Chemical profiling and rapid discrimination of Blumea riparia and Blumea megacephala by UPLC-Q-Exactive-MS/MS and HPLC / 中草药·英文版

OBJECTIVE@#To rapidly identify the two morphologies and chemical properties of similar herbal medicines, Blumea riparia and B. megacephala as the basis for chemical constituent analysis.@*METHODS@#UPLC-Q-Exactive-MS/MS was utilized for profiling and identification of the constituents in B. riparia and B. megacephala. Chemical pattern recognition (CPR) was further used to compare and distinguish the two herbs and to identify their potential characteristic markers. Then, an HPLC method was established for quality evaluation.@*RESULTS@#A total of 93 constituents are identified, including 54 phenolic acids, 35 flavonoids, two saccharides, one phenolic acid glycoside, and one other constituent, of which 67 were identified in B. riparia and B. megacephala for the first time. CPR indicates that B. riparia and B. megacephala samples can be distinguished from each other based on the LC-MS data. The isochlorogenic acid A to cryptochlorogenic acid peak area ratio calculated from the HPLC chromatograms was proposed as a differentiation index for distinguishing and quality control of B. riparia and B. megacephala.@*CONCLUSION@#This study demonstrates significant differences between B. riparia and B. megacephala in terms of chemical composition. The results provide a rapid and simple strategy for the comparison and evaluation of the quality of B. riparia and B. megacephala.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification / 中国天然药物

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.

Chang Wei Qing Decoction enhances the anti-tumor effect of PD-1 inhibitor therapy by regulating the immune microenvironment and gut microbiota in colorectal cancer / 中国天然药物

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.

Prediction of CW chord after cataract surgery from IOL Master 700 measurement data based on SVR algorithm and BP neural network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes in the Chang-Warning chord(CW chord)before and after cataract surgery using the IOL Master 700 and predict the CW chord using an artificial intelligence prediction model and preoperative measurement data.METHODS: The analysis was conducted on the preoperative and postoperative IOL Master 700 measurements of 304 cataract patients. This included astigmatism vector value, average keratometry, axial length, anterior chamber depth, lens thickness, corneal central thickness, white-to-white, the position of the Purkinje reflex I image relative to the corneal center and pupil center, and the CW chord. A prediction model based on the SVR algorithm and the BP neural network algorithm was established to predict the postoperative CW chord using the preoperative CW chord and ocular biological parameters.RESULTS: The X component of the CW chord showed a slight shift in the temporal direction in both the left and right eyes after cataract surgery, while the Y component changed little. The SVR model, using the preoperative CW chord and other preoperative biometric parameters as input data, was able to predict the X and Y components of the CW chord more accurately than the BP neural network.CONCLUSION: The CW chord can be directly measured with a coaxial fixation light using various biometers, corneal topographers, or tomographers. The use of the SVR algorithm can accurately predict the postoperative CW chord before cataract surgery.

Mechanism of effect of Zhuang medicine Semiliquidambar cathayen. Sis Chang on depression inflammation based on network pharmacology, molecular docking and animal experiments / 中国药理学通报

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.

Effect and mechanism of matrine on steatosis Chang Liver cells induced by oleic acid / 中国药房

OBJECTIVE To investigate the effects of matrine （MT） on steatosis Chang Liver cell model induced by oleic acid （OA） and its possible mechanism. METHODS Chang Liver cells were divided into blank group， model group and MT low-dose， medium-dose group and high-dose groups （0.1， 0.5， 1.0 mmol/L）. Except for blank group， the other groups were treated with 1.0 mmol/L OA for 24 h to establish steatosis model， and MT groups were given corresponding concentrations of drugs for 24 h. The activities of steatosis Chang Liver cells were observed； the morphologies of intracellular lipid droplets were observed and lipid content was also determined. The contents of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）]， as well as mRNA and protein expressions of farnesoid X receptor （FXR）， cytochrome P450 7A1 （CYP7A1） and fibroblast growth factor 19 （FGF19） were all detected. RESULTS OA and MT had no significant effect on the activity of Chang Liver cells. After OA treatment， orange lipid droplets formed in cytoplasm； compared with blank group， relative lipid content and the levels of liver function indexes were increased significantly， while the mRNA and protein expressions of FXR， CYP7A1 and FGF19 were down-regulated significantly （P＜0.05）. After treatment of low， medium and high concentrations of MT， above indexes were all reversed significantly （P＜0.05）. CONCLUSIONS MT could significantly improve the lipid content and liver function indexes of steatosis Chang Liver cells induced by OA though regulating FXR/CYP7A1/ FGF19 signaling pathway.

Cathayanalactone G and other constituents from leaves and twigs of Callicarpa cathayana / 中草药·英文版

Objective: To study the chemical constituents from the leaves and twigs of Callicarpa cathayana. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel, MCI gel CHP 20P/P120, Sephadex LH-20, and HPLC. The structures of the compounds were determined by HR-ESI-MS, 1D and 2D NMR data. Results: A total of 24 compounds were isolated from the 85% methanol extract of leaves and twigs of C. cathayana. They were identified as cathayanalactone G (1), a new diterpene, and 23 known compounds as patagonic acid (2), (-)-16-hydroxycledroda-3,13-dien-16,15-olide-18-oic acid (3), 15-methoxypatagonic acid (4), oleanolic acid (5), ursolic acid (6), siaresinolic acid (7), pomolic acid (8), α-amyrin (9), tormentic acid (10), lupeol (11), 5,7-dihydroxy-3,4′-dimethoxyflavone (12), 5,4′-dihydroxy-3,7,3′-dimethoxyfla-vone (13), 5-hydroxy-3,6,7,4′- tetramethoxyflavone (14), salvigenin (15), kaemferol (16), astragalin (17), pinoresinol 4-O-β-D-glucopyranoside (18), paulownin (19), β-sitosterol (20), β-sitosterol β-D-glucopyranoside (21), 5-hydroxy-coumarin (22), isocopoletin (23), and 4-hydroxycinnamic acid (24). Conclusion: Compound 1 is a new labdane diterpene. Compounds 10, 13, 16 and 17 are isolated from the genus Callicarpa for the first time. Compounds 7, 8, 9, 12, 14, 23 and 24 are reported from C. cathayana for the first time.

Comparative authentication of Semiliquidambar cathayensis and its substituted species via macroscopic and microscopic features / 中草药·英文版

Objective: Ban Fenghe recorded in the Quality Standard of Yao Medicine of Guangxi Zhuang Autonomous Region (Volume 1) is derived from the dried stems and leaves of Semiliquidambar cathayensis. It is usually confused with medicinal herbs from Pterospermum heterophyllum and Dendropanax dentiger. However, they are very different in chemical composition, and should not be used as the same drug. To ensure their safety and efficacy, a method based on macroscopic and microscopic characteristics was developed to distinguish them. Methods: A total of 14 batches of Ban Fenghe samples from three species were collected from different producing areas in China. The macroscopic characteristics were examined by observing external traits. The tissue structures of transverse sections of stems and leaves, the leaf epidermis, and the powder were observed microscopically. Results: The branchlets and leaf surfaces of S. cathayensis and P. heterophyllum were hairy, especially the lower leaf surfaces of P. heterophyllum were densely covered with hairs, but those of D. dentiger were hairless. The pericyclic fibers of S. cathayensis stems were intermittently distributed in a circular shape and accompanied by stone cells, whereas those of P. heterophyllum and D. dentiger were bundled without stone cells. So stone cells and hairs were present in S. cathayensis powder, stone cells were not found in P. heterophyllum and D. dentiger powder, and hairs were not present in D. dentiger powder. The distribution sites, sizes and types of secretory tissues of these three species were also different in transverse sections of stems and leaves. Stomata on the lower epidermis of S. cathayensis leaves were paracytic, whereas those of P. heterophyllum and D. dentiger were anomocytic. Conclusion: Ban Fenghe drugs derived from S. cathayensis could readily be distinguished from those of P. heterophyllum and D. dentiger by macroscopic and microscopic features.

Perioperative symptom changes of 104 cases of myasthenia gravis / 中国综合临床

Objective:To discuss the perioperative symptom change rule of patients with myasthenia gravis(MG), and to provide a theoretical basis for preventing and reducing the surgical risk of patients with MG.Methods:The clinical data of 104 patients who underwent thymectomy in the Department of Thoracic Surgery of the Second Affiliated Hospital of Zhengzhou University from 2015 to 2019 were retrospectively analyzed. According to the degree of the impact of MG symptoms on the body's physiology and life, the "MG dynamic classification standard" was formulated, which was divided into type 0-type Ⅳ according to the severity of MG symptoms. The symptoms of each patient of "admission", "preoperative" and "postoperative" are classified according to the "dynamic classification criteria", and the number of "admission", "preoperative" and "postoperative" were counted respectively. Based on the statistical analysis of each patient's type changes, the perioperative symptom changes of myasthenia gravis patients were summarized.Results:1. "Admission" classification: 12 cases of type 0, 42 cases of type Ⅰ, 32 cases of type Ⅱ, 12 cases of type Ⅲ, 5 cases of type Ⅳa, and 1 case of type Ⅳb. 2. "Preoperative" classification: 44 cases of type 0, 34 cases of type Ⅰ, 14 cases of type Ⅱ, 12 cases of type Ⅲ; 68 cases of preoperative symptom reduction (65.4%, 68/104), 36 cases of preoperative symptom stable (34.6%, 36/104). Asymptomatic aggravation. 3. "Postoperative" classification: 49 cases of type 0, 21 cases of type Ⅰ, 11 cases of type Ⅱ, 10 cases of type Ⅲ, 9 cases of type Ⅳa, 4 cases of type Ⅳb; 33 cases (31.7%, 33/104) had postoperative symptoms aggravated. Among the patients with worsening symptoms after surgery, 5 cases (15.2%, 5/33) worsened on the first day after surgery, 9 cases (27.2%, 9/33) worsened on the second day after surgery, and 13 cases (39.4%, 13/33) worsened on the third day after surgery. There were 4 cases (12.1%, 4/33) worsened on the 4th day, and 2 cases (6.1%, 2/33) worsened on the 5th day after surgery.Conclusion:MG patients had different conditions at admission. After individualized perioperative treatment, more than half of the patients' symptoms alleviated to varying degrees. After the operation, the symptoms of MG will be temporarily aggravated due to the effects of surgery and anesthesia, and the aggravation period is mostly on 1-3 days. Reasonable selection of low-risk MG patients for surgery, avoiding the superposition of other influencing factors in the postoperative exacerbation period, is expected to reduce the occurrence of postoperative crises in MG patients.

Chang'an II Decoction ( II )-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Chang'an II Decoction ( II ))-containing serum on intestinal epithelial barrier dysfunction in rats.@*METHODS@#Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang'an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang'an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang'an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang'an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot.@*RESULTS@#Chang'an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang'an II-H group. Additionally, Chang'an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus.@*CONCLUSION@#High-dose Chang'an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.

Effect of Medicated Serum Prepared with Chang'an Ⅰ Prescription on Sensitized Mast Cell Degranulation / 中国实验方剂学杂志

Objective:To observe the influence of Chang'an Ⅰ prescription drug-containing serum on IgE-mediated RBL-2H3 cell degranulation model， and explore the mechanism of Chang'an Ⅰ prescription in inhibiting RBL-2H3 activation degranulation and releasing inflammatory mediators with v-yes-1 Yanaguchi sarcoma viral related oncogene homolog （Lyn）/spleen tyrosine protein kinase （Syk）/mitogen-activated protein kinase （MAPK） signal pathway. Method:Preparation for Chang'an Ⅰ prescription serum. Animal group， SD male rats were randomly divided into Chang'an Ⅰ prescription serum high， medium， low dose， and blank control groups with 10 rats in each group. Dosage： 10 mL·kg-1 distilled water was given to blank control group， while Chang'an Ⅰ prescription serum high， medium and low dose groups were respectively given to the Chang'an Ⅰ prescription concentrated crude drug with concentration of 1.15，2.30，4.60 g·kg-1， respectively once a day for 7 days continuously and then blood was taken from aorta ventralis and centrifuged. Ketotifen as the positive control drug. Mast cells are counted with toluidine blue staining. Cellular release of β-aminohexose was detected by colorimetric method. Contents of MCT， TNF-α， MCP-1 and histamine were measured by enzyme-linked immunosorbent assay （ELISA） kits， Lyn/Syk/MAPK protein levels were detected by immunoblotting. Result:For cell activation and degranulation， compared with the blank control group， the model group had more cell degranulation （P<0.05）， compared with model group， the cell degranulation rate of each dose group of Chang'an Ⅰ prescription decreased （P<0.05）. The release rate of β-hexosamine in each dose group of Chang'an Ⅰ prescription decreased significantly （P<0.01）. For the release of active mediators， compared with the blank control group， the contents of histamine， MCT， TNF-α and MCP-1 all increased in the model group （P<0.01）， compared with the model group， the contents in each dose group of Chang'an Ⅰ prescription all decreased significantly （P<0.01）. Compared with the normal group， the phosphorylation levels of Lyn and Syk， extracellular regulatory protein kinase 1/2（ERK1/2）， c-Jun N-terminal kinase （JNK）， and mitogen-activated protein kinase p38 increased in the model group （P<0.05）. Compared with the model group， the Lyn， Syk and ERK1/2， JNK and p38 protein phosphorylation levels reduced in Chang'an Ⅰ prescription group （P<0.05）. Conclusion:Chang'an Ⅰ prescription drug-containing serum down-regulates the phosphorylation levels of proteins Lyn， Syk， and ERK1/2， JNK， and p38， inhibits RBL-2H3 cell activation and degranulation， reduces the release of cytokines and chemokines， such as histamine， MCT， TNF-α and MCP-1， it may be one of its mechanisms for treating IBS-D visceral hypersensitivity.

Coumarins from Notopterygium incisum and their inhibitory effect against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells / 中草药

Objective: To study coumarins from Notopterygium incisum and their anti-inflammatory effect. Methods: Coumarins were separated and purified by repeated column chromatography on silica gel and HPLC, and their chemical structures were determined by spectral data analyses of MS and NMR. Lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells accompanying overproduction of pro-inflammatory mediator nitric oxide (NO) were applied to investigate the anti-inflammatory effect of these purified coumarins. Results: Twenty-four coumarins were obtained and identified as isoimperatorin (1), angenomalin (2), psoralen (3), bergapten (4), capillarin (5), osthenol (6), 5-dehydronotopterol (7), anhydronotopoloxide (8), 7'-O-methylnotoptol (9), bergamottin (10), 7-isopentenyloxy-6-methoxy-coumarin (11), pabulenol (12), notopterol (13), demethylfuropinarine (14), notoptol (15), cnidilin (16), 6-isopentenyloxyumbelliferone (17), nodakenitin (18), isopimpinellin (19), nodakenin (20), decuroside V (21), decuroside I (22), marmesin-11-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (23), and forbesoside (24), respectively. Coumarins 7-10, 13, and 15 exhibited potent inhibitory activity against LPS-induced NO production in RAW 264.7 cells with half maximal inhibitory concentration values from 8.50 to 35.12 μmol/L. Conclusion: Compound 7 is a new natural product; compound 17 is obtained from the roots and rhizomes of N. incisum for the first time; Unsaturated double bond on C-5 in the aromatic ring significantly improved the anti-inflammatory activity of coumarins.

AnewlignanfromstemsofTrigonostemonlutescens / 中草药

Objective: To study the chemical constituents in the stems of Trigonostemonlutescens. Methods:Silica gel column chromatography and semi-preparative high performance liquid chromatography were used for separation and purification. The structures were identified by NMR, IR, MS and other spectral techniques. Toxicity of compounds 1-4 on human lung cancer A549 cells, cervical cancer Hela cells and breast cancer MCF-7 cells was determined by the MTT method. Results: Four lignans were isolated from the stems of T. lutescens. The structures were identified as 5,5'-dimethoxylclemaphenol A (1), syringaresinol (2), lirioresinol B dimethyl ether (3) and clemaphenol A (4). Conclusion:Compound1 is a new compound, and compounds 2-4 are isolated from this genus for the first time. Compounds 1-4 have certain cytotoxic activity on A549, HeLa and MCF-7 human tumor cells.

Professor experience in treatment of dysmenorrhea with "three-regulation and one-harmonization" therapy of acupuncture / 中国针灸

The clinical experience of professor in treatment of dysmenorrhea with "three-regulation and one-harmonization" therapy of acupuncture was introduced. Professor invented a needling technique for "three-regulation and one-harmonization", meaning regulation, blood regulation and regulation of meridian tendon region as well as the spirit () harmonization. In regulation, the extreme fine needles are used to regulate movement of the whole function with the coordination of respiration and the corresponding acupoint prescriptions. In blood regulation, the special small bleeding device is selected and the bloodletting theory is improved for bloodletting at the specific stagnant site. In the regulation of meridian tendon region, a special sterile injection needle is chosen to release the cord-like mass. The spirit harmonization is exerted in combination with regulation. During acupuncture, the spirit of both the clinical practitioner and the patient should be in a harmonized spirit condition, coordinated with respiration regulation. In the treatment with acupuncture therapy of "three-regulation and one-harmonization" for dysmenorrhea, bloodletting therapy is used firstly to remove stasis, secondly, the "releasing cord-like mass" technique is followed to regulate meridian tendon region, finally, the fine needling technique is adopted to regulate and harmonize spirit. The clinical effect is definite in clinical practice.

Pharmacological network-based study on interventional mechanism of Gu-Chang-Zhi-Xie pills for treatment of irritable bowel syndrome / 药学学报

This study was designed to explore the interventional mechanism involving "multi-components, multi-targets and multi-pathways" of Gu-Chang-Zhi-Xie pills (GCZX) for treatment of irritable bowel syndrome (IBS) using pharmacological network technology. Firstly, 96 active ingredients from GCZX pills were screened by ADME parameter filtration and chemical space principal component analysis, and the targets of anti-IBS function were predicted using PharmMapper online database. Secondly, AutoDock Vina was used to validate the docking between the active ingredients and predicted disease targets, and to establish the corresponding relationship between "pharmacodynamic molecules and target proteins". Finally, the target elements were mapped into the KEGG biological pathway by CluoGO plug-in, which further elucidates the potential relationship between the key targets and the mechanism of action of Gu-Chang-Zhi-Xie pills for treatment of IBS. The results showed that most of the top 11 key pharmacodynamic molecules were isoquinoline alkaloids, which mainly acted on inflammatory or pain targets, with different degrees of anti-inflammatory and analgesic effects. A total of 39 key targets were identified, including TPH1, TNF-α, IL-6, IFN-γ, MAO-A and IL-10. These targets were mapped to 29 KEGG pathways, of which the P-value of 5-HT signaling pathway was the smallest. Therefore, the pharmacodynamic molecules mainly act on 6 core targets and may play a major role in the regulation of 5-HT signal synthesis or transport pathway. This study sets an example for drug development and mechanistic investigation using innovative technology.

Effects of phytohormones and lignin on growth of Antrodia cinnamomea mycelium / 中草药

Objective: To investigate the effects of phytohormones and lignin on the growth of Antrodia cinnamomea mycelium, and to determine the content of crude polysaccharide and crude triterpenoid and antioxidant activity of cultured products. Methods The product cultured by solid-state fermentation in petri dish was ultrasonically extracted. The phenol-sulfuric acid method was selected to determine the content of crude polysaccharide of the extract, and the vanillin-glacial acetic acid method was used to determine the content of crude triterpenoids of the extract. The half-clearing concentrations (IC50) of DPPH free radicals and ABTS free radicals were indexes for evaluating the anti-oxidant activity of the culture product. Results Sampling near the outer edge of the mycelium layer after 20 d of culture was performed by the activation method to obtain inoculated raw materials with better growth activity; The basal medium with good growth, high content of crude polysaccharide and crude triterpenoids was modified PCA medium; On the basis of this medium, the mycelia with 0.5 g/L lignin added into the medium grew fastest, and the diameter of mycelium layer increased to 1.19 times of the control group; When the concentration of IBA was 0.5 mg/L, the dry weight of mycelium was increased by 89.51% compared with the control group, and the yield of crude polysaccharide was increased by 130.57% compared with the control group, which was much higher than other groups. The content and yield of triterpenoids were also increased significantly, 61.31% higher than the control group, and crude triterpenoids yield reached 133.24 mg/L; The content of crude triterpenoids in mycelium was the highest (5.62%) when adding 0.5 g/L powder of Cinnamomum kanehirai, which was 84.26% higher than that of the control group; In addition, the addition of plant hormones and lignin to the culture medium has a certain effect on the anti-oxidant capacity of the Antrodia cinnamomea mycelium, on the whole, the experimental group had good anti-oxidant activity after adding different substances. Conclusion By adding phytohormone and lignin to the modified PCA medium, the growth of the mycelium of Antrodia cinnamomea can be effectively promoted, the content of the active ingredient can be increased, and the anti-oxidant activity can be enhanced.

Chemical constituents of coumarins compounds from Notopterygium incisum and their anti-oxidant activity / 中草药

Objective: To investigate the coumarin compounds from Notopterygium incisum and their anti-oxidant activities. Methods The coumarin compounds and their analogues were separated and purified by recrystallization, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. The structure was identified by modern spectroscopy. The isolated compound was tested for anti-oxidant activity by DPPH and ABTS assay. Results Ten compounds were isolated from the dichloromethane extraction layer of 70% ethanol extract, which were identified as bergaptol (1), d-laserpitin (2), falcarindiol (3), phenethyl ferulate (4), selinidin (5), archangelicin (6), notoptol (7), nodakenetin (8), (+)-cis-khellactone (9), and oxypeucedanin hydrate (10). The anti-oxidant activity of these compounds was tested by DPPH and ABTS methods. Conclusion Compounds 2 and 6 are isolated from this plant for the first time. Compounds 1 and 7 have shown the strongest anti-oxidant activity. The structure-activity relationship (SAR) studies revealed the -OH and unsaturated double bond on C-5′ in the aromatic ring significantly improved the anti-oxidant activity than other coumarin compounds.

Geographic distribution of genetic variation of natural populations in an endangered and rarely herb Notopterygium forbesii var. oviforme / 中草药

Objective: In order to determine the geographic distribution of genetic variation and structure of natural populations in an endangered and rarely medicinal herb Notopterygium forbesii var. oviforme. Methods The primers of polymorphic microsatellite molecular markers of N. forbesii var. oviforme were firstly developed using the next generation reduced-representation sequencing technology. Then, the genetic polymorphisms of the whole geographical distributional population samples of N. forbesii var. oviforme were investigated based on the polymorphic SSRs. Results:A total of 780 SSR-containing DNA sequences were obtained by genome De novo assembly. Ten pairs of polymorphic SSR primers were developed and used to analyze the genetic variability of 105 individuals from six natural populations that covered the entire geographical distributions of N. forbesii var. oviforme. The results showed that the number of observed alleles (No) per locus varied between 1 and 6 (mean = 3.530). The mean observed heterozygosity (Ho) per population ranged from 0.305 to 0.457. These finds suggested that N. forbesii var. oviforme had the moderate to high level of genetic variability. Bayesian clustering analyses demonstrated that the six natural populations of N. forbesii var. oviforme have formed two clear genetic lineages. The gene flow and/or genetic introgression have occurred between these two groups. Conclusion:The next generation reduced-representation sequencing technology largely enriched SSRs database of N. forbesii var. oviforme. The geographic distribution patterns of genetic variations of N. forbesii var. oviforme may be related to the long evolutionary history of species and pollen dispersal of long distance among different natural populations.

Study on coumarins of Trigonostemon lutescens / 中草药

Objective To study the chemical constituents in 95% ethanol aqueous extract of Trigonostemon lutescens. Methods The open silica gel, MCI, Sephadex LH-20 column chromatography, and the semi-preparative HPLC were used to isolate and purify the chemical constituents from the EtOAc fraction of T. lutescens. The structures of the isolates were elucidated by their physiochemical properties, NMR, and MS spectroscopic data, as well as comparison with literature data. Results Eleven compounds were isolated from the EtOAc fraction of the 95% aqueous EtOH extract of T. lutescens, and their structures were identified as seven coumarins, auraptenol (1), meranzin hydrate (2), xanthotoxin (3), bergapten (4), isoimpinellin (5), alloisoimperatorin (6), and isodemethylfuropinarine (7); Two phenylalanine glycosides, 3,4-dihydroxy allylbenzene-4-O-β-D-glucopyranoside (8) and 1-O-β-D-glucopyranosyl-4- allylbenzene (9); One phenylethanol, 1-(2-ethylphenyl)-1,2-ethanediol (10); One alkaloid, 8-hydroxy-3-methoxy-5H-pyrido [2,1-c] pyrazin-5-one (11). Conclusion All these compounds are isolated from the genus Trigonostemon for the first time.

Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D).</p><p><b>METHOD</b>A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests.</p><p><b>RESULTS</b>A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant.</p><p><b>CONCLUSION</b>Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).</p>