Xingnaojing injection alleviates cerebral ischemia/reperfusion injury through regulating endoplasmic reticulum stress in Vivo and in Vitro.

Background: Xingnaojing (XNJ) injection, an extract derived from traditional Chinese medicine, is commonly used to treat ischemic stroke (IS). Previous studies have shown that XNJ has the ability to alleviate apoptosis in cerebral ischemia-reperfusion injury. However, the potential mechanisms have not been clarified. Objective: To identify the neuroprotective effect of XNJ and explore whether XNJ inhibits cell apoptosis associated with endoplasmic reticulum stress (ERS) after IS. Methods: In this study, cultured hippocampal neurons from mouse embryos and Sprague-Dawley rats were assigned randomly to four groups: sham, model, XNJ, and edaravone. The treatment groups were administered 2 h after modelling. Neurological deficit scores and motor performance tests were performed after 24 h of modelling. Additionally, pathomorphology, cell apoptosis and calcium content were evaluated. To ascertain the expression of ERS proteins, western blotting and polymerase chain reaction were employed. Results: The results indicated that XNJ treatment resulted in a notable decrease in infarct volume, apoptosis and missteps compared with the model group. XNJ also exhibited improvements in neurological function, grip strength and motor time. The calcium content significantly reduced in XNJ group. The XNJ administration resulted in a reduction in the levels of proteins associated with ERS including CHOP, GRP78, Bax, caspase-12, caspase-9, and cleaved-caspase-3, but an increase of the Bcl-2/Bax ratio. Furthermore, the downregulation of mRNA expression of CHOP, GRP78, caspase-12, caspase-9, and caspase-3 was confirmed in both cultured neurons and rat model. Conclusion: These findings suggest that XNJ may alleviate apoptosis by modulating the ERS-induced apoptosis pathway, making it a potential novel therapeutic approach for ischemic stroke.

Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification.

AIM: The incidence of ulcerative colitis (UC) is increasing steadily in developed countries, it is plaguing nearly 1 million people in the United States and European countries, while developing countries have had a rapidly increased incidence over the past decades. Curcuma is widely used in treating malaria, UC, Crohn's disease, and colon cancer, which lead to diarrhea and bloody stool. However, the systemic mechanism of curcuma in treating UC is still unclear. Our work was supposed to expound how does curcuma alleviate UC in a comprehensive and systematic way by network pharmacology, molecular docking, and experiment verification. METHODS: Traditional Chinese Medicine System Pharmacology Database (TCMSP), Shanghai Chemistry & Chemical Industry Data Platform (SGST), and papers published in Chinese Network Knowledge Infrastructure (CNKI) and PubMed were used to collect the chemical constituents of curcuma based on ADME (absorption, distribution, metabolism, and excretion). And effective targets were predicted by Swiss Target Prediction to establish the curcuma-related database. The disease targets of UC were screened by GeneCards and DrugBank databases, and Wayne (Venn) analysis was carried out with curcuma targets to determine the intersection targets. AutoDock software and TCMNPAS system were used to dock the core chemical components of curcuma with key UC targets. Protein interaction (PPI) network was constructed based on the STRING database and Cytoscape software. Gene function GO analysis and KEGG pathway enrichment analysis were carried out by using Metascape database. Finally, HE staining was performed to identify the inflammatory infiltration and expression difference in TNF-α and STAT3 before and after the treatment of curcuma which was verified by immunoblotting. RESULTS: Twelve active components containing 148 target genes were selected from curcuma. Potential therapeutic targets of curcuma in the treatment of UC were acquired from 54 overlapped targets from UC and curcuma. Molecular docking was used to filter the exact 24 core proteins interacting with compounds whose docking energy is lower than -5.5 and stronger than that of 5-aminosalicylic acid (5-ASA). GO and KEGG analyses showed that these targets were highly correlated with EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, MAPK signaling pathway, and inflammatory bowel disease (IBD). Experiments verified curcuma relieved pathological manifestation and decreased the expression of TNF-α and STAT3. CONCLUSION: Curcuma relieved the colon inflammation of ulcerative colitis via inactivating TNF pathway, inflammatory bowel disease pathway, and epithelial cell signaling in Helicobacter pylori infection pathway, probably by binding to STAT3 and TNF-α.

A meta-analysis of the clinical efficacy of Tanreqing injection combined with antibiotics vs antibiotics alone for treating pulmonary infection secondary to intracerebral hemorrhage.

BACKGROUND: Pulmonary infection is the most common complication to develop after intracerebral hemorrhage (ICH). Antibiotics have certain limitations when used to treat pulmonary infection, while Tanreqing injection (TRQI) is extensively used to treat pulmonary infection as an adjuvant to antibiotics. The aim of this meta-analysis was to investigate the clinical efficacy of TRQI for the treatment of lung infection secondary to ICH. METHODS: Randomized controlled trials (RCTs) assessing the combination of TRQI and antibiotics compared to antibiotics alone for pulmonary infection after ICH were comprehensively searched for in 7 electronic databases from their establishment to August 2020. Two independent researchers conducted the literature retrieval, screening, and data extraction. The assessment tool of Cochrane risk of bias and Review Manager 5.3 software were applied to assess the methodological quality and analyze the data, respectively. RESULTS: Seventeen RCTs involving 1122 patients with pulmonary infection after ICH were included. Compared to antibiotics alone, the combination treatment enhanced the clinical effective rate, shortened the hospital stay, reduced the white blood cell, procalcitonin, and C-reactive protein levels, ameliorated the times to the resolution of fever, cough, and lung rales, and increased the oxygenation index. The evidence indicated that TRQI combined with antibiotics caused no adverse reactions. CONCLUSIONS: Our study showed that the combination of TRQI and antibiotics was effective for treating pulmonary infection after ICH. However, high-quality multicenter RCTs are needed to further verify the clinical efficacy of TRQI due to the publication bias and the low methodological quality of the included RCTs.

Xuesaitong exerts long-term neuroprotection for stroke recovery by inhibiting the ROCKII pathway, in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuesaitong (XST) is a traditional Chinese medicine injection with neuroprotective properties and has been extensively used to treat stroke for many years. The main component of XST is Panax notoginseng saponins (PNS), which is the main extract of the Chinese herbal medicine Panax notoginseng. AIM OF THE STUDY: In this study, we investigated whether XST provided long-term neuroprotection by inhibiting neurite outgrowth inhibitor-A (Nogo-A) and the ROCKII pathway in experimental rats after middle cerebral artery occlusion (MCAO) and in SH-SY5Y cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R). MATERIALS AND METHODS: Rats with permanent MCAO were administered XST, Y27632, XST plus Y27632, and nimodipine for 14 and 28 days. Successful MCAO onset was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological deficit score (NDS) was used to assess neurological impairment. Hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) were performed to evaluate cerebral ischemic injury and the neuroprotective capability of XST. Nogo-A levels and the ROCKII pathway were detected by IHC analysis, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) to explore the protective mechanism of XST. OGD/R model was established in SH-SY5Y cells. Cell counting kit 8 (CCK8) was applied to detect the optimum OGD time and XST concentration. The expression levels Nogo-A and ROCKII pathway were determined using western blotting. RESULTS: Our results showed that XST reduced neurological dysfunction and pathological damage, promoted weight gain and synaptic regeneration, reduced Nogo-A mRNA and protein levels, and inhibited the ROCKII pathway in MCAO rats. CCK8 assay displayed that the optimal OGD time and optimal XST concentration were 7 h and 20 µg/mL respectively in SH-SY5Y cells. XST could evidently inhibit OGD/R-induced Nogo-A protein expression and ROCKII pathway activation in SH-SY5Y cells. CONCLUSIONS: The present study suggested that XST exerted long-term neuroprotective effects that assisted in stroke recovery, possibly through inhibition of the ROCKII pathway.

Clinical Efficacy of Tonic Traditional Chinese Medicine Injection on Acute Cerebral Infarction: A Bayesian Network Meta-Analysis.

Western medicine (WM) has certain limitations in terms of treating acute cerebral infarction (ACI), while tonic traditional Chinese medicine injections (TCMIs) have been shown to have obvious clinical effects as an adjunct to WM for ACI. However, most randomized controlled trials (RCTs) to date have not performed direct comparisons of efficacy among tonic TCMIs. This study designed a Bayesian network meta-analysis (NMA) to explore the therapeutic effect of tonic TCMIs on ACI. A comprehensive search of RCTs of TCMIs combined with WM for ACI was conducted using electronic databases for studies dated from the start date of each database until February 2020. Stata 13.0 and ADDIS 1.16.7 software were used to plot and analyze the data. Sixty-six RCTs with a total of 5,989 patients involving 7 kinds of tonic TCMIs were included. Among TCMIs, Shenfu injection (SFI) + WM ranked first in terms of improving clinical efficacy and the activities of daily living (ADLs) rating and reducing interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. While Ciwujia injection (CI) + WM was the best choice for reducing neurological impairment and the high-cut viscosity of whole blood (HCV). Shenmai injection (SI) + WM had the greatest effects in terms of decreasing the levels of low-cut viscosity of whole blood (LCV), fibrinogen (FIB), and plasma viscosity (PV). Based on the cluster analysis of the clinical efficacy and the neurological impairment, CI + WM and Shenqifuzheng (SQI) + WM were the best options for treating ACI. With respect to adverse drug reactions (ADRs), 35 RCTs did not monitor ADRs during treatment. In conclusion, tonic TCMIs could assist WM in benefiting patients with ACI. However, due to the limitations of the current study, strict monitoring of ADRs and data from high-quality RCTs will be required in future to verify the advantage of TCMIs.

Revealing the Pharmacological Mechanism of Acorus tatarinowii in the Treatment of Ischemic Stroke Based on Network Pharmacology.

AIM: Stroke is the second significant cause for death, with ischemic stroke (IS) being the main type threatening human being's health. Acorus tatarinowii (AT) is widely used in the treatment of Alzheimer disease, epilepsy, depression, and stroke, which leads to disorders of consciousness disease. However, the systemic mechanism of AT treating IS is unexplicit. This article is supposed to explain why AT has an effect on the treatment of IS in a comprehensive and systematic way by network pharmacology. METHODS AND MATERIALS: ADME (absorbed, distributed, metabolized, and excreted) is an important property for screening-related compounds in AT, which were screening out of TCMSP, TCMID, Chemistry Database, and literature from CNKI. Then, these targets related to screened compounds were predicted via Swiss Targets, when AT-related targets database was established. The gene targets related to IS were collected from DisGeNET and GeneCards. IS-AT is a common protein interactive network established by STRING Database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analysed by IS-AT common target genes. Cytoscape software was used to establish a visualized network for active compounds-core targets and core target proteins-proteins interactive network. Furthermore, we drew a signal pathway picture about its effect to reveal the basic mechanism of AT against IS systematically. RESULTS: There were 53 active compounds screened from AT, inferring the main therapeutic substances as follows: bisasaricin, 3-cyclohexene-1-methanol-α,α,4-trimethyl,acetate, cis,cis,cis-7,10,13-hexadecatrienal, hydroxyacoronene, nerolidol, galgravin, veraguensin, 2'-o-methyl isoliquiritigenin, gamma-asarone, and alpha-asarone. We obtained 398 related targets, 63 of which were the same as the IS-related genes from targets prediction. Except for GRM2, remaining 62 target genes have an interactive relation, respectively. The top 10 degree core target genes were IL6, TNF, IL1B, TLR4, NOS3, MAPK1, PTGS2, VEGFA, JUN, and MMP9. There were more than 20 terms of biological process, 7 terms of cellular components, and 14 terms of molecular function through GO enrichment analysis and 13 terms of signal pathway from KEGG enrichment analysis based on P < 0.05. CONCLUSION: AT had a therapeutic effect for ischemic via multicomponent, multitarget, and multisignal pathway, which provided a novel research aspect for AT against IS.

Topical use of Jiawei Simiao Yongan Gao to prevent radiodermatitis in patients with head and neck cancer: A retrospective cohort study.

Radiodermatitis is a common side effect of radiotherapy, but currently there is no standard treatment for its prevention. This study aimed to observe the effect of topical application of a paste based on traditional Chinese medicine, Jiawei Simiao Yongan Gao, on radiodermatitis caused by radiotherapy for patients with head and neck cancer.This was a retrospective cohort study of 40 patients with head and neck cancer evaluated during their radiotherapy. Of these, 20 patients were treated with Jiawei Simiao Yongan Gao on the irradiated skin from the beginning of radiotherapy (JSY group). The other 20 patients were given standard nursing (standard group). Acute skin reactions were classified according to the radiation-induced skin reaction assessment scale (RISRAS) and American radiation therapy oncology group (RTOG) acute toxicity grading criteria every 2 weeks, and adverse effects were recorded until the end of the radiotherapy.The two groups showed differences in severity of radiodermatitis. At 0 to 30 Gy, the skin reactions were similar in the two groups, while above 40 Gy the skin reactions were significantly lower grade in the JSY group (P < .05). At 0 to 20 Gy, there was no statistical significance (P > .05); but above 30 Gy they were lower in the JSY group (P < .05).Jiawei Simiao Yongan Gao effectively alleviated acute radiodermatitis caused by radiotherapy of head and neck cancer patients compared with standard nursing.

[Natural inducing factors of peach bud dormancy and roles of Ca2+ in the dormancy induction].

Taking two-year-old peach tree of cv 'Chunjie' as test material, the natural inducing factors of peach bud dormancy and the roles of Ca2+ in the dormancy induction were studied. The results revealed that peach plant was very sensitive to short sunlight and/or natural low temperature. These two factors could induce growth cessation, dormancy, and freezing-resistance development, but their action mechanisms differed with each other. Short sunlight induced the dormancy first and the freezing-resistance then, whereas natural low temperature was in adverse. In case of the cofunction of short sunlight and low temperature, i.e., under the natural condition, short sunlight was the main factor inducing growth cessation, dormancy, and freezing-resistance development, while natural low temperature was the secondary one. The inducement effect of short sunlight was closely related to the actions of Ca2+, because Ca2+ played a messenger role in the signal transduction of short sunlight. In the experiment of supplemental light, it was found that with the decrease of temperature, the Ca2+ had an increasing influx from the vacuole, intercellular space, and cell wall to the cytosol and nuclei. At the same time, plant growth slowed down and finally ceased, dormancy started then, and freezing-resistance developed, which indicated that as a messenger in the signal transduction of natural low temperature, Ca2+ played an important role in the inducement of growth cessation, dormancy, and freezing-resistance development by natural low temperature.

Characterization of murine grancalcin specifically expressed in leukocytes and its possible role in host defense against bacterial infection.

Such phagocytic leukocytes as macrophages and neutrophils are the key cellular components of innate immunity. The actin cytoskeleton is essential for their recruitment and activation in infected tissues. We have previously identified p65/L-plastin with Ca(2+)-, calmodulin-, and beta-actin-binding domains in macrophages. In order to further investigate the p65/L-plastin-involved cellular functions, we cloned the cDNA for murine grancalcin, a possible binding partner of p65/L-plastin. According to the sequence, grancalcin is a member of the penta-EF-hand protein family. We prepared recombinant (r) grancalcin for functional studies and found that it exhibited Ca(2+)-dependent precipitation. High-titer antibodies against the protein enabled us to detect intracellular grancalcin. A flow cytometric analysis revealed grancalcin to be highly expressed in macrophages and neutrophils. The protein was particularly abundant in those cells recovered from bacteria-infected sites. Immunohistochemical studies clarified that grancalcin was translocated to the actin cytoskeleton in macrophages upon exposure to bacterial lipopolysaccharide. These findings suggest that grancalcin plays a key role in leukocyte-specific functions that are responsible for host defense.