ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Exploration in the Mechanism of Ginsenoside Rg5 for the Treatment of Osteosarcoma by Network Pharmacology and Molecular Docking.

OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.

Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.

Scorpion Venom Heat-Resistant Synthesized Peptide Increases Stress Resistance and Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1-Like Signal Pathway.

Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect Caenorhabditis elegans (C. elegans) against ß-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat-resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used C. elegans as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP in vivo. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation in vivo. Using gene-specific mutation of C. elegans, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.

Lignans and Terpenoids from the Leaves of Schisandra chinensis.

Fifteen constituents, including one new lignan (schisandroside E) and one new terpenoid (schisandenoid A) as well as nine known lignans and four known terpenoids, were isolated from Schisandra chinensis leaves. The structures of schisandroside E and schisandenoid A were established by entirely meticulous spectroscopic analysis (NMR, MS, CD, IR and UV). All compounds were tested for cytotoxicity against MGC-803, Caco-2 and Ishikawa cell lines. Some compounds showed strong cytotoxicity against these three cancer cell lines with IC50 <1 µm.

Clinical Research on Treatment of Acute Cerebral Infarction with ‘Sanjiao Regular Sequence Therapy’ / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy of Sanjiao Cidi therapy on acute cerebral infarction and its effect on levels of S100-β protein （S100-β）， tumor necrosis factor-α （TNF-α）， hypersensitive C-reactive protein （hs-CRP） and neuropeptide （NPY）. Method:One hundred and eighty patients were randomly divided into control group （90 cases） and observation group （90 cases） by random number table. Patients in control group got aspirin enteric-coated tablets， 100 mg/time， 1 time/day， edaravone injection （injected within 30 minutes） for 14 days， 30 mg/time， 2 times/day， simvastatin tablets， 20 mg/time， 1 time/day. In addition to the basic therapy of meloxicam tablets， patients in observation group were also treated with Sanjiao Cidi therapy. In the first step， patients got Guizhi therapy to dredge Zhongjiao and Shangjiao， 1 dose/day， for 8 days. In the second step， patients got Sini therapy to dredge Zhongjiao and Xiajiao， 1 dose/day， for 10 days. In the third step， patients got Tianjing Gubentherapy， 1 dose/day， for 10 days. The course of treatment was 4 weeks. Before the treatment， and at the first， second， third and fourth weeks after treatment， National Institutes of Health Stroke Scale （NIHSS） was scored. And before and after treatment， function scale of fuglmeyer （FMA）， ability of daily life activities （ADL）， mini-mental state examination （MMSE） and main symptoms of traditional Chinese medicine were scored. Comprehensive assessment of patient report outcome （PRO） was made. And levels of S100-β， hs-CRP， TNF-α and NPY were detected. And the incidence rate of pulmonary infection， urinary infection， skeletal myalgia， shoulder hand syndrome and shoulder subluxation of patients were recorded during hospitalization. Result:The clinical efficacy in observation group was better than that in control group （Z=2.141， P<0.05）. Scores of NIHSS in observation group were lower than those in control group at the first， second， third and fourth weeks after treatment （P<0.01）. Scores of upper limb， legs and the total scores from FMA were higher than those in control group （P<0.01）. Scores of the main symptoms of traditional Chinese medicine， symptoms， psychological and social scores， total scores of PRO， S100-β， hs-CRP， TNF-α and NPY were lower than those in the observation group （P<0.01）. And scores of ADL and MMSE were higher than those in control group （P<0.01）. Total incidence of complications in observation group was 27.27%（21/77）， which was lower than 46.15%（36/78） in control group （χ2=5.941， P<0.05）. Conclusion:In addition to conventional western medicine treatment， Sanjiao Cidi therapy can treat the patients with acute cerebral infarction， alleviate the degree of neurological deficit， improve the cognitive function， motor function of limbs and the ability of daily life， reduce the main symptoms of traditional Chinese medicine， the incidence of complications and the inflammatory response， protect the nerve cells， with a better clinical efficacy and comprehensive effect in patients than pure Western medicine.

Research progress on chemical constituents and biological activities from Turpinia species / 中国中药杂志

Turpinia species have been used as local Chinese medicines. It has been widely concerned about their antibacterial and anti-inflammatory effects. Modern studies showed that the chemical constituents of Turpina species include flavonoids, triterpenoids, megastigans and phenoli acids. Its pharmacological research mainly focused on antibacterial, anti-inflammatory, antioxidant, analgesic, and immuneregulation effect. In this paper, the chemical compositions and pharmacological activities of Turpinia species were summarized, in order to provide scientific basis for the further development and utilization of Turpinia species.

Developing spectrum-toxicity relationship with rough set theory for hepatotoxicity material basis of Polygonum multiflorum / 中国中药杂志

Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.

Effect of herbal cake-partitioned moxibustion on MEK1/2 and ERK1/2 expressions of gastric tissues in rats with spleen deficiency syndrome / 针灸推拿医学（英文版）

Objective:To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods:Sixty Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a ranitidine group (group C), and a herbal cake-partitioned moxibustion group (group D) by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang (Radix et Rhizoma Rhei). After successful modeling, the rats in group C were treated with 25 mg/(kg·bw) ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/(kg·bw) at 8:00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin (HE) staining. The protein expressions of MEK1/2 and ERK1/2 in the gastric tissues were detected by immunohistochemistry. Results:After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK1/2 and ERK1/2 in gastric tissues of the other groups were significantly higher (P<0.01). Compared with group B, the protein expressions of MEK1/2 and ERK1/2 in group C and D were significantly higher (allP<0.01). Compared with group C, the protein expressions of MEK1/2 and ERK1/2 in group D were significantly higher (P<0.01). Conclusion: Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK1/2 and ERK1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.

Clinical efficacy of Chenshi Qingfei Decoction on rheumatoid arthritis and interstitial lung disease / 中成药

AIM To explore the efficacy of Chenshi Qingfei Decoction (Pseudostellariae Radix,Ophiopogonis Radix,Adenophorae Radix,etc.) against rheumatoid arthritis and interstitial lung disease (RA-ILD).METHODS Based on Prednisolone,RA-ILD patients were randomly divided into control group and observation group by random number table and randomized block design.The observation group took Chenshi Qingfei Decoction.The treatment course was three months for both groups.Before the treatment,the activity of the disease (DAS28) was assessed and ESR,CRP,RF,CCP were measured.Before and after the treatment,high resolution-CT (HRCT) was conducted and graded,and symptoms and signs were graded.RESULTS After the treatment,the effective rate of cough,expectoration and breath hard in the syndromes of Chinese traditional medicine was 71％ in the observation group and 23％ in the control group (P ＜0.01).The effective rate of improved lung imaging by HRCT was 68％ in the observation group but 13％ in the control group (P ＜0.01).CONCLUSION Based on the immunosuppressive agents therapy in RA,Chenshi Qingfei Decoction can relieve clinical symptoms of cough,expectoration and breath hard,and reduce area and degree of interstitial lung disease by HRCT.

Effect of herbal cake-partitioned moxibustion on MEK1/2 and ERK1/2 expressions of gastric tissues in rats with spleen deficiency syndrome / 针灸推拿医学（英文版）

Objective:To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods:Sixty Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a ranitidine group (group C), and a herbal cake-partitioned moxibustion group (group D) by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang (Radix et Rhizoma Rhei). After successful modeling, the rats in group C were treated with 25 mg/(kg·bw) ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/(kg·bw) at 8:00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin (HE) staining. The protein expressions of MEK1/2 and ERK1/2 in the gastric tissues were detected by immunohistochemistry. Results:After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK1/2 and ERK1/2 in gastric tissues of the other groups were significantly higher (P<0.01). Compared with group B, the protein expressions of MEK1/2 and ERK1/2 in group C and D were significantly higher (allP<0.01). Compared with group C, the protein expressions of MEK1/2 and ERK1/2 in group D were significantly higher (P<0.01). Conclusion: Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK1/2 and ERK1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.

Clinical efficacy of Chenshi Qingfei Decoction on rheumatoid arthritis and interstitial lung disease / 中成药

AIM To explore the efficacy of Chenshi Qingfei Decoction (Pseudostellariae Radix,Ophiopogonis Radix,Adenophorae Radix,etc.) against rheumatoid arthritis and interstitial lung disease (RA-ILD).METHODS Based on Prednisolone,RA-ILD patients were randomly divided into control group and observation group by random number table and randomized block design.The observation group took Chenshi Qingfei Decoction.The treatment course was three months for both groups.Before the treatment,the activity of the disease (DAS28) was assessed and ESR,CRP,RF,CCP were measured.Before and after the treatment,high resolution-CT (HRCT) was conducted and graded,and symptoms and signs were graded.RESULTS After the treatment,the effective rate of cough,expectoration and breath hard in the syndromes of Chinese traditional medicine was 71％ in the observation group and 23％ in the control group (P ＜0.01).The effective rate of improved lung imaging by HRCT was 68％ in the observation group but 13％ in the control group (P ＜0.01).CONCLUSION Based on the immunosuppressive agents therapy in RA,Chenshi Qingfei Decoction can relieve clinical symptoms of cough,expectoration and breath hard,and reduce area and degree of interstitial lung disease by HRCT.

Qualitative and quantitative analysis of Evodiae Fructus based on the UPLC technology / 中国中药杂志

An UPLC method was developed for the studies of fingerprint and quantification of multi-components for Evodiae Fructus. The chromatographic separation was performed on a C₁₈ column (2.1 mm×50 mm,1.7 μm) with mobile phase of 0.2% formic acid-acetonitrile and 0.2% formic acid-water in gradient mode, and the detection wavelength was set at 320 nm．Dehydroevodiamine was used as the reference peak, there were 24 common peaks in the fingerprint of 29 samples were detected, and among them 10 chromatographic peaks were identified with the reference substance and they were neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, hyperin, isorhamnetin-3-O-β-D-rutinoside, dehydroevodiamine, evodiamine, rutaecarpine, evocarpine and dihydroevocarpine. The fingerprint data was evaluated with similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (Version 2008A), and the similarity of 19 batches of Evodiae Fructus was greater than 0.9 in the 29 samples. In addition, 9 components including neochlorogenic acid, chlorogenic acid, hyperin, isorhamnetin-3-O-β-D-rutinoside, dehydroevodiamine, evodiamine, rutaecarpine, evocarpine and dihydroevocarpine were simultaneously determined at the same chromatographic conditions, whose peak area integral values showed good linear relationship at the range of 0.000 46-0.138, 0.000 146-0.175, 0.000 412-0.124, 0.000 448-0.134, 0.000 452-0.136, 0.003 38-0.169, 0.000 44-0.132, 0.001 07-0.128, 0.001 71-0.128, respectively. Their average recoveries were 100.3%, 100.4%, 101.6%, 97.51%, 102.9%, 101.4%, 103.8%, 104.0%, 95.99%, and RSD were 2.4%, 2.0%, 3.0%, 0.80%, 1.9%, 2.1%, 1.1%, 2.2%, 2.4%, respectively. The established UPLC method not only realized the full separation of all chemical constituents of Evodiae Fructus within 20 minutes, but also achieved the chromatographic fingerprint determination and simultaneous multi-components determination of Evodiae Fructus at the same chromatographic conditions. Compared with other methods in literatures, the method has the following characteristics of strong specificity, good separation, high purity of chromatographic peaks, simplity and feasibility, which provides better means for the simultaneous qualitative and quantitative analysis of Evodiae Fructus.

Xitong Wan attenuates inflammation development through inhibiting the activation of nuclear factor-κB in rats with adjuvant-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xitong Wan (XTW), a traditional Chinese herbs formula, has been used to treat "Bi Zheng" in the clinical practice of traditional Chinese medicine (TCM) for hundreds of years. However, no scientific validation is available on the anti-rheumatic effect of XTW. AIM OF STUDY: This study was carried out to investigate the effects of XTW on joints swelling, joints destruction, production of inflammatory mediators and nuclear factor-κB (NF-κB) activation in rats with adjuvant-induced arthritis (AIA). MATERIALS AND METHODS: AIA was induced by intradermal injection of Complete Freund's adjuvant in the footpad of Wistar rats. Paw volume was measured every 7 days during XTW treatment. Histological score was calculated by hematoxylin and eosin staining. Osteoclast number in articular tissues was counted by tartrate-resistant acid phosphatase staining. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in serum were detected by enzyme-linked immunosorbent assay. Levels of NF-κBp65 and inhibitor of NF-κB (IκB)α in synovium were analyzed by Western blot assay. RESULTS: Compared with AIA group rats, XTW significantly decreased the paw volume of AIA rats. Meanwhile, XTW significantly reduced the histological score and osteoclast number in articular tissues of AIA rats. In addition, XTW markedly abated the levels of TNF-α, IL-1ß and IL-6 in serum, as well as enhanced the level of IκBα in synovium of AIA rats. However, XTW did not show significant effect on the level of p65 in synovium of AIA rats. CONCLUSIONS: These results suggest that XTW attenuates the inflammation development through inhibiting the NF-κB-mediated proinflammatory cytokines production in AIA rats. Our study provides the scientific evidence of XTW on treatment of rheumatoid arthritis in the clinical practice of TCM.

Long-term toxicity study of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys by intravenous injection.

rAd5-hTERTC27, a replication-defective adenovirus vector carrying hTERTC27, has been proposed for possible use against hepatocellular carcinoma (HCC). In this study, we investigated the long-term toxicity of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys. rAd5-hTERTC27 was administered intravenously once a week for 13 weeks followed by a one-month recovery period. As of 4 months, all animals displayed overall good health. Anti-adenoviral antibodies emerged in a dose-independent manner. The levels of complement components, C3 and C4, in the rAd5-hTERTC27 middle-dose and high-dose groups and C4 in the rAd5-EGFP group increased significantly after the 2nd treatment in monkeys. Slight-mild pathological changes of the liver occurred only in the rAd5-hTERTC27 high-dose group (2/16) in rats and not in any other group in either rats or monkeys. With the increase of the dose, the incidence of lymphocyte depletion in the spleen of rats and reactive hyperplasia of the splenic corpuscle in monkeys increased. However, the changes in the liver and spleen were reversible. Given the above data, intravenous administration of rAd5-hTERTC27 (up to 4×10(10)VP/kg in rats and 0.9×10(10)VP/kg in monkeys) appears to be well-tolerated, providing support for its potentially safe use in clinical trials for the treatment of HCC.

Pharmacology research on PXR as a potential target in screening bioactive components of Chinese material medica / 中国中药杂志

Pregnane X receptor (PXR) is key transcription factors which mainly regulate the expression of CYP3A genes. At the molecular level, PXR has been revealed the protection mechanism of the body against xenochemicals and a major mode of the drug-drug interactions. Besides playing an important role in drug metabolism and interactions, PXR and its target genes also play an important role in maintaining normal physiological function and homeostasis. Therefore, it is necessary to study the regulation of PXR and its related pharmacological effects of TCM and natural products, and to provide new clues for the new pharmacological pathway.

Cardiotoxicity study of Shenfu compatibility in rats based on metabonomics / 中国中药杂志

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.

Effects of Reduning injection on activity of hepatic microsomal CYP450 isozymes in rats / 中国中药杂志

To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.

Effect of Siwu decoction on function and expression of P-glycoprotein in Caco-2 cells / 中国中药杂志

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.