of years. An increasing number of the laboratory research on Buyang Huanwu decoction used in treating cerebral ischemia-reperfusion injury have been published recently. However, the problem of methodological and reporting quality of some studies is lack of assessment. This study aims to evaluate the methodological and reporting quality of the research on Buyang Huanwu decoction against experimental cerebral ischemia-reperfusion injury. A comprehensive search on six databases was performed. Two researchers independently screened the literature considering the eligibility criteria. Methodological and reporting quality of the included studies were evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline. Forty-five studies met the inclusion criteria. No study achieved a decent overall rating in using the SYRCLE tool (percentage of items with "low risk" ≥ 50%). Of the 22 items on the SYRCLE tool, only 7 items (31.82%) were rated as "low risk" in more than 50% of the included studies. Of the 39 items of ARRIVE guideline, 14 (35.9%) items were rated as "yes" in more than 50% of the included studies. The methodological and reporting quality of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury was substandard, which needed to be further improved. The limitations should be addressed when planning similar studies in the future. Additionally, these findings provided evidence-based guidance for future preclinical studies evaluating the efficacy of Buyang Huanwu decoction in the treatment of cerebral ischemia-reperfusion injury.

Response of vegetation phenology to urbanization in urban agglomeration areas: A dynamic urban-rural gradient perspective.

Being an important theme in global warming, the response of vegetation phenology to urbanization has become an increasing concern at both the local and global levels. Previous studies have focused on spatial or temporal responses across urban-rural gradients; thus, the influence of urbanization on vegetation phenology along the dynamic urbanization gradient has not been well quantified. In this study, we comprehensively analyzed the response of vegetation phenology to urbanization in the Guangdong-Hong Kong-Macao Greater Bay Area (GHM-GBA) from a dynamic urban-rural gradient perspective. The results show that the response of vegetation phenology to urbanization level has a distinct spatiotemporal difference across the urban-rural gradient. Compared to rural areas, the change rate of advancements in the start-of-season (SOS) in urban domains was 1.16 DOY/year and that of the end-of-season (EOS) was 0.63 days/year from 2001 to 2020. In the GHM-GBA region, 61.03 % of the remote sensing pixels showed an advancing trend for SOS and 55.75 % for EOS. Urbanization advanced the SOS and EOS but did not extend the growing season length, and the SOS and EOS were advanced by 7 and 6 days along the urban-to-rural gradient, respectively. For every 10 % increase in urbanization levels, the SOS and EOS advanced by 1.085 and 1.091 days across the urban-rural gradient, respectively; the spring land surface temperature (LST) advanced the SOS at a rate of 1.71 days/°C, while the autumn LST advanced the EOS at a rate of 1.88 days/°C. The phenological shift in the urban-rural gradient was more significant than that over time, which was mainly because of land surface warming under different urbanization levels. These quantitative findings are of great importance for understanding the complicated impacts of urbanization on vegetation phenology and for developing models to predict vegetation phenological changes under future urbanization.

The antidepressant effects and serum metabonomics of bifid triple viable capsule in a rat model of chronic unpredictable mild stress.

Background: Probiotics have shown potential antidepressant effects. This study evaluated the effect and probable mechanisms of bifid triple viable capsules (BTVCs) on a rat model of chronic unpredictable mild stress (CUMS). Materials and methods: Rats were randomly divided into Normal, CUMS model, fluoxetine hydrochloride (FLX), BTVCs, and FLX+BTVCs groups. Depressive-like behaviours, pathological changes in the hippocampus, changes in serum metabolites and potential biomarkers, and metabolic pathways were detected via behavioural tests, haematoxylin-eosin staining, nissl staining, non-targetted metabolomics, and ingenuity pathway analysis (IPA). Results: The rats displayed depressive-like behaviours after CUMS exposure, but BTVCs ameliorated the depressive-like behaviours. In addition, the pathological results showed that the hippocampal tissue was damaged in rats after CUMS exposure and that the damage was effectively alleviated by treatment with BTVCs. A total of 20 potential biomarkers were identified. Treatment with BTVCs regulated D-phenylalanine, methoxyeugenol, (±)-myristoylcarnitine, 18:3 (6Z, 9Z, 12Z) /P-18:1 (11Z), propionyl-L-carnitine, and arachidonic acid (AA) concentrations, all compounds that are involved with biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, linoleic acid metabolism and AA metabolism. The IPA demonstrated that endothelin-1 signalling and cyclic adenosine monophosphate response element binding protein (CREB) signalling in neurons may be involved in the development of depression. Conclusion: Our findings suggest that BTVCs can alleviate depressive-like behaviours, restore damage to the hippocampus in CUMS rats and regulate serum metabolism, which may be related to endothelin-1 signalling or CREB signalling in neurons.

Solvent directed chemically divergent synthesis of ß-lactams and α-amino acid derivatives with chiral isothiourea.

A protocol for the chemically divergent synthesis of ß-lactams and α-amino acid derivatives with isothiourea (ITU) catalysis by switching solvents was developed. The stereospecific Mannich reaction occurring between imine and C(1)-ammonium enolate generated zwitterionic intermediates, which underwent intramolecular lactamization and afforded ß-lactam derivatives when DCM and CH3CN were used as solvents. However, when EtOH was used as the solvent, the intermediates underwent an intermolecular esterification reaction, and α-amino acid derivatives were produced. Detailed mechanistic experiments were conducted to prove that these two kinds of products came from the same intermediates. Furthermore, chemically diversified transformations of ß-lactam and α-amino acid derivatives were achieved.

Photoredox/nickel dual catalyzed stereospecific synthesis of distal alkenyl ketones.

The selective C-C bond deconstruction/refunctionalization via a photoredox/nickel dual-catalyzed hydroalkylation of alkynes is developed under mild reaction conditions. In this protocol, a broad range of alkyl- and aryl-alkynes could react smoothly with cycloalkanols, affording the corresponding distal and site-specific vinyl-substituted ketones with high yields and excellent regioselectivities. Moreover, DFT calculations verified that the electron-rich behavior of aromatics and weak Brønsted bases have a common effect on the photocatalytic oxidant ring-opening of cyclobutanols.

Current Lifetime of Single-Nanoparticle Collision for Sizing Nanoparticles.

Accurate size analysis of nanoparticles (NPs) is vital for nanotechnology. However, this cannot be realized based on conventional single-nanoparticle collision (SNC) because the current intensity, a thermodynamic parameter of SNC for sizing NPs, is always smaller than the theoretical value due to the effect of NP movements on the electrode surface. Herein, a size-dependent dynamic parameter of SNC, current lifetime, which refers to the time that the current intensity decays to 1/e of the original value, was originally utilized to distinguish differently sized NPs. Results showed that the current lifetime increased with NP size. After taking the current lifetime into account rather than the current intensity, the overlap rates for the peak-type current transients of differently sized Pt NPs (10 and 15 nm) and Au NPs (18 and 35 nm) reduced from 73 and 7% to 45 and 0%, respectively, which were closer to the theoretical values (29 and 0%). Hence, the proposed SNC dynamics-based method holds great potential for developing reliable electrochemical approaches to evaluate NP sizes accurately.

Efficacy and safety of abdominal acupuncture for insomnia: A protocol of systematic review and meta-analysis.

BACKGROUND: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function, but psychological patients also cause great damage. Abdominal acupuncture (AA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of abdominal acupuncture in the treatment of insomnia. METHODS: Literature on abdominal acupuncture for insomnia in the PubMed, Excerpt Medica Database(Embase), Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang databases were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of AA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy and safety. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study aimed to evaluate the current status of AA treatment for insomnia, with the aim of illustrating the effectiveness and safety of abdominal acupuncture. CONCLUSION: This study will provide high-quality evidence to evaluate the effectiveness and safety of AA in treating insomnia.Registration: INPLASY2021100088.

Anti-inflammatory and osteoprotective effects of Chikusetsusaponin â £a on rheumatoid arthritis via the JAK/STAT signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease, for which no economical and safe target drug treatment is available. Chikusetsusaponin Ⅳa (CS-IVa), an active compound in Panax japonicus C.A. Mey, has a good anti-inflammatory effect, but whether this compound can serve as a targeted drug for RA and the corresponding therapeutic mechanism remain unclear. PURPOSE: To investigate the anti-inflammatory and bone-protecting effects of CS-IVa on RA and the possible corresponding mechanisms of action. METHODS: Biomarkers and underlying pathological mechanisms were examined by performing a bioinformatics analysis of RA synovial gene expression data profiles, and the feasibility of CS-IVa treatment for RA was predicted using molecular docking and molecular dynamics simulation techniques. Histomorphological and molecular biology techniques were used to verify the feasibility and molecular mechanism of CS-IVa treatment for RA in vivo using a collagen-induced arthritis (CIA) model. RESULTS: CS-IVa alleviated symptoms and reduced the immune organ index, arthritis index, hind paw thickness, and number of swollen joints in the foot for CIA mice. Bioinformatics analysis suggested that interferon-gamma (IFN-γ), interleukin-1 ß (IL-1ß), and the Janus kinase/signal transduction and activator of transcription (JAK/STAT) pathway played important roles in the pathogenesis of RA. The results of molecular docking and molecular dynamics simulations showed that CS-IVa bound effectively to IFN-γ and IL-1ß and that the combined pose has good stability and flexibility. The histomorphological results showed that CS-IVa reduced joint histopathology scores, OARSI scores, and TRAP-positive cell counts. Molecular biology analysis indicated that CS-IVa reduced the concentration of inflammatory factors in the peripheral serum of CIA mice and suppressed the mRNA expression of these factors in the spleen in a dose-dependent manner. The protein expression level of the JAK/STAT pathway was also inhibited by CS-IVa. CONCLUSION: The results of the current study demonstrate a novel inhibitory effect of CS-IVa on inflammation and bone destruction in CIA mice, and the mechanism may be related to the JAK/STAT signaling pathway, which provides new insights into the development of CS-IVa as a therapeutic agent for RA.

An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a crucial factor leading to a poor prognosis for ischemic stroke patients. As a novel Chinese medicine formula, Naotaifang (NTF) was proven to exhibit a neuroprotective effect against ischemic stroke, clinically, and to alleviate CIRI in animals. However, the mechanisms underlying the beneficial effect have not been fully elucidated. METHODS: In this study, we combined a network pharmacology approach and an in vivo experiment to explore the specific effects and underlying mechanisms of NTF in the treatment of ischemia-reperfusion injury. A research strategy based on network pharmacology, combining target prediction, network construction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking was used to predict the targets of NTF in treating the ischemic stroke and CIRI. On the other hand, we used HPLC and HRMS to identify biologically active components of NTF. Middle cerebral artery occlusion models in rats were utilized to evaluate the effect and the underlying mechanisms of NTF against CIRI after ischemic stroke. RESULTS: Network pharmacology analysis revealed 43 potential targets and 14 signaling pathways for the treatment of NTF against CIRI after ischemic stroke. Functional enrichment analysis showed that a STAT3/PI3K/AKT signaling pathway serves as the target for in vivo experimental study validation. The results of animal experiments showed that NTF significantly alleviated CIRI by decreasing neurological score, infarct volume, numbers of apoptotic neuronal cells, increasing density of dendritic spines and survival of neurons. Furthermore, NTF could increase the expression of p-STAT3, PI3K, p-AKT. In addition, the detection of apoptosis-related factors showed that the NTF could raise the expression of Bcl-2 and reduce the expression of Bax. CONCLUSION: This network pharmacological and experimental study indicated that NTF, as a therapeutic candidate for the management of CIRI following ischemic stroke, may exert a protective effect through the STAT3/PI3K/AKT signaling pathway.

Acupuncture for experimental cerebral ischemia/reperfusion injury: a systematic review of methodology and reporting quality.

OBJECTIVES: Preclinical research is essential to the advancement of science but susceptible to insufficient reporting and methodological shortcomings, which compromise internal validity. We aimed to systematically assess the methodological and reporting quality of studies conducted on acupuncture for experimental cerebral ischemia/reperfusion injury (CIRI). METHODS: A comprehensive search in six databases was performed for animal research concerning acupuncture for CIRI. Two authors independently selected articles, extracted data, and assessed the methodological and reporting quality of identified articles using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool, and Animal Research: Reporting In Vivo Experiments (ARRIVE) guideline, respectively. RESULTS: A total of 24 studies were identified. Only 1 article (4%) achieved a decent overall rating in using SYRCLE (percentage of items with "low risk" ⩾50%). Of the 22 items on the SYRCLE tool, only 8 items (37%) were rated as "low risk" of bias in more than 50% of the included studies. Of the 39 items of ARRIVE, 20 (51%) items were rated as "low risk" in more than 50% of the included studies. CONCLUSIONS: The methodological and reporting quality of included studies was generally low, which demands further improvement. These findings should inform the development of evidence-based guidelines for future preclinical research assessing the effect of acupuncture on CIRI.

Dynamic Effects on Migratory Aptitudes in Carbocation Reactions.

Carbocation rearrangement reactions are of great significance to synthetic and biosynthetic chemistry. In pursuit of a scale of inherent migratory aptitude that takes into account dynamic effects, both uphill and downhill ab initio molecular dynamics (AIMD) simulations were used to examine competing migration events in a model system designed to remove steric and electronic biases. The results of these simulations were combined with detailed investigations of potential energy surface topography and variational transition state theory calculations to reveal the importance of nonstatistical dynamic effects on migratory aptitude.

Umbilical acupuncture for insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function but also causes great damage psychological.Umbilical acupuncture (UA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of UA in the treatment of insomnia. METHODS: Literature on UA for insomnia in PubMed, Excerpt Medica Database, the Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Database were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of UA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy, and safety. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study aimed to evaluate the current status of UA treatment for insomnia, with the aim of illustrating the effectiveness and safety of UA. CONCLUSION: This study will provides a high-quality evidence to evaluate the effectiveness and safety of UA in treating insomnia. REGISTRATION: PROSPERO CRD42021283036.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.