Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Shenlian extract attenuates TNF-α-induced ECV304 injury by regulating Nrf2/Keap1 signaling pathway / 中国中药杂志

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.

Therapeutic Efficacies of Wujiwan at Different Compatibilities in Treatment of Irritable Bowel Syndrome / 中国实验方剂学杂志

Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities （No.1 and No.2） on irritable bowel syndrome （IBS） based on neuro-endocrine-immune network， and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine （TCM）. Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty （PTCA） in suckling rats. The animals were randomly divided into a control group， a model group， a dicetel group （0.01 g·kg^-1）， low- （0.335 g·kg^-<bold>¹</bold>）， medium- （0.67 g·kg^-<bold>¹</bold>）， and high-dose （1.34 g·kg^-<bold>¹</bold>） No. 1 Wujiwan groups， and low- （0.385 g·kg^-<bold>¹</bold>）， medium- （0.77 g·kg^-<bold>¹</bold>）， and high-dose （1.54 g·kg^-<bold>¹</bold>） No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells （MC） in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine （5-HT）， substance P （SP）， somatostatin （SS）， and vasoactive intestinal peptide （VIP） in the blood/colon tissue were detected by enzyme-linked immunosorbent assay （ELISA） and immunohistochemistry （IHC） assay. Result:There was no significant difference in body weight among different groups. Compared with the control group， the model group exhibited decreased thresholds of abdominal elevation and bow back elevation （<italic>P<</italic>0.01）， increased density of MCs in the colon tissue （<italic>P<</italic>0.05）， up-regulated levels of 5-HT， SP， and SS in the blood and colon tissue （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and elevated VIP level in the colon tissue （<italic>P</italic><0.05）. Compared with the model group， Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation （<italic>P</italic><0.01）， diminish the count of MC in the colon tissue （<italic>P</italic><0.05）， and reduce the levels of 5-HT， SP， SS， and VIP （<italic>P</italic><0.05）. As demonstrated by the comparison of No. 1 and No. 2 Wujiwan， No. 1 was superior to No. 2 in reducing the concentrations of 5-HT， SP， and SS in the blood， especially in 5-HT （<italic>P</italic><0.01）. No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan， No. 2 significantly reduced SP expression， and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups （<italic>P</italic><0.05）. Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect， No. 1 was superior to No. 2， while in terms of local effect， No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics， while No. 2 had an advantageous effect on intestinal sensation over No. 1.

Effect and Mechanism of Shenlian Formula in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

Investigation of Transdermal Constituents and Molecular Mechanism of Euodiae Fructus in Treatment of Diarrhea by Transdermal Drug Delivery Based on Integrated Pharmacology and UPLC-Q-TOF-MS / 中国实验方剂学杂志

Objective:To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method:Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances， analysis of UNIFI system and mass spectrometry. On this basis， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， SymMap， DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets， which were used for the Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Finally， Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract， including quinolone alkaloids， limonins， indole alkaloids， organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis， signaling pathways of inflammatory response， cell proliferation， nutrient regulation and energy metabolism， signal transduction， bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion:In this study， the transdermal constituents of Euodiae Fructus are identified for the first time， they can participate in the regulation of intestinal inflammation， maintain the integrity of intestinal mucosa， repaire and adjust the metabolism of the body by acting on Rac protein family， phosphatidylinositol 3-kinase， cytochrome P450 enzymes and aldo-keto reductase， respectively. In general， the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.

Effect Analysis of Artemisiae Annuae Herba and Chuanxiong Rhizoma in Treatment of Cerebral Malaria Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio^® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.

Mechanism of Shengmaiyin (Dangshen Prescription) in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine （ETCM）, and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation，Visualization and Integrated Discovery（DAVID）. Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.

Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model / 中国中药杂志

This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.

Effects of Different Types of Electroacupuncture on Expression of High Mobility Group Box Protein-1 and Interleukin-10 in Hippocampus of APP/PS1 Mice / 中国康复理论与实践

@#Objective To compare the effect of impulse electroacupuncture (impulse-EA) and music electroacupuncture (music-EA) for Tongdu Qishen on spatial learning and memory, and expression of cytokine in the hippocampus of APP/PS1 mice. Methods A total of 32 APP/PS1 double transgenic male mice were randomly divided into model group (n=8), drug group (n=8), impulse-EA group (n=8) and music-EA group (n=8), the same background and age male C57BL/6 mice were observed as normal group (n=8). The impulse-EA group and music-EA group accepted EA at Baihui (GV20) and Yintang (GV29), connected with their own electroacupuncture stimulators, for 20 minuts, then, they were pricked Renzhong (GV26) for a while. The drug group accepted donepezil hydrochloride 0.92 mg/kg intra-gastrically. The normal group, model group and drug group were grabbed and bounded in the same way. After 15 days of treatment, they were assessed with Morris water maze. The expression of high mobility group box pro-tein-1 (HMGB1) and interleukin-10 (IL-10) in hippocampus were measured with immunohistochemistry and Western blotting. Results The escape latency shortened inEA groups compared with that of the model group since the fourth day of Morris water maze training (P<0.05), and it was the least in the music-EA group; and the ratio of swimming across the target quadrant increased (P<0.05), but there was no significant difference between EA groups (P>0.05). The ex-pression of HMGB1 decreased (P<0.05) and the expression of IL-10 increased (P<0.05) in EA groups com-pared with that of the model group, and HMGB1 decreased more and IL-10 increased more in the music-EA group than in the impulse-EA group (P<0.05), according to the measurement in immunohistochemistry, not in Western blotting. Conclusion Both impulse-EA and music-EA based on Tongdu Qishen can promote the recovery of the learning and memory in APP/PS1 mice, and music-EA may do more effectively in inhibition of pro-inflammatory factors and promotion of the anti-inflammatory factors.

Research initiative of new thought on "main effect" of TCM formulae--new thinking on mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae / 中国中药杂志

This article proposes a new thought on the study of "main effect" of traditional Chinese medicine (TCM) formulae. The blood concentrations of the pharmacodynamic substances of Chinese material medica（CMM）are usually very low, with lower toxic and side effects than western medicine. Therefore, according to a recent hypothesis of additive effect of multiple components for a single target, local targets in multi-component multi-target synergistic effect network of TCM may have the additive effect of similar components. Studies on the disposition of CMM showed that a constituent could bebio-transformed to many metabolites; these compounds with a similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the hypothesis of "additive effect". The authors of this article further believe that additive effect of TCM multi-components only comes up under a limited conditions/concentration. Because of the complexity of TCM-organism system, the complex effect of multicomponent addition and competition/antagonism is more likely to appear in single targets of drug effect. This complex effect may be the key to impact the synergistic effect of TCM multi-targets. In theory, choose and create a single target additive effect could realize the scientific compatibility of TCM and improve the curative effect and attenuate toxicity. According to the clinical demand and under the guidance of the above thought, we proposed the "main effect" of TCM formulae. Because traditional Chinese medicine (compounds) have diverse and complex effects, how to better study TCM formulae compatibility mechanism and improve the curative effect? Efforts shall be made to select one or several effects relating to clinical specific syndromes from the complex and diverse effects of TCM as the "main effect". The "main effect" of TCM formulae is the macroscopic manifestation of the synergistic effect of multi-component/multi-target. The study of the Formulae "main effect" can contain at least two aspects: one is the study of pharmacokinetic application of TCM formulae, and another is the study for pharmacodynamics effect. In the study of main effect, there are two main elements. First, which drug targets are directly related to the main effect? This requires identifying the target network. Second, which drug components positively or negatively control the single target of the target network? And what change in single target effect as well as the multi-target synergistic effect will be caused by the regulatory component concentration or the change in number? These two elements is the key to elucidate the mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae. Through the study of the main effect, the clinical curative effect and the mechanism of the TCM formulae shall be improved.

Protection of Shenlian extracts to PM2.5 infected RAW 264.7 cell damage / 中国中药杂志

The aim of this research is to investigate the protection of PM2.5 infected RAW264.7 cell by traditional Chinese medicine (TCM)--Shenlian(SL) extracts and to establish the damage model. We use cell growth, cell damage and oxidative stress related markers, and inflammatory cytokines as observation index to evaluate the protection of PM2.5 infected RAW264.7 by SL extract. The results showed that 50 mg x L(-1) PM2.5 could cause cell particle deposition, inhibit the growth of cells, and significantly increase the cell supernatant of LDH, NO release quantity and intracellular reactive oxygen species (ROS) level during 4 h and 24 h. In the intervention of SL extract 50, 25, 10 mg x L(-1), the particle deposition of RAW264.7 cells, cell supernatant of LDH, NO, IL(-1) beta release, MCP-1 was significantly decreased, the SOD activity increased significantly. It shows that SL extracts of PM2.5 infected RAW264.7 cell damage has obvious protective effect, the effect may be related to the direct protection of cells, reduce oxidative stress and inflammatory injury.

Current status of traditional Chinese medicine on reversing tumor multi-drug resistance / 中国中药杂志

Multi-drug resistance (MDR) is one of the major obstacles to successful chemotherapy for tumors. Traditional Chinese medicine that can reverse MDR has been intensely studied because of its low toxicity, high efficacy and multi-targets. In recent years, more and more traditional Chinese medicine (TCM) has been found to be effective in reversing MDR. In this review, we analyze the current status of traditional Chinese medicine on reversing tumor MDR and describe recent progress on it.

Pathogenesis of plaque destabilization induced by PM2.5 exposure and coping strategies / 中国中药杂志

With the increasingly more serious environmental pollution in China in recent years, effective intervention with PM25-induced health risks has become a major scientific issue to be addressed urgently in medical research field in China. NOD-like receptors (NLRs) are a family of cytoplasmic pattern-recognition receptors that have critical roles in innate immunity. On the basis of study progresses in international cardiovascular disease research "Fine particulate matter exposure is a modifiable risk factor for the morbidity and mortality of cardiovascular diseases", and with reference to the current understanding of pulmonary inflammation and oxidative stress in PM2.5-induced acute coronary syndrome, this study intended to investigate whether intracellular pattern recognition NL-RP3 plays a important role in the inital event of PM2.5 induced vessel inflammation as a foreign matter in the process of plaque destabilization and to thoroughly explore the underlying mechanisms responsible for PM2.5-induced acute cardiovascular events. On the other hand, it also studies the feasibility of using traditional Chinese medicine to treat plaque destabilization cause by PM2.5 exposure and discuss it's pathogenesis and intervention strategy based on TCM theory. This paper in order to provide scientific basis for social focal issues in public health proactively and offers the references for relevant research.

Research on bioactive ingredients in rat liver after oral administration of different combinations of Wuji pill / 中国中药杂志

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.

Effect on M1 macrophages of shenlian extracts / 中国中药杂志

This study discusses the effects of Shenlian extracts (SL) on M1 macrophages in atherosclerosis. The MTT assay was used to detect the growth inhibition rates of RAW264.7 cells. RAW264.7 cells were stimulated with murine interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) to induce M1 macrophages. The different concentrations of SL extracts (high-dose 50 mg x L(-1), moderate-dose 25 mg x L(-1), low-dose 12.5 mg x L(-1)) were added. The CD86 of M1 macrophages in cell membrane was measured by flow cytometry. The mRNA expression of iNOS and TNF-alpha gene was detected by reverse transcription PCR (RT-PCR). And the supernatants were collected, the content of IL-6 and TNF-alpha were detected with ELISA kits. The results of this experiment show that the expression of the cell membrane molecule CD86, iNOS and TNF-alpha gene, the content of IL-6 and TNF-alpha was obviously increased in M1 macrophages by IFN-gamma and LPS. The different doses of SL extract could reduce the expression of the above indicators. The above experimental results demonstrate that IFN-gamma combined LPS can induce RAW264.7 cell to type into M1 macrophages, and SL extracts can inhibit M1 macrophages.

Divergent immunomodulatory effects of extracts and phenolic compounds from the fern Osmunda japonica Thunb / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study possible immunobiological potential of Osmunda japonica Thunb.</p><p><b>METHODS</b>Immunomodulatory effects of ethanol extracts prepared from rhizomes of O. japonica and phenolic compounds isolated from the extracts were investigated under the in vitro conditions using the rat peritoneal cells (2×10(6)/mL; 24 h culture). Biosynthesis of nitric oxide (NO) was assayed by Griess reagent, production of prostaglandin E2 (PGE2) and secretion of cytokines were determined by enzyme-linked immunoabsorbent assay.</p><p><b>RESULTS</b>The extracts activated dose dependently, with the onset at 2.5-5 μmol/L concentrations, the high output NO production, and secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Mild enhancement of NO was produced by the aldehyde-type phenolics 4-hydroxybenzaldehyde and 3,4-hydroxybenzaldehyde. In contrasts, the acetone-type phenolics 4-hydroxybenzalacetone and 3,4-hydroxybenzalacetone inhibited production of immune mediators including cytokines (TNF-α, IL-1β, IL-6), NO, and PGE2. The 3,4-hydroxybenzalacetone was more effective than 4-hydroxybenzaldehyde. The IC50s estimates ranged within the interval of 5-10 μmol/L. No signs of cytotoxicity were observed up to the 50 μmol/L concentration of the compounds.</p><p><b>CONCLUSION</b>Phenolic compounds contained in medicinal herb Osmunda japonica possess distinct immunomodulatory activity.</p>

Study on metabolism of Coptis chinensis alkaloids from different compatibility of Wuji Wan in human intestinal flora / 中国中药杂志

<p><b>OBJECTIVE</b>To study the metabolism of berberine and palmatine in prescription compatibility of Wuji Wan in human intestinal flora.</p><p><b>METHOD</b>The L9 (3(4)) orthogonal design was adopted to compare prescription compatibility of nine groups of Wuji Wan composed of Coptis chinensis, Evodiae and fried Radix paeoniae alba into and single ingredient of C. chinensis. They were cultivated with fresh human excrements under anaerobic conditions for 24 h. A HPLC-UV method was adopted for determining berberine and palmatine in bacteria culture medium, in order to compare the metabolism of the two components in different prescription compatibility.</p><p><b>RESULT</b>Metabolism of berberine was positively correlated with doses, whereas metabolism of palmatine was negatively correlated with doses in extracts from C. chinensis. Compound compatibility speeded up the metabolism of berberine in low dose, which was positively related to the doses of Evodiae and fried Paeoniae Alba Radix; meanwhile Compound compatibility slowed down the metabolism of berberine in high dose, which was negatively related to the dose of Evodiae. Compound compatibility speeded up the metabolism of palmatine in high dose, which was negatively related to the doses of Evodiae and fried Paeoniae Alba Radix.</p><p><b>CONCLUSION</b>The metabolism of the compatibility of Wuji Wan speeds up, when Coptis chinensis components metabolite rapidly in intestinal flora; while the metabolism of the compatibility of Wuji Wan slows down, when C. chinensis components metabolite slowly in intestinal flora. Therefore, they show a balanced effect. Additionally, different proportion of C. chinensis, Evodiae and fried Paeoniae Alba Radix cause difference in metabolism speed of berberine and palmatine to some extent.</p>

Effect of Shenlian extracts on blood flow and vessel pathological changes in rabbits carotid atherosclerosis model induced by low shear stress / 中国中药杂志

Lipid accumulation in the vessel wall and tunica intima vasorum pathological changes are important factors in the development of atherosclerosis, which are closely related with hemodynamics. In this paper, we established a model of local low shear stress in rabbits using carotid artery cannula and a high cholesterol diet for 2 weeks, 4 weeks and 8 weeks. The effects of Shenlian extract on blood flow, vascular pathology formation and lipid metabolism were assessed by electromagnetic blood flow meter and hematoxylin-eosin staining of the proximal end in carotid artery at different times. The results demonstrate that the relationship between blood flow and shear stress for control, atorvastatin, Shenlian extract high-dose, Shenlian extract middle-dose, and Shenlian extract low-dose were linearly related. The blood flow and the shear stress of proximal end in carotid artery of Shenlian extract (1.12, 2.24, 4.48 g x kg(-1)), and atorvastatin (4.7 x 10(-4) g x kg(-1)) were significantly (P < 0.05)increased compared with the control. Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) ,and high density lipoprotein cholesterol (HDL-C) were markedly decreased with the increasing of dose and time. This study is the first to prove that the inhibition of Shenlian extract on low shear stress (LSS) induces rabbits carotid atherosclerosis with increasing blood flow and decreasing lipids and vessel pathological changes.

Absorption of extractive Rhizoma Coptidis in rat everted gut scas / 中国中药杂志

<p><b>OBJECTIVE</b>Using in vitro everted gut seas to research the intestinal absorption of the extractive Rhizoma Coptidis at the different intestinal section and the different density.</p><p><b>METHOD</b>Berberine (BER) and palmatine (PAL) which are representative compositions of the extractive Rhizoma Coptidis in everted gut seas are detected by HPLC, and calculated the absorption parameter to describe the character of absorption.</p><p><b>RESULT</b>The absorption of BER and PAL is linearity in different intestine and different dose, and the square of coefficient correlation exceed 0.9, which consistent with zero order rate process. The K(a) of BER and PAL increases along with the raised dosage of the extractive Rhizoma Coptidis (P < 0.05), indicated it is the passive absorption. The absorption of BER and PAL in the jejunum is the most quick, the ileum and colon are slower.</p><p><b>CONCLUSION</b>In the different dosage of extractive Rhizoma Coptidis, the absorption of BER and PAL Conforms to the zero order rate process at the different intestine, and is the passive absorption.</p>