Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Exploring potential pharmacological mechanisms of Yiqi Tuomin Decoction in the treatment of allergic rhinitis utilizing network pharmacology prediction and molecular docking-based strategies: experimental research.

Yiqi Tuomin Decoction (YTD), which originated from the theory of lung deficiency and cold in Chinese medicine, is a common Chinese herbal formula used against allergic rhinitis (AR). In our otolaryngology department, this prescription has been used to treat so many AR patients with lung-deficiency-related colds for nearly 30 years. However, the mechanism of its ingredient-target is still unclear. Based on our early experiments and clinical case studies, in this paper, we explore the mechanism of YTD systematically against AR using bioinformatic methods of network pharmacology and molecular docking. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen the active ingredients and targets of YTD. The AR-related targets were retrieved from OMIM, GeneCards, TTD, DisGeNET, DrugBank databases, and PharmGKB. The Venn database was used to screen the potential core targets. After that, the STRING database was used to construct the protein-protein interaction (PPI) of the core targets and then visualize it by Cytoscape. The Gene Ontology (GO)-enriched processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the core targets were analyzed by the KOBAS-I database and Sangerbox. Molecular docking was used to assess interactions between potential targets and active ingredients. Results: A total of 169 active ingredients and 238 targets of YTD were predicted. YTD shared 115 common targets with AR from the Venn database. The GO-enriched processes and KEGG pathways indicate that genes involved in inflammation and oxidative stress, accompanying the MAPK signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and Th1 and Th2 cell differentiation, may play a mediated effect in YTD. The docking results showed good binding ability between the active ingredients and the selected targets. Conclusions: Our study systematically indicated the underlying mechanism of YTD against AR from the perspective of bioinformatics. By studying the active ingredients of YTD, we obtained molecular mechanisms and established a reliable method and molecular theoretical basis for the sensible development of Chinese medicine in the treatment of AR.

Origanum vulgare L. leaves extract alleviates testis and sperm damages induced by finasteride: Biochemical, Immunohistological and apoptosis genes based evidences.

The aim of the current study was to investigate antioxidant, anti-inflammatory and anti-apoptotic effects of Origanum vulgare on finasteride-induced oxidative injury in mouse testis and sperm parameters. Thirty BALB/c mice were divided into 5 groups: negative control, received 0.5 ml/day distilled water; positive control, received 25 mg/kg finasteride orally; and three groups received 100, 200 and 400 mg/kg/day O. vulgare extract plus 25 mg kg-1  day-1 finasteride for 35 days. At day 36, serum luteinising hormone, follicle-stimulating hormone and testosterone, inflammatory cytokines (IL-6, TNF-α, IL-1ß), glutathione peroxidase, superoxide dismutase and nitric oxide levels were assessed. Also, apoptotic changes investigated through genes expression and immunohistochemical staining. Finasteride in 35 days resulted in significant destructive alterations in the testis architecture, suppressed antioxidant enzymes and increased lipid peroxidation. The expression of Bcl-2 was down-regulated, whereas p53 and caspase-3 were up-regulated. Origanum vulgare improved the serum level of hormones and restored the antioxidant defence. 200 and 400 mg/kg/day of O. vulgare alleviated the testis structure and sperm parameters, up-regulated the anti-apoptotic gene Bcl-2 and down-regulated the p53, caspase-3 genes in treated groups. The findings indicate that O. vulgare extract improved function and structure of testis tissue against finasteride-induced testicular toxicity.

Gano oil: A novel antinociceptive agent extracted from Ganoderma lucidum inhibits paw oedema and relieves pain by hypnotic and analgesic actions of fatty acid amides.

ETHNOPHARMACOLOGICAL RELEVANCE: Lingzhi or Reishi - Ganoderma lucidum (Fr.) P. Karst is an extensively used medicinal mushroom in folklore and traditional medicine in south East Asia to treat a number of diseases. Lingzhi is known as 'mushroom of immortality' in Chinese folklore. In Traditional Chinese Medicine it is considered as a panacea to cure all diseases. AIM OF THE STUDY: This study aims to evaluate antinociceptive effect of Gano oil, a novel fatty acid rich extract obtained from G. lucidum and identification of the active principle. MATERIALS & METHODS: Gano oil extracted from Ganoderma lucidum was evaluated for inhibition of formalin-induced paw oedema on Swiss albino mice by oral administration as well as topical application. Antinociceptive activity of Gano oil was tested by acetic acid - induced abdominal writhing test as well as hot plate test. Free radical scavenging activity was determined by DPPH assay. COX enzyme inhibiting activity was assayed using different concentrations of Gano oil exposed to LPS stimulated RAW 264.7 cell line. NF-kB inhibiting activity of Gano oil was assayed using Lentix-293T P65 Ds Red stable cell line by fluorescent imaging and flow cytometry analysis. Chemical profile of Gano oil was ascertained by HPTLC analysis and active principle was identified by HRLCMS analysis. RESULTS: The oral administration of Gano oil at doses of 10,25, 50 mg/kg b.wt showed 42, 58 and 73% inhibition of paw oedema while topical applications at dose of 1,5 and 10% reduced 33, 50 and 58% oedema respectively. Acetic acid writhing test showed that Gano oil inhibited 44.44% contortions (p < 0.001) and while in hot plate method Gano oil at 25 mg/kg b. wt showed response latency of 30.0 ±â€¯2.08 s for 120 min compared to base 1.65 ±â€¯0.32 s (p < 0.01). Gano oil at 100 µg/ml inhibited 50% COX enzyme activity (p < 0.01). High throughput flurescent imaging and flow cytometry assay revealed marked ability of Gano oil to inhibit NF-kB activity. Gano oil was found to possess dose dependent free radical scavenging activity as evident from DPPH assay. HPTLC analysis of Gano oil indicated the chemical figure print. HR LC-MS analysis showed the major chemical components were fatty acid amides namely, Oleamide, C18H35NO, M+281, Hexadecanamide, C16H33NO, M+255 and 9-oxo-10 (E) Octadecadienoic acid, C18H30O3 M+294. CONCLUSION: Fatty acid rich Gano oil extracted from G.lucidum is a novel antinociceptive agent capable to inhibit oedema by oral administration as well as topical application. The results indicate the pharmacological interest, clinical significance and therapeutic use. The finding suggests that Gano oil might be a potent natural product based analgesic. The effect might be assigned to the fatty acid amide constituents especially oleamide which has been demonstrated to have analgesic and hypnotic actions.

Spatiotemporal SERT expression in cortical map development.

The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders.

Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

OBJECTIVE: To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. METHODS: A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. RESULTS: After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. CONCLUSION: Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

Identification of novel targets for seasonal allergic rhinitis during and outside the pollen season by microarray analysis.

CONCLUSION: FOS, JUN, and DUSP1 could be used as candidate targets for the treatment of seasonal allergic rhinitis (SAR) during the pollen season, while KLF4 and CD163 could be used as candidate targets outside the pollen season. OBJECTIVES: The aim of this study is to screen novel genes related to SAR during and outside the pollen season, by using microarray analysis. METHODS: The mRNA expression profile (GSE50101) of CD4(+) T cells from SAR and healthy controls during and outside the pollen season was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were then screened with the cut-off criteria of fold change larger than 1.5 and p-value less than 0.05. RESULTS: A total of 47 DEGs were identified. Ten DEGs were shared by SAR patient samples during and outside the pollen season, while four and 23 DEGs were specific to during and outside the pollen season, respectively. Five miRNAs were screened in this study. Among these miRNAs, miR-139, miR-101, miR-29A, and miR-181 could target FOS; miR-200 and miR-29A could target KLF4; miR-101 and miR-200 could target DUSP1; miR-139 and miR-181 could target JUN and CD163, respectively.

The involvement of retinoic acid receptor-alpha in corticotropin-releasing hormone gene expression and affective disorders.

BACKGROUND: Corticotropin-releasing hormone (CRH) is considered the central driving force in the stress response and plays a key role in the pathogenesis of depression. Retinoic acid (RA) has been suggested by clinical studies to be associated with affective disorders. METHODS: First, hypothalamic tissues of 12 patients with affective disorders and 12 matched control subjects were studied by double-label immunofluorescence to analyze the expression of CRH and retinoic acid receptor-alpha (RAR-alpha). Second, critical genes involved in the RA signaling pathways were analyzed in a rat model of depression. Finally, the regulatory effect of RAR-alpha on CRH gene expression was studied in vitro. RESULTS: We found that the expression of RAR-alpha was colocalized with CRH neurons in human hypothalamic paraventricular nucleus (PVN). The density of RAR-alpha-immunoreactive neurons and CRH-RAR-alpha double-staining neurons was significantly increased in the PVN of patients with affective disorders. The ratio of the CRH-RAR-alpha double-staining neurons to the CRH-immunoreactive neurons in affective disorder patients was also increased. Recruitment of RAR-alpha by the CRH promoter was observed in the rat hypothalamus. A dysregulated RA metabolism and signaling was also found in the hypothalamus of a rat model for depression. Finally, in vitro studies demonstrated that RAR-alpha mediated an upregulation of CRH gene expression. CONCLUSIONS: These results suggest that RAR-alpha might contribute to regulating the activity of CRH neurons in vivo, and the vulnerable character of the critical proteins in RA signaling pathways might provide novel targets for therapeutic strategies for depression.