Modified Xiaoyao Erxian Decoction in Treatment of Mood Disorders in Perimenopausal Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Xiaoyao Erxian decoction in the treatment of mood disorders among perimenopausal syndrome due to kidney deficiency and liver depression and its effects on monoamine neurotransmitters and brain-derived neurotrophic factor （BDNF）. Method:According to the random number table， 108 patients were divided into a control group （54 cases） and an observation group （54 cases）. Control group were treated with Shugan Jieyu capsule orally， two capsules per time， two times per day， while those in the observation group received the modified Xiaoyao Erxian decoction， one bag per day， for 12 consecutive weeks. Before and after treatment， the Hamilton Anxiety Scale （HAMA）， 17-item Hamilton Depression Rating Scale （HAMD-17）， modified Kupperman Index （KI）， Pittsburgh Sleep Quality Index （PSQI）， Menopause-specific Quality of Life （MENQOL） and kidney deficiency and liver depression syndrome scores were calculated. The levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， BDNF， 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA） were detected， followed by safety evaluation. Result:The HAMA， HAMD-17， KI， kidney deficiency and liver depression syndrome， PSQI， and MENQOL scores of the observation group were lower than those of the control group （<italic>P</italic><0.01）， whereas the 5-HT， E₂， DA， NE， and BDNF levels in the observation group were higher （<italic>P</italic><0.01）. The clinical efficacy of the observation group was superior to that in the control group （<italic>Z</italic>=2.184， <italic>P</italic><0.05）. No adverse reactions occurred after the oral administration of Chinese medicinal preparations. Conclusion:The modified Xiaoyao Erxian decoction effectively alleviates the mood disorders and other related symptoms of perimenopausal syndrome due to kidney deficiency and liver depression by regulating the monoamine neurotransmitters， BDNF， and E₂， without inducing obvious side effects.

Mechanism of Modified Erzhiwan Combined with Epimedium for Atherosclerosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective::In this study, a network pharmacology-based method was applied to analyze the mechanism of modified Erzhiwan combined with epimedium in treatment of atherosclerosis. Method::The compounds and targets of modified Erzhiwan combined with epimedium were screened in traditional Chinese medicine(TCM) systems pharmacology database and analysis platform (TCMSP) and bioinformatics analysis tool for molecular mechanism of TCM (BATMAN-TCM). Mang related databases were applied to find the target-related to atherosclerosis.The common targets of modified Erzhiwan combined with epimedium and atherosclerosis were got by venn diagrams.Cytoscape 3.6.1 was used to construct ingredients-disease-targets networks.Then protein-protein interaction (PPI) analysis of ingredients-disease-targets was builed in STRING database, and was visualized by Cytoscape 3.6.1, then important modules were analyzed with Moleculaar complex detection(MCODE). Biological information annotation databases (DAVID) was used to carry on gene ontology (GO) analysis and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway. Result::A total of 38 active ingredients and 266 potential targets of modified Erzhiwan combined with epimedium were obtained from TCMSP and BATMAN-TCM, 254 atherosclerosis-related targets were retrieved from disease database.Then 52 common targets were obtained and 14 core genes were screened.Biological processes were related to inflammatory response, regulation of insulin secretion, positive regulation of nitric oxide biosynthetic process, etc.The biological pathways mainly included tumor necrosis factor signaling pathway, NF-kappa B(NF-κB)signaling pathway, peroxisome proliferators-activated receptors signaling pathway and so on. Conclusion::Modified Erzhiwan combined with epimedium may play the anti-atherosclerosis role by estrogen-like effect through attach estrogen receptor, inhibiting inflammation and improving insulin resistance, which may provide guidance for further experimental research.

Mechanism of Erzhiwan on Hepatocellular Carcinoma Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To explore the possible mechanisms of Erzhiwan in the treatment of hepatocellular carcinoma (HCC) based on the network pharmacology. Method::The candidate active components and targets of Ligustri Lucidi Fructus and Ecliptae Herba were obtained through retrieval of the traditional Chinese medicine (TCM) systems pharmacology database (TCMSP) and literatures. Through Uniprot database and the human genome database (GeneCards), the overlapping genes of Erzhiwan and hepatocellular carcinoma were collected. The " candidate active components-targets" network of Ligustri Lucidi Fructus and Ecliptae Herba was built with Cytoscape 3.6.0 software. Drug target proteins and disease targets were mapped, and Venn map was drawn by Omicshare database. Major targets interaction network was formed by using String database and " Generate style from statistics" tool in Cytoscape 3.6.0 software. Molecular docking with active components was carried out by Systems Dock Web Site. The Gene Ontology (GO) classification enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the targets were carried out in DAVID database. Result::Totally 21 active components, including beta-sitosterol, quercetin, luteolin, demethylwedelolactone, kaempferol, and 151 targets, including tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), N-terminal kinase (JUN), proto-oncogene (c-MYC), matrix metalloproteinase-9 (MMP-9) of Erzhiwan were collected. Erzhiwan exerts its effects on HCC mainly by acting on signal pathways, including Hepatitis B, TNF, Phosphatidylinositol-3-kinase (PI3K/Akt), tumor suppressor gene p53 and Toll-like receptor. Conclusion::Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways of Erzhiwan in the treatment of HCC, providing a direction for further studies.

Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology / 中国实验方剂学杂志

Objective: To explain the "multi-components, multi-targets, multi-pathways" mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network, then the classified enrichment analysis of gene ontology (GO) and pathway enrichment analysis (KEGG) were carried out on the main function of its gene sets, so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result: Erzhiwan has 19 components in IPA; and apigenin,luteolin,oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3 (CHRM3), muscarinic acetylcholine receptor M2 (CHRM2), urokinase plasminogen activator receptor (PLAUR), kinin releasing enzyme 3 (KLK3), cadherin 1 (CDH1), chemokines 3 (CCL3) and metalloproteinase-1 (MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways, and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions, inducing apoptosis, inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).

Effect of Erzhiwan on Invasion and Metastasis of Human Colon Cancer Cells / 中国实验方剂学杂志

Objective: To investigate the effect of Erzhiwan (EZW) on the invasion and metastasis of human colon cancer HCT116 cells. Method: The abilities of invasion (number of transmembrane cells) and migration (relative width of 48 h scratch) were observed by Transwell assay. Western blot was used to detect vascular endothelial growth factor (VEGF) and E-cadherin protein, respectively. Result: ① Transwell results showed that compared with the blank control group, the number of model piercing cells in each drug group was decreased (PPPPPPPP-1 L-OHP combined with 10% EZW group was lower than that in L-OHP group (PP-1 L-OHP combined with 10% EZW group and L-OHP group increased the expression of E-cadherin protein significantly. Compared with L-OHP group, the expression of E-cadherin protein was the highest (PConclusion: EZW can inhibit the invasion and metastasis of colon cancer HCT116 cells, and the best effect is achieved after combined with L-OHP. This may be related to the decrease of VEGF protein expression and the increase of E-cadherin protein expression after combination with L-OHP.

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells / 中国天然药物

Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

Stability of multiple components in Er-Zhi-Wan (water honey pills) by UPLC-Q/TOF-MS / 中草药

Objective: According to the ICH guideline, the long-term stability and accelerated stability testing for Er-Zhi-Wan (water honey pills) has been carried out on the basis of the qualitative and quantitative analysis on multiple components in Er-Zhi-Wan by using UPLC-Q-TOF/MS method. In addition, the influence factors of the preparation (packing material and sealing process) were investigated by UPLC method. Methods: The analysis was performed on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with the mixture of acetonitrile-water-formic acid as mobile phase, the flow rate was 0.2 mL/min and MS scanning mode was positive and negative. According to the ICH guideline, the 18 months long-term stability [(25 ± 2) ℃, relative humidity (RH) of (60 ± 5)%], accelerated stability testing [(40 ± 2) ℃, RH of (75 ± 5)%], and influence factors of preparation (packing material and sealing process) for Er-Zhi-Wan (water honey pills) have been carried out by the UPLC method. Results: A total of 20 chemical compounds (salidroside, wedelolactone, 10-hydroxyoleoside dimethyl ester, oleoside-11 methyl ester, loganic acid, echinacoside, nuezhengslaside, oleuropein acid, verbascoside/isoverbascoside, nuezhenoside, specnuezhenide, ligustroflavone, isomer of specnuezhenide, safghanoside F, isonuezhenide, nuezhenidic acid, oleuropein, nuezhenoside-G13, oleonuezhenide, and 3-O-cis-p-coumaroyltormentic acid) were identified in the qualitative study. The content of these compounds was measured by the established quantitative and semi-quantitative research methods. In long-term stability testing, the 20 compounds were all remained stable. However, in the accelerated testing, the content of 11 chemical compounds (10-hydroxyoleoside dimethyl eser, echinacoside, nuezhengslaside, oleuropein acid, verbascoside, nuezhenide, specnuezhenide, ligustroflavone, nuezhenidic acid, nuezhenoside-G13, and oleonuezhenide) decreased obviously. Taking soda-lime glass as the packaging material, the stability of Er-Zhi-Wan (water honey pills) was improved than the commercial package under the same sealing conditions. The airtightness of the packaging materials played a significant part on the pill's stability under different sealing conditions. Conclusion: The study offers the scientific and technical support for the quality control and the clinical safety of the preparation in Chinese materia medica.

Research progress on hepatoprotective effects of Erzhiwan and its components / 药学实践杂志

Erzhiwan includes two components of Chinese herbal medicines - Ligustri Lucidi Fructus and Herba Eclip-tae .Ligustri Lucidi Fructus ,Herba Ecliptae and their formulation have various hepatoprotective effects .There are many ac-tive ingredients in the formulation ,such as triterpenes ,iridoids ,phenethyl alcohol-glucosides ,coumarin ethers ,etc .They can resist various chemistry-induced hepatic injury ,ischemia reperfusion induced hepatic injury ,and hepatic fibrosis .The mecha-nisms of hepatoprotective effect include anti-oxidative stress ,anti-inflammatory ,inhibition of hyperplasia and activation of liver stellate cell ,motivating the apoptosis of liver stellate cell ,influencing the metabolic processes of liver cell ,ect .We reviewed and summarized the hepatoprotective effects of Erzhiwan and its components Ligustri Lucidi Fructus and Herba Ecliptae and explore the mechanisms of hepatoprotective effect in order to provide information for further research of pharmacodynamic ma-terial base .

Effect of Chinese Hebal Compound of Different Treating Principles on uPA of Cholestasis-induced Liver Fibrosis Rat / 中国中医药信息杂志

Objective To study the effects of the Chinese herbal compound (Erzhiwan, Shixiaosan and combined formula) on cholestasis-induced liver fibrosis rat’s uPA. Methods Bile duct ligation method was used to make the model of cholestasis-induced liver fibrosis. One week after the operation, the rats were randomly divided into five group (model group, UDCA group, Erzhiwan group, Shixiaosan group and hefang group). Each medicine intervention group was given corresponding medicine by intragastric administration. Sham and model group were given sodium chloride with equal dosage. At the end of 4th week, all rats were sacrificed and sampled. General state of health, hepatic function (ALT, AST, ALP, TBil) and pathological histology of hepatic tissue were recorded and measured. Results Compared with the sham group, the level of ALT, AST, ALP, TBil and the degree of liver fibrosis in model group were advanced significantly. Compared with model group, three Chinese herbal compound decreased serum level of ALP, ALT and AST (P