[Improvement effect of cinnamaldehyde on reserpine-induced Parkinson's disease rat model].

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Zhumian Granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia. AIM OF THE STUDY: This research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia. MATERIALS AND METHODS: This study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling. RESULTS: ZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death. CONCLUSIONS: This research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.

Huanglian-banxia promotes gastric motility of diabetic rats by modulating brain-gut neurotransmitters through MAPK signaling pathway.

BACKGROUND: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian-banxia (HL-BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL-BX in modulating brain-gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. METHODS: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5- hydroxytryptamine (5-HT), and glucagon-like peptide -1 (GLP-1) in the serum were measured by enzyme-linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high-pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. KEY RESULTS: HL-BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL-BX administration caused a significant increase in SP, GLP-1, and 5-HT, but a significant decrease in DA and NE. Interestingly, HL-BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL-BX. CONCLUSIONS: These results indicated that HL-BX promoted gastric motility by regulating brain-gut neurotransmitters through the MAPK signaling pathway. HL-BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis.

Waste Coffee Ground-Derived Porous Carbon for Neurochemical Detection.

We present an optimized synthetic method for repurposing coffee waste to create controllable, uniform porous carbon frameworks for biosensor applications to enhance neurotransmitter detection with fast-scan cyclic voltammetry. Harnessing porous carbon structures from biowastes is a common practice for low-cost energy storage applications; however, repurposing biowastes for biosensing applications has not been explored. Waste coffee ground-derived porous carbon was synthesized by chemical activation to form multivoid, hierarchical porous carbon, and this synthesis was specifically optimized for porous uniformity and electrochemical detection. These materials, when modified on carbon-fiber microelectrodes, exhibited high surface roughness and pore distribution, which contributed to significant improvements in electrochemical reversibility and oxidative current for dopamine (3.5 ± 0.4-fold) and other neurochemicals. Capacitive current increases were small, showing evidence of small increases in electroactive surface area. Local trapping of dopamine within the pores led to improved electrochemical reversibility and frequency-independent behavior. Overall, we demonstrate an optimized biowaste-derived porous carbon synthesis for neurotransmitter detection for the first time and show material utility for viable neurotransmitter detection within a tissue matrix. This work supports the notion that controlled surface nanogeometries play a key role in electrochemical detection.

The Interplay between Neurotransmitters and Calcium Dynamics in Retinal Synapses during Development, Health, and Disease.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium (Ca2+) dynamics, offering important insights into developmental processes, physiological functioning, and disease progression. Neurotransmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neurotransmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with Ca2+ dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, gamma-aminobutyric acid (GABA), glycine, dopamine, and acetylcholine (ACh) and their interplay with Ca2+ dynamics. This conceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Xiaoyaosan promotes neurotransmitter transmission and alleviates CUMS-induced depression by regulating the expression of Oct1 and Oct3 in astrocytes of the prefrontal cortex.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription for the treatment of liver depression and qi stagnation, and pharmacological studies have shown that XYS has great potential to reverse depression. However, anti-depression targets and the mechanism of XYS are still not entirely clear. AIM OF THE STUDY: The present study aims to explore and verify the anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant effect of XYS was assessed in rats with depression induced by chronic unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in different brain regions were measured using ELISA. The expression of organic cation transporters (Octs) were detected by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the correlation between Octs and depression-like behavior. Then, the effects of XYS on the behavior, neurotransmitter concentration, and Octs expression in D22-induced rats were examined. Finally, primary astrocytes were used to verify the mechanism of XYS exerting anti-depressant activity by regulating Octs. RESULTS: The result showed that XYS had a significant positive impact on the behavior of depression rats induced by CUMS. XYS also improved the secretion of 5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 expression in the PFC. These results suggest that XYS has the potential to alleviate depression by enhancing the secretion of neurotransmitters. This may be related to XYS regulation of Oct's expression. When the expression of Octs was inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was able to reverse this behavior, indicating that Octs play a significant role in the development of depression and XYS may exert its antidepressant effects through the regulation of Octs. Furthermore, the study also found that dopamine uptake decreased after inhibiting the expression of Octs, and XYS-containing serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant effects by promoting dopamine uptake to improve neurotransmitter transport by regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: The antidepressant effect of XYS may be attributed to its ability to regulate the expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting neurotransmitter transport.

Acrylamide exposure induces growth retardation, neurotoxicity, stress, and immune/antioxidant disruption in Nile tilapia (Oreochromis niloticus): The alleviative effects of Chlorella vulgaris diets.

This study looked at the toxic impacts of water-born acrylamide (ACR) on Nile tilapia (Oreochromis niloticus) in terms of behaviors, growth, immune/antioxidant parameters and their regulating genes, biochemical indices, tissue architecture, and resistance to Aeromonas hydrophila. As well as the probable ameliorative effect of Chlorella vulgaris (CV) microalgae as a feed additive against ACR exposure was studied. The 96-h lethal concentration 50 of ACR was investigated and found to be 34.67 mg/L for O. niloticus. For the chronic exposure study, a total of 180 healthy O. niloticus (24.33 ± 0.03 g) were allocated into four groups in tri-replicates (15 fish/replicate), C (control) and ACR groups were fed a basal diet and exposed to 0 and 1/10 of 96-h LC50 of ACR (3.46 mg/L), respectively. ACR+ CV5 and ACR+ CV10 groups were fed basal diets with 5 % and 10 % CV supplements, respectively and exposed to 1/10 of 96-h LC50 of ACR for 60 days. After the exposure trial (60 days) the experimental groups were challenged with A. hydrophila. The findings demonstrated that ACR exposure induced growth retardation (P˂0.01) (lower final body weight, body weight gain, specific growth rate, feed intake, protein efficiency ratio, final body length, and condition factor as well as higher feed conversion ratio). A substantial decrease in the immune/antioxidant parameters (P˂0.05) (lysozyme, serum bactericidal activity %, superoxide dismutase, and reduced glutathione) and neurotransmitter (acetylcholine esterase) (P˂0.01) was noticed with ACR exposure. A substantial increase (P˂0.01) in the serum levels of hepato-renal indicators, lipid peroxidation biomarker, and cortisol was noticed as a result of ACR exposure. ACR exposure resulted in up-regulation (P˂0.05) of the pro-inflammatory cytokines and down-regulation (P˂0.05) of the antioxidant-related gene expression. Furthermore, the hepatic, renal, brain, and splenic tissues were badly affected by ACR exposure. ACR-exposed fish were more sensitive to A. hydrophila infection and recorded the lowest survival rate (P˂0.01). Feeding the ACR-exposed fish with CV diets significantly improved the growth and immune/antioxidant status, as well as modulating the hepatorenal functions, stress, and neurotransmitter level compared to the exposed-non fed fish. In addition, modulation of the pro-inflammatory and antioxidant-related gene expression was noticed by CV supplementation. Dietary CV improved the tissue architecture and increased the resistance to A. hydrophila challenge in the ACR-exposed fish. Noteworthy, the inclusion of 10 % CV produced better results than 5 %. Overall, CV diets could be added as a feed supplement in the O. niloticus diet to boost the fish's health, productivity, and resistance to A. hydrophila challenge during ACR exposure.

Gut production of GABA by a probiotic formula: an in vitro study.

The objective of this study was to evaluate the influence of a probiotic formula on the production of neuroactive compounds in different parts of the colon in batch culture and in vitro gut simulator experiments. Thirteen lactic acid bacterial strains, belonging to the species Levilactobacillus brevis, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Ligilactobacillus salivarius, Streptococcus thermophilus, were characterised for their in vitro ability to produce neurotransmitters. L. brevis P30021 and L. plantarum P30025 were selected based on their capability to produce γ-aminobutyric acid (GABA) and acetylcholine in vitro. A probiotic formulation with potential psychobiotic activity was prepared and tested in a batch culture of human microbiota monitoring the formation of GABA and acetylcholine. Samples of the three colonic tracts were taken from the Simulator of the Human Intestinal Microbiota (SHIME®) evaluating the production of GABA and other neurotransmitters by LC-MS. Short chain fatty acids (SCFA) by GC and microbiota composition by 16S rRNA gene sequencing were also determined. Probiotic supplementation led to the formation of GABA and acetylcholine with a decrease in glutamate concentrations in the in vitro batch fermentation. Production of GABA after the treatment with probiotics was confirmed in the SHIME® short-term experiment. No differences in short-chain fatty acids were observed up to 72 h of fermentation. Different microbiota composition was found in the three different parts of the colon, with a higher abundance of Veillonellaceae in the ascending colon vessels. The probiotic-exposed microbiota showed higher levels of Bacteroides, a gut microbe associated with anti-inflammatory activities and a potential GABA producer. Results demonstrate the impact of the tested probiotic formula on gut microbiota structure and GABA production. In conclusion, the probiotic treatment changed the microbiota composition and increased neuroactive metabolites production, indicating promising potential as psychobiotics, even if further clinical evidence is needed to confirm the effectiveness of these probiotics in improving mental health.

Tongdu Tiaoshen acupuncture combined with Bobath rehabilitation training for upper limb spasm after stroke: a randomized controlled trial. / 通督调神法针刺联合Bobathåº·å¤è®­ç»ƒæ²»ç–—å’ä¸­åŽä¸Šè‚¢ç—‰æŒ›ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe clinical effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) acupuncture combined with Bobath rehabilitation training in the treatment of upper limb spasm after stroke. METHODS: A total of 66 patients with upper limb spasm after stroke were randomly divided into an observation group (33 cases, 1 case dropped out) and a control group (33 cases, 2 cases dropped out). The control group received Bobath rehabilitation training. On the basis of the control group, the patients in the observation group received Tongdu Tiaoshen acupuncture at Baihui (GV 20), Fengfu (GV 16), Mingmen (GV 4), Yaoyangguan (GV 3) and bilateral C4-T1 Jiaji points (EX-B 2), etc. Both groups were treated once a day, with 6 days of continuous treatment followed by 1 day of rest, and totally 4 weeks were required. The modified Ashworth scale ( MAS ) grade, Fugl-Meyer assessment of upper extremity ( FMA-UE ) score, modified Barthel index ( MBI ) score, serum level of neurotransmitter (glutamic acid [Glu] and γ-aminobutyric acid [GABA]) were compared between the two groups before and after treatment, and the clinical effect was evaluated. RESULTS: After treatment, MAS grade and serum level of Glu in the two groups were lower than those before treatment (P<0.05), and FMA-UE, MBI scores and serum level of GABA were higher than those before treatment (P<0.05). The MAS grade and serum level of Glu in the observation group were lower than those in the control group (P<0.05), and the FMA-UE, MBI scores and serum level of GABA were higher than those in the control group (P<0.05). The total effective rate of the observation group was 87.5% (28/32), which was better than 45.2% (14/31) of the control group (P<0.05). CONCLUSIONS: The combination of Tongdu Tiaoshen acupuncture and Bobath rehabilitation training can effectively reduce the upper limb muscle tension level of patients with upper limb spasm after stroke, improve upper limb motor function, enhance self-care ability, and regulate serum level of neurotransmitter.

Research on the mechanism of regulating spleen-deficient obesity in rats by bawei guben huashi jiangzhi decoction based on multi-omics analysis.

ETHNOPHARMACOLOGY RELEVANCE: Bawei Guben Huashi Jiangzhi Decoction (BGHJ), a traditional Chinese compound formula, comprises eight Chinese medicinal herbs: Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Cassiae Semen, Lysimachiae Herba, Edgeworthiae Gardner Flos, Oryzae Semen cum Monasco, Nelumbinis Folium, and Alismatis Rhizoma. It has the therapeutic effects of improving digestive and absorptive functions of the gastrointestinal tract, reducing cholesterol levels, and helping to lose weight. Therefore, BGHJ is mainly used to treat spleen-deficient obesity (SDO) clinically. AIM OF THE STUDY: This study aims to examine the efficacy and mechanism of BGHJ in a model of SDO in rats, as well as the potentially involved constituents entering the blood and differential metabolites. METHODS: The SDO rat model was replicated utilizing a high-fat and high-sugar diet in conjunction with exhaustive swimming. Subsequently, the rats were subjected to a six-week intervention comprising varying dosages of BGHJ and a positive control, orlistat. To evaluate the efficacy of BGHJ on SDO model rats, we first measured the rats' body weight, body surface temperature, spleen index, as well as biochemical indicators in the serum and colon, and then assessed the pathological state of the colon and liver. Afterward, we analyzed the 16S rDNA gut microbiota, non-targeted serum metabolomics, and serum pharmacology to study the main active components of BGHJ and its action mechanism against SDO model rats. In addition, we constructed a network diagram for overall visualization and analysis, and experimentally verified the predicted results. Finally, we used quantitative polymerase chain reaction (qPCR) to detect the gene expression of proopiomelanocortin (POMC) and neuropeptide Y (NPY) indicators in rat hypothalamic neurons. We quantitatively targeted the detection of neurotransmitters dopamine (DA), acetylcholine (Ach), 5-hydroxytryptamine (5-HT), and noradrenaline (NA) in rat hypothalamus. RESULTS: The results demonstrated that all dosage regimens of BGHJ exhibited the capacity to moderately modulate parameters including body weight, surface temperature, spleen index, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), 5-HT, interleukin 6 (IL-6) and interleukin 17 (IL-17), while concurrently reducing hepatic lipid droplet deposition and restoring intestinal integrity. Subsequent experimental results showed that we successfully identified 27 blood components of BGHJ and identified 52 differential metabolites in SDO model rats. At the same time, the experiment proved that BGHJ could effectively inhibit the metabolic pathway of arachidonic acid. In addition, BGHJ can also restore the intestinal microbiota composition of SDO model rats. Finally, we also found that BGHJ could regulate the expression of hypothalamic neurons and neurotransmitters. CONCLUSIONS: The research revealed the main active ingredients of BGHJ and its mechanism against SDO model rats through gut microbiota, non-target serum metabolomics, and serum drug chemistry.

Potential therapeutic effects of Chinese herbal medicine in postpartum depression: Mechanisms and future directions.

ETHNOPHARMACOLOGICAL RELEVANCE: Postpartum depression (PPD) is a common psychiatric disorder in women after childbirth. Per data from epidemiologic studies, PPD affects about 5%-26.32% of postpartum mothers worldwide. Biological factors underlying this condition are multiple and complex and have received extensive inquiries for the roles they play in PPD. Chinese herbal medicine (CHM), which is widely used as a complementary and alternative therapy for neurological disorders, possesses multi-component, multi-target, multi-access, and low side effect therapeutic characteristics. CHM has already shown efficacy in the treatment of PPD, and a lot more research exploring the mechanisms of its potential therapeutic effects is being conducted. AIM OF THE REVIEW: This review provides an in-depth and comprehensive overview of the underlying mechanisms of PPD, as well as samples the progress made in researching the potential role of CHM in treating the disorder. MATERIALS AND METHODS: Literature was searched comprehensively in scholarly electronic databases, including PubMed, Web of Science, Scopus, CNKI and WanFang DATA, using the search terms "postpartum depression", "genetic", "hormone", "immune", "neuroinflammation", "inflammation", "neurotransmitter", "neurogenesis", "brain-gut axis", "traditional Chinese medicine", "Chinese herbal medicine", "herb", and an assorted combination of these terms. RESULTS: PPD is closely associated with genetics, as well as with the hormones, immune inflammatory, and neurotransmitter systems, neurogenesis, and gut microbes, and these biological factors often interact and work together to cause PPD. For example, inflammatory factors could suppress the production of the neurotransmitter serotonin by inducing the regulation of tryptophan-kynurenine in the direction of neurotoxicity. Many CHM constituents improve anxiety- and depression-like behaviors by interfering with the above-mentioned mechanisms and have shown decent efficacy clinically against PPD. For example, Shen-Qi-Jie-Yu-Fang invigorates the neuroendocrine system by boosting the hormone levels of hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes, regulating the imbalance of Treg/T-helper cells (Th) 17 and Th1/Th2, and modulating neurotransmitter system to play antidepressant roles. The Shenguiren Mixture interferes with the extracellular signal-regulated kinase (ERK) pathway to enhance the number, morphology and apoptosis of neurons in the hippocampus of PPD rats. Other herbal extracts and active ingredients of CHM, such as Paeoniflorin, hypericin, timosaponin B-III and more, also manage depression by remedying the neuroendocrine system and reducing neuroinflammation. CONCLUSIONS: The pathogenesis of PPD is complex and diverse, with the main pathogenesis not clear. Still, CHM constituents, like Shen-Qi-Jie-Yu-Fang, the Shenguiren Mixture, Paeoniflorin, hypericin and other Chinese Medicinal Formulae, active monomers and Crude extracts, treats PPD through multifaceted interventions. Therefore, developing more CHM components for the treatment of PPD is an essential step forward.

Jiao-tai-wan and its effective component-berberine improve diabetes and depressive disorder through the cAMP/PKA/CREB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-tai-wan (JTW), a classic herbal formula of traditional Chinese medicine recorded in Han Shi Yi Tong, has been used to alleviate sleep disorders since ancient times. In modern pharmacological research, JTW has been adopted for treating diabetes mellitus and even exerts antidepressant effects. However, the potential mechanisms deserve further elucidation. AIM OF THE STUDY: The prevalence of diabetes mellitus combined with depressive disorder (DD) is continuing to increase, yet it is currently under-recognized and its treatment remains inadequate. The present study aims to explore the underlying therapeutics and mechanisms of JTW on DD. MATERIALS AND METHODS: Chronic restraint stress was used on db/db mice to construct a mouse model of DD. The therapeutic effects of JTW were assessed by glucolipid metabolic indexes, behavioral tests, and depression-related neurotransmitter levels. The inflammatory status and cell apoptosis of different mice were investigated and the changes in the cAMP/PKA/CREB pathway were detected. Combining the results of fingerprinting with molecular docking, the active components of JTW were screened. A cellular model was constructed by intervention of glucose combined with corticosterone (CORT). The levels of apoptosis and depression-related neurotransmitters in HT-22 cells were examined, and the changes in the cAMP/PKA/CREB pathway were tested. Finally, the activator and inhibitor of the PKA protein were used for reverse validation experiments. RESULTS: JTW could improve the impaired glucose tolerance, lipid metabolism disorders, and depression-like symptoms in DD mice. Meanwhile, JTW could alleviate the inflammatory status, suppress the microglia activation, and improve hippocampal neuron apoptosis in DD mice. The dual effects of JTW might be associated with the activation of the cAMP/PKA/CREB pathway. Berberine (Ber) was identified for the in vitro experiment, it could reverse the apoptosis of HT-22 cells and up-regulate the depression-related neurotransmitter levels, and the effects of Ber were related to the activation of the cAMP/PKA/CREB pathway as well. CONCLUSION: JTW could exert both hypoglycemic and antidepressant effects through activating the cAMP/PKA/CREB signaling pathway, its active component, Ber, could improve the damage to HT-22 cells induced by glucose combined with CORT via the activation of the cAMP/PKA/CREB pathway. Ber may be one of the effective components of the dual effects of JTW.

Atractylenolide I improves behaviors in mice with depression-like phenotype by modulating neurotransmitter balance via 5-HT2A.

To explore the antidepressant effects and targets of atractylenolide I (ATR) through a network pharmacological approach. Relevant targets of ATR and depression analyzed by network pharmacology were scored (identifying 5-HT2A targets). Through elevated plus maze, open field, tail suspension, and forced swimming tests, the behavioral changes of mice with depression (chronic unpredictable mild stress [CUMS]) were examined, and the levels of neurotransmitters including serotonin, dopamine, and norepinephrine (5-HT, DA, and NE) were determined. The binding of ATR to 5-HT2A was verified by small molecular-protein docking. ATR improved the behaviors of CUMS mice, elevated their levels of neurotransmitters 5-HT, DA, and NE, and exerted a protective effect on their nerve cell injury. After 5-HT2A knockout, ATR failed to further improve the CUMS behaviors. According to the results of small molecular-protein docking and network pharmacological analysis, ATR acted as an inhibitor by binding to 5-HT2A. ATR can improve the behaviors and modulate the neurotransmitters of CUMS mice by targeting 5-HT2A.

Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.

Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.

Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.

Antidepressant-like effects of Jieyu Chufan capsules in the olfactory bulbectomy rat model.

The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.

Understanding Why Homeopathic Medicines are Used for Menopause: Searching for Insights into Neuroendocrine Features.

BACKGROUND: Menopause is a physiological event that marks the end of a woman's reproductive stage in life. Vasomotor symptoms and changes in mood are among its most important effects. Homeopathy has been used for many years in treating menopausal complaints, though clinical and pre-clinical research in this field is limited. Homeopathy often bases its prescription on neuropsychiatric symptoms, but it is unknown if homeopathic medicines (HMs) exert a neuroendocrine effect that causes an improvement in vasomotor symptoms and mood during menopause. OBJECTIVES: The study's objectives were to address the pathophysiological changes of menopause that could help in the understanding of the possible effect of HMs at a neuroendocrine level, to review the current evidence for two of the most frequently prescribed HMs for menopause (Lachesis mutus and Sepia officinalis), and to discuss the future directions of research in this field. METHODS: An extensive literature search for the pathophysiologic events of menopause and depression, as well as for the current evidence for HMs in menopause and depression, was performed. RESULTS: Neuroendocrine changes are involved in the pathophysiology of vasomotor symptoms and changes in mood during menopause. Gonadal hormones modulate neurotransmitter systems. Both play a role in mood disorders and temperature regulation. It has been demonstrated that Gelsemium sempervirens, Ignatia amara and Chamomilla matricaria exert anxiolytic effects in rodent models. Lachesis mutus and Sepia officinalis are frequently prescribed for important neuropsychiatric and vasomotor symptoms. Dopamine, a neurotransmitter involved in mood, is among the constituents of the ink of the common cuttlefish, Sepia officinalis. CONCLUSION: Based on all the pathophysiologic events of menopause and the improvement in menopausal complaints that certain HMs show in daily practice, these medicines might have a direct or indirect neuroendocrine effect in the body, possibly triggered via an as-yet unidentified biological mechanism. Many unanswered questions in this field require further pre-clinical and clinical research.

Zhi-Zi-Hou-Po decoction alleviates depressive-like behavior and promotes hippocampal neurogenesis in chronic unpredictable mild stress induced mice via activating the BDNF/TrkB/CREB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po decoction (ZZHP), a traditional Chinese medicine (TCM) classic recipe, has been extensively applied for the remedy of depression. However, the underlying mechanism of ZZHP hasn't been fully elucidated and it needs to be further clarified. AIM OF STUDY: The aim of the study is to uncover the mechanisms of ZZHP's effect on depression. MATERIALS AND METHODS: C57BL/6 mice were employed to establish Chronic Unpredictable Mild Stress (CUMS) models. Behavioral tests were conducted for evaluating the antidepressant effects of ZZHP. Then, the monoamine neurotransmitters in the hippocampus through High Performance Liquid Chromatography Electrochemical Detection (HPLC-ECD) were utilized to assess the effect of ZZHP on the maintenance of monoamine neurotransmitter homeostasis. Immunofluorescence staining and Golgi staining were detected to analyze the effects of ZZHP on neuroplasticity in the hippocampus. Western Blot (WB) was utilized to examine the effects of ZZHP on BDNF/TrkB/CREB pathways. Finally, behavioral tests, WB and immunofluorescence staining were repeated after TrkB receptor antagonist was added to further confirm the underlying mechanism. RESULTS: Our results shown that ZZHP attenuated depressive-like symptoms in CUMS mice. Moreover, ZZHP remarkably reversed the reduction and maintained the homeostasis of monoamine neurotransmitters in the hippocampus. Simultaneously, ZZHP protected neuronal synaptic plasticity and promoted hippocampal neurogenesis. Furthermore, ZZHP stimulated the BDNF/TrkB/CREB pathway in the hippocampus. The addition of TrkB receptor antagonist inhibited the antidepressant effects of ZZHP, suggesting that ZZHP could not work without triggering the BDNF/TrkB/CREB pathway. CONCLUSION: This study demonstrates that ZZHP can alleviate depressive-like behavior and promote hippocampal neurogenesis in CUMS mice via activating the BDNF/TrkB/CREB pathway.

Berberine exerts antidepressant effects in vivo and in vitro through the PI3K/AKT/CREB/BDNF signaling pathway.

BACKGROUND: Depression, a global neuropsychiatric disorder, brings a serious burden to patients and society as its incidence continues to rise. Berberine is one of the main compounds of a variety of Chinese herbal medicines and has been shown to have multiple pharmacological effects. However, whether berberine can exert antidepressant effects in vivo and in vitro and its related mechanisms remain to be explored. METHODS: The chronic restraint stress (CRS) method and corticosterone (CORT) were applied to simulate depression-like behavior in vivo and neuronal apoptosis in vitro, respectively. The antidepressant effects of berberine were evaluated by behavioral tests and changes in the content of monoamine neurotransmitters. Inflammatory cytokines were detected and immunofluorescence staining was used to observe the expression levels of apoptosis-related proteins. RT-qPCR and Western blot were used to examine the mRNA and protein expression (or phosphorylation) levels of biomarkers of the PI3K/AKT/CREB/BDNF signaling pathways. RESULTS: Behavioral tests and levels of neurotransmitters proved that berberine could effectively ameliorate depression-like symptoms in CRS mice. Meanwhile, the results of ELISA and immunofluorescence staining showed that berberine could alleviate inflammatory status and reduce cell apoptosis in vivo and in vitro. Moreover, the changes of the PI3K/AKT/CREB/BDNF signaling pathway induced by CRS or CORT in mouse hippocampus or HT-22 cells were significantly reversed by berberine. CONCLUSION: Our current study suggested that berberine could exert antidepressant effects in vitro and in vivo, which may be associated with the PI3K/AKT/CREB/BDNF signaling pathway.