Astragaloside IV targeting autophagy of T cells improves inflammation of asthma.

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.

Role of cellular senescence in inflammatory lung diseases.

Cellular senescence, a characteristic sign of aging, classically refers to permanent cell proliferation arrest and is a vital contributor to the pathogenesis of cancer and age-related illnesses. A lot of imperative scientific research has shown that senescent cell aggregation and the release of senescence-associated secretory phenotype (SASP) components can cause lung inflammatory diseases as well. In this study, the most recent scientific progress on cellular senescence and phenotypes was reviewed, including their impact on lung inflammation and the contributions of these findings to understanding the underlying mechanisms and clinical relevance of cell and developmental biology. Within a dozen pro-senescent stimuli, the irreparable DNA damage, oxidative stress, and telomere erosion are all crucial in the long-term accumulation of senescent cells, resulting in sustained inflammatory stress activation in the respiratory system. An emerging role for cellular senescence in inflammatory lung diseases was proposed in this review, followed by the identification of the main ambiguities, thus further understanding this event and the potential to control cellular senescence and pro-inflammatory response activation. In addition, novel therapeutic strategies for the modulation of cellular senescence that might help to attenuate inflammatory lung conditions and improve disease outcomes were also presented in this research.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway.

CONTEXT: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. OBJECTIVE: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. MATERIALS AND METHODS: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3ß/mTOR signalling pathway. RESULTS: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. DISCUSSION AND CONCLUSION: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

Iristectorigenin A exerts novel protective properties against airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice: Iristectorigenin A ameliorates asthma phenotype.

BACKGROUND: Despite the substantial amount of efforts made to reduce morbidity and improve respiratory management, asthma control remained a major challenge for severe patients. Plant isoflavones, one of the most estrogenic compounds, are considered a potential alternative therapy for asthma. Iristectorigenin A, a naturally occurring isoflavone, is extracted from a variety of medical plants and its biological activity has not been reported previously. PURPOSE: In present study, we aim to reveal the potential therapeutic role of Iristectorigenin A against acute asthmatic mice. STUDY DESIGN: We established ovalbumin (OVA) induced asthmatic murine model and orally administrated Iristectorigenin A at concentration of 5 and 10 mg/kg and dexamethasone as a positive control substance. METHODS: Asthmatic murine model was established with OVA sensitization and challenge. Lung function was assessed with FinePoint Ventilation system recording lung resistance (RI) and lung compliance (Cydn). White cells were sorted and counted in BALF. Histopathological assessment was conducted by H&E, PAS, and Masson's trichrome staining on paraffin embedded lung tissues. BALF content of IL-4, IL-5, IL-33, IL-13, INF-γ, IL-9 and serum IgE, IgG1 were measured using ELISA kit. Expression levels of mRNAs associated with inflammatory cytokines and goblet cell metaplasia were evaluated via quantitative RT-PCR. Protein expression levels of FOXA3, MUC5AC, SPDEF were estimated by immunohistochemistry on lung tissue, while NOTCH1 and NOTCH2 expressions were evaluated by western blotting analysis. RESULTS: Iristectorigenin A resulted in improved airway hyperresponsiveness (AHR) mirrored by decreased RI and increased Cydn. With Iristectorigenin A, we also observed reduced number of BALF leukocytes, improved inflammatory cell infiltration in lung tissue, decreased content of BALF IL-4, IL-5, IL-33, but not IL-13, INF-γ, IL-9, and their mRNA levels, along with decreased levels of OVA-specific IgE, IgG1 in asthmatic mice. Additionally, Iristectorigenin A exhibited significant therapeutic potential on attenuating mucus production reflected by mitigated FOXA3 and MUC5AC immunostaining on the airway epithelium, as well as decreased mRNAs associated with goblet cell metaplasia. At last, a decrease in elevated expression level of NOTCH2, but not NOTCH1, in asthmatic mice lung tissue was observed by western blotting analysis. CONCLUSION: Our study provides strong evidence that Iristectorigenin A can be potential therapeutic agent ameliorating airway inflammation and mucus hypersecretion in allergic asthma. This is a first research reported the potential of Iristectorigenin A as an alternative therapeutic agent.

Baicalin ameliorates cigarette smoke-induced airway inflammation in rats by modulating HDAC2/NF-κB/PAI-1 signalling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease distinguished by airway remodelling and progressive inflammation. PAI-1 is an important regulator of fibrosis. Recent studies have shown that PAI-1 seems to be involved in COPD progression. Elevated levels of PAI-1 have been found in the lungs of patients with acute inflammation. PAI-1 has been shown to regulate the levels of proinflammatory cytokines in the lungs, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, indicating that PAI-1 may play a fundamental role during inflammation. In the present study, we investigated the anti-inflammatory role of baicalin, the main active component of Scutellaria baicalensis, against cigarette smoke (extract) (CS/CSE)-induced airway inflammation in vivo and in vitro. For the in vivo study, SD rats were exposed to CS for 1 h/day, 6 days/week, for 24 weeks and treated with baicalin (40, 80 and 160 mg/kg) or budesonide (0.2 mg/kg). For this study, HBE cells were pretreated with baicalin (10, 20, 40 µM) or dexamethasone (10-7 M) and then exposed to CSE. We found that baicalin treatment could ameliorate CS-induced airway inflammatory infiltration in rats and decrease PAI-1 expression. The ELISA results showed that baicalin significantly inhibited the levels of TNF-α and IL-1ß in CS/CSE-exposed rats and cells. Mechanistic studies showed that baicalin enhanced histone deacetylase 2 (HDAC2) protein expression and inhibited the expression of NF-κB and its downstream target PAI-1, and these effects were reversed by the HDAC2 inhibitor CAY-10683. In conclusion, baicalin ameliorated CS-induced airway inflammation in rats, and these effects were partially attributed to the modulation of HDAC2/NF-κB/PAI-1 signalling.

Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells.

BACKGROUND: Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. AIM: To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss. METHODS: We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo. RESULTS: The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features. CONCLUSION: Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Loki Zupa (LKZP) decoction is one of the herbal prescriptions in traditional Uyghur medicine, which is commonly used for treating airway abnormality. However, underlying pathological mechanism and pathways involved has not been well studied. OBJECTIVES: In this paper, we aim to further confirmed the anti-inflammatory and anti-fibrotic role of LKZP decoction in airway, and uncover the passible mechanism involved via comprehensive quantitative proteomic DIA-MS analysis. MATERIALS AND METHODS: Mice asthmatic model was established with sensitizing and challenging with OVA. Lung function, pathological status, and inflammatory cytokines were assessed. Total of nine lung tissues were analyzed using proteomic DIA-MS analysis and 18 lung tissues were subjected to PRM validation. RESULTS: Total of 704 differentially expressed proteins (DEPs) (363 up regulated, 341 down regulated) were quantified in comparison of asthmatic and healthy mice, while 152 DEPs (91 up regulated, 61 down regulated) were quantified in LKZP decoction treated compared to asthmatic mice. Total of 21 proteins were overlapped between three groups. ECM-receptor interaction was significantly enriched and commonly shared between downregulated DEPs in asthma and upregulated DEPs in LKZP decoction treated mice. Total of 20 proteins were subjected to parallel reaction monitoring (PRM) analysis and 16 of which were quantified. At last, two proteins, RMB 10 and COL6A6, were validated with significant difference (P < 0.001) in protein abundance. CONCLUSIONS: Our results suggest that attenuated airway inflammation and fibrosis caused by LKZP decoction may associated with ECM-receptor interaction and RMB 10 and COL6A6 may be targeted by LKZP decoction in OVA-induced asthmatic mice.

Small molecules for mesenchymal stem cell fate determination.

Mesenchymal stem cells (MSCs) are adult stem cells harboring self-renewal and multilineage differentiation potential that are capable of differentiating into osteoblasts, adipocytes, or chondrocytes in vitro, and regulating the bone marrow microenvironment and adipose tissue remodeling in vivo. The process of fate determination is initiated by signaling molecules that drive MSCs into a specific lineage. Impairment of MSC fate determination leads to different bone and adipose tissue-related diseases, including aging, osteoporosis, and insulin resistance. Much progress has been made in recent years in discovering small molecules and their underlying mechanisms control the cell fate of MSCs both in vitro and in vivo. In this review, we summarize recent findings in applying small molecules to the trilineage commitment of MSCs, for instance, genistein, medicarpin, and icariin for the osteogenic cell fate commitment; isorhamnetin, risedronate, and arctigenin for pro-adipogenesis; and atractylenolides and dihydroartemisinin for chondrogenic fate determination. We highlight the underlying mechanisms, including direct regulation, epigenetic modification, and post-translational modification of signaling molecules in the AMPK, MAPK, Notch, PI3K/AKT, Hedgehog signaling pathways etc. and discuss the small molecules that are currently being studied in clinical trials. The target-based manipulation of lineage-specific commitment by small molecules offers substantial insights into bone marrow microenvironment regulation, adipose tissue homeostasis, and therapeutic strategies for MSC-related diseases.

Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice.

OBJECTIVE: To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice. METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay. RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01). CONCLUSION: Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.

Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade.

The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 µM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 µM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.

Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling.

BACKGROUND: Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated. METHODS: Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting. RESULTS: Here we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV. CONCLUSIONS: AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.

Glucose transporter-1 as an independent prognostic marker for cancer: a meta-analysis.

OBJECTIVE: Glucose transporter-1 (GLUT-1) as the major glucose transporter present in human cells is found overexpressed in a proportion of human malignancies. This meta-analysis is attempted to assess the prognostic significance of GLUT-1 for survival in various cancers. MATERIALS AND METHODS: We conducted an electronic search using the databases PubMed, Embase and Web of Science, from inception to Oct 20th, 2016. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Fourty-one studies with a total of 4794 patients were included. High GLUT-1 expression was significantly associated with poorer prognosis [overall survival: HR = 1.833 (95% CI: 1.597-2.069, P < 0.0001); disease-free survival: HR = 1.838 (95% CI: 1.264-2.673, P < 0.0001); progression-free survival: HR = 2.451 (95% CI: 1.668-3.233, P < 0.0001); disease specific survival: HR = 1.96 (95% CI: 1.05-2.871, P < 0.0001)]. CONCLUSIONS: High GLUT-1 expression may be an independent prognostic marker to predict poor survival in various types of cancers. Further clinical trials with high quality need to be conducted to confirm our conclusion.

Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors.

Solid tumors contain a huge mass of malignant tumors other than hematological malignancies. Novel therapies based on bio-safe agents against solid tumors are urgently required. Baicalin and its aglycone baicalein, the major bioactive flavones derived from Scutellaria baicalensis, have potential roles in the management of cancer. The chemopreventive properties governed by baicalin and baicalein were multi-fold, via apoptosis induction, autophagy triggering, cell cycle arrest, inhibition of 12-lipoxygenase and metastasis suppression. However, their poor solubility and low oral bioavailability severely limited the clinical application. This extensive review focused on the promising anti-cancer activities of baicalin and baicalein and new techniques to improve their bioavailability.

Analysis of glucose metabolism of (18)F-FDG in major depression patients using PET imaging: Correlation of salivary cortisol and α-amylase.

Current diagnosis of Major depressive disorder (MDD) depends on its clinical symptoms, not on the results of any laboratory examinations. Establishing biological markers for diagnosis of MDD is one of the most important problems to be solved in psychiatry practice. MDD patients (n=8) and a healthy control group (n=8) were recruited in this study. Hamilton Depression Rating Scale (HAM-D) assessments were completed and saliva samples were collected for assessments of salivary cortisol and salivary α-amylase (sAA). PET examination was performed. Salivary cortisol and sAA in the MDD patients group were significantly higher than the healthy control group (P<0.001). MDD patients showed lower glucose metabolism of 18F-FDG in Cingulate Gyrus (BA24), Superior Frontal Gyrus (BA6), Rectal Gyrus (BA11) and Orbital Gyrus (BA11/47) compared with the healthy control group. The severity of depression, salivary cortisol and sAA correlated negatively with regional glucose metabolism in Cingulate Gyrus (BA 24), Superior Frontal Gyrus (BA 6), Rectal Gyrus (BA 11) and Orbital Gyrus (BA 11/47). The combination of salivary cortisol, sAA, superior frontal gyrus and rectal gyrus was the potential predictor of depression for MDD patients (ΔR(2)=0.981, p<0.001). The present study showed that, MDD patients group showed higher salivary cortisol, sAA levels and lower glucose metabolism of (18)F-FDG in several brain areas compared with the healthy control group. The combination of salivary cortisol, sAA, glucose metabolism of (18)F-FDG of superior frontal gyrus and rectal gyrus may serve as a simple clinical tool for the early diagnosis of MDD.

Moxibustion upregulates hippocampal progranulin expression.

In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4) and Zusanli (ST36, bilateral) were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

[Establishment of Social Stress Induced Depression-like Animal Model in Mice of C57BL/6 Strain and Behavioral Assessments].

OBJECTIVE: To establish social stress induced depression-like model in mice of C57BL/6 strain, and to assess its reliability using differenf behavioral methods. METHODS: Totally 20 male mice of C57BL/6 strain were divided into the normal group and the stress model group by random digit table,10 in each group. Another 10 CD1 mice were subjected to social stress. Mice in the normal control group received no stress, while those in the model group received social stress for 10 successive days. Behavioral assessment was performed using social interaction test (SIT), the elevated plus-maze (EPM) test, tail suspension test (TST), respectively. Serum cortisol level was detected by ELISA to assess the reliability of the model. RESULTS: In the social interaction test when the social target (CDI mice) was inexistent, mice in the normal control group spent longer time in the social interaction zone and less time in the corner zone (P < 0.05); mice in the model group spent less time in the social interaction zone and more time in the corner zone (P < 0.05). Compared with the normal group when CDI mice existed, mice in the model group spent less time in the social interaction zone and more time in the corner zone (P < 0.05). Compared with the normal control group, the total times for entry into open arms, close arms, and the maze were obviously reduced (P < 0.05), and the proportion of entering open arms was significantly reduced (P < 0.05) in the model group. In TST, the motionless time within the last 4 mm was prolonged in the model group (P < 0.05). The serum cortisol level in the model group was obviously elevated (P < 0.01). CONCLUSION: Social stress induced depression-like animal model in mice of C57BL/6 straineasquite reliable and possibly suitable to be used in integrative medicine research of combination of disease and syndrome model.

Electroacupuncture regulate hypothalamic-pituitary-adrenal axis and enhance hippocampal serotonin system in a rat model of depression.

Hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathogenesis of depression. Dysfunction of the hippocampal serotonin (5-hydroxytryptamine, 5-HT) system has been shown to be a key factor in depression. There is growing evidence that electro-acupuncture (EA) has antidepressant-like effect. However, the effect of EA on HPA axis and hippocampal serotonin system remains unknown. In our study, we investigated the antidepressant-like effect and mechanism of EA for depression rat models. Depression in rats was induced by chronic unpredictable mild stress (CUMS). EA treatment was administered once daily to CUMS rats for 14 days. The acupoints (ST36, bilateral and CV4) were selected. Untreated CUMS rats and normal rats were used as controls. Behavioral tests including forced swim test and open-field test were performed to evaluate the antidepressant effects of EA treatment. Hypothalamic corticotropin-releasing hormone (CRH) mRNA, plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were estimated as indices of HPA axis activity. Enzyme linked immunosorbent assay (ELISA) was performed to determine the concentrations of 5-HT in the hippocampus. Real-time PCR(RT-PCR)and Western blot were respectively used to detect the mRNA and protein levels of 5-hydroxytryptamine 1A receptor (5-HT1AR) in the hippocampus. Our results showed that EA treatment reversed the behavioral deficiency induced by CUMS in rats. EA treatment decreased CRH mRNA expression in the hypothalamic, and ACTH and CORT level in plasma, and markedly increased 5-HT concentration, 5-HT1AR (mRNA and protein) expression in the hippocampus. These results indicated that EA treatment could act on depression by modulating HPA axis and enhancing hippocampal 5-HT/5-HT1AR in CUMS Rats.