Spectrum-effect relationship of total anthraquinone extract of Cassia seeds against fluorouracil-induced liver injury in mice / 南方医科大学学报

OBJECTIVE@#To investigate the spectrum-effect relationship between the total anthraquinone extract of Cassia seeds and fluorouracil (5-Fu)-induced liver injury in mice and identify the effective components in the extract.@*METHODS@#A mouse model of liver injury was established by intraperitoneal injection of 5-Fu, with bifendate as the positive control. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in the liver tissue were detected to investigate the effect of the total anthraquinone extract of Cassia seeds (0.4, 0.8 and 1.6 g/kg) on liver injury induced by 5-Fu. HPLC fingerprints of 10 batches of the total anthraquinone extracts were established to analyze the spectrum- effectiveness of the extract against 5- Fu- induced liver injury in mice and screen the effective components using the grey correlation method.@*RESULTS@#The 5- Fu- treated mice showed significant differences in liver function parameters from the normal control mice (P < 0.05), suggesting successful modelling. Compared with those in the model group, serum ALT and AST activities were decreased, SOD and T- AOC activities significantly increased, and MPO level was significantly lowered in the mice treated with the total anthraquinone extract (all P < 0.05). HPLC fingerprints of the 31 components in the total anthraquinone extract of Cassia seeds showed good correlations with the potency index of 5-Fu-induced liver injury but with varying correlation strengths. The top 15 components with known correlations included aurantio-obtusina (peak 6), rhein (peak 11), emodin (peak 22), chrysophanol (peak 29) and physcion (peak 30).@*CONCLUSION@#The effective components in the total anthraquinone extract of Cassia seeds, including aurantio-obtusina, rhein, emodin, chrysophanol, and physcion, are coordinated to produce protective effects against 5-Fu-induced liver injury in mice.

Effect of Rhizophagus intraradices on growth of Salvia miltiorrhiza / 中国中药杂志

The study aimed to explore the effects of inoculation of Rhizophagus intraradices on the biomass, effective component content, and endogenous hormone content of Salvia miltiorrhiza through pot experiments. The number of leaves, plant height, dry weight of aboveground and underground parts, branch number, root number, root length, root diameter, and other biomass were mea-sured by weighing and counting methods. The content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, and other effective components was determined by ultra-high performance liquid chromatography. The content of ABA and GA_3 was determined by triple quadrupole mass spectrometry. The correlations between biomass and effective components and between effective components and plant hormones ABA and GA_3 were analyzed. The results showed that R. intraradices significan-tly increased the aboveground dry weight, leaf number, and root number of S. miltiorrhiza by 0.24-0.65 times, respectively. The content of salvianolic acid B and rosmarinic acid in the aboveground part and the content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, and tanshinone Ⅱ_A in the underground part were significantly increased by 0.44-1.78 times, respectively. R. intraradices infection significantly increased the GA_3/ABA values of aboveground and underground parts by 3.82 and 76.47 times, respectively. The correlation analysis showed that caffeic acid, the effective component of the aboveground part, was significantly positively correlated with plant height, tanshinone Ⅱ_A, the effective component of the underground part, was significantly positively correlated with biomass root number, cryptotanshinone, and dry weight, while rosmarinic acid was significantly negatively correlated with dry weight. There were significant positive correlations between cryptotanshinone and ABA, tanshinone Ⅱ_A and ABA and GA_3, and caffeic acid and GA_3. In conclusion, R. intraradices can promote the accumulation of biomass and secondary metabolites of S. miltiorrhiza and regulate the balance between plant hormones ABA and GA_3, thereby promoting the growth of S. miltiorrhiza.

Analysis on Material Basis of Anti-COPD Effect of Euphorbia helioscopia Based on Serum Pharmacochemistry and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C18 column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.

Research progress on effective components，pharmacological mechanisms and clinical use of Polyporus umbellatus in diuresis-promotion and dampness-clearance / 中国药房

Polyporus umbellatus， as a traditional Chinese medicine for promoting diuresis and clearing dampness， mainly contains steroids and polysaccharides. It is usually used to treat diseases of urinary system. In this paper， the research progress of the effective components， pharmacological mechanisms and clinical use of P. umbellatus in diuresis-promotion and dampness- clearance is reviewed. Steroids such as ergosterone， peroxyergosterone， ergosta-7，22-dien-3-one and P. umbellatus polysaccharide PPS1， PPS2， PPS3， GUMP-1-1 and GUMP-1-2 promote diuresis and eliminate dampness through diuresis， renal protection， anti- inflammatory， bacteriostatic and immunomodulatory effects. Traditional Chinese medicine compound preparations such as P. umbellatus powder， P. umbellatus decoction， and Wuling powder have significant effects in treating urinary tract infections， lithiasis， renal edema and lesions， which providing reference for the further development and application of P. umbellatus.

Lipid-lowering Effect of Active Components in Common Chinese Medicine： A Review / 中国实验方剂学杂志

Dyslipidemia is a common metabolic disease caused by abnormal lipoprotein metabolism in human body. According to pathogenesis， it is divided into primary dyslipidemia and secondary dyslipidemia. The former is caused by genetic defects， and the latter is caused by diseases， drugs， unhealthy diets， and lifestyle. The clinical manifestations are xanthoma， arteriosclerosis， and other symptoms of coronary heart disease and peripheral vascular disease. Dyslipidemia can cause a variety of diseases， such as cardiovascular disease， diabetes， and cancer， seriously threatening people's quality of life and life safety， so the research on drugs against dyslipidemia is more urgent. In spite of manifest efficacy， chemical antilipemic agents such as lovastatin are accompanied by some adverse reactions， and there is recurrence after drug withdrawal. Compared with chemical drugs， Chinese medicine has the advantages of multi-pathway， multi-target， multi-level regulation of dyslipidemia， with few side effects. Modern medical research has shown that Chinese medicine can affect lipid synthesis， decomposition， and absorption and improve liver lipid and bile acid metabolism by regulating the peroxisome proliferator-activated receptor （PPAR） signaling pathway， AMP-activated protein kinase （AMPK） signaling pathway， cyclic adenosine monophosphate （cAMP） signaling pathway， adipocytokine signaling pathway， farnesoid X receptor （FXR）/small heterodimer partner （SHP） signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， etc.， thereby exerting a role in lowering lipid. Therefore， this paper summarized the mechanism of effective components in Chinese medicine in lowering blood lipid to provide new ideas and a theoretical basis for the prevention and treatment of lipid metabolic diseases by Chinese medicine in clinical practice.

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract / 中国天然药物

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.

Content Difference of Effective Components of Cynomorii Herba Between Different Producing Areas and Its Response to Environmental Factors / 中国实验方剂学杂志

ObjectiveTo explore the content difference of gallic acid，protocatechuic acid，catechin，total flavonoids， and total polysaccharides in Cynomorii Herba between different producing areas and the correlation between effective components and environmental factors. MethodNinety-five batches of Cynomorii Herba samples were collected from 12 major producing areas in five provinces （autonomous regions）， including Gansu，Inner Mongolia，Xinjiang，Qinghai， and Ningxia，and the geographical-climatic factors such as altitude，longitude and latitude，climate type，annual average frost-free period，annual rainfall，annual sunshine hours，annual average temperature， and annual average evaporation were recorded. The content of gallic acid，protocatechuic acid， and catechin in Cynomorii Herba was determined by high-performance liquid chromatography （HPLC），and the mathematical model of the correlation between the content of chemical components and environmental factors was optimized and established. ResultPearson correlation analysis showed that protocatechuic acid content in Cynomorii Herba increased with the increase in annual average frost-free period and annual average temperature， and catechin content increased with the increase in the annual average frost-free period，annual sunshine hours， and annual average evaporation，while total polysaccharides content decreased with the increase in altitude. Redundancy analysis （RDA） showed that the annual average frost-free period， annual average evaporation，annual sunshine hours， and altitude had great influences on the content of effective components in Cynomorii Herba. Curve fitting showed that the optimal conditions for the growth of Cynomorii Herba were as follows： altitude of 800-2 000 m，annual average frost-free period of 80-110 d， annual rainfall of 110-300 mm，annual sunshine hours of 2 400-3 000 h， annual average temperature of 2.2-8.8 ℃，and annual average evaporation of 1 700-2 500 mm. ConclusionThe content of effective components in Cynomorii Herba is diverse in terms of producing areas and shows a clear response rule to environmental factors. The areas suitable for growing and artificial cultivation introduction are those with high altitude，short annual average frost-free period，low annual rainfall，large average evaporation，long sunshine hours， and low annual average temperature.

Research progress on effective components and mechanisms of anti-depressive Chinese medicine / 中国中药杂志

Since the pathogenesis of depression is complicated, the therapeutic effects of western medicine are poor accompanied by severe side effects. Chinese medicine has unique advantages in the treatment based on syndrome differentiation and contains many effective components against depression, including flavonoids, terpenes, phenylpropanoids, quinones, and alkaloids. These chemical components can delay the course of the disease, improve the curative effect, and reduce side effects of western medicine by regulating the biochemical abnormalities of monoamine neurotransmitters, brain tissue protein content, and internal environment as well as energy metabolism to make the treatment of Chinese medicine highlighted and recognized. This study systematically reviewed the effective components and mechanisms of anti-depressive Chinese medicine to inspire the rational development and utilization of new Chinese medicines against depression.

"Six-step strategy" for effective compounds in Chinese medicinal prescriptions based on in vitro-in vivo integration and its application in research on component-based Chinese medicine / 中国中药杂志

The discovery and identification of effective components are pivotal in the research on Chinese medicinal prescriptions. Given two basic conditions for effective components in Chinese medicinal prescriptions, i.e., active structure and a certain level of drug exposure in the body(including the intestine), a "six-step strategy" for the effective compounds in Chinese medicinal prescriptions based on in vitro-in vivo integration(SSS for short) has been proposed and established, as well as the key technologies. SSS contains qualitative and quantitative analyses of components in five steps, including those in Chinese medicinal extract, intestinal contents, portal vein blood, liver, and peripheral blood. The components(prototype components and metabolites) with a certain exposure level(including in the intestine) and those with large differences between in vitro content and in vivo exposure or in exposure among various parts in the body are selected as the minority prioritized candidates. The sixth step is to screen the pharmacological activity of candidate components specifically extracted from Chinese medicinal materials or artificially synthesized. SSS can significantly narrow the screening range, enhance the hit rate, and speed up the identification of effective components specifically targeting indications. Based on the effective components identified by the SSS, the "upstream" can be linked(mechanism research based on the effective components with clear structures) and the "downstream" can be combined(development of innovative component-based Chinese medicine with definite pharmacodynamic composition). In this study, the concept of component-based Chinese medicine and specific applications of SSS in the development of component-based Chinese medicine are also introduced.

Screening of effective antioxidant components from Trichosanthes extract and assessment of their antioxidant activity / 南方医科大学学报

OBJECTIVE@#To screen the effective antioxidant components in Trichosanthes extract based on the mean value of Deng's correlation degree and assess the antioxidant activity of the identified components.@*METHOD@#High-performance liquid chromatography (HPLC) was used to obtain the fingerprints of Trichosanthes extract, and the clearance rates of DPPH · and O2-· by 3, 9 and 27 mg/mL Trichosanthes extract were determined. The antioxidant spectrum effect of Trichosanthes extract was analyzed by calculating the mean value of Deng's correlation degree to screen the effective antioxidant component group. According to the contents of each known components in the antioxidant effective component group, mixed solutions of the components were prepared and tested for their clearance rates of DPPH · and O2-·.@*RESULTS@#The 36 common peaks in HPLC fingerprints of Trichosanthes extract showed different degrees of correlation with DPPH · and O2-· clearance. The common peaks with a correlation degree greater than the median value included peaks 21, 36, 8, 31, 14, 5, 27, 2, 24, 15, 18, 33, 22, 34, 35, 19, 28 and 25. The 5 components, namely kaempferol (peak 36), isoquercitrin (peak 8), luteolin (peak 31), rutin (peak 5) and apigenin (peak 35), were tentatively identified to constitute the effective antioxidant component group with a mass ratio 3∶2∶2∶ 1∶1 in Trichosanthes extract. The prepared mixed solutions of antioxidant effective component group (6.12, 2.04, and 0.68 μg/mL) showed clearance rates of DPPH · of 65.4%, 64.0% and 61.0%, and clearance rates of O2-· of 12.9%, 9.5% and 8.3%, respectively.@*CONCLUSION@#We identified the material basis for the antioxidant activity of Trichosanthes and screened the antioxidant effective component group in Trichosanthes extract.

New Progress in Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Diabetes and Its Complications / 中国实验方剂学杂志

Diabetes is a worldwide public health problem that seriously threats human health. Long-term metabolic disorders， as the main cause of multi-system complications and death in the later stage of diabetes， can cause multi-system damage， leading to chronic progressive lesions in the eyes， kidneys， nerves， heart， blood vessels and other tissues and organs， as well as functional decline and failure. The low risk of side effects and new treatment strategies remain an area to be explored in clinical treatment of diabetes. Salviae Miltiorrhizae Radix et Rhizoma （SM） is one of the commonly used herbs in traditional Chinese medicine （TCM）， with the main effect of activating blood circulation and removing blood stasis. In recent years， it has been found that SM shows good performance in lowering blood sugar and treating diabetes complications. Data mining information has also shown that the drugs of activating blood circulation and removing blood stasis are now common drugs in clinical treatment of diabetes， and SM has the highest use frequency， with significant curative effect. In addition， TCM is a kind of treatment with composite components and multiple targets， and so people are increasingly interested in its effective components and carry out extensive researches. This article summarized the experimental verification of SM extract and its components （tanshinone A， tanshinone B， tanshinone ⅡA， tanshinone I， protocatechuic aldehyde， polysaccharide， and total polyphenol acid） in various diabetes models in improving glucolipid metabolism， improving heart function in patients with diabetes， alleviating the motor and sensory deficits caused by diabetes， preventing the occurence of the diabetic retinopathy， recovery of liver and kidney structure and function damage in diabetic patients， and helping to resist high sugar-induced atrophic cavitation potential. It may inhibit hyperglycemia-induced vascular injury with polyol pathway activation， reduce the formation of advanced glycation end products， inhibit protein kinase C pathway activation and hexosamine pathway activation， and alleviate oxidative stress caused by excessive production of peroxides in mitochondrial electron transport chain during hyperglycemia to play a role of treatment， and provide reference for clinical application.

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice / 中国中药杂志

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Review on factors influencing separation and purification of Chinese materia medica components by macroporous adsorption resin / 中草药

In recent years, macroporous adsorption resin has been widely used in the purification and separation of natural medicine and effective components of Chinese materia medica, the purification of compound Chinese medicine preparations, the removal of harmful impurities due to the advantages of stable physical and chemical properties, high selectivity, strong adsorption capacity and easy elution, recyclable use and regeneration treatment, economic and environmental protection, convenient preparation molding and so on. By summarizing the preparation, properties, classification and working principle of macroporous adsorption resin, the influencing factors and purification process of Chinese materia medica components were reviewed. The purpose of this paper is to explore the important factors affecting the purification of Chinese materia medica components by macroporous adsorption resin, and provide reference for improving the purification effect of Chinese materia medica components.

Influences of ancient processing method steaming with black bean and drying and pharmacopoeia processing method continuous steaming with black bean decoction on 12 components of Polygoni Multiflori Radix / 中草药

Objective: To explore the influence of ancient processing method black bean "nine cycles of steaming and drying" and modern pharmacopoeia processing method continuous steaming with black bean decoction on the main components of Polygoni Multiflori Radix (PMR). Methods: Simulating the time arrangement of "nine cycles of steaming and drying", samples were prepared using three processing methods: ancient method that raw PMR (rPMR) and black bean were steamed in layers and then dried, modern method that rPMR were steamed with black bean decoction and then dried, the method recorded in Chinese Pharmacopoeia that rPMR were steamed continuously with black bean decoction; The determination method of 12 components in rPMR and processed PMR (pPMR) was established using ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UPLC-QqQ-MS/ MS), and 12 components in all samples processed by different methods were determined; The results was analyzed combining with t test, principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). Results: A reliable UPLC-QqQ-MS/MS method was established for the determination of emodin, physcion, rhein, emodin-8-O-β-D-glucoside, physcion-8-O-β-D-glucoside, cis-2,3,5,4'-tetrahydroxylstilbene-2-O-β-D-glucoside (cis-THSG), trans-2, 3,5,4'-tetrahydroxylstilbene- 2-O-β-D-glucoside (trans-THSG), polydatin, resveratrol, epicatechin, rutin and hyperoside. With the prolongation of steaming time, the content of 12 effective components changed obviously: the content of free anthraquinone was decreased first and then increased; The content of anthraquinone glycoside, cis-THSG, polydatin and hyperoside was increased first and then decreased; The content of trans-THSG, resveratrol, epicatechin and rutin was decreased; The components content were closely related to the auxiliary materials, steaming operation methods and processing time, the influence of operation methods was greater than that of auxiliary materials on the quality of pPMR. Conclusion: The ancient processing method steaming with black bean and drying could not be equated with the modern pharmacopoeia processing method continuous steaming with black bean decoction in terms of the content of effective components. The result provides experimental basis for inheriting and developing the traditional processing method of PMR.

Effect of Zengmian Yiliu Formula and Its Effective Components on Notch/Jagged1 Signaling Pathway of Ovarian Cancer Stem Cell Transplanted Tumor in Nude Mice / 中国实验方剂学杂志

Objective:To observe the effect of Zengmian Yiliu （ZMYL） formula and its effective components （PAWU） on the growth inhibition of ovarian cancer stem cell transplanted tumor in nude mice and the Notch signal receptor （Notch） / Notch signal ligand 1 （Jagged1） signal pathway in tumor tissue. Method:Ovarian cancer stem cells were cultured in serum-free suspension to establish the transplanted tumor model of ovarian cancer stem cells in nude mice， and then divided into model group， ZMYL group （36 g·kg-1）， PAWU group （5.8 g·kg-1）， cisplatin （DDP） group （2.5 g·kg-1）， and PAWU （5.8 g·kg-1） + DDP group （2.5 mg·kg-1）.After successful modeling， the drugs were given by gavage for 21 days.To observe the effect of Zengmian Yiliu decoction and its effective components on tumor weight in nude mice， the morphological changes of tumor cells were observed under light microscope， immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were used to detect the expressions of Notch 1， Jagged1， Hairy and enhancer of split 1 （Hes1） protein and mRNA in tumor tissues. Result:The tumor inhibition rates of ZMYL， PAWU， DDP and combination groups were 35.91%， 32.94%， 57.65% and 69.05%， respectively.Compared with the model group， the tumor weight of ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with PAWU group， the tumor weight of combination groups decreased significantly （P<0.05）.Immunohistochemistry showed that compared with the model group， the positive expressions of Notch1， Jagged1 in ZMYL group， PAWU group， DDP group and combination groups were down-regulated （P<0.05），and the positive expressions of Hes1 in ZMYL group， DDP group and combination groups were down-regulated （P<0.05）.Compared with combination groups， the positive expressions of Notch1， Jagged1 and Hes1 in ZMYL group， PAWU group， DDP group were up-regulated （P<0.05）. Real time PCR showed that compared with the model group， the expressions of Notch1 mRNA in ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with model group， the expressions of Jagged1 and Hes1 mRNA in ZMYL group， PAWU group and combination groups decreased significantly （P<0.05）.Compared with DDP group， the expressions of Notch1， Jagged1 and Hes1 mRNA in combination groups decreased significantly （P<0.05）. Conclusion:The growth of ovarian cancer stem cells transplanted in nude mice can be inhibited by Zengmian Yiliu formula and its effective components.The effective components have a significant synergistic effect in the combination with cisplatin.Its mechanism is correlated to the inhibition of Notch/Jagged1 signaling pathway activation.

Research progress on effective components of Chinese materia medica in regulating autophagy / 中国中药杂志

Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.

Genetic Diversity and Association Analysis between Medicinal Components and ISSR Markers in Astragali Radix / 中国药学杂志

OBJECTIVE: To study and exploit Chinese medicine Astragali Radix, the molecular markers that relates to the phenotypic traits on medicinal components of Astragali Radix and would be detected. METHODS: The genetic diversity of 43 Astragali Radix samples was analyzed with ISSR molecular marker technique and then the population genetic structure was studied through 13 selected markers. The association analysis between ISSR markers and 4 phenotypic traits of medicinal components were performed with GLM (general linear model) programs in Tassel 2.1. Certain genetic diversity was discovered among the 43 Astragali Radix samples. RESULTS: The genetic distance varied between 0.050 6 and 0.743 8, with an average of 0.274 1. Moreover, the cultivated Astragali Radix from Ningxia and Gansu province closely related to the wild Astragali Radix collected from Liupanshan town in Ningxia. On the other hand, No. 340 had the farthest relationship with other Astragali Radix. The content of polysaccharide, total saponins, total flavonoids, and Astragaloside IV ranged between 7.693-27.840 mg•g-1, 7.167-17.579 mg•g-1, 2.212-6.164 mg•g-1 and 6.070-107.920 μg•g-1, respectively. Meanwhile, linear regression analysis indicated that there was a significant positive correlation between the content of the total saponins and that of flavonoids (r=0.650 5,P=2.3×10-6<0.01), while the content of astragaloside had no significant correlation with that of polysaccharide, total saponins and total flavonoids. The population genetic structural analysis showed that the 43 samples were divided into 4 subgroups. There were total of 34 locus in 13 ISSR markers significantly associated (P<0.01) with the content of polysaccharide,total saponins, flavonoids and astragaloside , and the rate of explanation on the phenotype of related marker ranged from 8.14% to 51.39%. Among the locus, 15 were related with astragaloside content at interpretation rates above 30%, 1 with polysaccharide content an interpretation rate reached as high as 51.39% with high threshold (P<1×10-5). CONCLUSION: These results would provide supporting evidence for identification and protection of germplasm resources as well as molecular marker-assisted breeding.

Network pharmacological analysis of Chaihu Guizhi Decoction for treating different diseases with same method on gastric ulcer and epilepsy / 中草药

Objective: Under the guidance of traditional Chinese medicine theory, this paper used network pharmacology model to explore the effective components and mechanism of “treating different diseases with same method” of Chaihu Guizhi Decoction (CHGZD) in treating gastric ulcer and epilepsy, which provided modern medical evidence for the theory of “treating different diseases with same method” of traditional Chinese medicine. Methods: The chemical constituents and potential targets of CHGZD were collected by TCMSP and TCMID databases. Disease targets of gastric ulcer and epilepsy were obtained in PubMed, CTD, and OMIM databases. Cytoscape 3.6.0 software was used to map CHGZD for gastric ulcer and epilepsy. The pharmacodynamic basis and molecular mechanism of the “treating different diseases with same method” network, and the functional and pathway enrichment analysis of gene targets was analyzed by DAVID 6.8 and KOBAS 3.0. Results: A total of 198 kinds of chemical constituents, 417 target targets, 114 gastric ulcer disease targets, and 461 epileptic disease targets were collected from CHGZD. Network analysis showed that 152 active components such as quercetin, beta-sitosterol, wogonin, kaempferol, and saikosaponin a in CHGZD played a role in the treatment of gastric ulcers and epilepsy through 17 common targets including PTGS2, VEGFA, TP53, IL6, and TNF, and 62 pathways such as pathways in cancer, and proteoglycans in cancer. Conclusion: The similar efficacy network composed of 17 common targets in gastric ulcer and epilepsy was the basis for CHGZD to play the role of “different disease and common treatment”. A total of 152 components work together through 62 pathways and 17 pathways to achieve the effect of “treating different diseases with same method”, which provides modern medical evidence for the traditional Chinese medicine to treat gastric ulcer and epilepsy from the liver and spleen.

Study on effective components and mechanism of Dachaihu Decoction in treatment of pancreatitis (syndrome of liver depression and qi stagnation) / 中草药

Objective: To study the effective components and mechanism of action of Dachaihu Decoction (DCHD) in the treatment of pancreatitis (syndrome of liver depression and qi stagnation). Methods: The PPI network and the multi-dimensional relationship network of “Chinese material medica prescription active ingredient key target” of DCHD in the treatment of pancreatitis with stagnation of liver qi. Based on network pharmacology, the software such as Cytoscape 3.6.0 was firstly used to construct the PPI interaction network of key targets in the Chinese material medica with the effect of soothing liver and regulating qi (“Shugan Liqi” in Chinese) and DCHD “Chinese material medica prescription-effective components-key target” multi-dimensional network for the treatment of pancreatitis, and then treat the two networks as an intersection to obtain the network of DCHD for the treatment of pancreatitis (syndrome of liver depression and qi stagnation) “Chinese material medica prescription-effective components-key target”, and finally analyzed with relevant software. Results: A total of 59 key targets for Shugan Liqi were obtained such as AKT1, VEGFA, and PRSS1; A total of 83 main active ingredients such as quercetin, kaempferol and baicalein were collected from DCHD. The treatment of pancreatitis (syndrome of liver depression and qi stagnation) involved 18 targets of Ganyu Qizhi such as PTGS2, DPP4, PRSS1, and 30 related biological processes and signaling pathways such as extracellular matrix degeadation, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: The multi-component and multi-target in DCHD are the basis for its efficacy. It is worthwhile to deeply think about the use of network pharmacology in the context of syndrome research.

Effect of Intestinal Flora in Rats on Metabolism and Transformation of Effective Components in Polygonum orientale Inflorescences / 中国实验方剂学杂志

Objective:To observe the metabolic characteristics of effective components from Polygonum orientale inflorescences in intestinal flora of rats. Method:The incubating samples of effective components from P. orientale inflorescences in rat intestinal flora in vitro were detected by UPLC-ESI-Q-TOF-MS/MS, the mobile phase was consisted of 0.1%formic acid solution-0.1%formic acid acetonitrile solution and eluted in gradient mode at a flow rate of 0.3 mL·min-1.The mass spectral analysis was detected with electrospray ionization under positive ion mode and negative ion mode.The metabolites and possible biotransformation pathways of effective components form P. orientale inflorescences in rat intestinal flora in vitro was analyzed by Metabolite ToolsTM, mass defect filtration(MDF) and other metabolite analysis techniques and combined with the accurate relative molecular weight of the compounds, the fragment ion information and the literature data. Result:Eighteen metabolites were detected after incubation of effective components from P. orientale inflorescences in rat intestinal flora.The main biotransformation pathways were reduction, oxidation, hydrolysis in Ⅰ phase reaction and methylation in Ⅱ phase reaction. Conclusion:The effective components of P. orientale inflorescences can be transformed into a variety of metabolites under the action of intestinal flora in rats.It is suggested that whether the metabolites are bioactive components should be considered when P. orientale inflorescences is used as medicine.