Drug clinical comprehensive evaluation of tetrandrine in the treatment of pneumoconiosis / 中华劳动卫生职业病杂志

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.

Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation / 中华放射医学与防护杂志

Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.

An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots / 中西医结合学报

Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (-OCH

Therapeutic prospect of tetrandrine against SARS-CoV-2 based on its pulmonary pharmacology and exposure character / 药学学报

As the main active compound of Stephania tetrandra S. Moore, tetrandrine (TET) has been used to treat silicosis for nearly 50 years. TET has clear therapeutic effect on pulmonary fibrosis and lung cancer. A recent study suggests that TET may inhibit the replication of SARS-CoV-2 by blocking the two-pore channel 2 (TPC2), revealing its potential as a natural medicine to treat COVID-19. To explore the material basis of TET targeting lung efficacy and its potential toxicity, available literatures related to the pharmacological activity on pulmonary, dosage, toxicity and pharmacokinetics of TET are systemically reviewed. The prospect and current problems of TET to be a therapeutic agent for COVID-19 are further investigated on this basis.

Effects of tetrandrine on proliferation, migration, and invasion of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.

Therapeutic effect of tetrandrine on silicosis rats and its toxic effect on liver and kidney function / 中国职业医学

OBJECTIVE: To explore the therapeutic effect of tetrandrine(TET) on silicosis model rats and its toxic effect on liver and kidney function. METHODS: The specific pathogen free healthy male Wistar rats were randomly divided into the control group, the model group and the TET group, with 14 rats in each group. By un-exposure tracheal injection method, the rats in the model and TET groups were given one-time tracheal infusion of free silicon dioxide suspension with a mass concentration of 50 g/L to establish the rat model of silicosis. Rats in the control group were infused with 1 mL of 0.9% sodium chloride solution with the same method. On the second day after the model was established, the TET group was given 30 mg/kg body mass of TET solution by gavage. The other two groups were given the same amount of 0.9% sodium chloride solution. The treatment was once per day, six times per week. Seven rats in each group were sacrificed on the 28 th and 56 th days after modeling. The morphological change of the lung, liver and kidney tissues of each group was observed. The enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1), interleukin(IL)-1β and IL-6, in the lung tissues of rats in each group. The activities of aminotransferase(ALT), aspartate aminotransferase(AST) and the levels blood urea nitrogen(BUN), creatinine(CRE) were detected by automatic biochemical analyzer. RESULTS: The lung organ coefficients of rats in the TET group were lower than those of the model group on the 28 th and 56 th days(all P<0.05). The lung organ coefficient of the rats in the TET group on the 56 th day was higher than that in the same group on the 28 th day(P<0.05). The lung tissue structure of the control group was normal. After modeling, the lung tissues of rats in model group showed different degrees of pathological changes such as alveolar structure destruction, inflammatory cell infiltration, and fibrosis on the 28 th and 56 th days. The degree of pathological changes in TET group was less than that of the model group. In the lung tissues of rats in the model group, the levels of TNF-α, TGF-β1, IL-1β and IL-6 were higher than those of the control group(all P<0.01). The levels of TNF-α, TGF-β1, IL-1β and IL-6 in the lung tissues of rats in the TET group were lower than that of the model group(all P<0.01), but there was no statistically significant difference when compared with the control group(all P>0.05). The activities of ALT and AST in the TET group were higher than those in the model group and the control group(all P<0.01). The level of serum BUN in TET group was higher than that in control group(P<0.01), but it showed no statistical difference when compared with the control group(P>0.05). The level of serum CRE in each group showed no significant difference(P>0.05). There were no abnormal pathological changes found in the liver and kidney tissues of rats in each group at different times. CONCLUSION: TET can reduce the inflammatory response in silicosis rats and improve lung tissue fibrosis; however, the therapeutic dose may have certain toxicity to the liver and kidney of the silicosis rats.

Bioassay guided fractionation of Cyclea peltata using in vitro RAW 264.7 cell culture, antioxidant assays and isolation of bioactive compound tetrandrine

Background: Cyclea peltata is one of the herbs mentioned in ancient scriptures of Ayurveda and is used indifferent types of Ayurvedic gritham preparations. Moreover, in traditional/tribal medicine C. peltata isused as digestive, anti-inflammatory, diuretic and to treat jaundice, digestive disorders, etc.Objective: Activity guided fractionation of C. peltata and in correlation with the levels of bioactivecompound tetrandrine.Materials and methods: Preliminary phytochemical screening, estimation of total alkaloid content,preparation of different extracts of C. peltata (crude extract CP, hexane extract HCP, chloroform extractCCP, methanol extract MCP, alkaloid fraction ACP). In vitro anti-inflammatory studies using RAW264.7 cells and in vitro antioxidant assays of the different extracts of C. peltata. HPTLC estimation oftetrandrine (TET) was carried out using solvent system toluene: ethyl acetate: diethylamine (7.2: 2: 0.8)and isolation of TET from ACP.Results: Preliminary phytochemical studies of C. peltata showed the presence of alkaloid content in allextracts. Whereas, saponins, steroids and terpenoids were detected in CP and CCP. ACP and TET showedsignificant in vitro anti-inflammatory and antioxidant activity when compared to other extracts. ACP andTET (100 mg/ml) treatment significantly inhibited the mRNA expression of iNOS, COX-2, TNF-a in LPStreated RAW 264.7 cells. HPTLC estimation of bioactive compound tetrandrine was highest in ACP228.4 mg/mg followed by CP-29.62 mg/mg, CCP-23.46 mg/mg, MCP-18.82 mg/mg and HCP-1.25 mg/mg. TEThas been isolated from ACP.Conclusion: The results of the present in vitro assays revealed that the alkaloid fraction (ACP) is the mostactive fraction when compared to other extracts and has a positive correlation with the levels of bioactivecompound tetrandrine.

Screening of HDAC3/8 Small Molecule Inhibitors from Traditional Chinese Medicine Based on Molecular Docking / 中国实验方剂学杂志

Objective::To discover a small molecule active ingredient of traditional Chinese medicine (TCM) with the inhibitory activity of histone deacetylase (HDAC) 3/8. Method::The molecular docking technique was performed by AutoDock 4.2.6 software. Trichostatin A (TSA) was used as a reference to screen 19 small molecular components from TCM, and the default docking conformation number was set to obtain the docking binding energy, active site amino acid residues and hydrogen bonds, and the biological activity was verified. Result::The binding energies of 19 small molecule components from TCM to HDAC3 and HDAC8 were different. Among them, ursolic acid, fangchinoline and tetrandrine have low binding energies to HDAC3 and HDAC8, and their binding activities were strong. The optimal binding energy of fangchinoline and HDAC3 at the site 1 was the lowest (-26.71 kJ·mol-1), and that of HDAC8 at the site 9 was the lowest (-26.84 kJ·mol-1). The optimal binding energy of tetrandrine and HDAC3 at the site 13 was the lowest (-26.38 kJ·mol-1), and that of HDAC8 at the site 12 was the lowest (-25.41 kJ·mol-1). In addition, the binding energy of ursolic acid and HDAC3 at the site 16 was the lowest (-25.83 kJ·mol-1), and that of HDAC8 at the site 8 was the lowest (-35.62 kJ·mol-1). Three kinds of amino acids at the docking site of small molecules were rendered by PyMOL 2.3.1.When ursolic acid was combined with HDAC3/8, the active sites produced two hydrogen bonds, and the interaction was strong, and many amino acids were connected at the active site. The fangchinoline formed two hydrogen bonds with the active site of HDAC3 and one hydrogen bond with the active site of HDAC8, and hydrophobic binding with some active site amino acids. There was no hydrogen bond between tetrandrine and HDAC3/8, and all docking sites were docked by 4 active amino acids. Three small molecules (ursolic acid, fangchinoline and tetrandrine) with the best docking effect had the inhibitory activity against HDAC3/8 at the concentration of 500 μmol·L-1 and 100 μmol·L-1, and the inhibitory activity was still optimal among the 10 selected small molecules. Conclusion::Among the screened 19 small molecules, ursolic acid, tetrandrine and fangchinoline may be the new anti-inflammatory drugs of HDAC3/8 inhibitory target, which provides a reference for further exploration and discovery of new anti-inflammatory drugs.

UPLC fingerprint-based analysis of differences in chemical components from different parts of Stephania tetrandra / 中草药

Objective: To analyze and compare UPLC fingerprints of root, rhizome, stem, and leaf of Stephania tetrandra, learn the differences in chemical component types and contents of main active components, and provide basis for rational development and utilization of S. tetrandra. Methods: UPLC was used to obtain characteristic chromatograms of different parts; The Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine (Version 2012) was run to capture the common peaks of different parts and calculate their similarity and analyze the characteristic peaks of different parts. SPSS 23.0 was run to compare the difference in component contents of the roots and rhizomes using the paired sample t-test. Results: The similarity in chemical composition between root and rhizome was 0.928, indicating they have similar chemical composition, and both of them contained tetrandrine and fangchinoline, the index components. The similarity between rhizome and leaf was 0.947; The similarity was low between stem, leaf and root and rhizome, and there were no tetrandrine and fangchinoline in the first two parts. The results of paired samples t-test show that the total content of chemical components in rhizome was higher than that in roots, and the mainly difference came from other non-index components, but there was no significant difference between tetrandrine and fangchinoline. Conclusion: Significant differences are present in chemical composition types and contents of different medicinal parts of S. tetrandra; The type of chemical components in rhizome is similar to that in root, and the content of some components in rhizome is significantly higher than that in root, which means that rhizomes can be used as an equivalent of roots. Stems and leaves cannot be a substitute for roots because they do not contain tetrandrine and fangchinoline, but they contain many other chemical components which can be utilized as a new resource.

Pharmacological effects and clinical application of tetrandrine: research advances / 国际药学研究杂志

Tetrandrine(TET)is a bisbenzyl isoquinoline alkaloid extracted from the plant Stephania tetrandra. TET is one of the important active ingredients of S.tetrandra, showing pharmacological effects mainly on the circulatory, respiratory and locomotor systems, such as the anti- inflammatory, anti-tumor, anti-arrhythmia, anti-hypertensive, anti-silicosis and fibrosis effect, and thus has a high clinical application value. This article reviews research achievements of the pharmacological effects, action mechanisms, dosage forms and clinical applications of TET, in order to provide reference for related research.

Quality Regionalization and Environmental Impact Factors Analysis Based on Main Active Ingredients of Stephaniae Tetrandrae Radix / 中国实验方剂学杂志

Objective:To investigate the quality regionalization and environmental impact factors of Stephaniae Tetrandrae Radix based on main active ingredients，and provide a reference for the determination of high-quality production areas and the dominant environmental factors affecting the content of Stephaniae Tetrandrae Radix. Method:Partial least squares regression analysis (PLS) and principal component analysis (PCA) were used to study the quality regionalization and environmental impact factors based on the main active ingredients of tetrandrine and fangchinoline, and investigate the environmental factors of the producing areas. Result:The content of fangchinoline was positively correlated with soil pH and annual average temperature，negatively correlated with latitude. The content of tetrandrine was positively correlated with soil pH，negatively correlated with annual rainfall and longitude. The total content was positively correlated with soil pH and annual average temperature，but negatively correlated with annual rainfall，latitude and longitude. Principal component analysis showed that the 50 production areas could be divided into four groups of quality formation. The groups with the highest scores were Shixing county in Guangdong，Shexian county in Anhui，Songxi county in Fujian，Nanxiong city in Guangdong and Xiangxiang city in Hunan，all of which were best areas for accumulation of the two main active ingredients. Conclusion:Soil pH，annual average temperature，annual rainfall，latitude and longitude are the main environmental factors affecting the main active ingredients of Stephaniae Tetrandrae Radix. The best areas for accumulation of tetrandrine and fangchinoline are Shixing county in Guangdong，Shexian county in Anhui，Songxi county in Fujian，Nanxiong city in Guangdong and Xiangxiang city in Hunan.

Effect of Tetrandrine on Col-I and FN in TGF-β1-induced MRC-5 Cells / 中国实验方剂学杂志

Objective:To investigate the effect of tetrandrine on transforming growth factor-β1（TGF-β1）stimulated MRC-5 cells. Method:Different concentrations of TGF-β1 (0, 2.5, 5, 10, 20, 40 μg·L-1) were applied to MRC-5 cells. Proliferation toxicity of TGF-β1 to MRC-5 was detected by cell counting kit-8 (CCK-8) method. Detection of alpha smooth muscle actin (α-SMA) and Vimentin's expression levels in MRC-5 by Western blot. Detection of changes of collagen I(Col-I) and fibronectin (FN)'s expression levels in MRC-5 supernatants by enzyme linked immunosorbent assay(ELISA) kit. And the appropriate concentration of TGF-β1 activated MRC-5 cells was screened. The appropriate concentration of TGF-β1 and different concentrations of Tet (0, 2.5, 5, 10, 20, 40 μmol·L-1) were applied to MRC-5 cells, and CCK-8 method was used to screen safe concentration again. Western blot was used to detect changes in α-SMA and Vimentin expression levels in MRC-5 cells, and ELISA method to detect changes in Col-I and FN in MRC-5 cell supernatant. Result:Compared with the blank group, 20，40 μg·L-1 of TGF-β1 had toxic effects on MRC-5 cells at 24 hours (P<0.05), and 10，20，40 μg·L-1 of TGF-β1 had toxic effects on MRC-5 cells at 48 h (P<0.05).When Tet is added for 24 h, the half inhibitory concentration (IC50) value was 14.07 μmol·L-1, and when cultured for 48 h, the IC50 value was 7.51 μmol·L-1. Compared with the blank group, the relative contents of α-SMA, FN and Col-I in the 5 μg·L-1 of TGF-β1 group were obviously increased (P<0.05), and the relative contents of Vimentin were significantly increased (P<0.01), and the relative contents of FN and Col-I, α-SMA and Vimentin in 10 μg·L-1 group were significantly increased (P<0.01). 10 μg·L-1 of TGF-β1 was co-cultured with Tet at different concentrations. Compared with the TGF-β1 group, the relative levels of α-SMA, Vimentin and FN in the 5 μmol·L-1 of Tet group were significantly reduced (P<0.01), and the relative levels of Col-I were obviously reduced (P<0.05). In the Tet 10 μmol·L-1 group, the relative contents of the α-SMA, Vimentin, FN and Col-I were significantly reduced (P<0.01). Conclusion:TGF-β1 can increase the levels of Col-I, FN and other extracellular matrices in MRC-5 cells, and Tet can effectively inhibit the occurrence of this change. It is suggested that Tet may inhibit secreting extracellular matrix of fibroblasts in the formation of pulmonary fibrosis.

Tetrandrine derivative HL-49 combined with cisplatin or adriamycin promotes apoptosis of triple-negative breast cancer MDA-MB-231 cells / 肿瘤

Objective: To investigate the effects of tetrandrine derivative HL-49 combined with cisplatin (DDP) or adriamycin (ADM) on the proliferation and apoptosis of triple-negative breast cancer MDAMB- 231 cells, and to explore the possible mechanism. Methods: MDA-MB -231 cells were treated with different concentrations of HL-49, DDP or ADM alone and HL-49 combined with DDP or ADM, respectively. The proliferation inhibitory rate of MDA-MB-231 cells was detected by MTT assay and the Q value was calculated. The colony forming ability of MDA-MB-231 cells was detected by plate cloning test. The apoptosis rate was detected by FCM method and the Q value was calculated. The expression levels of Bloom's symdrome helicase (BLM), breast cancer susceptibility gene 1 (BRCA1), DNA repair key enzyme Rad51, apoptosis-related protein caspase 3, caspase 8, caspase 10, Bax, p53 and Bcl-2 were detected by Western blotting. Results: The proliferation inhibitory rate of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was significantly higher than that in HL-49, DDP or ADM alone group (all P < 0 05); the Q values of HL-49 (1 or 2 μmol/L) combined with DDP (5 or 10 μmol/L) were 2.04, 1.88, 1.87 and 1.83, respectively; while the Q values of HL-49 (1 or 2 μmol/L) combined with ADM (2 or 5 μmol/L) were 1.37, 1.21, 1.36 and 1.23, respectively. The colony formation number of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was significantly lower than that in HL-49, DDP or ADM alone group (all P < 0 05). The apoptosis rate of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was higher than that in HL-49, DDP or ADM alone group (all P < 0 05); the Q values of HL-49 (1 or 2 μmol/L) combined with DDP (5 or 10 μmol/L) were 1.20, 1.35, 1.70 and 2.06, respectively; the Q values of HL-49 (1 or 2 μmol/L) combined with ADM (2 or 5 μmol/L) were 1.48, 1.17, 1.99 and 2.13, respectively. The above results suggested that HL-49 and DDP (or ADM) had synergistic effects. As compared with HL-49, DDP or ADM alone group, the expression levels of caspase 3, caspase 8, caspase 10 and Bax proteins in HL-49 combined with DDP or ADM group were up-regulated, and the expression levels of Rad51, BRCA1, BLM, p53 and Bcl-2 proteins were down-regulated (all P < 0. 05). Conclusion: Tetrandrine derivative HL-49 combined with DDP or ADM has synergetic effect. The anti-tumor activity of the combination treatment is related to the induction of apoptosis in triple-negative breast cancer MDA-MB-231 cells.

Therapeutic effect of dihydroartemisinin on pulmonary fibrosis in rats with dust / 中华劳动卫生职业病杂志

Objective@#To observe the therapeutic effect of dihydroartemisinin on pulmonary fibrosis in rats exposed to dust, and compare the therapeutic effects of dihydroartemisinin and tetrandrine.@*Methods@#Sixty male Sprague-Dawley rats were randomly divided into control group, model group, treatment group 1 and treatment group 2, with 15 rats in each group. The model group and the treatment group were stained with disposable non-exposure silica tracheal instillation method. The drug was administered on the second day after the dust was applied. The treatment group was given with dihydroartemisinin 75 mg/kg, the treatment group was given tetrahexine 22 mg/kg, model group and control group were intragastrically administered with 1 ml of normal saline per 100 g of body mass. The drug was administered for 6 days per week for 28 days. Rats were sacrificed on the 7th, 14th and 28th day after dusting, and the lung tissues of rats were taken, detection of rat lung coefficient, ELISA was used to detect transforming growth factor-1(TGF-1)and Smad 2/3 in rat lung tissues, type I collagen (Col-I) expression level, pathological changes of rat lung tissue, immunohistochemical observation of rat lung tissue TGF-1 and Col-I protein expression. Statistial analysis was proformed with SPSS 19.0. The mean cornparis between graups wad perfomed using a completely randonized one-way (ANOVA).@*Results@#The expressions of TGF-1, Smad 2/3 and Col-I in the lung tissue of the treatment group were significantly lower than those in the model group (P< 0.05), but the difference between the treatment group 1 and the treatment group 2 Not statistically significant (P>0.05). The results of immunohistochemistry showed that the TGF-1 and Col-I proteins in the interstitial of the model group showed strong positive expression. The expression of TGF-1 and Col-I protein in the lung interstitial of the treated group was weaker than that of the model group.@*Conclusion@#Dihydroartemisinin can down-regulate the level of inflammatory cytokines in rat lung tissue. It is possible to inhibit pulmonary fibrosis by intervening in the TGF-β1/Smad 2/3 signaling pathway, but the therapeutic effect between DHA and tetrandrine is not significantly different in a short time.

Study on the Effects of Tetrandrine on Proliferation and Migration ，Invasion Ability of Neuroblastoma Cells and Its Mechanism / 中国药房

OBJECTIVE： To investigate the effects of tetrandrine （TET） on the proliferation and migration， invasion ability of neuroblastoma cells and its mechanism. METHODS： Human neuroblastoma cell lines IMR-32 and SH-SY5Y were chosen as objects. MTT assay was used to detect the effects of 0 （blank control）， 2.5， 5， 10， 15， 20 μmol/L TET on cell proliferation. The transmembrane number of normal control group （TET concentration of 0 μmol/L） and TET group （10 μmol/L for IMR-32 cells， 15 μmol/L for SH-SY5Y cells） were investigated by Transwell cell migration and invasion experiments. The protein levels of MMP-2， MMP-9， β-catenin， GSK3β and p-GSK3β in IMR-32 cells and SH-SY5Y cells were tested by Western blotting assay after treated with TET of above concentrations. RESULTS： TET with 5， 10， 15， 20 μmol/L can reduce the survival rate of IMR-32 cells and SH-SY5Y cells significantly （P＜0.05 or P＜0.01）. IC50 of which to IMR-32 cells and SH-SY5Y cells were 10.148 and 14.461 μmol/L， respectively. Results of migration and invasion experiments showed that compared with normal control group， the number of transmembrane cells was decreased significantly in TET group （P＜0.01）. Results of Western blotting assay showed that compared with normal control group， the protein expression levels of MMP-2，MMP-9，β-catenin and p-GSK3β were decreased significantly in TET group （P＜0.01）. CONCLUSIONS： TET shows significant inhibitory effects on the proliferation， migration and invasion ability of neuroblastoma cells， the mechanism of which may be associated with down-regulating the protein expression of MMP-2 and MMP-9 and inhibiting Wnt/β-catenin signaling pathway.

Intranasal tetrandrine temperature-sensitive gel for treatment of post-traumatic stress disorder / 药学学报

The traditional systemic treatment of post-traumatic stress disorder (PTSD) requires a long time period for an effect and has obvious side effects. In this study, tetrandrine temperature-sensitive gel (TTG) was prepared for treatment of PTSD in mice by nasal administration. TTG was prepared with poloxamer as matrix, the gelation temperature was suitable (<32 ℃) and the gelation time was short (1.32 min). Rheology experiments demonstrated that TTG has temperature sensitivity. In vivo imaging system of small animals proved that TTG nasal cavity retention time was so long. The cilia toxic test of toad showed that the formulation was safe. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. The mice were randomly assigned into healthy group, model group and TTG group. The PTSD model of mice was established by single prolonged stress (SPS) and foot-shock method to generate anxiety and fear behavior. On the day 0 of TTG administration, SPS model mice were evaluated by the elevated plus maze (EPM). Percentages of open arm entries number (OE), latency of open arm entries (OL) and the residence time of open arm entries (OT) all indicated that the SPS model was successfully established. On the 7th day of TTG administration, TTG increased the OE and OT, decreased the OL of SPS mice. The feard behavior of mice in the foot-shock model was tested using conditioned fear box, 7 days of TTG treatment can reduce the freezing time of the mice obviously. The pathological changes of hippocampus, prefrontal cortex and amygdala were observed by H&E histological sections and c-fos immunohistochemical expression. The main influenced areas of PTSD were revealed to be the CA1 of hippocampus, prefrontal cortex and amygdala. All of the above indicated that TTG is a convenient, safe and effective drug for PTSD treatment, and will provide a new choice for clinical management of PTSD.

Study on relationship between IGFBP-5/p53 axis and anti-proliferation effect of tetrandrine in MCF-7 cells / 中国药理学通报

Aim To study the effect of tetrandrine ( Tet ) on proliferation of MCF-7 breast cancer cells and the possible mechanism underlying this biological process. Methods CCK-8, flow cytometric and Western blot were introduced to analyze the effect of Tet on proliferation and apoptosis in MCF-7 cells.Re-al-time PCR and/or Western blot assay were employed to detect the effect of Tet on expression of IGFBP-5 , p53 and MDM2.CCK-8 and recombinant adenovirus were utilized to determine the effect of IGFBP-5 on the proliferation inhibitory effect of Tet .Western blot assay was introduced to evaluate the effect of IGFBP-5 on p53 which was induced by Tet .Results Tet inhibited the proliferation , arrested cell cycle at G 1 phase and decreased the expression of PCNA concentration dependently in MCF-7 cells.Meanwhile, Tet increased the percentage of apoptotic cells , the level of Bad and reduced the level of Bcl-2.Tet increased the expres-sion of IGFBP-5 either mRNA or protein , over-expres-sion of IGFBP-5 enhanced the anti-proliferation activity of Tet in MCF-7 cells, but knockdown of IGFBP-5 at-tenuated this effect of Tet .Tet increased the level of p53 and decreased that of MDM2, and exogenous IG-FBP-5 enhanced the effect of Tet on p53 and MDM2, respectively .Conclusion Tet can inhibit the prolifer-ation of MCF-7 cells, and this activity is partly media-ted by increasing the function of p 53 signal , which may be triggered by the Tet-induced IGFBP-5.

Optimization of preparation process and dissolution test of tetrandrine dropping pills / 中草药

Objective: To optimize the preparation process of tetrandrine dropping pills (TDP) and investigate the in vitro dissolution rate. Methods: Plackett-Burman experimental design was used to screen the critical factors in the preparation process of TDP from the ratio of matrix, ratio of matrix to drug, dropping temperature, dropping rate, dropping distance, and condensate temperature. The forming rate and weight variation of TDP were used as the evaluation index, the parameters in the preparation process of TDP were optimized by using the Box-Behnken response surface method. Moreover, the in vitro dissolution rate of TDP was compared with tetrandrine tablets by rotating basket method. Results: The Plackett-Burman experimental design results showed that the ratio of matrix, dropping temperature and condensate temperature had a significant effect on the forming rate of TDP. The optimum preparation parameters by Box-Behnken response surface method were as follows: the ratio of matrix was 2.6∶1, dropping temperature was 82.4 ℃ and condensation temperature was 7.5 ℃ with high forming rate, good roundness, stable weight, and fast drug dissolution rate of TDP. Conclusion: The quality of TDP by experimental design method can meet the requirements and can be further amplified.

Combination of tetrandrine and paclitaxel overcomes multidrug resistance on C6/MDR glioma cells / 中草药

Objective To investigate the feasibility of tetrandrine combined with paclitaxel (PTX) in multidrug resistance reversal on C6/MDR glioma cells, and explore the potential molecular mechanisms. Methods Through the comparison of non-resistant glioma C6 cells and drug-resistant glioma C6/MDR cells, the cytotoxicity of against C6/MDR (or C6) cells were assayed by MTT method. The intracellular accumulation of PTX and Rhodamine 123 (R123) were determined by high performance liquid chromatography (HPLC) and flow cytometry, respectively. The cell apoptosis induction of C6/MDR (or C6) cells was detected by AnnexinV-PE/7-AAD staining method after various intervention of PTX, tetrandrine, and PTX + HfA. P-glycoprotein (P-gp) expression and P-gp ATPase activity were evaluated through P-gp antibody binding assay kit and Pgp-GloTM assay systems, respectively. Results The half maximal inhibitory concentration (IC50) of tetrandrine + PTX against C6/MDR cells were (5.88 ± 0.43) nmol/L. The C6/MDR intracellular accumulation of PTX and R123 were increased by 9.4-fold and 12.3-fold in the presence of 10 μmol/L tetrandrine. Accordingly, the apoptosis rate of C6/MDR cells treated with tetrandrine + PTX was 2.3-fold higher than PTX treatment. The tetrandrine-mediated multidrug resistance reversal was involved with the downregulation of P-gp expression and the stimulation of P-gp ATPase activity. Conclusion The combination of tetrandrine and PTX had a potential of overcoming multidrug resistance on C6/MDR glioma cells in vitro.

Preparation of chitosan nano-particles loaded tetrandrine and its inhibitory effects on the proliferation of human pterygium fibroblast cells / 眼科新进展

Objective To investigate the inhibitory effects of chitosan nano-particles loaded tetrandrine (Tet) on proliferation of cultured pterygium fibroblasts.Methods The deoxycholic acid-modified chitosan (DAMC) derivative was synthesized through amidation reaction,and their properties were investigated.The viability of human pterygium fibroblasts (HPF) was evaluated by cell counting kit-8 (CCK-8) assay after cells were interacted with Tet/DAMC nano-particles on day 1,3 and 5.Results The synthesized chitosan derivative and Tet formed drug-loaded nano-particles,and the agent-loading capacity was approximately 76％,and the sizes of agent-loaded nano-particles were 50-500 nm,with Zeta potential values being positive.The result of in vitro drug release experiment indicated that the nano-particles constantly released Tet in a controlled manner within 48 h.The viability of HPF in Tet group was (60.70 ± 2.30) ％,(50.22 ± 2.35) ％,(21.99 ± 2.07) ％ on day 1,3,5,respectively,but the corresponding data in Tet/DAMC group was (79.77 ±2.09)％,(63.24 ±2.83)％,(40.28 ± 1.19)％,respectively.The CCK-8 assay demonstrated that the Tet/DAMC nano-particles could inhibit HPF proliferation,and presented lower toxicity than Tet alone.Conclusion Chitosan nano-particles loaded tetrandrine exhibits a sustained agent-release behavior,which has obvious inhibitory effects on the proliferation of human pterygium fibroblasts,but its cytotoxicity is significantly lower than the original drug's,thereby possessing a great promise for improving the outcome of Tet for the prevention of pterygium recurrence.