AIMS:B cells play dual roles in host defense and immunosuppression during inflammatory diseases such as sepsis. We investigated the role of the chromatin regulator PTIP in maintaining B cell survival and functional integrity during innate immune activation. MATERIALS AND METHODS:B cell-specific PTIP-deficient mice were subjected to lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4)-mediated inflammation. Apoptosis, exhaustion phenotypes, cytokine production, and survival were assessed. Molecular mechanisms were dissected through analysis of apoptotic regulators and inflammatory cytokine signaling pathways. KEY FINDINGS:PTIP deficiency significantly increased activation-induced cell death by upregulating Fas and downregulating Bcl-2, thereby enhancing both extrinsic and intrinsic apoptotic pathways. Mechanistically, PTIP suppressed Fas expression via its N-terminal BRCT1-2 domains independently of BAFF-R, TACI, or IRF4 signaling. Instead, excessive TNF-α and IFN-γ signaling promoted Fas upregulation in PTIP-deficient B cells, linking inflammatory cytokine signals to chromatin-dependent apoptotic regulation. In addition to promoting apoptosis, loss of PTIP accelerated B cell exhaustion during acute inflammation, characterized by increased IL-10 production, elevated inhibitory receptor expression, and reduced MHC II expression. These cellular defects translated in vivo into heightened systemic immunosuppression, aggravated clinical manifestations, and reduced survival following LPS challenge. SIGNIFICANCE:Our findings identify PTIP as a critical chromatin-based regulator of B cell homeostasis during innate immune responses. Targeting PTIP-dependent pathways may provide therapeutic opportunities to restore immune balance in inflammatory diseases.

Major depressive disorder (MDD) is not reducible to a single neurotransmitter deficit. Current explanations commonly involve monoaminergic dysfunction, hypothalamic-pituitary-adrenal axis dysregulation, immune-inflammatory activation, impaired neuroplasticity and synaptic dysfunction, together with metabolic and neurovascular abnormalities. Lipidomic studies have repeatedly identified glycerophospholipid abnormalities in MDD, but their mechanistic meaning remains unresolved because changes in bulk lipid abundance do not explain how altered lipid metabolism becomes a receptor-level neural signal. This review develops a testable interpretation of the lysophosphatidylcholine (LPC)-autotaxin (ATX)-lysophosphatidic acid (LPA)-LPA receptor (LPAR) axis in which LPC species generated during phospholipid turnover provide ATX substrates, ATX activity determines local LPA generation, LPA production and inactivation shape ligand availability, and LPAR signaling links the lipid product to neural output. This structure shifts the focus from total lipid abundance to matched assessment of lipid species, enzyme activity, anatomical site and receptor subtype. Human studies report lower serum and cerebrospinal fluid (CSF) ATX in MDD, lower CSF LPA 22:6 in MDD and schizophrenia, and negative total LPA findings that caution against biomarker oversimplification. Depression-relevant and broader stress- or anxiety-related experimental studies show that ATX, LPA and LPAR perturbation can affect hippocampal function, synaptic physiology, emotional behavior and stress resilience. The key unresolved issue is whether brain-accessible LPC species, active ATX, locally generated LPA, LPA inactivation capacity and receptor-specific output can be demonstrated within the same MDD-relevant fluid, brain-interface site or neural circuit. Future work should therefore move from fluid-level association toward pathway closure through targeted and spatial lipidomics, anatomical ATX activity mapping, LPA inactivation assays, blood-brain barrier (BBB)/interface analysis, LPAR perturbation and matched circuit or behavioral readouts.

RATIONALE:Accurate quantification of neurotransmitters and hormones within the hypothalamic-pituitary-adrenal (HPA) axis is essential for elucidating their pathological roles in neurodegenerative diseases. METHODS:In this study, a solid-phase extraction (SPE) combined with hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-UPLC-MS/MS) method was developed for the simultaneous determination of 12 endogenous compounds in the HPA axis. The method was fully validated according to FDA standards. RESULTS:All analytes showed good linearity over the concentration range of 0.19-19.53 ng/mL, with lower limits of quantification (LLOQs) ranging from 0.19 to 19.53 ng/mL. Accuracy (relative bias) and precision (relative standard deviation) were within ±15%. Matrix effects were evaluated (85.7%-114.3%), and extraction efficiencies were found to be satisfactory (89.1%-108.9%). Compared with other LC-MS-based techniques, this method effectively eliminates interference from endogenous substances by utilizing SPE columns. CONCLUSIONS:The proposed method exhibited excellent performance in terms of linearity, precision, accuracy, stability, and matrix effects, demonstrating superior practicality and reliability for the analysis of complex biological samples.

Background: In recent years, abnormal total zinc levels in serum have emerged as a robust indicator of anxiety disorder. However, measuring total zinc level requires sophisticated instrumentation and specialized personnel. Therefore, if the specific association between Zn2+ in serum and anxiety disorder can be elucidated, it is promising to develop rapid and convenient diagnostic methods for anxiety disorder. In the field of Zn2+ detection, Electrochemical detection has been investigated as a means to quantify Zn2+ with precision, rapidity and cost-effectiveness. Nevertheless, most current electrochemical systems lack specificity. Results: In this study, the relationship between anxiety disorder and serum Zn2+ level was first elucidated, with research finding indicating that anxiety in mice correlated with a marked decline in serum Zn2+ level. Subsequently, a sensitive and specific electrochemical sensor was developed to detect Zn2+ with outstanding detection performance for the diagnosis of anxiety disorder. In this sensor, covalent organic framework material (COFTp-Th) was utilized to load a substantial amount of gold nanoparticles (AuNPs) via Au-N bonds to obtain COFTp-ThAuNPs material. AuNPs can enhance electrode catalysis and conductivity and served as a platform for subsequent material integration. Furthermore, a large quantity of Zincon reagent for specific recognition and detection of Zn2+ was loaded onto the AuNPs through Au-S and Au-N bonds to improve electrode specificity, resulting in the construction of the target electrode modified material of COFTp-Th-AuNPs-Zincon. Significance: Long-range ordered COFTp-Th can adsorb Zn2+ through its rich tetradentate coordination ONNO chelation sites formed by Tp and Th, representing the primary signal amplification. Simultaneously, the abundant Zincon in COFTp-Th-AuNPs-Zincon material with high affinity for the specific recognition and detection of Zn2+ contributed to secondary signal amplification. This approach leads to a significant improvement in the detection performance of Zn2+ and holds promise for providing robust support for the diagnosis and monitoring of anxiety disorder.

Introduction : Pulsatillae Radix (PR) (Baitouweng), a heat-clearing and detoxifying herb in traditional Chinese medicine with a long history of treating dysentery and intestinal disorders, contains Pulsatillae Radix Saponins (PRS) as its primary active constituents. PRS has demonstrated therapeutic efficacy in ulcerative colitis (UC), however, the mechanism through which PRS achieves anti-inflammatory effects via immune modulation remains unclear. In this study, a dextran sulfate sodium (DSS)-induced UC model was established in C57BL/6 mice to evaluate the therapeutic efficacy of PRS and further elucidate its potential anti-inflammatory mechanism mediated by immunomodulation. Methods : DSS-induced UC model was established in C57BL/6 mice to evaluate the therapeutic effects of PRS. Disease progression and treatment efficacy were assessed by monitoring the disease activity index (DAI), body weight changes, colon length, spleen index, and histopathological alterations in colon tissues. To elucidate the underlying mechanisms, immunofluorescence, molecular docking, flow cytometry, qPCR, and ELISA were employed. Results The results showed that PRS treatment alleviated body weight loss, reduced colon damage, improved splenomegaly, and mitigated diarrhea symptoms in UC mice. PRS also preserved colonic mucosal integrity and decreased inflammatory cell infiltration, significantly ameliorating pathological manifestations and disease severity. Further mechanistic investigations revealed that PRS markedly upregulated the expression levels of GPR43 and MUC2 in the colon, enhanced their spatial distribution and co-localization, and exerted anti-inflammatory effects by suppressing excessive secretion from CD11b⁺LY-6G⁺ cells and restoring the Th17/Treg balance. Conclusion This study elucidates the mechanism by which PRS regulates Th17/Treg immune imbalance and neutrophil recruitment through GPR43, and provides a foundational basis for understanding the mechanistic link between immunomodulation and anti-inflammatory effects in natural medicinal compounds with anti-inflammatory potential.

[This corrects the article DOI: 10.3389/fphar.2024.1424834.].

Currently, Drosophila is widely used to study brain diseases. Unfortunately, Drosophila still lacks a mature and stable model for research on depression. This study addressed this issue by systematically exploring external stress and intrinsic susceptibility factors (Drosophila strains, adult/larval forms) that may influence the establishment and reproducibility of the stress-induced model. On this basis, the parameters are optimized. The results indicate Drosophila strains and forms are critical factors influencing model establishment, while external stress is the primary cause affecting the model's mortality rate. Compared with the other four strains, Canton-S are the most susceptible to chronic unpredictable mild stress (CUMS). Larval forms exhibit lower reactivity to external stress compared to adults. Parameter variations greatly influence model mortality rates from cold/heat/starvation stress. The model methodology validation study conducted subsequently through assessments of face, construct, and predictive validity demonstrates that the model exhibits face (neurobehavioral differences), structural (neurotransmitter changes in the Drosophila brain), and predictive (behavioral changes after fluoxetine treatment) validity. Additionally, spatial behavior experiments in Drosophila provide more realistic activity patterns compared to planar behavior, minimizing potential errors in interpreting lateral movements of the Drosophila, and it is recommended that this metric be included in model evaluation. This study presents a comprehensive set of methods for establishing and evaluating a depression-like behavior model and offers greater convenience for research on the pathogenesis of depression, as well as the screening, efficacy evaluation, and mechanistic studies of antidepressant drugs.

ETHNOPHARMACOLOGICAL RELEVANCE:Citrus medica L. has been cultivated in China for over two thousand years, with the effects of soothing the liver, regulating qi. Studies have shown that it can relieve anxiety. Its combination with other traditional Chinese medicines has been widely used in clinical practice assist in the treatment of anxiety and depression. The essential oil rich in peel is important active substance of Citrus medica L. A large number of studies have confirmed that essential oils are commonly used to relieve pain, psychological stress and induce relaxation. However, there are currently no studies on the effects of Citrus medica L. essential oil (CEO) on anxiety. AIM OF THE STUDY:Anxiety has become the most common mental illness worldwide, so effective and diverse prevention and control methods are urgently needed. The main objective of this study is to evaluate the therapeutic effect and optimal administration route of CEO on anxiety caused by different susceptibility factors, and to further explore its potential mechanism for improving anxiety, providing scientific guidance for the application of CEO. MATERIALS AND METHODS:Induce anxiety models caused by fatigue or stress, and use animal behavior as an indicator to evaluate the CEO. To illustrate the underlying mechanisms of anti-anxiety effect of CEO, histological examination, immunofluorescence staining and Western Blot were carried out. RESULTS:The results showed that the safer inhalation administration was more effective. Compared with the stress-induced anxiety model, CEO has a more obvious effect on fatigue-induced anxiety. After CEO administration, the frequency, time, and movement distance of fatigue-type anxious mice in Open Field Test (OFT) increased significantly. During Elevated Plus Maze Test (EPM), the mice spent more time and have more entry in the open arm. Further research found that CEO can significantly increase cerebral blood flow, recover damaged neurons in the hippocampus. RNA-seq analysis investigated that CEO can significantly improve gene expression in the hippocampus of fatigue accompanied anxiety mice. The underlying mechanism is significantly related to cholinergic system pathways. Further research found that the alpha-7 nicotinic acetylcholine receptor (α7-nAChR) in anxious mice was down-regulated, accompanied by decreased activation of its downstream ERK/CREB. Inhaling essential oil improved fatigue-induced anxiety by reversing this phenomenon. CONCLUSIONS:The results demonstrated that CEO have a significant anti-anxiety effect, especially fatigue induced anxiety. Our research results verify the accuracy and effectiveness of symptomatic treatment strategies for anxiety caused by different susceptibility factors, and provide scientific guidance for the rational use of CEO.

Saponins, the primary bioactive components of Achyranthes bidentata Blume (AB), exhibit neuroprotective and anti-inflammatory properties. However, the lack of pharmacokinetic (PK) data, particularly on tissue distribution and first-pass effects, critically hinders their therapeutic development. Therefore, a rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method (9-min run time) was validated to simultaneously quantify five AB saponins in mice tissues (brain, heart, liver, spleen, lung, kidney; n = 5 per time point) at 10, 30, 60, 120, 240 min post-administration. The method demonstrated excellent linearity (R-2 > 0.99, 1-2500 ng/mL), precision (RSD <= 7.04 %), accuracy (85%-115 %), and recovery rates (86.6%-97.2 %, RSD <= 11.39 %) per ICH M10 guidelines. The results demonstrate that the saponin concentrations in various tissues after IG and IP administration were lower compared to those after IV administration, with levels reaching only 10 % of the latter. Although all these compounds are pentacyclic triterpenoid saponins with an oleanane skeleton, their tissue distribution in vivo varies significantly. The elimination of achyranthoside D, ginsenoside R0, and araloside A is relatively slow in various tissues. In contrast, chikusetsusaponin IVa is rapidly eliminated from various tissues. The ability of four saponins to cross the blood-brain barrier is highly beneficial for the development of therapeutic drugs for central nervous system diseases. Additionally, the results from different administration routes indicate that AB saponins may exhibit a pronounced gastrointestinal and hepatic first-pass effect in vivo, which should be considered in future research. This study can guide multi-route study of AB saponins provides critical insights for formulation optimization and dosing regimen design to mitigate first-pass effects

Biofouling, the accumulation of organisms on submerged surfaces, significantly impairs vessel performance and hinders maritime industry development. The development of effective coatings has become an efficient solution to this problem. Cerium oxide nanoparticles (CeO2NPs) were synthesized on dopamine-modified 5083 aluminum alloy (Al) surfaces by mussel-inspired chemistry. The CeO2NPs can be fully exposed to the coating surface using this method, and CeO2 nanocoating exhibited haloperoxidase-like activity. CeO2 nanocoatings have an excellent ability to inhibit the attachment of P. tricornutum, E. coli, and Bacillus sp., and their numbers were reduced by 96.03%, 94.41%, and 88.44%, respectively. The outstanding antiadhesion capability of the coating was attributed to its potent antibacterial properties and quorum quenching effect. Furthermore, the CeO2 nanocoating demonstrated outstanding corrosion resistance, with an impedance modulus 46.9 times higher than that of the Al sample. This approach presents a sustainable and environmentally friendly surface modification model for enhancing the performance of antifouling and anticorrosion in aluminum materials.

In situ real-time quantitative analysis of intracellular hydrogen peroxide (H2O2) is of great value in understanding whether neurons have transient high reactivity to oxygen (O2) changes in the microenvironment and whether they can be reversed. In this article, we successfully synthesized iron porphyrin covalent organic framework (FeTPP-COF) using iron porphyrin-based framework material and constructed a novel PtNPs/FeTPPCOF/CFE (carbon fiber electrode) sandwich electrochemical sensor, which realized the detection of H2O2 and vesicle count in a single hippocampal neuron cell (HT22). The results showed that the sensitivity of our electrochemical sensor is primarily enhanced through abundant platinum nanoparticles (PtNPs), meanwhile, while FeTPP-COF could effectively capture O2, significantly increasing the probability of molecular collisions, catalyzing the reduction of O2 to H2O2 using FeTPP-COF (formed by iron porphyrin) achieves secondary sensitivity amplification. The linear range of H2O2 detection by electrochemical sensor based on timed current changes is 1 mu M to 140 mu M (R2 = 0.9993). Due to the dual sensitivity amplification strategy, the detection limit is as low as 2.9 nM. This demonstrates the feasibility of amplifying the sensitivity of interlayer sensors using porphyrin-based COFs. It is worth noting that the formation of an instantaneous hypoxic microenvironment in extracellular immediately leads to an excessive increase in the number of vesicles released and H2O2 content, and this change could be reversed by oxygen therapy to alleviate the damage. This discovery provides new insights into how hypoxia affects nervous system function and provides a new technique for tracking the dynamic changes of H2O2 within a single cell during hypoxia.

OBJECTIVES:Curcumae Rhizoma (CR) is a traditional Chinese medicine used frequently in clinics, which contains volatile components that exhibit various active effects. This study explores the effect of Curcumae Rhizoma volatile oil (CRVO) on depressive mice and its possible mechanism of action. METHODS:Chemical composition of CRVO was analysed by GC-MS. DPPH and ABTS free radical scavenging assays were used to evaluate the in vitro antioxidant capacity of CRVO. A chronic unpredictable mild stress (CUMS) model was used to evaluate the antidepressant effect of CRVO. The effects of CRVO on oxidative stress in vivo were investigated using Nissl staining, ELISA and transmission electron microscopy. The Nrf2/HO-1/NQO1 signalling pathway was detected by western blotting and immunofluorescence. ML385, a Nrf2 inhibitor was used to validate the effect of Nrf2 on CUMS mice with CRVO treatment. KEY FINDINGS:Phytochemical analysis showed that CRVO is rich in its characteristic components, including curzerene (31.1%), curdione (30.56%), and germacrone (12.44%). In vivo, the administration of CRVO significantly ameliorated CUMS-induced depressive-like behaviours. In addition, inhalation of CRVO significantly alleviated the oxidative stress caused by CUMS and improved neuronal damage and mitochondrial dysfunction. The results of mechanistic studies showed that the mechanism of action is related to the Nrf2/HO-1/NQO1 pathway and the antioxidant and antidepressant effects of CRVO were weakened when ML385 was used. CONCLUSIONS:In summary, by regulating the Nrf2 pathway, inhalation of CRVO can reduce oxidative stress in depressed mice, thereby reducing neuronal damage and mitochondrial dysfunction to alleviate depression-like behaviours. Our study offers a prospective research foundation to meet the diversity of clinical medication.

Styphnolobium japonicum (L.) Schott, is an ornamental species of Leguminosae, widely planted as a roadside tree in north regions of China (Kite et al. 2007). In mid-June of 2022, 45 ca. 30-year-old plants of S. japonicum growing along roadsides in Dalian, China were found to be infected by a polypore fungus that appeared to be killing many of these plants. The infected trees show leaf wilt early in the growing season, and in mid-summer, pale yellow fruiting bodies appeared at the base of the tree trunks. The fruiting bodies were effused-reflexed, with a pale yellow to yellow-brown pileus when dry, and gradually formed whitish pores on their undersurface. Over two years, approximately 15% of S. japonicum trees became infected in a ca. 10-ha area. Thirteen morphologically identical strains were generated from 20 samples by collecting 8 mm3 tissue pieces from 20 fruiting body stroma and growing these out on potato dextrose agar (PDA). The basidiospores from field collected fruiting bodies were abundantly produced in pores which were circular and 4-6 per mm, hemispherical and dropletshaped, hyaline, thick-walled and smooth, (5.8-6.9)×(4.8-5.7) μm. On PDA, the mycelia were initially white and sparse, later becoming fluffy in the center, white at the margins, and pale yellow on the underside. These morphological characteristics were consistent with Perenniporia spp., as described recently in Cui et al. (2019). To further confirm species identification, representative isolate DL was selected for molecular identification. The small subunit (SSU), internal transcribed spacer (ITS), and large subunit (LSU) of the ribosomal DNA (rDNA) were amplified with primers NS1/NS4, ITS1/ITS4 (White et al 1990), and LROR/LR7 (Aveskamp et al. 2010), respectively. The sequences were uploaded to GenBank as accession OQ592891 for ITS; OQ629793 for SSU; and OQ629858 for LSU. Sequence comparisons against the GenBank database showed 99% to 100% identity (GenBank accessions KX081110.1, MG847270.1, JF706344.1) with a strain of Perenniporia fraxinea (Bull.) Ryvarden [syn.: Vanderbylia fraxinea (Bull.) D.A. Reid]. Phylogenetic analysis also placed these isolates in a highly supported clade with the other isolates of Perenniporia fraxinea. To test pathogenicity, fresh hyphal plugs were inoculated onto sterile wounds artificially punctured on the stem surface of five healthy one-year-old S. japonicum seedlings, and plants were incubated at 28℃ with a 12-hour photoperiod in a humid chamber for 7 days. PDA plugs were used as controls and the pathogenicity test was repeated three times. After 7 days, lesions were observed on all inoculated stems, while the mock-inoculated stems were asymptomatic, and no fungal pathogen was isolated. The same fungus was re-isolated from the inoculated wounds to complete Koch's Postulates. The original pathogenic and the re-isolated inoculated fungus was identified as P. fraxinea. This fungus has also been found on Robinia pseudoacacia in Japan (Matsumoto et al. 2023) and in Germany (Kehr et al. 2020). However, to our knowledge, this is the first report of P. fraxinea causing heart rot of S. japonicum in China. The wide occurrence of this pathogenic fungus on stem bases of S. japonicum, and its lethal effect on host plants should be given more attention by landscape maintenance workers and extension agents.

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. A total of 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs’ content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI and ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and the VH/CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum were significantly up-regulated in the NSB group. Additionally, SOD (p < 0.05) and the T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05), showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, and serum anti-inflammatory cytokines, and by regulating the intestinal barrier function and antioxidant capacity, SCFAs’ content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

Ethnopharmacological relevanceCitri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders.Aim of the studyThe aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms.Materials and methodsThis study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety.ResultsThe results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb.ConclusionsThe study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

Background Since the pathogenesis of depression is complex, antidepressant therapy remains unsatisfactory. Recent evidence suggests a link between depression and lipid metabolism. Saikosaponin (SS) exhibits antidepression and lipid-regulating effects in modern pharmacology. However, it is unknown whether lipid regulation is the key mechanism of the SS antidepressant effect and how it works. Purpose In this study, we investigated the relationship between the antidepressant activity of SS and the regulation of lipid metabolism and explored potential mechanisms. Methods APOE-/- mice, in combination with the chronic unpredictable mild stress (CUMS) model, were used to study the relationship between SS antidepressant activity and lipid metabolism through behavioral, electrophysiological techniques, and non-targeted lipidomics. Western blot, primary cell culture technology, and laser speckle cerebral blood flow imaging were employed to elucidate potential mechanisms. GraphPad Prism was used for statistical analysis, and p < 0.05 was considered statistically significant. Results APOE-/- mice exhibit more severe depressive-like behavior and dysregulation of sphingolipid metabolism in CUMS. SS alleviates depressive behavior and cortical sphingolipid metabolism disorder caused by CUMS, but has no effect on APOE-/- mice. SS alleviates the imbalance between ceramide (Cer) and sphingomyelin (SM) through acidic sphingomyelinase (AMSase). In addition, SS regulates neuronal glutamate release via sphingolipid metabolism, thereby alleviating the CUMS-induced inhibition of neurovascular coupling (regulates metabotropic glutamate receptor and IP3 receptor), which ameliorates the reduction of cerebral blood flow in depressed mice. Conclusion Our study highlights the role of lipid metabolism in the antidepressant activity of SS and explores its underlying mechanisms. This study provided new insights into the better understanding of the antidepressant mechanisms of phytomedicine while increasing the possibility of lipid metabolism as a therapeutic strategy for depression.