Mechanism of Toxic Chinese Medicinals Against Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer ranks the seventh and sixth in morbidity and mortality among the malignant tumors， respectively. In traditional Chinese medicine， toxic medicinals are commonly used to enhance the efficacy on esophageal cancer. In recent years， as natural drugs have become the focus of research on anti-tumor drugs， toxic Chinese medicinals have received wide attention. It has been found that a variety of toxic Chinese medicinals have significant anti-esophageal cancer effect. In this study， articles on the treatment of esophageal cancer were retrieved from SinoMed， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP， and the toxic Chinese medicinals in the articles were summarized. It was found that the toxic Paridis Rhizoma， Gekko， Cremastrae Pseudobulbus Pleiones Pseudobulbus， Scolopendra， Hirudo， Sophorae Tonkinesis Radix et Rhizoma， Scorpio， and Bufonis Corium were mainly used for the treatment of this cancer. They can be classified into the heat-clearing and toxin-removing medicinals， toxin-counteracting medicinals， phlegm-resolving medicinals， and blood-activating and stasis-resolving medicinals. Most of them were pungent （19，52.78%） or bitter （17，47.22%）. The majority had the meridian tropism toward liver （25， 69.44%）， spleen （13， 36.11%）， and lung （12， 33.33%）. According to the research on the above commonly used toxic Chinese medicinals， most of them have anti-tumor effect and some have been reported to have anti-esophageal cancer effect. The mechanism is mainly the inhibition of proliferation. To be specific， they exert the anti-cancer effect by suppressing the proliferation， migration， and differentiation of cancer cells， inducing cell cycle arrest， and activating B-cell lymphoma/leukemia-2 （Bcl-2）-associated X protein （Bax）/Bcl-2/Caspase signaling pathway to induce apoptosis. In this paper， the commonly used toxic Chinese medicinals for the treatment of esophageal cancer were statistically analyzed， and the mechanisms were summarized， in order to provide a reference for the clinical rational use of toxic Chinese medicinals and the research on the mechanisms for their efficacy.

Meridian Tropism of Components in Bupleuri Radix Based on Nonalcoholic Steatohepatitis Model and Principal Component Analysis / 中国实验方剂学杂志

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg-1）， XYS-CH group （2.445 g·kg-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.

Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics / 药学学报

The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (Ka) and disassociation constant (Kd), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.

Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: Network-molecular docking-LC-MS analysis / 中西医结合学报

OBJECTIVE@#Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.@*METHODS@#To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.@*RESULTS@#For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.@*CONCLUSION@#RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.

Analysis on Medication Rules of Traditional Chinese Medicine for Treatment of Diabetic Peripheral Neuropathy Based on Clinical Literature / 中国实验方剂学杂志

Objective:To investigate the medication rules of traditional Chinese medicine (TCM) for the treatment of diabetic peripheral neuropathy (DPN).Method:The literature published in China Knowledge Resource Integrated Database (CNKI), Wanfang Database, China Biomedical Literature Service System (SinoMed), VIP Database and PubMeb from 2008 to 2019 were retrieved by setting the topics of diabetic peripheral neuropathy and TCM. After screening, a database was established to analyze the medication rules (efficacy, frequency, flavor and meridian tropism, common couplet medicinals and core medicines) of TCM by frequency statistics, association rules and data statistical methods of constructing complex networks.Result:A total of 461 papers for treatment of DPN were included in this study, including 275 kinds of TCM and a total frequency of 6 361 times. Astragali Radix had the highest frequency. Among all kinds of medicinal materials, activating blood circulation and removing stasis was the most commonly used medicine, followed by Qi-invigorating medicine. Flavor of medicines was mainly sugariness and warm, and most of their meridian tropism was liver meridian. After the analysis by association rules, the couplet medicinals with the highest support was Astragali Radix-Angelicae Sinensis Radix. The core medicines obtained by complex network analysis were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Spatholobi Caulis, Cinnamomi Ramulus, Carthami Flos, Pheretima, Paeoniae Radix Rubra, Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen.Conclusion:This study comprehensively analyzes the medication rules of TCM clinical treatment of DPN. The main treatment methods of TCM for DPN are invigorating Qi and blood, activating blood circulation and removing stasis, activating meridians to stop pain, which can provide guidance for the TCM clinical use and new Chinese medicines research and development of DPN.

Discussion on the academic system of "theory, method, recipe and degree" in s infantile Chinese massage of the western part of Hunan province / 中国针灸

The theory and technique of s infantile Chinese massage of the western part of Hunan province are reviewed in clinical diagnosis and treatment and the core theoretical system is refined. Based on clinical experiences and in consideration of the analysis on relevant literature, the academic system of s infantile Chinese massage of the western part of Hunan province is summarized as four aspects, named "theory, method, recipe and degree". "Theory" refers to the four diagnostic methods and eight principle in terms of diagnosis and treatment and the therapeutic emphasis on the main disorders of organs in children. "Method" refers to promotion and restriction of five elements, meridian tropism in treatment. "Recipe" refers to the selection of acupoints, optimization of therapeutic techniques and the key in the composition of the herbs with different roles considered, named monarch herb, minister herb, assistant herb and guiding herb. "Degree" refers to the strength and intensity of manipulation to ensure the optimal effect. All of the aforementioned reviews provide the reference to theoretic study on this Chinese massage school.

Flavor and meridian tropism classification analysis of Callianthemum taipaicum / 中国中药杂志

To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, >0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.

Relationship between Tissue Distributions of Modified Wuzi Yanzong Prescription () in Rats and Meridian Tropism Theory / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription (, MWP) in rats and meridian tropism theory.</p><p><b>METHODS</b>A high-performance liquid chromatography with Fourier transform-mass spectrometry (HPLC-FT) method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature.</p><p><b>RESULTS</b>Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine.</p><p><b>CONCLUSION</b>The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.</p>

Study on meridian tropism of Evodiae Fructus based on receptors of its secondary metabolites using system biological method / 中草药

Objective Using meridian tropism of Evodiae Fructus as an example, a new method was built based on system biological method to study the tropism of Chinese herbal medicine from the view of secondary metabolites acting with protein receptors. Methods After establishing the complex secondary metabolites compounds-receptors network of Evodiae Fructus, the receptors connecting with at least five compounds were selected. These functions and tissue distribution of receptors were compared with the traditional efficacy and meridian viscera and organs of Evodiae Fructus. Results A total of 34 receptors of secondary metabolites of Evodiae Fructus were acquired. Their functions and distributions were consistent highly with the traditional efficacy and meridian tropism of Evodiae Fructus locating anatomical organs and tissues. Conclusion This original innovation method clearly elucidated the modern scientific material basis and mechanism of the meridian tropism of Chinese herbal medicine from the aspect of component action receptor. Also it will be of important reference value for the study of promoting meridian tropism.

Could Huatuo Jiaji (EX-B 2) Acupoint Be Assigned to the Governor Vessel ? / 针刺研究

The meridian tropism of acupoints is an important academic way to recognize and deal with the relationship between acupoints and meridians in acupuncture medicine. The Huatuo Jiaji (EX-B 2) (Jiaji for short) acupoint family consisting of 34 points has long been considered to be an important extra-acupoint since the ancient times of China and is widely employed in clinical practice through continuous development in Chinese past generations. The present paper introduces 1) historical origin and development of EX-B 2, and 2) intercorrelation among the EX-B 2, spine and the Governor Vessel in anatomical positions. On the basis of these, we also discuss the possibility of that EX-B 2 is assigned to the Governor Vessel, its academic significance including common features and actions in physiological and pathological aspects and clinical significance in diagnosis and treatment of disorders.

Antirheumatic substance and meridian tropism of Loranthus parasiticus based on "syndrome-efficacy-analysis of biological samples" / 中国中药杂志

To study the antirheumatic substance of Loranthus parasiticus and observe the relationship between its in vivo distribution and meridian tropism in rats by establishing adjuvant arthritis models corresponding to effectiveness. All rats except the negative control group were injected with 0.1 mL Freund's complete adjuvant on the left foot. After 8 days, the rats in negative control group and model group were given with normal saline while the rats in positive control group were given with tripterygium glycosides suspension 10 mg•kg-1, and the rats in L. parasiticus treatment groups were given with high(10 g•kg ⁻¹), medium(5 g•kg ⁻¹) and low(2.5 g•kg ⁻¹) dose decoction for 21 days. The left rear ankle joint diameter of rats were measured every 7 days from the 9th day of modeling. On the 22nd day, eyeball blood of part rats in L. parasiticus high-dose group was taken at different time points, and then they were sacrificed to take heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine and brain tissues. For the remaining rats, eyeball blood was taken 30 min after drug treatment, and their left rear ankle joints were taken to detect interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels in serum by ELISA method; rutin, avicularin and quercitrin levels in the tissues of high-dose group were detected by HPLC; pharmacokinetic parameters were analyzed by using DAS 2.0. Our results showed that L. parasiticus decoction could significantly improve the paw edema situation of adjuvant arthritis model rats, and reduce IL-1β and TNF-α levels in rat serum. The in vivo efficacy substance analysis in rats showed that rutin was only present in the stomach with a small amount. AUC0-t of avicularin was stomach > small intestine > kidney, and the duration time in vivo was kidney=stomach > small intestine > lung > heart. AUC0-t of quercitrin was stomach > kidney > liver > heart > lung > spleen > small intestine > brain > large intestine > serum, and the duration time in vivo was kidney=liver=small intestine=brain=lung=spleen=heart=stomach > large intestine > serum. The research indicated that L. parasiticus decoction was effective in treating rats with adjuvant arthritis. Avicularin and quercitrin are important ingredients of L. parasiticus in antirheumatism therapy. The distribution of avicularin and quercitrin in rats were consistent with traditional understanding that L. parasiticus could attribute to the kidney and liver meridians.

Fuzzy Cluster Analysis of Compositae Involved in Effective Patent of TCM Extract Combination on Drug Properties / 中国药房

OBJECTIVE:To classify the drug properties of Compositae involved in effective patent of TCM extract combina-tion. METHODS:Property,flavor and the meridian tropism of TCM were used as the parameters;by computer analysis software, fuzzy cluster analysis was conducted from Compositae mostly involved in effective patent of TCM extract combination which ap-proved before Jan. 1st in 2015 and kept till May 30th in 2015. RESULTS & CONCLUSIONS:27 ingredients of Compositae were involved with the functions as protecting liver almost. They were classified into 5 categories. The first category included 10 ingredi-ents as Dendranthema morifolium which were cold,bitter to taste,and in the liver and lung meridian,and all of them contained flavonoids compounds;the second category included 3 ingredients as Gnaphalium affine of which flavonoids compounds were main medicinal components;the third category included 5 ingredients as Atractylodes lancea which could protect liver and contained vola-tile oil;the forth category included 4 ingredients as Tussilago farfara which showed anti-inflammatory and anti-tumor effect;the fifth category included 5 ingredients as Erigeron breviscapus which contained ingredients for cardiovascular disease. Those catego-ries were similar not only in property,flavor and the meridian tropism,but also in active ingredients and effects. The researchers should further research TCM of which pharmacologic action are not well understood,by means of make reference to known TCM in the same category,and make preparation to save time and enlarge medicinal resource.

Meridian Tropism of Polygoni Avicularis Herba by Tissue Distribution of Avicularin in Rats / 中草药·英文版

Objective To observe the meridian tropism of Polygoni Avicularis Herba by tissue distribution of avicularin in rats.Methods Tissue distribution of avicularin in rat following a single iv administration was appointed and observed.HPLC method was established and validated for the determination of avicularin in rat tissues.Results Kidney and bladder were the most important target tissue of avicularin.Conclusion HPLC method is successfully applied to tissues distribution study of avicularin after iv administration to rats,and the results explain Polygoni Avicularis Herba on bladder tropism reasonably.