1.Anti-cancer Effect and Mechanism of Chinese Herbal Medicine Saponins: A Review
Mingtao ZHU ; Yanpin SUN ; Yimeng WANG ; Haodong BAI ; Bingyou YANG ; Qiuhong WANG ; Haixue KUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):236-245
Cancer, one of the deadliest diseases caused by cells escaping homeostasis, abnormal proliferation, and abnormal differentiation, is fast becoming one of the most burdensome diseases of this century. With decades of human research and cognitive changes in cancer, cancer treatment is also developing rapidly, but there is still a lack of effective treatment and countermeasures. Especially, the search for safe, efficient, and non-toxic drugs has become a long-term goal in the field of cancer. Saponins extracted and separated from traditional Chinese medicine can improve cancer through various pathways and have almost no toxic side effects. Therefore, the research on the anti-cancer effect of saponins is heating up. It is found that saponins play anti-tumor roles by inhibiting proliferation, metastasis, and angiogenesis of cancer cells, promoting apoptosis of cancer cells, inducing autophagy of tumor cells, and regulating miRNA expression and immune functions. Chinese herbal medicine saponins can regulate secretory glycoprotein /β-catenin (Wnt/β-catenin), adenylate activated protein kinase (AMPK), nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Janus kinase/activator of signal transduction and transcription 3 (JAK/ STAT3), hypoxia-inducible factor-1α (HIF-1α), Toll-like receptor (TLR), and other related signaling pathways to get involved in the proliferation, metastasis, angiogenesis, apoptosis, autophagy, and other processes of cancer cells, thus interfering with the progression of cancer. Therefore, the focus of this review is to update the discovery and evaluation of Chinese herbal medicine saponins with anti-cancer properties, clarify their mechanism of action, including the progress of related signaling pathways, and deepen the understanding of the anti-cancer function of Chinese herbal medicine saponins, so as to provide a new perspective and direction for the prevention and treatment of tumors by traditional Chinese medicine and better promote the development and utilization of resources.
2.Study on protective effect and mechanism of Bupleurum chinense polysaccharides on acute liver injury in mice
Yuchan CHEN ; Donghui PENG ; Yanping SUN ; Qiuhong WANG ; Haixue KUANG
China Pharmacy 2024;35(19):2352-2357
OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides (BCP) on acute liver injury (ALI) in mice. METHODS Overall 40 mice were randomly divided into normal group, model group, positive control group (Baogan tablet, 550 mg/kg), BCP high-dose and low-dose groups (400, 100 mg/kg), with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration, except for the normal group, mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h, the liver and spleen indexes of mice were measured, and the pathological changes of liver and spleen tissue were observed; the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were detected, and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in serum and liver tissue of mice were determined, as well as the protein expression levels of nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR4), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in liver tissue were also detected. RESULTS Compared with the normal group, the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells; spleen enlargement, increased bleeding and decreased lymphocytes were observed, liver and spleen indexes were increased significantly (P<0.01); the serum levels of AST, ALT and LDH, the levels of TNF-α, IL-6 and IL-1β in serum and liver tissue, as well as the MDA level, protein expressions of TLR4, NF- κB and HO-1 in liver tissue were all increased significantly (P<0.05 or P<0.01). The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly (P<0.05). Compared with the model group, the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups, and most of liver and spleen indexes, the above indexes of serum and liver tissue were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS BCP has a protective effect on ALI, the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.
3.Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases
Huanhuan CUI ; Ling TANG ; Can CUI ; Zhuxing YAO ; Zhimin YANG ; Haixue WANG
JOURNAL OF RARE DISEASES 2024;3(2):175-180
Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients,difficult recruitment,long trial period,and frequent video interviews during the trial.Therefore,in the clinical operation of rare diseases,a decentralized clinical trials(DCT)model based on the"patient-cen-tred"research and development concept is implemented.With the help of decentralized elements and digital health technology,the barriers of geographical restrictions can be overcome and subjects do not have to be limit-ed to traditional clinical trial sites(hospitals/research centers),which can significantly reduce the burden on subjects,increase their representation,and obtain a wider range of scientific research data.To guide the indus-try's scientific and standardized application of DCT in the research and development of drugs for rare diseases,the Center for Drug Evaluation of the National Medical Products Administration(NMPA)organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases.This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs.It aims to solve the difficult and key problems during rare disease drug research and development,improve the efficiency and optimize patient experience.This article,combining the research and development concepts in the guideline,explains the current research and develop-ment thinking on the application of DCT in the research and development of rare disease drugs,with a view of providing reference for the industry.
4.Recombinant porcine interferon-gamma expressed in CHO cells and its antiviral activity.
Lingyun WANG ; Rongzeng HAO ; Yang YANG ; Yajun LI ; Bingzhou LU ; Yuhan MAO ; Yue ZHANG ; Zhenli GONG ; Yanhong LIU ; Meng QI ; Yi RU ; Haixue ZHENG
Chinese Journal of Biotechnology 2023;39(12):4784-4795
The aim of this study was to produce recombinant porcine interferon gamma (rPoIFN-γ) by Chinese hamster ovarian (CHO) cells expression system and to analyze its antiviral activity. Firstly, we constructed the recombinant eukaryotic expression plasmid pcDNA3.1-PoIFN-γ and transfected into suspension cultured CHO cells for secretory expression of rPoIFN-γ. The rPoIFN-γ was purified by affinity chromatography and identified with SDS-PAGE and Western blotting. Subsequently, the cytotoxicity of rPoIFN-γ was analyzed by CCK-8 test, and the antiviral activity of rPoIFN-γ was evaluated using standard procedures in VSV/PK-15 (virus/cell) test system. Finally the anti-Seneca virus A (SVA) of rPoIFN-γ activity and the induction of interferon-stimulated genes (ISGs) and cytokines were also analyzed. The results showed that rPoIFN-γ could successfully expressed in the supernatant of CHO cells. CCK-8 assays indicated that rPoIFN-γ did not show cytotoxicity on IBRS-2 cells. The biological activity of rPoIFN-γ was 5.59×107 U/mg in VSV/PK-15 system. Moreover, rPoIFN-γ could induced the expression of ISGs and cytokines, and significantly inhibited the replication of SVA. In conclusion, the high activity of rPoIFN-γ was successfully prepared by CHO cells expression system, which showed strong antiviral activity on SVA. This study may facilitate the investigation of rPoIFN-γ function and the development of novel genetically engineered antiviral drugs.
Swine
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Animals
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Cricetinae
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Interferon-gamma/pharmacology*
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Cricetulus
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CHO Cells
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Sincalide
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Recombinant Proteins/pharmacology*
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Antiviral Agents/pharmacology*
5.Epilepsy Treated by Traditional Chinese Medicine Based on Syndrome Differentiation: A Review
Fazhi SU ; Yanping SUN ; Chenxi BAI ; Wensen ZHANG ; Bingyou YANG ; Qiuhong WANG ; Haixue KUANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):200-211
Epilepsy is a chronic brain disease characterized by seizures, and is one of the most common nervous system diseases in clinic practice with the recurrent, transient, and refractory characteristics. Clinically, western medicine therapy is mainly adopted in the treatment of epilepsy, but it is not conducive to long-term use for patients on account of severe side effects, which can result in abnormalities in the digestive system, central nervous system, hematopoietic system, urinary system, and liver function to varying degrees. Syndrome differentiation is usually used for the treatment of epilepsy by traditional Chinese medicine (TCM), which can avoid the side effects of western medicine treatment on the basis of improving patients' syndromes. The literature on TCM in the treatment of epilepsy in China and abroad indicates that the syndrome differentiation in TCM is often based on phlegm, blood stasis, wind, and deficiency, and the treatment methods include acupuncture, acupoint catgut embedding, moxibustion, Chinese medicine monomer, drug pair, and compound decoction. The various treatments of TCM play an important role in the comprehensive treatment of epilepsy through multiple channels and links, such as reducing the degree and number of seizures. This paper comprehensively summarized the clinical experience of TCM in the treatment of epilepsy, systematically expounded various treatment methods and ideas of TCM in the treatment of epilepsy, and deeply discussed the mechanism of TCM in the treatment of epilepsy, aiming to provide a theoretical basis for the clinical formulation of a reasonable individualized treatment plan for epilepsy and diversified ideas for the more effective treatment of epilepsy by TCM.
6.Research progress on the mechanism of promoting fracture healing by traditional Chinese medicine monomer components and compound formulas
Zhihong ZHANG ; Yanping SUN ; Donghui PENG ; Na CUI ; Yuanning ZENG ; Haixue KUANG ; Qiuhong WANG
China Pharmacy 2023;34(17):2172-2176
Traditional Chinese medicine has the characteristics of multiple components, pathways, and targets in the treatment of fracture healing, and has good therapeutic advantages and potential for fractures with complex pathological mechanisms. Based on this, the author summarized the mechanism of promoting fracture healing by the monomer components and compound formulas of traditional Chinese medicine and found that visfatin A, puerarin, and others can activate the mitogen-activated protein kinase (MAPK) signaling pathway; Xugudan, Guben zenggu formula and others can activate bone morphogenetic protein (BMP) signaling pathway; baicalin, Achyranthes bidentata polysaccharides and others can activate Wnt/β -catenin signaling pathway; apigenin, notoginsenoside and others can activate receptor activator of nuclear factor-κB (NF-κB)/receptor activator of NF-κB ligand/osteoprotegerin (RANK/RANKL/OPG) signaling pathway; Compound huoxue jiegu capsule, Jiangu granule and others can inhibit phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway; icariin can activate Notch signaling pathway; Taohong siwu decoction, crocin and others can activate Hippo signaling pathway; jujuboside A and osthole can inhibit NF-κB signaling pathway, and thus promote fracture healing.
7.Establishment of fingerprint and content determination of 3 differential components in Rheum palmatum before and after steaming with wine derived from different producing areas
Xiaohui RONG ; Yan LIU ; Qiuru WANG ; Ziwei LI ; Haixue KUANG ; Bingyou YANG
China Pharmacy 2022;33(3):280-286
OBJECTIVE To establish H PLC fingerprint of Rheum palmatum before and after steaming with wine ,and to determine the contents of 3 differential components. METHODS HPLC method was used to establish the fingerprints of 15 batches of R. palmatum (before wine-steaming )and prepared rhubarb (after wine-steaming )and the similarity evaluation was conducted. The chemical pattern recognition analysis was carried out by principal component analysis ,cluster analysis ,partial least squares- discriminant analysis and orthogonal partial least squares-discriminant analysis. The contents of gallic acid ,resveratrol-4′-O- glucoside and resveratrol- 4′-O-(6″-galloyl)-glucoside in 30 batches of samples were determined. RESULTS In the fingerprint study,48 common peaks were demarcated for R. palmatum and 47 for prepared rhubarb as well as 17 common peaks were identified by reference substance. Cluster analysis and principal component analysis showed that R. palmatum derived from Qinghai before and after steaming with wine could be distinguished from those from Sichuan and Gansu. The results of content determination showed that the contents of 3 differential components in R. palmatum derived from Qinghai before and after steaming with wine were higher than those from other two production areas ;the contents of gallic acid in prepared rhubarb derived from those production areas were higher than R. palmatum ;the contents of resveratrol- 4′-O-glucoside and resveratrol- 4′-O- (6″-galloyl)-glucoside in R. palmatum derived from those production areas were higher than prepared rhubarb. CONCLUSIONS Fingerprint and content determination method established in this study can quickly ,scientifically and accurately evaluate the quality of R. palmatum from different producing areas before and after wine steaming ,which provide a basis for the processing specification and quality control of R. palmatum .
8.Meridian Tropism of Components in Bupleuri Radix Based on Nonalcoholic Steatohepatitis Model and Principal Component Analysis
Feihui HONG ; Jiexin CHEN ; Yuchan CHEN ; Huimin LI ; Donghui PENG ; Zhibin SHEN ; Yonggang XIA ; Qiuhong WANG ; Haixue KUANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):53-60
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.
9.Study on Isolation ,Purification and in vitro Antioxidant Activity of the Polysaccharides from Cucumis satiuus
Zhihong ZHANG ; Na XING ; Donghui PENG ; Qiuhong WANG ; Haixue KUANG
China Pharmacy 2021;32(4):432-438
OBJECTIVE:To isolate and purify the polysaccharides from Cucumis satiuus ,and to investigate its in vitro antioxidant activity. METHODS :The crude polysaccharides (CCL)were extracted from C. satiuus by water extraction and alcohol precipitation. CCL was separated and purified on Amberlite FPA 90Cl anion and Amberlite FPC 3500H cation exchange resin column and DEAE cellulose 52 column,so as to obtain 3 kinds of polysaccharides as CCL-M 2,CCL-M3,CCL-M6. The purity , molecular weight ,structure and monosaccharide composition of 3 kinds of polysaccharides were analyzed by HPLC-ELSD , UPLC-QTOF/MS,UV and IR. Using vitamin C (VC)as positive control ,the scavenging activity of CCL-M 2,CCL-M3 and CCL-M6(0.4,0.8,1.2,1.6,2.0 mg/mL)to 1,1-dibenzene-2-trinitrobenzene free radicals (DPPH·),hydroxyl free radicals (·OH) and superoxycyclic anion free radicals (O2-·)were investigated ,and IC50 was calculated. RESULTS :CCL-M2,CCL-M3 and CCL-M6 were homogeneous polysaccharides in the form of pyranose ,with molecular weights of 9.614×106,2.024×107 and 3.343× 107 Da,respectively. CCL-M 2 monosaccharides were composed of rhamnose ,semi-lactose aldehyde acid ,glucose, semi-lactose and arabic sugar ,with a molar ratio of 5.1∶2.6∶1.7∶1.4∶31.6. CCL-M 3 and CCL-M 6 monosaccharides were composed of mannose, rhamnose,glucose,semi-lactose,arabic sugar ,with a molar ratio of 1.7 ∶ 3.8 ∶ 6.4 ∶ 3.3 ∶ 1.3 and 1.3 ∶ 3.0 ∶ 3.2 ∶ 4.4 ∶ 8.9. The results of antioxidant activity in vitro showed that 3 kinds of homogeneous polysaccharides had certain scavenging activity on DPPH ·,·OH and O 2-·;the order of scavenging activity to DPPH ·was VC >CCL-M2>CCL-M3>CCL-M6(IC50 was 0.309, 1.240, 1.489 and 1.713 mg/mL); the order of scavenging activity to ·OH was VC >CCL-M2>CCL-M6>CCL-M3(IC50 was 0.968,1.032,1.233,1.356 mg/mL);the order of scavenging activity to O 2 -· was VC >CCL-M2>CCL-M3>CCL-M6 (IC50 was 0.335, 0.379, 0.812, 1.662 mg/mL). CONCLUSIONS:3 kinds of monosaccharides in the form of pyranose are isolated from C. satiuus ,and all of them have antioxidant activity in vitro ,and CCL-M 2 is the best.
10.School health personnel in primary and secondary schools in China
ZHAO Tianjie, ZHU Guangrong, HU Zhen, YAO Haizhou, WANG Haixue, MA Jun,DONG Yanhui
Chinese Journal of School Health 2021;42(11):1732-1735
Objective:
To understand the current status of the team structure of health personnel in primary and secondary schools, and to provide suggestions and references for strengthening and optimizing school health workforce.
Methods:
A nationwide stratified random cluster sampling method was adopted to select provinces for investigation in stratification from 2015-2016, a total of 16 provinces, autonomous regions, and municipalities directly under the Central Government, 26 survey sites, 10 027 primary and secondary schools, 9 536 questionnaires of health personnel were collected.
Results:
Among the 9 536 school health staffs, there were various types of positions, and different types of schools had different position types construction. Elementary schools had the most part time health care teachers, accounting for 77.6%, while full time school doctors only accounting 10.0%; high schools had the most full time school doctors, accounting for 65.7%, and part time health care teachers only accounting for 15.1 %. There were various employment channels, with the most transfer jobs in schools, accounting for 70.7%. The series of professional titles were diverse, with the teaching profession accounting for 67.4%. Most of school health teachers had junior and intermediate professional titles, accounting for 42.6%, respectively. Proportion of medium, medium low, and low level of salary accounted for 39.3%, 27.9% and 21.1% respectively.
Conclusion
The educational background and age distribution of school health personnel is reasonable, but the proportions of medical background and full time school doctors are relatively low. School health personnel have various job types, professional titles, salary level, and limited space of career development. Top level design from the policy level, and clearly defined improve the structure of school health personnel to meet the needs of high quality development of school health work in the new era.


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