The Experts below are selected from a list of 534 Experts worldwide ranked by ideXlab platform
Hua Zhou - One of the best experts on this subject based on the ideXlab platform.
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α7 nicotinic acetylcholine receptor is a novel mediator of Sinomenine anti inflammation effect in macrophages stimulated by lipopolysaccharide
Shock, 2015Co-Authors: Jinfang Luo, Hua Zhou, Liang Liu, Bingbing Xie, Jianxin Liu, Junyue Wang, Peixun Wang, Yan DongAbstract:Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effects and has been used for rheumatoid arthritis treatment in China. This study aims to verify the hypothesis that SIN acts on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit the activation of macrophages stimulated by lipopolysaccharide. The prototypical α7nAChR antagonist α-bungarotoxin and mecamylamine attenuated the effect of SIN on tumor necrosis factor-α and interleukin-6 in RAW264.7 murine macrophage-like cells and primary peritoneal macrophages of mouse induced by lipopolysaccharide. With the knockdown of α7nAChR expression in RAW264.7 cells by small interfering RNA, the inhibitory effect of SIN on tumor necrosis factor-α and interleukin-6 was reversed. Sinomenine decreased p65 expression in nuclear and increased IκBα expression in cytoplasm, and these effects were reversed by the α7nAChR small interfering RNA as well. These results indicate that the anti-inflammatory effects of SIN on macrophages in vitro depend on α7nAChR.
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Sinomenine ameliorates arthritis via MMPs, TIMPs, and cytokines in rats.
Biochemical and Biophysical Research Communications, 2008Co-Authors: Hua Zhou, Yuen-fan Wong, Jue WangAbstract:Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that results in progressive joint destruction and substantial morbidity. The stem of the Chinese medicinal plant, Sinomenium acutum Rehder & Wilson (Family Menispermaceae), has been used to treat various rheumatic and arthritic diseases, of which the major bioactive component is Sinomenine. We investigated the nature and molecular mechanisms of the anti-arthritic effect of Sinomenine on collagen-induced arthritis in female Wistar rats. The results showed that Sinomenine markedly suppressed the incidence and disease progression of established CIA, showing as dramatic reduction of paw swelling, ESR, and arthritic scores. Sinomenine suppressed the production of proinflammatory cytokines IL-1β and IL-6 in serum, inhibited the protein expressions and activities of MMP-2 and MMP-9, and elevated the protein expressions and activities of TIMP-1 and TIMP-3 in rat paw tissues.
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the effects of Sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model
Journal of Ethnopharmacology, 2006Co-Authors: Kelvin Chan, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Zhong Qiu Liu, Liang LiuAbstract:Paeoniflorin and Sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that Sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of Sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, Sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, Sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that Sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.
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the pharmacokinetics and tissue distribution of Sinomenine in rats and its protein binding ability in vitro
Life Sciences, 2005Co-Authors: Zhong Qiu Liu, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Kelvin Chan, Liang LiuAbstract:Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining Sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg Sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of Sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of Sinomenine. Examination of the protein binding ability showed that Sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that Sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.
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influence of co administrated Sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats
Journal of Ethnopharmacology, 2005Co-Authors: Hua Zhou, Yuen-fan Wong, Zhi Hong Jiang, Hongxi Xu, Kelvin ChanAbstract:Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutumRehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and Sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with Sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague–Dawley rats (n =6 , 250–300 g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of Sinomenine, the peak plasma concentration of paeoniflorin was elevated ( P < 0.01), the peak time was delayed (P < 0.01), the AUC0–t was increased (P < 0.001), the mean residence time (MRT) was prolonged (P < 0.01), the CL was decreased (P < 0.01) and the Vd was reduced (P < 0.05). These results indicate that Sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats. © 2005 Elsevier Ireland Ltd. All rights reserved.
Liang Liu - One of the best experts on this subject based on the ideXlab platform.
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α7 nicotinic acetylcholine receptor is a novel mediator of Sinomenine anti inflammation effect in macrophages stimulated by lipopolysaccharide
Shock, 2015Co-Authors: Jinfang Luo, Hua Zhou, Liang Liu, Bingbing Xie, Jianxin Liu, Junyue Wang, Peixun Wang, Yan DongAbstract:Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effects and has been used for rheumatoid arthritis treatment in China. This study aims to verify the hypothesis that SIN acts on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit the activation of macrophages stimulated by lipopolysaccharide. The prototypical α7nAChR antagonist α-bungarotoxin and mecamylamine attenuated the effect of SIN on tumor necrosis factor-α and interleukin-6 in RAW264.7 murine macrophage-like cells and primary peritoneal macrophages of mouse induced by lipopolysaccharide. With the knockdown of α7nAChR expression in RAW264.7 cells by small interfering RNA, the inhibitory effect of SIN on tumor necrosis factor-α and interleukin-6 was reversed. Sinomenine decreased p65 expression in nuclear and increased IκBα expression in cytoplasm, and these effects were reversed by the α7nAChR small interfering RNA as well. These results indicate that the anti-inflammatory effects of SIN on macrophages in vitro depend on α7nAChR.
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An Ultra-High Performance Liquid Chromatographic-Tandem Mass Spectrometric Method for the Determination of Sinomenine in Human Plasma after Transdermal Delivery of the Zhengqing Fengtongning Injection
MDPI AG, 2015Co-Authors: Tingbo Chen, Zheng Xiang, Gengting Dong, Pei Luo, Ping Qiu, Shenzhi Wang, Baoming Huang, Yingyi Wen, Liang LiuAbstract:A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of Sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract Sinomenine. Separation was carried out on a C18 column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for Sinomenine quantification. The working assay range for Sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze Sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained Sinomenine within the concentration range 0.4131–4.407 ng/mL
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the effects of Sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model
Journal of Ethnopharmacology, 2006Co-Authors: Kelvin Chan, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Zhong Qiu Liu, Liang LiuAbstract:Paeoniflorin and Sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that Sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of Sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, Sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, Sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that Sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.
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the pharmacokinetics and tissue distribution of Sinomenine in rats and its protein binding ability in vitro
Life Sciences, 2005Co-Authors: Zhong Qiu Liu, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Kelvin Chan, Liang LiuAbstract:Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining Sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg Sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of Sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of Sinomenine. Examination of the protein binding ability showed that Sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that Sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.
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influence of co administrated Sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats
Journal of Ethnopharmacology, 2005Co-Authors: Zhong Qiu Liu, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Liang Liu, Ying Xie, Xiong Cai, Kelvin ChanAbstract:Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and Sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with Sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected] g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of Sinomenine, the peak plasma concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced (P<0.05). These results indicate that Sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.
Qing-yong Chang - One of the best experts on this subject based on the ideXlab platform.
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Sinomenine sensitizes multidrug resistant colon cancer cells caco 2 to doxorubicin by downregulation of mdr 1 expression
PLOS ONE, 2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that Sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of Sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that Sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.
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COX-2 over expressed in MDR-Caco-2 cells, which could be reversed by Sinomenine.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:MDR-Caco-2 cells were incubated without doxorubicin for a week before experiments. Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) Western blot analysis of Sinomenine and celecoxib mediated effect on COX-2 expression in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (B) The relative band density values in the COX-2 expression lanes are described in the bar chat. (C) Real-time PCR analysis of COX-2 expression in Caco-2 cells and MDR-Caco-2 cells treated with or without Sinomenine and celecoxib. Beta-actin was used as the internal reference for the detection of COX-2 expression. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
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Effects of Sinomenine, celecoxib, and Sinomenine plus PGE2 on cell proliferation in Caco-2 and MDR-Caco-2 cells.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Caco-2 and MDR-Caco-2 cells were treated for 48 h with doxorubicin (10−5 to 10 µM) alone or in combination with Sinomenine (500 µM), celecoxib (25 µM), or Sinomenine (500 µM) plus PGE2 (1 µM). Cell viability was then determined by MTT assay. Ct group (A and C) refers to doxorubicin-treated Caco-2 group and Ct group (B and D) refer to doxorubicin-treated MDR-Caco-2 group. Data are presented as the mean ± SE. (n = 3) of a representative experiment performed in triplicate. **P
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Effect of Sinomenine (Sino) on expression of P-gp (MDR1) in MDR-Caco-2 cells.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Multidrug-resistant Caco-2 (MDR-Caco-2) cells were developed by exposure of Caco-2 cells to increasing concentrations of doxorubicin (from 0.1 µM to 1.6 µM in 7 days). MDR-Caco-2 cells were incubated without doxorubicin for a week before experiments. Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) immunocytochemistry targeting P-gp (green). (B) Western blot analysis of Sinomenine and celecoxib mediated effect on P-gp expression in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (C) The relative band density values in the P-gp expression lanes are described in the bar chat. (D) Real-time PCR analysis of MDR1 expression in Caco-2 cells and MDR-Caco-2 cells treated with or without Sinomenine. Beta-actin was used as the internal reference for the detection of MDR1 expression. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
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NF-κB pathway was activated in MDR-Caco-2 cells, which was suppressed by Sinomenine and celecoxib.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) immunocytochemistry targeting P65 (green). (B) Western blot analysis of Sinomenine and celecoxib mediated effect on nuclear translocation of P65 in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (C) The relative band density values in the nuclear expression P65 lanes are described in the bar chat. (D) The relative band density values in the cytoplasmic p-IκB-α lanes are described in the bar chat. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
Kelvin Chan - One of the best experts on this subject based on the ideXlab platform.
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the effects of Sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model
Journal of Ethnopharmacology, 2006Co-Authors: Kelvin Chan, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Zhong Qiu Liu, Liang LiuAbstract:Paeoniflorin and Sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that Sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of Sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, Sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, Sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that Sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.
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the pharmacokinetics and tissue distribution of Sinomenine in rats and its protein binding ability in vitro
Life Sciences, 2005Co-Authors: Zhong Qiu Liu, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Kelvin Chan, Liang LiuAbstract:Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining Sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg Sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of Sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of Sinomenine. Examination of the protein binding ability showed that Sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that Sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.
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influence of co administrated Sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats
Journal of Ethnopharmacology, 2005Co-Authors: Hua Zhou, Yuen-fan Wong, Zhi Hong Jiang, Hongxi Xu, Kelvin ChanAbstract:Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutumRehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and Sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with Sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague–Dawley rats (n =6 , 250–300 g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of Sinomenine, the peak plasma concentration of paeoniflorin was elevated ( P < 0.01), the peak time was delayed (P < 0.01), the AUC0–t was increased (P < 0.001), the mean residence time (MRT) was prolonged (P < 0.01), the CL was decreased (P < 0.01) and the Vd was reduced (P < 0.05). These results indicate that Sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats. © 2005 Elsevier Ireland Ltd. All rights reserved.
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influence of co administrated Sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats
Journal of Ethnopharmacology, 2005Co-Authors: Zhong Qiu Liu, Yuen-fan Wong, Zhi Hong Jiang, Hua Zhou, Liang Liu, Ying Xie, Xiong Cai, Kelvin ChanAbstract:Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and Sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with Sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected] g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of Sinomenine, the peak plasma concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced (P<0.05). These results indicate that Sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.
Zhen Liu - One of the best experts on this subject based on the ideXlab platform.
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Sinomenine sensitizes multidrug resistant colon cancer cells caco 2 to doxorubicin by downregulation of mdr 1 expression
PLOS ONE, 2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that Sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of Sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that Sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.
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COX-2 over expressed in MDR-Caco-2 cells, which could be reversed by Sinomenine.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:MDR-Caco-2 cells were incubated without doxorubicin for a week before experiments. Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) Western blot analysis of Sinomenine and celecoxib mediated effect on COX-2 expression in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (B) The relative band density values in the COX-2 expression lanes are described in the bar chat. (C) Real-time PCR analysis of COX-2 expression in Caco-2 cells and MDR-Caco-2 cells treated with or without Sinomenine and celecoxib. Beta-actin was used as the internal reference for the detection of COX-2 expression. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
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Effects of Sinomenine, celecoxib, and Sinomenine plus PGE2 on cell proliferation in Caco-2 and MDR-Caco-2 cells.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Caco-2 and MDR-Caco-2 cells were treated for 48 h with doxorubicin (10−5 to 10 µM) alone or in combination with Sinomenine (500 µM), celecoxib (25 µM), or Sinomenine (500 µM) plus PGE2 (1 µM). Cell viability was then determined by MTT assay. Ct group (A and C) refers to doxorubicin-treated Caco-2 group and Ct group (B and D) refer to doxorubicin-treated MDR-Caco-2 group. Data are presented as the mean ± SE. (n = 3) of a representative experiment performed in triplicate. **P
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Effect of Sinomenine (Sino) on expression of P-gp (MDR1) in MDR-Caco-2 cells.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Multidrug-resistant Caco-2 (MDR-Caco-2) cells were developed by exposure of Caco-2 cells to increasing concentrations of doxorubicin (from 0.1 µM to 1.6 µM in 7 days). MDR-Caco-2 cells were incubated without doxorubicin for a week before experiments. Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) immunocytochemistry targeting P-gp (green). (B) Western blot analysis of Sinomenine and celecoxib mediated effect on P-gp expression in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (C) The relative band density values in the P-gp expression lanes are described in the bar chat. (D) Real-time PCR analysis of MDR1 expression in Caco-2 cells and MDR-Caco-2 cells treated with or without Sinomenine. Beta-actin was used as the internal reference for the detection of MDR1 expression. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
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NF-κB pathway was activated in MDR-Caco-2 cells, which was suppressed by Sinomenine and celecoxib.
2014Co-Authors: Zhen Liu, Zhi-jun Duan, Jiu-yang Chang, Zhi-feng Zhang, Rui Chu, Ke-hang Dai, Qing-yong ChangAbstract:Then MDR-Caco-2 cells were treated with or without Sinomenine (500 µM) and celecoxib (25 µM) for 48 hours. (A) immunocytochemistry targeting P65 (green). (B) Western blot analysis of Sinomenine and celecoxib mediated effect on nuclear translocation of P65 in Caco-2 cells and MDR-Caco-2 cells. Antibody to beta-actin was used to ensure equal loading of protein in each lane. (C) The relative band density values in the nuclear expression P65 lanes are described in the bar chat. (D) The relative band density values in the cytoplasmic p-IκB-α lanes are described in the bar chat. All the results above are expressed as the means ± SE (n = 3) of three independent experiments. *, P
