Concentrations Of Matrine Research Articles

Downregulated miR-21 mediates matrine-induced apoptosis via the PTEN/Akt signaling pathway in FTC-133 human follicular thyroid cancer cells.

Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC-133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC-133 cells in a dose- and time-dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC-133 cells. The expression level of microRNA (miR)-21 was analyzed by reverse transcription-quantitative PCR (RT-qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)-Akt were detected by RT-qPCR analysis and western blotting, respectively. The expression of miR-21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p-Akt was downregulated in the FTC-133 cells. The effects of miR-21 mimics and miR-21 inhibitor on the expression of miR-21, PTEN and Akt in FTC-133 cells, and the effect of miR-21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC-133 cells via the miR-21/PTEN/Akt signaling pathway.

Matrine inhibits the proliferation of pituitary tumor cells by decreasing Foxo3a phosphorylation and promoting Foxo3a nuclear localization.

Pituitary tumors account for 10% of intracranial cancer, and are difficult to treat with chemotherapy. The aim of the present study was to explore the role of matrine on the proliferation of pituitary cancer cells, as well as the molecular mechanism of matrine in progression and development of pituitary tumors. Matrine significantly suppressed the proliferation of pituitary cancer cells in a dose- and time-dependent manner. Western blotting results showed that the phosphorylation levels of AKT serine/threonine kinase (Akt) and forkhead box O3A (Foxo3a) decreased as the concentration of matrine increased. Matrine increased the nuclear localization of Foxo3a and the expression of proapoptotic genes, such as BCL2 like 11 and BCL2 associated X apoptosis regulator, and inhibited the levels of cytoplasmic Foxo3a. In conclusion, matrine promoted cell death of pituitary cancer cells and was involved in Akt/Foxo3a signaling pathway.

Effect of matrine on reducing damage to bovine mammary epithelial cells induced by Staphylococcus aureus alpha-hemolysin.

Taking bacterial virulence factors as targets is a new therapy for treating host bacterial infection. The aim of this study was to investigate the effect of matrine on α-hemolysin production of Staphylococcus aureus (S. aureus) and reducing the damage to bovine mammary epithelial cells (BMECs) induced by S. aureus α-hemolysin. Subinhibitory concentrations of matrine decreased the production of α-hemolysin in none dose-dependent manner and matrine exhibited a protective effect on S. aureus-induced BMECs injury. The results indicated that the structure of matrine may potentially be used as a basic structure for development of drugs aimed at curing and preventing dairy bovine mastitis.

Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC-7721 cell line.

The existence of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) is regarded as the cause of tumor formation and recurrence. Matrine has been reported to exhibit antitumor effects in cancer cells. In the present study, a preliminary study was performed on the mechanisms of matrine on hepatocellular carcinoma (HCC) stem-like cells. The HCC SMMC-7721 cell line was cultured in tumor stem cell-specific medium to form spheres, and different concentrations (1, 2 and 5 mg/kg) of cisplatin were then used in order to purify the most drug-resistant cells, which were used as CSLCs. An MTT assay was performed to detect the inhibitory effects of matrine against CSLC proliferation. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to detect changes in cell adhesion regulating gene (CAR), E-cadherin, laminin and fibronectin. As a result, using tryptose sulfite cycloserine medium culture and cisplatin-resistance screening, CSLCs were successfully isolated from the SMMC-7721 cell line. Matrine inhibited the proliferation of CSLCs in vitro. The results of qPCR and western blot analysis demonstrated that matrine upregulated the expression of CAR, E-cadherin, laminin and fibronectin in CSLCs compared with the control treatment. A certain concentration of matrine exhibited antitumor effects on HCC stem like cells.

Matrine suppresses cardiac fibrosis by inhibiting the TGF‑β/Smad pathway in experimental diabetic cardiomyopathy.

Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized. MTT assay was used to select non-cytotoxic concentrations of matrine, which were subsequently used to treat isolated cardiac fibroblasts incubated under various conditions. Western blotting was performed to assess activation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. Rats with DbCM exhibited impaired heart compliance and left ventricular (LV) functions. Excessive collagen deposition in cardiac tissue was also observed. Furthermore, TGF-β1/R-Smad (Smad2/3) signaling was revealed to be markedly activated; however, the expression of inhibitory Smad (I-Smad, also termed Smad7) was reduced in DbCM. Matrine administration led to a marked recovery in LV function and heart compliance by exerting inhibitory effects on TGF-β1/R-Smad signaling pathway-induced fibrosis without affecting I-Smad. Incubation with a high concentration of glucose triggered the TGF-β1/R-Smad (Smad2/3) signaling pathway and suppressed I-Smad signaling transduction in cultured cardiac fibroblasts, which led to an increase in the synthesis of collagen. After cardiac fibroblasts had been treated with matrine at non-cytotoxic concentrations without affecting I-Smad, matrine blocked TGF-β1/R-Smad signaling transduction to repress collagen production and deposition. In conclusion, the results of the present study demonstrated that TGF-β1/Smad signaling-associated cardiac fibrosis is involved in the impairment of heart compliance and LV dysfunction in DbCM. By exerting therapeutic effects against cardiac fibrosis via its influence on TGF-β1/Smad signaling, matrine exhibited cardioprotective effects in DbCM.

Matrine suppresses the migration and invasion of NSCLC cells by inhibiting PAX2-induced epithelial-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro. Cell Counting Kit-8 assay was used to evaluate the cell viability. Transwell assay was used to detect the migration and invasion abilities. Microarray assay was used to analyze the differentiated expression genes with or without matrine treatment. Western blotting and real-time polymerase chain reaction were applied to detect the expressions of PAX2, E-cadherin and N-cadherin. Our study showed that matrine could suppress the proliferative activity of NSCLC cells in a dose- and time-dependent manner. Further investigation discovered that the migration and invasion of NSCLC cells were significantly inhibited by treatment with different concentrations of matrine. Microarray assay, real-time polymerase chain reaction and western blotting showed that matrine could significantly decrease the expression of PAX2. In addition, epithelial-mesenchymal transition and related proteins were decreased. In conclusion, matrine may block PAX2 expression to interfere with epithelial-mesenchymal transition signaling pathway that ultimately inhibit the migration and invasion of NSCLC cells in vitro. Matrine might serve as a potential agent for NSCLC treatment.

Treatment mechanism of matrine in combination with irinotecan for colon cancer.

The inhibitory effect of matrine (MA) was studied in combination with irinotecan (CPT-11) on proliferation of human colon carcinoma cell line HT29. We also explored the mechanism of cell apoptosis induction in HT29. HT29 cells were treated with different concentrations of MA and CPT-11 alone and in combination. The growth inhibition in HT29 cells was evaluated using MTT assay. Apoptosis was detected using AV-PI double staining flow cytometry. Transmission electron microscopy was used to detect structural changes in cells. Topoisomerase (TOPO) I, Bax and Caspase-3 expression levels were evaluated using western blot analysis. MA and CPT-11 alone and in combination, inhibited the proliferation of HT29 cells, whereas the combination treatment exhibited higher inhibitory effect (P<0.01). This suggests the existence of synergistic cytotoxicity. Compared with each treatment alone, the combination treatment caused more significant damage to cell structure, and caused a significantly higher apoptosis rate (P<0.01). Additionally, the combination treatment increased TOPO I, Bax and Caspase-3 expression levels (P<0.01). In conclusion, MA in combination with CPT-11 synergistically inhibited HT29 cell proliferation and induced apoptosis in these cells. The mechanism may be related to upregulation of the TOPO I, Bax and Caspase-3 protein expression.

Ursolic acid benzaldehyde chalcone, leads to inhibition of cell proliferation and arrests cycle in G1/G0 phase in colon cancer.

The present study investigates the effect of matrine on colon cancer cell viability and apoptosis and tumor growth in mice xenograft model. The results from MTT assay revealed a concentration and time dependent reduction in viability of HCT8 and HT29 colon cancer cells by matrine. The viability of HCT8 and HT29 cells was reduced to 24.67 and 29.32% on treatment with 4 µM/ml concentration of matrine after 48 h (P < 0.05). The results from flow cytometry revealed increase in population of HCT8 and HT29 cells to 77.6 ± 0.3 and 54.0 ± 5.4%, respectively compared to 1.4 ± 0.3 and 2.4 ± 0.7% in control on exposure to 1 µM/ml concentration of matrine. Histone H2AX phosphorylation and expression of Myt1, cyclin A2, cyclin B1 and p53 were increased in HCT8 and HT29 cells on treatment with matrine for 48 h. Matrine treatment also increased the phosphorylation of cdc2 significantly compared to control cells at 48 h (P < 0.05). Results from Annexin-V/FITC-staining showed increase in proportion of apoptotic cells in HCT8 and HT29 cells 67.52 and 68.56 on treatment with 1 µM/ml of matrine. Matrine treatment caused a marked reduction in the growth of HCT8 cell xenograft after 21 days. Thus matrine inhibits cell viability, induces apoptosis and inhibits tumor growth in colon cancer.

Development of a Novel Electrochemical Sensor for Determination of Matrine in Sophora flavescens.

A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with increased oxidation peak currents and the decreased over-potential in the redox process of MT, indicating the great enhancement of electrocatalytic activity toward the oxidation of MT by the composite of GNs and HA. Under the optimized conditions, the oxidation peak currents were related linearly with the concentration of MT, ranging from 2 μM to 3 mM, and the detection limit (S/N = 3) was 1.2 μM. In addition, the proposed electrochemical sensor can be successfully applied in the quantitative determination of MT in Sophora flavescens extract.

Matrine reduces the proliferation of A549cells via the p53/p21/PCNA/eIF4E signaling pathway.

The aim of the present study was to investigate how matrine affects the proliferation of A549 human lung adenocarcinoma cells via the p53/p21/proliferating cell nuclear antigen (PCNA)/eukaryotic translation initiation factor 4E (eIF4E) signaling pathway. The effect of different concentrations of matrine on the proliferation of A549 cells was investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The migration of A549 cells following exposure to varied concentrations of matrine was detected using a Transwell cell migration assay. The effect of 240 mg/l matrine on the apoptotic rate of A549 cells was determined using flow cytometry. The change in the mRNA and protein expression levels of p53, p21, PCNA and eIF4E following exposure to matrine were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The increase of matrine from 60–240 mg/l led to reduced cell migration and inhibition of A549 cell proliferation. The apoptotic rate of A549 cells when treated with 240 mg/l matrine was significantly different when compared with the untreated control. The mRNA expression levels of p53 and p21 in the group treated with 240 mg/l matrine were significantly higher compared with the control group. The mRNA expression levels of PCNA and eIF4E were significantly lower in the 240 mg/l matrine-treated group compared with the control. The protein expression levels of p53 and p21 were significantly higher in the 240 mg/l matrine group compared with the control group. Treatment with 240 mg/l matrine reduced the protein expression levels of PCNA and eIF4E. Matrine also reduced the migration ability of A549 cells and inhibited their proliferation, which may be associated with the overexpression of p53 and p21, and the reduction of PCNA and eIF4E expression levels.

Effect of matrine and oxymatrine on proliferation and apoptosis and signaling transduction of janus kinase-signal transduction and activators of transcription family in SMMC-7721 cell line

Objective To study the effect of matrlne and oxymatrine on prolifemtion and apoptosis and janus kinase (JAK)-signal transduction and activators of transcription family (STAT) signaling transduefion pathway in SMMC-7721 cell line. Methods Application of matrine and Oxymatrine intervention of hepatocellular carcinoma SMMC-7721 by methyl thiazol tetrazolium (MTT) assay on the proliferation effect of matrine and oxymatrine in hepatocellular carcinoma cells, using double fluorescent staining observation of matrine and Oxymatrine intervention on apoptosis of hepatocellular carcinoma cell line SMMC-7721 rate changes, and to detect the matrine and oxymatrine real-time quantitative polymerase chain reaction (Real-time PCR) on hepatocellular carcinoma SMMC-7721 Star3 and STAT5 mRNA cells. With P<0.05 as a statistical significance. Results (1) With matrine and oxymatrine concentration and action time increased, cell proliferation rate, matrine and Oxymatrine effect each time group cell proliferation inhibition rate and concentration was positively correlated (r=0.851-0.989), the proliferation of matrine and oxymatrine in each concentration group at different time compared to cell inhibition the rate difference was statistically significant. (2) In double fluorescence detection, the living cells were stained with acridine orange (AO) green, apoptotic cells were stained with ethidium bromide (EB) orange orange. The apoptosis rate of matrine 2.5 mg/ml 48 h group was 52.1%, and the apoptosis rate of 48 h group was 29.6%, which showed that the same concentration of matrine was significantly more than that of 2.5 mg/ml (χ2=9.100, P=0.003). (3) The expression levels of Star3 and mRNA STAT5 were significantly decreased after different concentrations of matrine and matrine in SMMC-7721 cells, and the difference was statistically significant. STAT3, STAT5 mRNA expression in control group cells was 0.76±0.06 and 0.72±0.04, the expression in 1.0 mg/ml matrine group is 0.50±0.04 and 0.43±0.03, the expression in 2.5mg/ml matrine group is 0.25±0.03 and 0.22±0.04, the expression in 1.0 mg/ml oxymatrine group is 0.64±0.03 and 0.60±0.06, the expression in 2.5 mg/ml oxymatrine group is 0.49±0.06 and 0.41±0.06. The effects of matrine on SMMC-7721 cells were more significant, and the difference was statistically significant. Conclusion Matrine and oxynmtrine inhibited the proliferation and induced the apoptosis of SMMC-7721 cells significantly. The mechanism of which might be related to the down-regulate of star3 and STAT5 mRNA and inhibit the signaling transduetion pathway. Key words: Matrlne; Oxymatrine; Proliferation; Apoptosis; Janus kinase-signal transduction and activators of transcription family pathway

Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway.

The induction of apoptosis-resistant rheumatoid synovial tissue cells has been related to constitutively active Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling in rheumatoid arthritis (RA). The excessive proliferation and inherent resistance to apoptosis of fibroblast-like synoviocytes (FLS) is an important mechanism by which RA originates. However, the effects of matrine on FLS in RA is unclear. The present study aimed to investigate the mechanism of action of matrine in a rat model of collagen-induced arthritis (CIA). The CIA model was established using bovine type II collagen. FLS were isolated from control and CIA rats, cultured in vitro, and confirmed to harbor fibroblast-like characteristics. After treatment of FLS with varying concentrations of matrine, the JAK2 inhibitor AG490, or a combination of both drugs, cell proliferation, apoptosis rate, expression of apoptotic markers and the activation of the JAK/STAT pathway were assessed. Additionally, CIA rats were administered either matrine or methotrexate by oral gavage to examine the effects of therapeutic intervention on arthritis pathogenesis. The arthritis index (AI) was measured and ankle joint structure was analyzed histologically to determine the severity of CIA. Furthermore, expression levels of apoptotic markers and members of the JAK/STAT family were also examined in vivo. Compared with the CIA group, matrine reduced AI and improved ankle pathology. Matrine also inhibited FLS proliferation, induced G0/G1 cell cycle arrest, and increased the rate of apoptosis in vitro. The effects of matrine on apoptosis induction were further confirmed by observations that Bcl-2 levels were decreased, whereas Bax and caspase-3 levels were increased in the matrine-treated synovial tissues and FLS. Finally, matrine treatment also diminished the phosphorylation, and hence activation of JAK2, STAT1 and STAT3. Our results suggest that matrine induces the apop-tosis of FLS from rats with CIA by inhibiting activation of the JAK/STAT signaling pathway.

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression.

The incidence rate of Parkinson's disease (PD) is ≤2% in Chinese individuals >65 years old, accounting for 40% of the global total of PD patients. The pathogenesis of PD is not yet clear, and oxidative stress-induced mitochondrial dysfunction is considered to be the main reason for the onset of PD. Studies have shown that matrine exhibits good antioxidant activity. Thus, the present study aimed to observe the protective effect and mechanism of matrine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuron damage. A total of 25 C57BL male mice were randomly divided into 5 groups, consisting of the control group (group A), the MPTP group (group B) and three matrine (4, 8 and 16 mg/kg) plus MPTP treatment groups (groups C, D and E, respectively). Results from a pole-climbing test and locomotor activity experiments were recorded. The mice were sacrificed 4 days later and brain dissection was performed. The levels of superoxide dismutase (SOD) and glutathione (GSH) were assessed. The expression level of tyrosine hydroxylase (TH) in the ventral midbrain was studied by immunofluorescence analysis. The expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) in the ventral midbrain was studied by western blot analysis. The experiments were repeated three times. Compared with control mice, the PD mice exhibited the typical behaviors associated with PD; matrine can alleviate this phenomenon, and with increasing matrine concentration, the symptoms were reduced significantly. Compared with the control mice, the PD mice had lower SOD and GSH activity, and matrine partially reversed the change in SOD and GSH activity. Immunofluorescence analysis showed that the level of TH in the ventral midbrain decreased significantly in the PD mice, and that the mice administered matrine showed higher expression of TH and levels of TH-positive cells. Western blotting results showed that the expression of Nrf2 in the ventral midbrain decreased significantly in the PD mice, and that matrine was able to reverse this phenomenon. In conclusion, by promoting antioxidant-related Nrf2 signaling pathways in the ventral midbrain, matrine can inhibit the oxidative damage of dopamine neurons in PD.

Matrine induces cell cycle arrest and apoptosis with recovery of the expression of miR-126 in the A549 non-small cell lung cancer cell line.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. Chemotherapy prolongs survival rates among patients with advanced disease, however, this is at the cost of clinically significant adverse effects. Matrine is an active component of traditional Chinese medicine and is a promising alternative drug for the treatment of NSCLC. In the present study, the therapeutic effects and the underlying molecular mechanisms of matrine on the A549 NSCLC cell line were investigated. A high concentration of matrine (1.0 mg/ml) significantly (P<0.05) inhibited cell proliferation, by 52.68±3.32%, under which cell shrinkage and disruption were observed. Flow cytometric analysis showed that the proportion of G1/G0 cells was significantly increased, whereas the proportions of S and G2/M cells were significantly decreased (P<0.05) following treatment with matrine for 48 h. These results indicated that cell arrest was induced by matrine. Upregulation of the expression of microRNA (miR)-126, followed by downregulation of the expression of its target gene, vascular endothelial growth factor, were detected following treatment with a low concentration of matrine (0.2 mg/ml) using reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. In conclusion, matrine induced cell cycle arrest and apoptosis, and recovered the expression of miR-126 in the A549 NSCLC cell line.

Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6

The matrine-type alkaloid, oxymatrine inhibits hepatitis B virus (HBV) replication but very little is known about these effects in other matrine-type alkaloids, including sophoridine and sophocarpine. Therefore, we compared the in vitro anti-HBV effects of matrine, oxymatrine, sophocarpine, and sophoridine by treating an HBV-transfected cell line (HepG2.2.15) with 0.4–1.6mM of the compounds for 24 or 72h. The levels of the HBV surface antigen (HBsAg) and e antigen (HBeAg) in the culture medium, as well as the intracellular and extracellular HBV DNA levels, were determined. Metabolomic analysis and detection of the mRNA level of p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor-associated factor (TRAF) 6, extracellular signal-regulated kinase (ERK) 1, NOD-like receptor family pyrin domain containing 10 (NLRP10), and caspase-1 were conducted in sophoridine-treated HepG2.2.15 cells. HepG2.2.15 cell exposure to 0.4–1.6mM sophocarpine or sophoridine for 24h reduced the HBsAg level of the medium more effectively than exposure to matrine and oxymatrine did, and reduced the HBeAg levels more effectively than these compounds did at 1.6mM. Sophoridine (0.4–1.6mM) reduced the cell medium HBV DNA levels more than the same concentrations of matrine, oxymatrine, or sophocarpine did. After 72h, 0.4 and 0.8mM sophoridine reduced HBsAg and intracellular HBV DNA levels more potently than matrine, oxymatrine, or sophocarpine did. Furthermore, sophoridine (0.8mM) potently reduced the cell medium HBeAg levels while the metabolomic analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine for 72h exhibited reduced cycloleucine and phytosphingosine levels. In addition, the mRNA expression analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine showed reduced levels of p38 MAPK, TRAF6, ERK1, NLRP10, and caspase-1. Sophoridine produced more potent anti-HBV effects than matrine, oxymatrine, and sophocarpine did. These effects may be related to the sophoridine-mediated reduction of p38 MAPK and TRAF6 levels.

Effect of Matrine on the expression of X-linked inhibitor of apoptosis protein in human rhabdomyosarcoma RD cells

Objective To investigate the effect of Matrine on the expression of X-linked inhibitor of apoptosis protein (XIAP) in human rhabdomyosarcoma RD cells in vitro. Methods Cultured human rhabdomyosarcoma RD cells were divided into Matrine intervention groups (0.5 g/L, 1.0 g/L and 1.5 g/L) and a control group.The proliferation-inhibition rates in RD cells treated with different concentrations of matrine were detected by methylthiazolyl blue colorimetric assay.Flow cytometry analysis was performed for the apoptosis rates of RD cells.Reverse transcription-polymerase chain reaction analysis was used to measure the XIAP mRNA expression. Results There was a significant difference in the proliferation-inhibition rates [0.5 g/L Matrine group: (15.84±2.58)%, 1.0 g/L Matrine group: (23.13±4.19)%, 1.5 g/L Matrine group: (30.32±3.02)%, and the control group: (8.92±1.23)%]; apoptotic rates [0.5 g/L Matrine group: (12.33±1.15)%, 1.0 g/L Matrine group: (16.67±0.99)%, 1.5 g/L Matrine group: (25.33±1.91)%, and the control group: (9.47±0.96)%]; XIAP mRNA expression(0.5 g/L Matrine group: 0.633±0.046, 1.0 g/L Matrine group: 0.441±0.055, 1.5 g/L Matrine group: 0.326±0.065, control group: 0.794±0.029)in RD cells among 0.5 g/L, 1.0 g/L, 1.5 g/L Matrine groups and the control group (F=14.15, 83.37, 50.57, all P<0.05). The proliferation-inhibition and apoptotic rates in RD cells were gradually increased with the increasing Matrine concentration.The expression of XIAP mRNA was significantly decreased in different Matrine groups compared with the control group, exhibiting a dose-dependent manner. Conclusions Matrine can inhibit the proliferation of RD cells and induce the apoptosis in a dose-dependent manner, which may be related to the down-regulated XIAP mRNA. Key words: Human rhabdomyosarcoma RD cell; Matrine; X-linked inhibitor of apoptosis protein

Effects and mechanisms of matrine on proliferation and apoptosis of human rhabdomyosarcoma RD cells line

Objective To investigate the effects of matrine on proliferation and apoptosis of human rhabdom-yosarcoma(RMS) RD cells line in vitro, to study the regulatory mechanism of Wnt/β-catenin pathway-influenced apoptosis of RD cells line by detecting the expressions of β-catenin protein, Bcl-2 protein and caspase-3 protein, and to explore Wnt/β-catenin mechanism during the process of RMS. Methods The human RMS RD cells line was treated with matrine of different concentrations (0.5, 1.0, 1.5, 2.0 g/L)for 48 hours respectively, and the proliferation inhibition rates of different concentrations of matrine on RD cells were detected by methyl thiazolyl tetrazolium assay, while the apoptosis rates by flow cytometry(FCM) and the expressions of β-catenin, Bcl-2 and caspase-3 by Wes-tern blot. Results The proliferation inhibition rates between control group and different concentrations of matrine groups were(13.70±0.25)%, (33.16±0.11)%, (42.96±0.90)%, (56.26±0.79)% and (67.89±0.63)%, respectively.The apoptosis rates were (5.49±0.96)%, (17.23±5.03)%, (25.84±4.17)%, (36.08±3.68)% and (47.79±4.82) %, respectively.The highest expression of β-catenin and Bcl-2 proteins and the minimum amount of caspase-3 protein were found in the control group.After intervention of matrine, the expressions of β-catenin and Bcl-2 reduced while the amount of caspase-3 rose significantly, which was concentration-dependent obviously.Differences were found between every concentration of matrine group with control group according to statistics (all P<0.05). Conclusions Matrine can inhibit proliferation and induce apoptosis of RD cells.Matrine can down-regulate the expression of β-catenin and Bcl-2 proteins in RD cells, while the amount of caspase-3 protein rises.Wnt/β-catenin signal pathway plays an important role in the apoptosis of RD cell induced by matrine, and its downstream proteins Bcl-2 and caspase-3 are also involved in the regulation of this process. Key words: Matrine; Rhabdomyosarcoma; Wnt Proteins; Cell apoptosis

Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK.

KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life and T max of matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively. C max and AUCinf of matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

A rapid, green and controllable method to fabricate the electrodeposition of a film of reduced graphene oxide as sensing materials for the determination of matrine

The electrodeposition of a film of reduced graphene oxide (ERGO) on a glassy carbon electrode (GCE) was achieved using pulse potential method (PPM) in the graphene oxide colloidal solution. For the first time, the electrodeposition of a film was applied to develop a high-sensitive electrochemical sensor for determination of matrine using linear sweep adsorptive stripping voltammetry (LSASV). Compared with bare GCE and ERGO film prepared by potentiostatic method (PM) modified electrode, the resulting electrodes (PP-ERGO/GCE) exhibited excellent response toward the oxidation of matrine by significantly enhancing the oxidation peak currents and decreasing the overpotential of matrine. Under the selected conditions, there exist the linear relation between the oxidation peak currents and matrine concentration in the range of 2.0×10−6–1.2×10−4molL−1, with detection limit of 5.0×10−7molL−1. At the same time, the method can be successfully applied to the quantitative determination of matrine in injection and its result is satisfactory.

Sensitive electrochemiluminescence detection of matrine based on Ru(bpy)32+and mesoporous silica nanosphere modified electrodes

In this paper, a simple and sensitive ECL sensor based on mesoporous silica (mSiO2) nanospheres was constructed for the quantitative detection of matrine (MT). Electrochemical and ECL behaviors were investigated with Ru(bpy)32+/mSiO2/Nafion modified electrodes and the sensor was used for the detection of matrine under a Ru(bpy)32+/tripropylamine (TPA) system. The influence of the pH and scan rate was studied. Under optimum conditions the experimental results indicated that the sensor had an excellent ECL efficiency and showed a good response to the concentration of MT with a linear range from 1.5 × 10−6 M to 2.0 × 10−3 M. The lowest detection limit was 0.5 μM with a relative standard deviation of 5.47%. This constructed ECL sensor could be applicable for real sample analysis.