Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) has become one of most frequent bone diseases worldwide with aging population. Lycii Fructus, a common plant fruit with the property of drug homologous food, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of Lycii Fructus against PMOP through using network pharmacology approach. The active ingredients of Lycii Fructus were obtained from Traditional Chinese Medicine System Pharmacology database. Target fishing was performed on these ingredients in UniProt database for identification of the relative targets. Then, we screened the targets related to PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and Lycii Fructus were obtained to perform protein-protein interaction, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis. A total of 35 active ingredients were identified in Lycii Fructus, and fished 158 related targets. Simultaneously, 292 targets associated with PMOP were obtained from GeneCards database and DisGeNET database. By drawing Venn diagram, 41 overlapping genes were obtained, and were considered as therapeutically relevant. Gene ontology enrichment analysis predicted that anti-inflammation and promotion of angiogenesis might be 2 potential mechanism of Lycii Fructus for PMOP treatment. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as IL-17 pathway, TNF pathway, MAPK pathway, PI3K-Akt signaling pathway and HIF signaling pathway were involved in regulating these 2 biological processes. Through the method of network pharmacology, we systematically investigated the mechanisms of Lycii Fructus against PMOP. The identified multi-targets and multi-pathways provide new insights to further determinate its exact pharmacological mechanisms.

Integrating Network Pharmacology and Experimental Verification to Explore the Targets and Mechanism for Panax Notoginseng Saponins against Coronary In-stent Restenosis.

BACKGROUND: Despite widespread application of drug-eluting stents in coronary intervention, in-stent restenosis (ISR) is still a daunting complication in clinical practice. Panax notoginseng saponins (PNS) are considered to be effective herb compounds for preventing ISR. OBJECTIVE: This study aimed to elucidate the targets and mechanisms of PNS in ISR prevention using network pharmacology approaches and experimental verification. METHODS: Relevant targets of PNS active compounds were collected from the HERB database and PharmMapper. The ISR-related targets were obtained from the GeneCards database and the Comparative Toxicogenomics Database. The GO and KEGG enrichment analysis was performed using R software. The String database and Cytoscape software were employed to build the PPI and compounds-targets-pathways-disease networks. Finally, Molecular docking performed by Autodock Vina and cellular experiments were used to validate network pharmacology results. RESULTS: There were 40 common targets between PNS targets and ISR targets. GO analysis revealed that these targets focused on multiple ISR-related biological processes, including cell proliferation and migration, cell adhesion, inflammatory response, and anti-thrombosis and so on. The KEGG enrichment results suggested that PNS could regulate multiple signaling pathways to inhibit or delay the development and occurrence of ISR. The molecular docking and cellular experiments results verified the network pharmacology results. CONCLUSION: This study demonstrated that the potential molecular mechanisms of PNS for ISR prevention involved multiple compounds, targets, and pathways. These findings provide a theoretical reference and experimental basis for the clinical application and product development of PNS for the prevention of ISR.

[Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema].

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

[Mystery of Yiyin decoction theory: rule discovery and evaluation strategy of atypical pharmacological effects of Chinese medicinal prescription].

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.

Overcoming Basal Autophagy, Kangai Injection Enhances Cisplatin Cytotoxicity by Regulating FOXO3a-Dependent Autophagic Cell Death and Apoptosis in Human Lung Adenocarcinoma A549/DDP Cells.

Cisplatin resistance is one of the major obstacles in the treatment of nonsmall cell lung cancer (NSCLC). Kangai injection (KAI), a Chinese herbal medicine, has been used in tumors as adjuvant treatment, but its exact antitumor mechanism is still unclear. In this study, we first demonstrated that cisplatin-resistant A549/DDP cells showed a higher level of basal autophagy in response to cisplatin treatment with increasing autophagic protein expression levels of Beclin 1, p62, and LC3 compared to cisplatin-sensitive A549/DDP cells; then, we assessed the antitumor effect of KAI in cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that KAI exhibited direct cytotoxic and chemosensitizing effects in A549/DDP cells. Combining KAI with cisplatin promoted A549/DDP cell apoptosis, which was confirmed by cell cycle arrest, condensed nuclear chromatin, annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, and apoptosis-related protein expression. In addition, combining KAI with cisplatin induced autophagic cell death in A549/DDP cells with a high level of basal autophagy, as indicated by an increase in LC3 spot count, an accumulation of Beclin 1 and LC3 II, and reduced p62 protein expression. We also found that the apoptosis and autophagic cell death induced by cotreatment of KAI and cisplatin in A549/DDP cells were FOXO3a-dependent as indicated by decreased p-FOXO3a expression and increased FOXO3a nuclear localization, respectively. Furthermore, the FOXO3a gene knockdown assay further confirmed that KAI enhanced cisplatin cytotoxicity in A549/DDP cells with a high level of basal autophagy by inducing apoptosis and autophagic cell death in a FOXO3a-dependent manner. These findings suggest that the combination of KAI and cisplatin might support the potential clinical treatment as a novel strategy to overcome cisplatin resistance.

Recent insights into oxidative metabolism of quercetin: catabolic profiles, degradation pathways, catalyzing metalloenzymes and molecular mechanisms.

Quercetin is the most abundant polyphenolic flavonoid (flavonol subclass) in vegetal foods and medicinal plants. This dietary chemopreventive agent has drawn significant interest for its multiple beneficial health effects ("polypharmacology") largely associated with the well-documented antioxidant properties. However, controversies exist in the literature due to its dual anti-/pro-oxidant character, poor stability/bioavailability but multifaceted bioactivities, leaving much confusion as to its exact roles in vivo. Increasing evidence indicates that a prior oxidation of quercetin to generate an array of chemical diverse products with redox-active/electrophilic moieties is emerging as a new linkage to its versatile actions. The present review aims to provide a comprehensive overview of the oxidative conversion of quercetin by systematically analyzing the current quercetin-related knowledge, with a particular focus on the complete spectrum of metabolite products, the enzymes involved in the catabolism and the underlying molecular mechanisms. Herein we review and compare the oxidation pathways, protein structures and catalytic patterns of the related metalloenzymes (phenol oxidases, heme enzymes and specially quercetinases), aiming for a deeper mechanistic understanding of the unusual biotransformation behaviors of quercetin and its seemingly controversial biological functions.

Huangqi Guizhi Wuwu Decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1ß/IL-6/MAPK/NF-kB pathway.

OBJECTIVE: This study explored the effects and mechanisms of Huangqi Guizhi Wuwu Decoction on chemotherapy-induced neuropathic pain (CINP). METHODS: Bodyweight and related behavioral testing of the rat model were utilized to investigate the effects of Huangqi Guizhi Wuwu Decoction on CINP. ELISA was used to measure the levels of TNF-α, IL-1ß, and IL-6, in the serum of chronic CINP rats. Immunohistochemistry and Western blot analysis were performed to detect the expression of MAPK pathway related-proteins namely ERK1/2, p38, and JNK, and the expression of downstream essential proteins such as c-Fos, CREB, and NF-κB. RESULTS: Body weight and related behavioral testing of the rat model suggests that Huangqi Guizhi Wuwu Decoction can improve the slow weight gain of oxaliplatin-induced chronic CINP model rats and effectively prevent and treat oxaliplatin-induced regular CIPN rat model of hyperalgesia. It can also oppress the mechanical pain threshold, cold pain threshold, and heat pain threshold decreased. Furthermore, by ELISA, immunohistochemistry, and western blot analysis, we found that Huangqi Guizhi Wuwu Decoction can down-regulate the levels of TNF-α, IL-1ß, and IL-6 in the serum of chronic CINP rats induced by oxaliplatin. It also suppresses the expression of MAPK pathway related-proteins ERK1/2, p38, and JNK. This results in a decrease in the expression of downstream essential proteins, c-Fos, CREB, and Nf-κB. CONCLUSIONS: In conclusion, we found that Huangqi Guizhi Wuwu Decoction can combat nerve cell injury, reduce pain sensitization, and prevent and repair the damage of nerve cells in the oxaliplatin CINP model rats via TNFα/IL-1ß/IL-6/MAPK/NF-kB pathway.

Temporal and tissue-specific transcriptome analyses reveal mechanistic insights into the Solidago canadensis response to cadmium contamination.

Understanding the cellular mechanisms mediating invasive plant adaptation to excessive cadmium (Cd) in environments is crucial for designing phytoremediation strategies for Cd-contaminated soils. Here we performed RNA sequencing on the root and leaf tissues of Solidago canadensis stressed by Cd for 0, 12, 24, and 48 h. Tissue-specific gene expression was notably significant, i.e., 76% (1667) of differentially expressed unigenes in the root and 78% (1856) in the leaf were exclusive to each tissue. Distinctive enrichment of gene functions was further observed in each tissue's response. In detail, adaptation of the root to Cd stress involved the up-regulation of genes encoding molecular chaperones (mainly heat shock proteins) and induction of some antioxidants, which may help cells scavenge reactive oxygen species (ROS). In comparison, leaf exposure to Cd ramped up the expression of genes associated with secondary metabolism, comprised mainly of cytochrome P450, but slowed down its photosynthetic functions, which seems to conserve energy for survival. Moreover, we highlighted candidate gene modules that are highly linked to physiological traits. Collectively, these observations suggest that S. canadensis may adopt a multipronged approach to actively cope with Cd stress, with both management of ROS accumulation and metabolic adjustment to optimize energy metabolism.

Rapid Determination and Quality Control of Pharmacological Volatiles of Turmeric (Curcuma longa L.) by Fast Gas Chromatography-Surface Acoustic Wave Sensor.

INTRODUCTION: A novel analytical method using fast gas chromatography combined with surface acoustic wave sensor (GC-SAW) was developed for rapid determination of the pharmacological volatiles of turmeric (Curcuma longa L.). METHODS: The volatile compounds in 20 turmeric samples, collected from different parts and different origins, were assessed by the fast GC-SAW. In addition, gas chromatography-mass spectrometry (GC-MS) was employed to confirm the chemical composition of the main volatiles. The digital fingerprint of turmeric was established and analysed by principal component analysis and cluster analysis. RESULTS: Curcumene (9.1%), ß-sesquiphellandrene (5.1%) and ar-turmerone (69.63%) were confirmed as the main pharmacological volatiles of turmeric. The content of ar-turmerone in lateral rhizome turmeric was significantly higher than that of top rhizome and ungrouped turmeric. The contents of curcumene and ß-sesquiphellandrene in top rhizome turmeric were higher than those in lateral and ungrouped turmeric. The 20 turmeric samples were divided into four categories, which reflected the quality characteristics of the turmeric from different parts and origins. CONCLUSION: The GC-SAW method can rapidly and accurately detect pharmacologically volatiles of turmeric, and it can be used in the quality control of turmeric.

Carbon nanocage-based nanozyme as an endogenous H2O2-activated oxygenerator for real-time bimodal imaging and enhanced phototherapy of esophageal cancer.

Intelligent phototherapy by theranostic nanosystems that can be activated by a tumor microenvironment has high sensitivity and specificity. However, hypoxia and low drug accumulation in tumors greatly limit its clinical application. Herein, we have designed a cage-like carbon-manganese nanozyme, which effectively relieves tumor hypoxia and delivers numerous photosensitizers (PSs) to the tumor site, for real-time imaging and enhanced phototherapy of esophageal cancer. Specifically, bovine serum albumin (BSA) was used as a template and reducing agent for preparing a BSA-MnO2 nanozyme; then a BSA-MnO2/IR820@OCNC (BMIOC) nanosystem was successfully synthesized by crosslinking BSA-MnO2 on the surface of IR820-loaded carboxylated carbon nanocages (OCNCs). Abundant PSs were successfully delivered to tumor sites via hollow OCNCs, and the final loading rate of IR820 reached 42.8%. The intratumor BMIOC nanosystem can be initiated by a tumor microenvironment to switch on its magnetic resonance (MR) imaging signal, and photothermal therapy (PTT) and photodynamic therapy (PDT) functions. Notably, the BSA-MnO2 nanozyme, with intrinsic catalase (CAT)-like activity, catalyzed endogenous H2O2 for oxygen generation to overcome tumor hypoxia and enhance PDT, thereby leading to more efficient therapeutic effects in combination with OCNC-elevated PTT. In addition, the H2O2-activated and acid-enhanced properties enable our nanosystem to be specific to tumors, protecting normal tissues from damage. By integrating a high drug loading capacity, a hypoxia regulation function, an enlarged phototherapy effect, and bimodal imaging into a nanozyme-mediated nanoreactor, this work realizes a "one for all" system and represents promising clinical translation for efficient esophageal cancer theranostics.

Tetrahydrocurcumin mitigates acute hypobaric hypoxia-induced cerebral oedema and inflammation through the NF-κB/VEGF/MMP-9 pathway.

High-altitude cerebral oedema (HACE) is a potentially fatal manifestation of high-altitude sickness and is caused partly by inflammation and the blood-brain barrier disruption. Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti-inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40 mg/kg) for 3 days significantly alleviated the increase in brain water content (BWC), interleukin-1ß (IL-1ß) and TNF-α levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH-induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O2 ) for 24 hr exhibited and increase in IL-1ß expression followed by an increase in vascular endothelial growth factor (VEGF) levels. Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase-9 (MMP-9), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH-induced cerebral oedema and inflammation is associated with the inhibition of the NF-κB/ VEGF/MMP-9 pathways.

Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/ß-Catenin Signaling Pathway in STZ-Induced Diabetic Rats.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms. METHODS: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p.o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/ß-catenin pathway (wnt1, ß-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively. RESULTS: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, ß-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment. CONCLUSION: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/ß-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.

Metabolome and Transcriptome Analysis of Hexaploid Solidago canadensis Roots Reveals its Invasive Capacity Related to Polyploidy.

Polyploid plants are more often invasive species than their diploid counterparts. As the invasiveness of a species is often linked to its production of allelopathic compounds, we hypothesize that differences in invasive ability between cytotypes may be due to their different ability to synthesize allelopathic metabolites. We test this using two cytotypes of Solidago canadensis as the model and use integrated metabolome and transcriptome data to resolve the question. Metabolome analysis identified 122 metabolites about flavonoids, phenylpropanoids and terpenoids, of which 57 were differentially accumulated between the two cytotypes. Transcriptome analysis showed that many differentially expressed genes (DEGs) were enriched in 'biosynthesis of secondary metabolites', 'plant hormone signal transduction', and 'MAPK signaling', covering most steps of plant allelopathic metabolite synthesis. Importantly, the differentially accumulated flavonoids, phenylpropanoids and terpenoids were closely correlated with related DEGs. Furthermore, 30 miRNAs were found to be negatively associated with putative targets, and they were thought to be involved in target gene expression regulation. These miRNAs probably play a vital role in the regulation of metabolite synthesis in hexaploid S. canadensis. The two cytotypes of S. canadensis differ in the allelopathic metabolite synthesis and this difference is associated with regulation of expression of a range of genes. These results suggest that changes in gene expression may underlying the increased invasive potential of the polyploidy.

Dexmedetomidine inhibits neuronal apoptosis by inducing Sigma-1 receptor signaling in cerebral ischemia-reperfusion injury.

Dexmedetomidine is known to alleviate cerebral ischemia-reperfusion injury (CIRI). We established a rat model of CIRI, which exhibited higher neurological deficit scores and a greater number of apoptotic cells in the cerebral ischemic penumbra than controls. Dexmedetomidine reversed the neuronal apoptosis and improved neurological function in this model. We then examined Sigma-1 receptor (Sig-1R) expression on the endoplasmic reticulum (ER) in brain tissues at different reperfusion time points. Sig-1R expression increased with CIRI and decreased with increasing reperfusion times. After 24 hours of reperfusion, dexmedetomidine upregulated Sig-1R expression, and ER stress proteins (GRP78, CHOP, JNK and Caspase-3) were detected in brain tissues with Western blotting. Moreover, GRP78 expression followed a pattern similar to Sig-1R. Dexmedetomidine induced GRP78 expression but inhibited CHOP, Caspase-3 and phosphorylated-JNK expression in brain tissues. A Sig-1R-specific inhibitor reduced GRP78 expression and partially inhibited the upregulation of GRP78 by dexmedetomidine. The inhibitor also increased CHOP and Caspase-3 expression and partially reversed the inhibitory effects of dexmedetomidine on these pro-apoptotic ER stress proteins. These results suggest that dexmedetomidine at least partially inhibits ER stress-induced apoptosis by activating Sig-1R, thereby attenuating brain damage after 24 hours of ischemia-reperfusion.

Notoginsenoside Fc Accelerates Reendothelialization following Vascular Injury in Diabetic Rats by Promoting Endothelial Cell Autophagy.

Interventional therapies, such as percutaneous transluminal angioplasty and endovascular stent implantation, are used widely for the treatment of diabetic peripheral vascular complications. Reendothelialization is an essential process in vascular injury following interventional therapy, and hyperglycemia in diabetes mellitus (DM) plays an important role in damaging endothelial layer integrity, leading to the retardance of reendothelialization and excessive neointimal formation. Notoginsenoside Fc (Fc), a novel saponin isolated from Panax notoginseng, effectively counteracts platelet aggregation. Nevertheless, the potential effects and molecular mechanisms of Fc on reendothelialization have yet to be explored. In this study, we present novel findings that show the benefit of Fc in accelerating reendothelialization and alleviating excessive neointimal formation following carotid artery injury in diabetic Sprague-Dawley rats in vivo. Simultaneously, the decreased autophagy of the injured carotid artery in diabetic rats was restored by Fc treatment. Our in vitro results also demonstrated that Fc promoted endothelial cell proliferation and migration under high-glucose treatment by increasing autophagy. In summary, this study supported the notion that Fc could accelerate reendothelialization following vascular injury in diabetic rats by promoting autophagy, suggesting that Fc may exert therapeutic benefits for early endothelial injury and restenosis following intervention in diabetes-associated vascular diseases.

Detecting Zn(II) Ions in Live Cells with Near-Infrared Fluorescent Probes.

Two near-infrared fluorescent probes (A and B) containing hemicyanine structures appended to dipicolylamine (DPA), and a dipicolylamine derivative where one pyridine was substituted with pyrazine, respectively, were synthesized and tested for the identification of Zn(II) ions in live cells. In both probes, an acetyl group is attached to the phenolic oxygen atom of the hemicyanine platform to decrease the probe fluorescence background. Probe A displays sensitive fluorescence responses and binds preferentially to Zn(II) ions over other metal ions such as Cd2+ ions with a low detection limit of 0.45 nM. In contrast, the emission spectra of probe B is not significantly affected if Zn(II) ions are added. Probe A possesses excellent membrane permeability and low cytotoxicity, allowing for sensitive imaging of both exogenously supplemented Zn(II) ions in live cells, and endogenously releases Zn(II) ions in cells after treatment of 2,2-dithiodipyridine.

Echinacoside alleviates hypobaric hypoxia-induced memory impairment in C57 mice.

Acute hypobaric hypoxia (HH) gives rise to persistent cognitive impairment, influencing memory function specifically. Echinacoside (ECH), one of the phenylethanoids isolated from the stems of Cistanche salsa, has been reported to prevent ischemia induced by neuronal injury traditionally. This study then tried to investigate whether ECH could alleviate HH-induced memory deficit. Ten C57 mice were used as control, and 50 were exposed to HH equivalent to 6,100 m for 7 days in a decompression chamber and were given ECH daily (50, 75, or 100 mg/kg) through gavage during the period of exposure. Cognitive performance was evaluated by the Morris water maze test. ECH, especially at 100 mg/kg, significantly reduced HH-induced memory decline. Furthermore, ECH increased the expression of nuclear factor E2 p45-related factor 2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and γ-glutamyl cysteine synthetase in mRNA and protein levels, suggesting that the Keap1-Nrf2-ARE signaling pathway might be involved in neuronal adaptation. The results indicate that ECH could prevent HH-induced memory impairment, which is associated with antioxidant effect of ECH in the hippocampus.

[Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry].

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response.

The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma (Gastrodia elata Blume), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N-methyl-d-aspartate (NMDA) receptors, and Ca2+/calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC). The GluN2A and GluN2B subunits of NMDA receptors, the GluR1 type of AMPA receptor, and CaMKII-α are key molecules responsible for neuroplasticity involved in chronic pain and the accompanying anxiety. Moreover, GAS administration reduced the activation of astrocyte and microglia and the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Therefore, GAS administration relieved chronic pain, exerted anxiolytic effects by regulating neuroplasticity molecules, and attenuated the inflammatory response by reducing the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice.