Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Pharmacodynamic Substances and Action Mechanisms of Chaihu Shugansan in Antidepressant Treatment： A Review / 中国实验方剂学杂志

Depression is a kind of complex mental illness， which is mainly treated by western medicine at present， but the effect of western antidepressant drugs is not good due to the combined influence of side effects and individual differences of patients. Depression is a "stagnation syndrome" in traditional Chinese medicine， and its treatment principle is to disperse stagnated liver Qi for relieving Qi stagnation. The classic traditional Chinese medicine formula Chaihu Shugansan （CHSGS） has a long history of treating depression and demonstrates significant therapeutic efficacy. Clinically， the addition and subtraction of CHSGS is flexible， but the properties of the active ingredients are vague， and the mechanism and function are unclear. In order to elucidate the pharmacodynamic basis and antidepressant mechanism of CHSGS， this article reviews the pharmacodynamic material basis of CHSGS， clinical research and antidepressant mechanism research progress. Clinically， CHSGS can treat various types of depression such as primary depression， post-stroke depression， and postpartum depression. This article summarizes 32 main ingredients of CHSGS， among which albiflorin， ferulic acid， naringin， hesperidin， saikosaponin a， glycyrrhetinic acid， tangeretin， meranzin hydrate， nobiletin and glycyrrhizic acid are the quality markers （Q-markers） for the antidepressant effect of CHSGS. The antidepressant mechanism of CHSGS is complex， including regulating monoamine neurotransmitters， hypothalamic-pituitary-adrenal （HPA） axis， neurotrophic factors， inflammatory response， cell damage-related pathways， oxidative stress， etc. This article helps to deeply understand the pharmacodynamic basis and mechanism of CHSGS in treating depression， and provides a theoretical basis for the clinical application of CHSGS in treating depression and the development of antidepressant drugs.

Bases científicas del principio de curación homeopática en la farmacología moderna / Scientific bases of the homeopathic healing principle in modern pharmacology

La homeopatía emplea el denominado 'principio de similares' como método terapéutico ­ el cual consiste en administrar medicamentos que provocan ciertos síntomas en individuos sanos para tratar síntomas similares en individuos enfermos (similia similibus curantur) - para inducir una reacción curativa secundaria del cuerpo en contra de sus propios trastornos. Esta reacción secundaria (vital, homeostática o paradójica) del cuerpo se basa en el 'efecto de rebote' de los fármacos modernos, un tipo de evento adverso que se produce después de interrumpir varias clases de fármacos prescritos según el 'principio de los contrarios' (contraria contrariis curantur). Objetivo: La presente revisión ha buscado justificar científicamente el principio de curación homeopática frente a la farmacología clínica y experimental a través de un estudio sistemático del efecto de rebote de los fármacos modernos o reacción paradójica del cuerpo. Métodos: Empleando como referencia estudios y revisiones sobre el tema publicados a partir de 1998, actualizamos los datos añadiendo estudios recientes incluidos en la base de datos PubMed. Resultados: El efecto de rebote se produce después de interrumpir varias clases de fármacos con acción contraria a los síntomas de las enfermedades, exacerbándolos a niveles superiores a aquellos previos al tratamiento. Independientemente de la enfermedad, fármaco, dosis y duración del tratamiento, el fenómeno del rebote se manifiesta en una pequeña proporción de los individuos susceptibles. Siguiendo las premisas homeopáticas, los fármacos modernos también podrían usarse según el principio de la similitud terapéutica, empleando entonces el efecto de rebote (reacción paradójica) con propósito curativo. Conclusiones: Evidenciado por cientos de estudios que constatan la similitud de conceptos y manifestaciones, el efecto de rebote de los fármacos modernos justifica científicamente el principio de la cura homeopática. Aunque el fenómeno de rebote es un evento adverso estudiado por la farmacología moderna, no es conocido por los profesionales de la atención médica, lo cual priva a los médicos de un conocimiento indispensable para el manejo seguro de los fármacos.

Homeopathy employs the so-called 'principle of similars' as therapeutic method - which consists in administering medicines that cause certain symptoms in healthy individuals to treat similar symptoms in sick individuals (similia similibus curantur) - to induce a secondary and healing reaction by the body against its own disorders. This secondary (vital, homeostatic or paradoxical) reaction of the body is based on the 'rebound effect' of modern drugs, a type of adverse event that occurs following discontinuation of several classes of drugs prescribed according to the 'principle of contraries' (contraria contrariis curantur). Aim: The present review sought to scientifically substantiate the homeopathic healing principle vis-à-vis experimental and clinical pharmacology through a systematic study of the rebound effect of modern drugs or paradoxical reaction of the body. Methods: Employing as reference studies and revisions on the subject published since 1998, we updated the data adding recent studies included in database PubMed. Results: The rebound effect occurs after discontinuation of several classes of drugs with action contrary to the symptoms of diseases, exacerbating them to levels above the ones before treatment. Regardless of disease, drug, dose and duration of treatment, the rebound phenomenon manifests in a small proportion of susceptible individuals. Following the homeopathic premises, modern drugs might also be used according to the principle of therapeutic similitude, thus employing the rebound effect (paradoxical reaction) with curative intent. Conclusions: Evidenced by hundreds of studies that attest to the similarity of concepts and manifestations, the rebound effect of modern drugs scientifically substantiates the principle of homeopathic cure. Although the rebound phenomenon is an adverse event studied by modern pharmacology, it is not known by health care professionals, thus depriving doctors of knowledge indispensable for safe management of drugs.

Pharmacodynamic evaluation of Polygonum capitatum nanofiber functional dressing / 中国药房

OBJECTIVE To evaluate the efficacy of the functional dressing of Polygonum capitatum nanofibers （P-PVP-PCL）. METHODS P-PVP-PCL were prepared by electrospinning technology， and the microstructure of P-PVP-PCL was observed. The antibacterial activity and antioxidant activity of P-PVP-PCL and its effects on the survival rate， adhesion and migration rate of mouse fibroblast L929 cells were investigated. The effects of medical gauze dressing， blank nanofiber dressing （PVP-PCL） and P- PVP-PCL on the healing rate of the wound were investigated by establishing the back skin wound model of rats. The pathological changes of the wound tissue and collagen fiber deposition were observed， as well as the number of platelet endothelial cell adhesion molecule-1 （CD31） positive blood vessels and the expression of transforming growth factor-β （TGF-β） protein in wound tissue. RESULTS P-PVP-PCL had a smooth surface and a double-layer structure at the cross-section. The inhibition rates of P-PVP-PCL against Staphylococcus aureus and Escherichia coli were （98.88±0.66）% and （94.75±1.41）% ， respectively. The antioxidant activity of P-PVP-PCL was （83.69±1.56）%， and the cell activity of the P-PVP-PCL group was significantly higher than those of the control group and PVP-PCL group （P＜0.05）. Compared with medical gauze dressings， P-PVP-PCL was more conducive to L929 cell adhesion； at 48 hours， the cell scratches in this group had basically healed. Compared with the medical gauze dressing group， the wound healing rates of the PVP-PCL group and the P-PVP-PCL group were significantly increased （P＜0.05）. On the 14th day of intervention， the wounds in the P-PVP-PCL group had basically healed， there was no dermal necrosis in the wound tissue， and the collagen fibers were arranged relatively neatly and the density was relatively uniform. The number of CD31 positive blood vessels and the expression of TGF-β protein showed a downward trend compared with the 7th day of intervention， and the number of CD31 positive blood vessels was significantly lower than those of the medical gauze dressing group and PVP-PCL group （P＜0.05）， but the protein expression of TGF- β was significantly higher than those of the medical gauze dressing group and the PVP-PCL group （P＜0.05）. CONCLUSIONS P-PVP-PCL has good antibacterial and antioxidant activity in E-mail：444096585@qq.com vitro， and can promote the proliferation， adhesion and migration of L929 cells. It can promote wound healing of rats in vivo.

Preparation of Baoyuan Chewable Tablets and Evaluation of Its Anti-fatigue Effect / 中国实验方剂学杂志

ObjectiveTo screen the preparation technology of Baoyuan chewable tablets and to preliminarily elucidate its anti-fatigue effect and mechanism. MethodTaking encapsulation rate of volatile oil， extract rate and extraction rate of active ingredients as indexes， single factor test and orthogonal test were used to optimize the volatile oil inclusion， aqueous decoction and formulation molding processes of Baoyuan chewable tablets. ICR rats were randomly divided into the blank group， model group， Gaoshan Hongjingtian oral liquids group（6.01 mL·kg-1） and and Baoyuan chewable tablets low， medium， and high dose groups（2.1， 4.2， 8.4 g·kg-1）， 8 mice in each group， and were administered by gastric gavage at the corresponding dose once a day， the blank and model groups were given equal volume of saline for 15 d. After the last administration for 30 min， the mice were loaded with 5% of the body mass of lead at the tail and swam until exhaustion to establish the fatigue model， and the weighted swimming time of the mice in each group was recorded， meanwhile， the muscle tissues of the mice were sliced， stained by hematoxylin-eosin（HE） and subjected to pathological observation， and the levels of blood urea nitrogen（BUN）， lactic acid（LA）， liver glycogen（LG）， activities of lactate dehydrogenase（LDH） and creatine kinase（CK） in the serum were determined. ResultThe optimal inclusion process of cinnamon oil in Baoyuan chewable tablets was 10∶1 for β-cyclodextrin-volatile oil， and inclusion at 50 ℃ for 2 h with saturated aqueous solution method. The optimal water extraction process was to extract twice， adding 10 times of water to extract for 50 min for the first time， and adding 9 times of water to extract for 40 min for the second time. The ratio of the extract of Baoyuan chewable tablets with microcrystalline cellulose， maltodextrin， mannitol， citric acid， magnesium stearate was 63∶13∶8∶17∶17∶1∶1， the tablets were pressed by wet granulation， the each tablet weight was 1.2 g， and the hardness was 60-80 N. Compared with the model group， Baoyuan chewable tablets low， medium， and high dose groups could significantly prolong the exhaustion time of mice in weight bearing swimming（P<0.05， P<0.01）， and improve the exercise endurance of the body， and the results of HE staining showed that all dose groups of Baoyuan chewable tablets could significantly improve the muscle tissue damage caused by exercise， significantly reduce the levels of BUN， LA and the activities of LDH and CK in serum（P<0.01）， and significantly increase the content of LG（P<0.05， P<0.01）. ConclusionThe optimized preparation process of Baoyuan chewable tablets is stable and feasible， and the preparation can improve exercise endurance by increasing the LG level in liver tissue， and relieve muscle soreness by accelerating the removal of LA from the body， and reduce CK and LDH activities to exert anti-fatigue effects.

Advances in metabolomics of cholangiocarcinoma / 药学实践杂志

As a highly malignant tumor, the diagnosis of cholangiocarcinoma (CCA) is often late and the prognosis is poor for which the early symptoms are atypical and the lack of accurate biomarkers. Metabolomics is an emerging science that researches the alterations of all endogenous small molecule metabolites in an organism under the influence of pathological, physiological or genetic modification. The development and progress of CCA is closely related to metabolism. Metabolomic is characterized by global analysis, high throughput and reflects real-time alterations in biology system, providing a new avenue for biomarker screening and diseases diagnosis and treatment. The advances of metabolomics studies on CCA in the recent years were reviewed in this paper which could provide the reference for further research.

Chemical Constituent Analysis of Tongxie Yaofang Decoction by UPLC-LTQ-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo rapidly identify the chemical constituents in Tongxie Yaofang decoction by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap-MS）. MethodChromatographic conditions were ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution （0-4 min， 5%-15%B； 4-10 min， 15%-25%B； 10-15 min， 25%-60%B； 15-20 min， 60%-90%B； 20-25 min， 90%-100%B； 25-27 min， 100%B； 27-30 min， 100%-5%B； 30-32 min， 5%B）， flow rate of 0.3 mL·min-1， column temperature at 35 ℃ and injection volume of 3 μL. UPLC-LTQ-Orbitrap-MS was equipped with an electrospray ionization（ESI）， the MS and MS/MS data were collected in positive and negative ion modes， and detection range was m/z 100-1 250. Combining the reference substance， chemical databases and related literature information， TraceFinder 4.1 and Xcalibur 2.1 were used to identify the chemical constituents of Tongxie Yaofang decoction. ResultA total of 90 compounds， mainly including flavonoids， coumarins， monoterpene glycosides， chromones and lactones， were identified from Tongxie Yaofang decoction. By attributing the sources of Chinese medicines for all identified compounds， 9 of them were found to be derived from Atractylodis Macrocephalae Rhizoma， 21 from Paeoniae Radix Alba， 24 from Citri Reticulatae Pericarpium， 29 from Saposhnikoviae Radix， and 7 from at least two Chinese medicines. ConclusionThe method can effectively， quickly and comprehensively identify the chemical components of Tongxie Yaofang decoction， and clarify the chemical composition. These identified compounds cover the main active ingredients of the four herbs with high abundance， which indicates that the extraction method and the ratio of the medicinal materials of Tongxie Yaofang are scientific， and can provide a reference for the research on the material basis and quality evaluation of this famous classical formula.

Pharmacodynamic Material Basis of Astragali Radix and Angelicae Sinensis Radix Drug Pair in Supplementing Qi and Activating Blood Circulation / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Progress in research methods or strategies of compatibility mechanism of traditional Chinese medicine prescriptions / 中国药房

Compound formulas of traditional Chinese medicines （TCM）， also known as prescription in clinic， refers to a form of medication in which several TCMs are selectively combined according to the certain compatibility principles and the needs of patient’s condition， based on syndrome differentiation and treatment. At present， the methods and strategies for investigating the compatibility mechanisms of TCM prescriptions mainly focus on the following two aspects: analysis of pharmacological substances （including chemical composition analysis of TCM， ingredients of TCM analysis in blood， and pharmacokinetic analysis） and pharmacological signaling pathways analysis （involving network pharmacology analysis， signal pathway indicator detection， and metabolomics analysis）. In future research， the compatibility relationships of TCM prescriptions should be explored according to the principles of “Qiqing Hehe”，“ Shengjiang Fuchen”，“ Junchen Zuoshi”， and “Siqi Wuwei”. The regularity of TCM prescriptions compatibility should be shown in the change regularity of chemical components， pharmacokinetics， pharmacological pathways， and chemical compositions of various ratios of TCMs. Based on the insurance of holistic efficacy of TCM prescriptions， the underlying mechanisms of compatibility should be uncovered， which will provide references for the optimization of clinical applications of prescriptions and new directions for the creation of innovative TCM prescriptions.

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers / 药物分析学报

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups / 中草药·英文版

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.

Historical Evolution and Modern Research Progress of Rehmanniae Radix / 中国实验方剂学杂志

Rehmanniae Radix is a common medicine of traditional Chinese medicine， which has the function of nourishing Yin and tonifying the kidney， and has a long application history of processing. This medicine was first recorded in Synopsis of Golden Chamber （《金匮要略》）， which was mainly produced by steaming and boiling. Its processing materials were diverse. In addition to rice wine， honey， Amomi Fructus， milk， Aquilariae Lignum Resinatum， and Carthami Flos were also recorded in ancient books， but with the evolution of time， the characteristic excipients gradually disappeared. Based on this， starting with different excipients， the author consulted the classics of materia medica and processing specifications in various regions， sorted out the historical evolution of Rehmanniae Radix processing， and explored new methods and new ideas to exert the maximum efficacy on this basis. At the same time， the effects of different processing excipients on the chemical components and pharmacodynamic effects of Rehmanniae Radix were analyzed. After literature review， it was found that Rehmanniae Radix mainly had the effects of clearing heat and cooling blood， nourishing Yin and generating fluid. Its traditional processing excipients generally used rice wine， Carthami Flos and others. After processing with different excipients， there was different effects on the chemical components and pharmacological effects of Rehmanniae Radix. In summary， this paper can provide useful reference for standardized research on different processed products of Rehmanniae Radix.

Molecular Mechanism Analysis of Dengzhan Shengmai Capsules Against Chronic Cerebral Hypoperfusion / 中国实验方剂学杂志

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules （DZSM） on chronic cerebral hypoperfusion （CCH）， network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group， model group， ginaton group （48 mg·kg-1）， DZSM low- and high-dose groups （0.040 5， 0.162 g·kg-1）. The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem， GeneCards， Metascape and other databases were used for targets collection and enrichment analysis. Besides， the association of ingredients targets of DZSM with disease targets of CCH， core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment， the crossing times， time spent in the target quadrant， movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， cytokine-cytokine receptor interaction， tumor necrosis factor （TNF） signaling pathway， blood circulation， angiogenesis， extracellular matrix and other related biological processes and pathways， and acting as targets such as interleukin-6 （IL-6）， TNF， insulin-like growth factor 1 （IGF1）， vascular endothelial growth factor A （VEGFA）， epidermal growth factor （EGF）. The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH， and its multi-component， multi-pathway， multi-target mechanism is also revealed， which provides a basis for further study of the mechanism.

Effect of Two Kinds of Compound Rhizosphere Growth-promoting Bacteria on Growth，Physiological Characteristics and Pharmacodynamic Components of Angelicae Sinensis Radix / 中国实验方剂学杂志

ObjectiveTo study the effects of foliar spraying of two kinds of compound rhizosphere growth-promoting agents on the growth and physiological characteristics of Angelicae Sinensis Radix （ASR）， as well as the pharmacodynamic components， in order to lay a foundation for providing functional microbial agents for ecological cultivation of ASR. MethodThe compound growth-promoting agents T1 （Pseudomonas CBS5， CBS7 and CBSB） and T2 （Bacillus 5C1， 5C5 and 5C7） with the concentration of 1×108 CFU·mL-1 were sprayed on the leaf surface of the field， and the sterile potato glucose broth medium was used as the control （CK）. The plant growth indexes of ASR were measured by conventional methods， the photosynthetic physiological indexes of ASR were measured by portable photosynthetic measurement system， the enzyme activities of plants and microorganisms were measured by kit method， and the endogenous hormone levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry. The contents of ferulic acid， senkyunolide I， coniferyl ferulate， senkyunolide A and Z-ligustilide were determined by high performance liquid chromatography. ResultCompared with CK， the two compound inoculants could promote the growth of ASR and increase the biomass， increase the leaf net photosynthetic rate， stomatal conductance， intercellular CO2 concentration， transpiration rate， increase catalase， peroxidase， superoxide dismutase， polyamine oxidase， diamine oxidase and polyphenol oxidase enzyme activities， increase endogenous jasmonic acid， cytokinin and gibberellin levels in plants， increase the contents of ferulic acid， senkyunolide A and Z-ligustilide， reduce the contents of malondialdehyde and abscisic acid， and reduce the incidence of root rot. ConclusionFoliar spraying of two kinds of rhizosphere compound growth-promoting agents can promote the growth， photosynthesis and stress resistance of ASR， and can improve the quality of ASR in different degrees. Comprehensive analysis shows that T1 treatment is better than T2 treatment in the growth-promoting and quality-enhancing of ASR.

Identification of chemical constituents in Zhachong Shisanwei Pills by UPLC-Q-TOF-MS/MS / 中国中药杂志

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 μm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.

Study on serum pharmacodynamic material basis of Gegen Qinlian Decoction in treatment of ulcerative colitis based on UHPLC-Q-Orbitrap-MS / 中国中药杂志

This study established a mouse model of ulcerative colitis and explored the serum transitional components of Gegen Qinlian Decoction by UHPLC-Q-Orbitrap-MS. Based on the exact relative molecular weight and MS/MS spectrum, 55 prototype components and 59 metabolites were identified from the model group, while 18 prototype components and 35 metabolites from the control group. The prototype components in serum were mainly flavonoids and the characteristic components of the model group were alkaloids. Glucuronidation, sulfonation, and glycosylation have been confirmed to be the main metabolic types in vivo. The results of comparative analysis of differences indicated that puerarin, baicalin, wogonoside, wogonin, chrysin, oroxylin A, berberine, berberrubine, and palmatine were the characteristic components in model state, which at the same time, were confirmed by pharmacological studies to be the serum pharmacodynamic material basis of Gegen Qinlian Decoction in the treatment of ulcerative colitis. This study has provided reference for explaining the metabolic transformation pattern and mechanism of action of Gegen Qinlian Decoction in vivo.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments / 中国中药杂志

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Research progress on pharmacokinetics and toxicity of vinorelbine / 中国药房

Vinorelbine（NVB）is a semisynthetic vinca alkaloid and can play an anti-tumor role by inhibiting the synthesis of tubulin. Its oral preparation has been used in the treatment of a variety of tumors as its convenience and good clinical response. The blood concentration of NVB is closely related to its curative effect and toxicity. Small variations in blood concentration may reduce the curative effect and even produce serious toxicity. There are some risks in the clinical drug use due to limited clinical data and effective pharmacodynamic monitoring methods. By reviewing the relevant literature at home and abroad ，this paper summarizes the research progress of in vivo pharmacokinetics and toxicity of NVB ，fully understands the pharmacokinetic characteristics and influencing factors of NVB ，the influencing factors of toxicity ，and the application status of pharmacokinetics in the adjustment of administration scheme ，so as to provide reference for its clinical rational use.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.