The network pharmacology study and molecular docking to investigate the potential mechanism of Acoritataninowii Rhizoma against Alzheimer's Disease.

Alzheimer's Disease is considered as an insidious neurodegenerative progressive disease but its pathogenesis has not been elucidated. Acoritataninowii Rhizoma exhibits anti-dementia effects as a traditional Chinese medicine (TCM), which is linked to its anti- Alzheimer's Disease mechanism. In this study, network pharmacology and molecular docking were used to examine the potential of Acoritataninowii Rhizoma for Alzheimer's Disease. In order to construct PPI networks and drug-component-target-disease networks, disease-related genes and proteins were gathered from the database. Gene ontology (GO), pathway enrichment (KEGG), and molecular docking were used to forecast the potential mechanism of Acoritataninowii Rhizoma on Alzheimer's disease. Therefore, 4 active ingredients and 81 target genes were screened from Acoritataninowii Rhizoma, 6765 specific target genes were screened from Alzheimer's Disease, and 61 drug-disease cross genes were validated. GO analysis showed that Acoritataninowii Rhizoma can regulate processes such as the protein serine/threonine kinase associated with MAPK. KeGG pathway analysis showed that the signaling pathways affected by Acoritataninowii Rhizoma were fluid shear stress and atherosclerosis, AGE-RAGE and other pathways. Molecular docking implied that the pharmacological influences of the bioactive constituents of Acoritataninowii Rhizoma (Cycloaartenol and kaempferol) on Alzheimer's Disease may related to ESR1 and AKT1, respectively. AKT1 and ESR1 may be the core target genes of the treatment for Alzheimer's disease. Kaempferol and Cycloartenol might be core bioactive constituents for treatment.

The potential mechanism of Bupleurum against anxiety was predicted by network pharmacology study and molecular docking.

Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear. Therefore, this unknown is predicted by network pharmacology study with molecular docking in the present study. The components of bupleurum were obtained from the databases. Genes associated with components and disease were also provided by databases. Overlapping genes between components and disease were analyzed. The network of medicine-components-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG) and molecular docking were conducted to predict the potential mechanisms of bupleurum on anxiety. A total of 9 bioactive components derived from bupleurum with 80 target genes were involved in anxiety. Neurotransmitter receptor activity, G protein-coupled amine receptor activity, regulation of blood circulation, neuroactive ligand-receptor interaction, calcium signaling pathway and salivary secretion may play significant roles in the anxiolytic of bupleurum. Molecular docking implicated that ACHE and MAOA showed high affinity for stigmasterol. Based on network pharmacology study with molecular docking, multi-component-multi-target-multi-pathway action mode of bupleurum on anxiety was elaborated. Stigmasterol might be the core bioactive component, while ACHE and MAOA might be the core target genes in the pharmacological profile of bupleurum on anxiety.

Exploring the Potential Antidepressant Mechanisms of Pinellia by Using the Network Pharmacology and Molecular Docking.

About 350 million people worldwide suffered from depression, but less than half of the patients received effective and regular treatments. Traditional Chinese Medicine (TCM) such as pinellia has been proven effective for antidepressant treatment with fewer side effects. However, the exact mechanisms remain unclear. Herein, we use the methods of network pharmacology and molecular docking to analyze the effective monomer components of pinellia and reveal the involved signaling pathways to produce antidepressant effects. TCMSP, BATMAN-TCM, and TCMID databases were utilized to analyze the bioactive ingredients and target genes derived from pinellia via the screening the molecular weight (MW), oral bioavailability (OB), blood-brain barrier (BBB) and drug similarity (DL). OMIM, TTD, DisGeNET, GeneCards and DrugBank databases were used to obtain key genes of depression. Then, the networks of protein-protein interaction (PPI) and "medicine-ingredients-targets-pathways" were built. The target signaling pathways were enriched by GO and KEGG by using R language. Furthermore, bioactive ingredients binding of the targets were verified by molecular docking. Nine active monomer ingredients and 96 pivotal gene targets were selected from pinellia. 10,124 disease genes and 87 drug-disease intersecting genes were verified. GO analysis proposed that the receptor activity of neurotransmitter, postsynaptic neurotransmitter, G protein-coupled neurotransmitter, and acetylcholine through the postsynaptic membrane could be modulated by pinellia. KEGG pathway analysis revealed that pinellia influenced depression-related neural tissue interaction, cholinergic synapse, serotonin activated synapse and calcium signaling pathway. Besides, the reliability and accuracy of results obtained from the indirect network pharmacology were validated by molecular docking. The bioactive components of pinellia made significant antidepressant effects by regulating the key target genes/proteins in the pathophysiology of depression.

A network pharmacology study with molecular docking to investigate the possibility of licorice against posttraumatic stress disorder.

Post traumatic stress disorder (PTSD) is a mental health condition that has a debilitating effect on a person's quality of life and leads to a high socioeconomic burden. Licorice has been demonstrated to have neuroprotective and antidepressant-like effects, but little is known about its effects for the treatment of PTSD. The present study aimed to explore the potential of licorice for PTSD therapy using a network pharmacology approach with molecular docking studies. The compounds of licorice were obtained from databases with screening by absorption, distribution, metabolism and excretion (ADME) evaluation. Genes associated with compounds or PTSD were obtained from public databases, and the genes overlapping between licorice compounds and PTSD were compared by Venn diagram. A network of medicine-ingredients-targets-disease was constructed, visualized, and analyzed using cytoscape software. Protein-protein interactions, gene ontology, pathway enrichment and molecular docking were performed to evaluate the effect of licorice for the treatment of PTSD. 69 potential compounds were screened after ADME evaluation. A total of 81 compound-related genes and 566 PTSD-related genes were identified in the databases with 27 overlapping genes. Licorice compounds (e.g., medicarpin, 7-methoxy-2-methyl isoflavone, shinpterocarpin, formononetin, licochalcone a) and target proteins (e.g., ESR1, PTGS2, NOS2, and ADRB2) with high degree in the network were involved in G protein-coupled receptor signaling pathways at the postsynaptic/synaptic membrane. Moreover, neuroactive ligand-receptor interactions, calcium signaling, cholinergic synapse, serotonergic synapse and adrenergic signaling in cardiomyocytes may play important roles in the treatment of PTSD by licorice. This study provides molecular evidence of the beneficial effects of licorice for the treatment of PTSD.

Translocator protein 18 kDa: a potential therapeutic biomarker for post traumatic stress disorder.

Post traumatic stress disorder (PTSD) is widely regarded as a stress-related and trauma disorder. The symptoms of PTSD are characterized as a spectrum of vulnerabilities after the exposure to an extremely traumatic stressor. Considering as one of complex mental disorders, little progress has been made toward its diagnostic biomarkers, despite the involvement of PTSD has been studied. Many studies into the underlying neurobiology of PTSD implicated the dysfunction of neurosteroids biosynthesis and neuorinflammatory processes. Translocator protein 18 kDa (TSPO) has been considered as one of the promising therapeutic biomarkers for neurological stress disorders (like PTSD, depression, anxiety, et al) without the benzodiazepine-like side effects. This protein participates in the formation of neurosteroids and modulation of neuroinflammation. The review outlines current knowledge involving the role of TSPO in the neuropathology of PTSD and the anti-PTSD-like effects of TSPO ligands.

The anxiolytic-like effects of puerarin are associated with the changes of monoaminergic neurotransmitters and biosynthesis of allopregnanolone in the brain.

Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted. Data showed that similar to the positive-control drug sertraline (Ser) (15 mg/kg, i.g.), the anxiolytic-like effects were produced by puerarin (60 and 120 mg/kg, i.g.) in VTCT and EMPT respectively without affecting locomotor activity in OFT. Moreover, the present study also found that consistent with Ser, the levels of allopregnanolone and serotonin (5-HT) in the prefrontal cortex and hippocampus were increased by puerarin (60 and 120 mg/kg, i.g.), respectively. In summary, the present study indicated that puerarin exerted the anxiolytic-like effects, which maybe associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain.

Anxiolytic-like effects of paeoniflorin in an animal model of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is the serious psychiatric disorder. Paeoniflorin (PF) produces the antidepressant-like properties. However, few studies are concerned about its anti-PTSD-like effects and mechanisms. To investigate these, the single prolonged stress (SPS) model was utilized. PTSD-like behavioral deficits in rats after exposure to SPS were improved by PF (10 and 20 mg/kg, i.p.), evidenced by blocking increased freezing time in contextual fear paradigm (CFP) and increased time and entries in open arms in elevated plus maze (EPM) test without affecting the locomotor activity in open field (OF) test. We also found that increased levels of corticosterone (Cort), corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) after exposure to SPS were reversed by PF (10 and 20 mg/kg, i.p.) in serum, respectively. Moreover, the decreased levels of serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus were reversed by PF (10 and 20 mg/kg, i.p.), respectively. In summary, the anti-PTSD-like activities of PF were associated with the modulation of HPA axis and 5-HT system activation.

The inulin-type oligosaccharides extract from morinda officinalis, a traditional Chinese herb, ameliorated behavioral deficits in an animal model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a severe psychiatric condition. The allopregnanolone biosynthesis has been implicated as one of the possible contributors to PTSD. Inulin-type oligosaccharides of morinda officinalis (IOMO) had been shown to be effective in the therapy of depression. However, few studies concern the anti-PTSD-like effects of IOMO. To evaluate this, the single prolonged stress (SPS) model was used in the present study. It had been shown that the behavioral deficits of SPS-treated rats were reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), which reversed the increased freezing time in contextual fear paradigm (CFP) and the decreased time and entries in open arms in the elevated plus maze (EPM) test without affecting the locomotor activity in the open field (OF) test. In addition, the decreased allopregnanolone in the prefrontal cortex, hippocampus, and amygdala was reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), respectively. In summary, the present study indicated that the IOMO exert anti-PTSD-like behaviors, which maybe associated with the brain allopregnanolone biosynthesis.

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder.

Recently, the translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR) and both the starting point and an important rate-limiting step in neurosteroidogenesis, has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD) because it affects the production of neurosteroids, reinforcing the hypothesis that selective TSPO ligands could potentially be used as anti-PTSD drugs. As expected, we showed that chronic treatment with YL-IPA08 [N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl)-7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, caused significant suppression of enhanced anxiety and contextual fear induced in the inescapable electric foot-shock-induced mouse model of PTSD and the time-dependent sensitization (TDS) procedure. These effects were completely blocked by the TSPO antagonist PK11195. Furthermore, YL-IPA08 could increase the level of allopregnanolone in the prefrontal cortex and serum of post-TDS rats, and these effects were antagonized by PK11195. In summary, the findings from the current study showed that YL-IPA08, a potent and selective TSPO ligand, had a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.

Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells.

O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7 MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P < 0.05). However, there was no significant difference in the 50% inhibition concentration (IC50) of TMZ between MGMT-positive and MGMT-negative GSCs (P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P <0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between migraine and five psychiatric disorders.

Background: The question of whether a correlation exists between migraine and five psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), anorexia nervosa (AN), bipolar disorder (BIP), and schizophrenia (SCZ), remains a matter of controversy. Hence, this research aims to investigate whether there is a possible association between migraine and five psychiatric disorders. Methods: We performed a bidirectional 2-sample Mendelian randomization (MR) analysis to assess the causality between migraine and five psychiatric disorders. Genetic associations of PTSD, MDD, AN, BIP, and SCZ were obtained from the Psychiatric Genomics Consortium (PGC) database and genetic associations of migraine with aura and migraine without aura were obtained from the FinnGen dataset. We used the inverse-variance weighted (IVW), weighted median, weighted mode, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR Egger regression methods to evaluate the association of genetically predicted exposure with the risk of outcome. Results: MR demonstrated that MDD was associated with a high risk of migraine without aura (OR = 1.930578, 95% confidence interview (CI): 1.224510, 3.043550, p < 0.05), but BIP was related to a low risk of migraine without aura (OR = 0.758650, 95%CI: 0.639601, 0.899858, p < 0.05). According to the results of reverse MR, migraine with aura was associated with a high risk of BIP (OR = 1.019100, 95%CI: 1.002538, 1.035935, p < 0.05), and migraine without aura was associated with an increased risk of AN (OR = 1.055634, 95%CI: 1.023859, 1.088394, p < 0.05). Conclusion: Our results provide evidence of the potential causal association between migraine and some psychiatric disorders. It may contribute to the prevention of migraine and some psychiatric disorders.

Exploring the potential mechanism of Kaixinsan powder for the same pathogenesis of PTSD and anxiety based on network pharmacology and molecular docking: A review.

BACKGROUND: Post-traumatic stress disorder (PTSD) and anxiety are common mental illnesses and there are many similar pathogenesis and clinical manifestations between PTSD and anxiety. Kaixinsan powder (KXS), a commonly used prescription in traditional Chinese medicine, has been widely used to treat PTSD and anxiety. This study aims to explore the potential mechanisms of KXS for the same pathogenesis of PTSD and anxiety using a network pharmacology approach. METHODS: The bioactive components and relevant target genes of KXS were obtained from the database about Traditional Chinese Medicine. The key genes of PTSD and anxiety were derived from disease databases. Subsequently, the network of protein-protein interaction and a network of "drug-components-disease-targets" was constructed. In order to treat PTSD and anxiety, gene ontology enrichment and signaling pathway enrichment were analyzed by using R language and components-core targets associated were validated by molecular docking. RESULTS: One hundred three targets of KXS in treating PTSD and anxiety were identified. The results of protein-protein interaction analysis and molecular docking indicated that AKT1 and IL-6 were crucial targets. Moreover, KEGG analysis has shown that neuroactive ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway may play crucial roles in treating PTSD and anxiety. Ten biological process, 10 molecular function, and 10 cellular component were revealed via gene ontology analysis. CONCLUSIONS: The network pharmacology study and molecular docking indicated that KXS treated anxiety and PTSD by multiple components, targets, and signaling pathways. These results provide an important reference for subsequent basic research on PTSD and anxiety.

Comparative efficacy and safety of antiviral traditional Chinese medicine injections for viral pneumonia: a systematic review and network meta-analysis.

BACKGROUND: Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP. RESEARCH DESIGN AND METHODS: Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes. RESULTS: A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP. CONCLUSIONS: This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.

Antidepressant-like effects of Z-ligustilide on chronic unpredictable mild stress-induced depression in rats.

Depression is a significant public health issue and its neuropathogenesis is associated with the dysfunction of progesterone and allopregnanolone biosynthesis. Z-ligustilide (LIG), one of the main components of the herb Angelica sinensis (Oliv.) Diels (AS), is reported to have antidepressant activities. The present study aimed to evaluate the antidepressant-like effects of LIG via behavioral tests and to measure the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. The results demonstrated that LIG (20 and 40 mg/kg) exerted antidepressant-like effects, confirmed by increased mobility, locomotion, rearing frequency and preference to sucrose. Furthermore, the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus were markedly increased following treatment with LIG (20 and 40 mg/kg), indicating that both neurosteroids could serve a significant role in the antidepressant-like effects of LIG.

Cytoprotective effects of paeoniflorin are associated with translocator protein 18 kDa.

Paeoniflorin (PF) is one of the important active components in peony that are known to produce the neuroprotective effects. However, the involved cytoprotective factors on brain astrocytes are remain unclear. Translocator protein 18 kDa (TSPO) and its downstream neurosteroids biosynthesis play a significant role in cytoprotection. Based on these, the role of TSPO and neurosteroids biosynthesis in the cytoprotective effects of PF is evaluated. The astrocyte cells were cultured and AC-5216 (TSPO ligand) was selected as the positive control drug. The cytoprotective effects of PF and the levels of neurosteroids were quantified by water-soluble tetrazolium assay and enzyme linked immunosorbent assay, respectively. The cytoprotective activities of PF were relevant to neurosteroids (e.g. progsterone and allopregnanolone) biosynthesis, while these effects were totally blocked by PK11195, trilostane and finasteride, respectively. In summary, the cytoprotective effects of PF maybe mediated by TSPO and neurosteroids biosynthesis. The findings may provide the new insights into the cytoprotective effects of PF.

Anti-PTSD-like effects of albiflorin extracted from Radix paeoniae Alba.

ETHNOPHARMACOLOGY RELEVANCE: Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder that is characterized by symptoms of re-experiencing, avoidance and hyperarousal, as well as social and professional dysfunction at least one month after the exposure to a traumatic event. Biosynthesis of allopregnanolone has been suggested as one of the important contributors to PTSD. Albiflorin (AF) extracted from Radix paeoniae Alba had been shown to be effective in the therapy of depression. However, few studies were concerned about the anti-PTSD-like effects of AF. AIM OF THE STUDY: The current study aimed to evaluate the anti-PTSD-like effects of AF in an animal model and its possible mechanism. MATERIALS AND METHODS: To evaluate this, the single prolonged stress (SPS) model was used in the present study. The SPS rats were administered by AF (at doses of 3.5, 7 and 14.0mg/kg, i.g.) after induction of SPS from days 2-13. After the exposure to SPS, behavioral assessments were conducted, including contextual fear paradigm (CFP), elevated plus-maze test (EPMT), open-field test (OFT). The rats were decapitated at the end of the behavioral tests and levels of allopregnanolone in prefrontal cortex, hippocampus and amygdala were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: It had been shown that behavioral deficits of SPS rats were reversed by AF (7.0 and 14.0mg/kg, i.g.), which attenuated the PTSD-like associated contextual freezing behavior in CFP and improved PTSD-like associated anxiogenic behavior in EPMT without affecting locomotor activity in OFT. Moreover, decreased levels of allopregnanolone in prefrontal cortex, hippocampus, and amygdala were reversed by AF (7.0 and 14.0mg/kg, i.g.), respectively. CONCLUSION: In summary, the present study indicated that AF exerted the anti-PTSD-like effects, which maybe associated with allopregnanolone biosynthesis in the brain.

Resveratrol ameliorated the behavioral deficits in a mouse model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction.

Puerarin ameliorated the behavioral deficits induced by chronic stress in rats.

The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.

Involvement of allopregnanolone in the anti-PTSD-like effects of AC-5216.

Cholesterol import into mitochondria through the translocator protein (18 KDa) (TSPO) is the starting point and an important rate-limiting step in neurosteroidogenesis. For this reason TSPO has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD). In an effort to explore the role of TSPO in mediating the anti-PTSD effect, we first assessed the effects of the TSPO ligand AC-5216 in alleviating the enhanced anxiety and fear response in a time-dependent sensitization (TDS) procedure, a rat PTSD animal model. In the present study, we showed that chronic treatment with AC-5216 caused significant suppression of the enhanced anxiety and contextual fear induced in post-TDS rats; these effects were blocked by PK11195. Furthermore, AC-5216 treatment increased the levels of allopregnanolone in the serum, prefrontal cortex, and hippocampus of post-TDS rats, and these effects were antagonized by PK11195. These results demonstrate that AC-5216 has a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.