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Chihiro Tohda - One of the best experts on this subject based on the ideXlab platform.

  • Data_Sheet_1_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.docx
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

  • Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice
    Frontiers Media S.A., 2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism

  • Video_2_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.MP4
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

Norio Tanabe - One of the best experts on this subject based on the ideXlab platform.

  • Data_Sheet_1_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.docx
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

  • Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice
    Frontiers Media S.A., 2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism

  • Video_2_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.MP4
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

Ming You - One of the best experts on this subject based on the ideXlab platform.

  • biopharmaceutical and pharmacokinetic characterization of Matrine as determined by a sensitive and robust uplc ms ms method
    Journal of Pharmaceutical and Biomedical Analysis, 2010
    Co-Authors: Zhen Yang, Song Gao, Taijun Yin, Kaustubh H Kulkarni, Yang Teng, Ming You
    Abstract:

    The purpose of this research was to develop a sensitive and reproducible UPLC-MS/MS method to analyze Matrine, an anticancer compound, and to use it to investigate its biopharmaceutical and pharmacokinetic behaviors in rats. A sensitive and fast UPLC-MS/MS method was successfully applied to determine Matrine in rat plasma, intestinal perfusate, bile, microsomes, and cell incubation media. The absolute oral bioavailability of Matrine is 17.1+/-5.4% at a dose of 2mg/kg Matrine. Matrine at 10microM was shown to have good permeability (42.5x10(-6)cm/s) across the Caco-2 cell monolayer, and the ratio of P(A-B) to P(B-A) was approximately equal to 1 at two different concentrations (1 and 10microM). Perfusion study showed that Matrine displayed significant differences (P<0.05) in permeability at different intestinal regions. The rank order of permeability was ileum (highest, P(w)=6.18), followed by colon (P(w)=2.07), duodenum (P(w)=0.61) and jejunum (P(w)=0.52). Rat liver microsome studies showed that CYP and UGTs were not involved in Matrine metabolism. In conclusion, a sensitive and reliable method capable of measuring Matrine in a variety of matrixes was developed and successfully used to determine absolute oral bioavailability of Matrine in rats, transport across Caco-2 cell monolayers, absorption in rat intestine, and metabolism in rat liver microsomes.

Tomoharu Kuboyama - One of the best experts on this subject based on the ideXlab platform.

  • Data_Sheet_1_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.docx
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

  • Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice
    Frontiers Media S.A., 2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism

  • Video_2_Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.MP4
    2018
    Co-Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
    Abstract:

    After spinal cord injury (SCI), reconstruction of neuronal tracts is very difficult because an inhibitory scar is formed at the lesion site, in which several axonal growth inhibitors, such as chondroitin sulfate proteoglycans (CSPG), accumulate. We previously found that Matrine, a major alkaloid in Sophora flavescens, enhanced axonal growth in neurons seeded on CSPG coating. The aims of this study were to investigate therapeutic effects of Matrine in SCI mice and to clarify the underlying mechanism. Matrine was orally administered to contusion SCI mice. In the Matrine-treated mice, motor dysfunction of the hindlimbs was improved, and the density of 5-HT-positive tracts was increased in the injured spinal cord. We explored putative direct binding proteins of Matrine in cultured neurons using drug affinity responsive target stability (DARTS). As a result, heat shock protein 90 (HSP90) was identified, and Matrine enhanced HSP90 chaperon activity. We then presumed that extracellular HSP90 is a Matrine-targeting signaling molecule, and found that specific blocking of extracellular HSP90 by a neutralizing antibody completely diminished Matrine-induced axonal growth and SCI amelioration. Our results suggest that Matrine enhances axonal growth and functional recovery in SCI mice by direct activation of extracellular HSP90. Matrine could be a significant candidate for therapeutic drugs for SCI with a novel mechanism.

Changzhong Wang - One of the best experts on this subject based on the ideXlab platform.

  • Matrine reduces yeast-to-hypha transition and resistance of a fluconazole-resistant strain of Candida albicans.
    Journal of applied microbiology, 2014
    Co-Authors: Jing Shao, Tianming Wang, Yuanyuan Yan, Gaoxiang Shi, Huijuan Cheng, Changzhong Wang
    Abstract:

    Aims To evaluate the potential effect of Matrine on reducing the growth of hypha and lowering the resistance of a fluconazole-resistant colony of Candida albicans. Methods and Results Candida albicans SC5314 and a fluconazole-resistant C. albicans 215 were used. As for C. albicans SC5314, minimal inhibitory concentration (MIC80) and effective concentration (EC50) were determined, 1 mg ml−1 Matrine could inhibit nearly 80% of planktonic growth by inverted microscope, 2 mg ml−1 Matrine suppressed 50% of metabolic activity of biofilm by XTT assay, vanishing hypha could be observed on spider agar containing 2 mg ml−1 Matrine, the expressions of three hypha-related genes, namely ALS 3, SUN 41 and PBS 2, were suppressed by 29, 45 and 61% by 2 mg ml−1 Matrine. Also, Matrine could lower the resistance of C. albicans 215, in either the free-floating form or the biofilm phenotype. Conclusions Matrine had favourable antifungal potential and might be able to reverse the fluconazole resistance of clinical isolates at relatively high concentration. The anti-candidal performance of Matrine could be tightly associated with yeast-to-hypha transition proved by spider agar test and qRT-PCR. Significance and Impact of Study More efforts are needed to find new antifungal agents. Matrine could be a potential candidate to fight against Candida-related infections by regulating yeast-to-hypha transition.