1.Mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis
Shaowa LYU ; Yunyu WU ; Quanli LIU ; Yuhan REN ; Yuyan GUO ; Haixue KUANG
China Pharmacy 2025;36(8):926-931
OBJECTIVE To explore the mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis (RA). METHODS The targets of main saponins in C. robustum Maxim were obtained from Swiss Target Prediction, and the RA treatment targets collected from the GeneCards and OMIM database were intercrossed to establish an interaction network based on network pharmacology. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. RA model was established by injecting complete Freund’s adjuvant into the back of rabbits for verification. The arthritis index score, knee diameter and pain threshold of rabbits were compared. Pathological examination of rabbit synovial tissue was carried out. The levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in rabbit serum and synovial fluid were detected. The phosphorylation levels of tyrosine protein Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) proteins in rabbit synovium were detected. RESULTS Network pharmacology identified 143 intersection targets between the drug and RA. After the construction of the “drug-component-target” network, the core components of the network were echinocystic acid, oleanolic acid, hederagenin, cauloside A and cauloside C, etc. Additionally, the top 10 core targets of PPI network were SRC, STAT3, MAPK1, EGFR, PIK3CA, MAPK3, GRB2, JUN, PTPN11 and JAK2. The results of KEGG pathway analysis showed that the JAK/STAT signaling pathway was mainly involved in the treatment of RA by joint injection of C. robustum Maxim. Results of validation test showed that compared with model group, joint injection of C. robustum Maxim could reduce the swelling of rabbit knee joint, relieve the hyperplasia of synovial layer, reduce the hyperplasia of lower connective tissue, and reduce the number of inflammatory cells and capillaries. The arthritis index score (excluding low-dose group of C. robustum Maxim), knee diameter, the levels of TNF-α, IL-1β and IL-6 in serum and synovial fluid, and the protein phosphorylation levels of JAK2 and STAT3 were decreased significantly (P<0.05 of P<0.01), while the pain threshold were reduced significantly (P<0.01). CONCLUSIONS The core components that may alleviate the inflammatory response of RA in joint injection of C. robustum Maxim could include echinocystic acid, oleanolic acid, hederagenin, cauloside A, and cauloside C. Its mechanism may be related to the inhibition of JAK/STAT signaling pathway and the reduction of inflammatory responses.
2.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.
3.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.
4.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.
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.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 .
7. Curcumin's prevention of inflammation-driven early gastric cancer and its molecular mechanism
Wensen ZHANG ; Na CUI ; Jin YE ; Bingyou YANG ; Yanping SUN ; Haixue KUANG
Chinese Herbal Medicines 2022;14(2):244-253
Worldwide, gastric cancer is the second leading cause of cancer deaths and the fifth most common malignant tumor. Gastric cancer is believed to be caused by a variety of factors, such as genetics, epigenetics, and environmental influences. Among the pathogenic factors, inflammation has been considered as one of the main risk factors for gastric cancer. There are currently limited ways to prevent gastric cancer. Although the combined application of aspirin and non-steroidal anti-inflammatory drugs can reduce the risk, it has great side effects and can easily cause gastric perforation or gastric bleeding. Therefore, an alternative plan is urgently needed. Curcumin is the yellow pigment in the rhizome of the plant turmeric. Current studies have found that curcumin has a protective effect on gastric mucosal damage caused by non-steroidal anti-inflammatory drugs, gastric mucosal damage in rats, and gastric mucosal damage caused by stress bleeding and Helicobacter pylori infection. Curcumin shows significant anti-inflammatory and anti-cancer activities by regulating DNA methylation, histone modification, nuclear factor erythrocyte 2 related factor 2 and other related signal pathways. In this article, the latest evidence of curcumin for epigenetic changes in gastric cancer and its potential contribution to gastric cancer were discussed.
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.Effects of five processing methods on compositions and contents of fatty oils in Descurainiae Semen
Hongwei LI ; Yanbang SHI ; Lianqi TIAN ; Haixue KUANG ; Xiaoke ZHENG ; Weisheng FENG
Chinese Traditional Patent Medicine 2017;39(8):1661-1665
AIM To investigate the effects of frost-like powder,steaming,stir-frying with wine,stir-frying with salt-water and stir-frying with vinegar on compositions and contents of fatty oils in Descurainiae Semen.METHODS Descurainiae Semen was processed by five methods,respectively.The fatty oils were extracted from various processed products by petroleum ether,which were then derivatized.GC-MS was adopted in the qualitative identification and quantitative determination.RESULTS Except for frost-like powder,various processing methods could increase the extraction rate of fatty oils.Compared with raw product,the quantities of fatty oils in various processed products were decreased,together with the increased contents.The main compositions of obtained fatty oils were unsaturated fatty acids,whose contents in various processed products (except stir-frying with vinegar product) were higher than those in the raw product.CONCLUSION The effects of different processing methods on compositions and contents of fatty oils in Descurainiae Semen show obvious differences,among which the processing effect of stir-frying with vinegar is not satisfactory.

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