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Kai Sun - One of the best experts on this subject based on the ideXlab platform.
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a molecular docking study Cepharanthine protects articular cartilage against arthritis by wnt pi3k tlr 3 signaling
Arabian Journal of Chemistry, 2021Co-Authors: Wenmin Zhao, Dongyun Yao, Ru Yang, Heshui Huo, Chenman Qin, Kai SunAbstract:Abstract Rheumatoid arthritis (RA) is an autoimmune disorder that causes joint inflammation and permanent disability in affected patients. This study investigated the protective effect of Cepharanthine treatment against Freund's adjuvant-induced RA in a rat model. RA was induced in rats by injection of incomplete Freund’s adjuvant (IFA) into the plantar surface on days 0 and 9. Cepharanthine at a dose of 10 or 20 mg/kg was administered intraperitoneally to separate groups of rats 12 days after the administration of IFA. The effects of Cepharanthine on RA were determined by measuring serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators. The expression levels of several proteins that regulate the Wnt/PI3K/Toll-like receptor (TLR)-3 pathway were measured via immunohistochemistry, western blotting and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assays. Molecular docking was performed to assess the interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. Our data revealed that Cepharanthine treatment attenuated serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators in RA rats. Analyses with qRT-PCR and western blotting revealed that the mRNA expression levels of Wnt/PI3K/TLR-3 pathway components were attenuated in Cepharanthine-treated RA rats. Cepharanthine also reduced chondrocyte apoptosis and autophagy. Molecular docking analysis revealed significant interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. In conclusion, the findings implied that Cepharanthine treatment attenuates chondrocyte autophagy, apoptosis and proliferation by regulating the Wnt/PI3K/TLR-3 pathway in RA rats.
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A molecular docking study: Cepharanthine protects articular cartilage against arthritis by Wnt/PI3K/TLR-3 signaling
Arabian Journal of Chemistry, 2021Co-Authors: Wenmin Zhao, Dongyun Yao, Ru Yang, Heshui Huo, Chenman Qin, Kai SunAbstract:Abstract Rheumatoid arthritis (RA) is an autoimmune disorder that causes joint inflammation and permanent disability in affected patients. This study investigated the protective effect of Cepharanthine treatment against Freund's adjuvant-induced RA in a rat model. RA was induced in rats by injection of incomplete Freund’s adjuvant (IFA) into the plantar surface on days 0 and 9. Cepharanthine at a dose of 10 or 20 mg/kg was administered intraperitoneally to separate groups of rats 12 days after the administration of IFA. The effects of Cepharanthine on RA were determined by measuring serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators. The expression levels of several proteins that regulate the Wnt/PI3K/Toll-like receptor (TLR)-3 pathway were measured via immunohistochemistry, western blotting and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assays. Molecular docking was performed to assess the interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. Our data revealed that Cepharanthine treatment attenuated serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators in RA rats. Analyses with qRT-PCR and western blotting revealed that the mRNA expression levels of Wnt/PI3K/TLR-3 pathway components were attenuated in Cepharanthine-treated RA rats. Cepharanthine also reduced chondrocyte apoptosis and autophagy. Molecular docking analysis revealed significant interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. In conclusion, the findings implied that Cepharanthine treatment attenuates chondrocyte autophagy, apoptosis and proliferation by regulating the Wnt/PI3K/TLR-3 pathway in RA rats.
Masayuki Azuma - One of the best experts on this subject based on the ideXlab platform.
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Cepharanthine Inhibits IFN-γ-Induced CXCL10 by Suppressing the JAK2/STAT1 Signal Pathway in Human Salivary Gland Ductal Cells
Inflammation, 2018Co-Authors: Keiko Aota, Tomoko Yamanoi, Koichi Kani, Masayuki AzumaAbstract:Cepharanthine, a biscolaurine alkaloid isolated from the plant Stephania cephalantha Hayata , has been reported to have potent anti-inflammatory properties. Here, we investigated the effects of Cepharanthine on the expression of CXCL10 (a CXC chemokine induced by interferon-gamma [IFN-γ] that has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions) in IFN-γ-treated human salivary gland cell lines. We observed that IFN-γ-induced CXCL10 production in NS-SV-DC cells (a human salivary gland ductal cell line), but not in NS-SV-AC cells (a human salivary gland acinar cell line). Cepharanthine inhibited the IFN-γ-induced CXCL10 production in NS-SV-DC cells. A Western blot analysis showed that Cepharanthine prevented the phosphorylation of JAK2 and STAT1, but did not interfere with the NF-κB pathway. Moreover, Cepharanthine inhibited the IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggest that Cepharanthine suppresses IFN-γ-induced CXCL10 production via the inhibition of the JAK2/STAT1 signaling pathway in human salivary gland ductal cells. Our findings also indicate that Cepharanthine could inhibit the chemotaxis of Jurkat T cells by reducing CXCL10 production.
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Cepharanthine inhibits ifn γ induced cxcl10 by suppressing the jak2 stat1 signal pathway in human salivary gland ductal cells
Inflammation, 2018Co-Authors: Keiko Aota, Tomoko Yamanoi, Koichi Kani, Masayuki AzumaAbstract:Cepharanthine, a biscolaurine alkaloid isolated from the plant Stephania cephalantha Hayata, has been reported to have potent anti-inflammatory properties. Here, we investigated the effects of Cepharanthine on the expression of CXCL10 (a CXC chemokine induced by interferon-gamma [IFN-γ] that has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions) in IFN-γ-treated human salivary gland cell lines. We observed that IFN-γ-induced CXCL10 production in NS-SV-DC cells (a human salivary gland ductal cell line), but not in NS-SV-AC cells (a human salivary gland acinar cell line). Cepharanthine inhibited the IFN-γ-induced CXCL10 production in NS-SV-DC cells. A Western blot analysis showed that Cepharanthine prevented the phosphorylation of JAK2 and STAT1, but did not interfere with the NF-κB pathway. Moreover, Cepharanthine inhibited the IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggest that Cepharanthine suppresses IFN-γ-induced CXCL10 production via the inhibition of the JAK2/STAT1 signaling pathway in human salivary gland ductal cells. Our findings also indicate that Cepharanthine could inhibit the chemotaxis of Jurkat T cells by reducing CXCL10 production.
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Treatment with the Biscoclaurine Alkaloid Cepharanthine Significantly Increases Salivary Secretion in Primary Sjögren's Syndrome Patients
2017Co-Authors: Tomoko Yamanoi, Keiko Aota, Yukihiro Momota, Masayuki AzumaAbstract:Objective: Our previous findings suggested that the suppression of tumor necrosis factoralpha (TNF-α)-induced matrix metalloproteinase (MMP)-9 production by the biscoclaurine alkaloid Cepharanthine could prevent the destruction of the acinar structure in the salivary glands of murine Sjogren's syndrome. Here, we examined the effect of Cepharanthine on the salivary secretion in primary Sjogren's syndrome (pSS) patients. Methods: In this single-center, open-label pilot study, 29 patients with pSS (28 women, 1 man) received 6 mg/day orally Cepharanthine for 12 months. Standard clinical assessments and stimulated salivary flow were examined at baseline and each month for 12 months in all 29 patients. In eight of the patients, inflammatory lesions in the salivary glands were histologically investigated before and after the Cepharanthine treatment. We analyzed the expressions of p65, phosphorylated IκB-α, MMP-9, and type IV collagen immunohistochemically. Results: All patients completed the study without any adverse events. A significant increase in salivary flow was observed after the Cepharanthine treatment compared to baseline. The serological analysis revealed that the 14 patients with an anti-Sjogren's-syndrome-related antigen A (anti-SSA/Ro) antibody value that was either negative or 64 U/ml did not. The immunohistochemical analysis demonstrated that although p65, phosphorylated IκB-α, and MMP-9 were more strongly stained in the acinar cells of the patients at baseline compared to the staining at the completion of Cepharanthine treatment, the continuity of type IV collagen was observed following the Cepharanthine treatment. These results indicate that Cepharanthine could inhibit the phosphorylation of IκB-α, followed by the prevention of MMP-9 activation and the stabilization of type IV collagen. Conclusions: Our findings suggest that Cepharanthine could be a promising agent for improving salivary secretion in pSS patients.
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suppression of tumor necrosis factor alpha induced matrix metalloproteinase 9 production in human salivary gland acinar cells by Cepharanthine occurs via down regulation of nuclear factor kappab a possible therapeutic agent for preventing the destruc
Arthritis & Rheumatism, 2002Co-Authors: Masayuki Azuma, Keiko Aota, Tetsuya Tamatani, Katsumi Motegi, Tsuyoshi Yamashita, Yuki Ashida, Yoshio Hayashi, Mitsunobu SatoAbstract:Objective Our previous results suggested that suppression of tumor necrosis factor α (TNFα)–induced matrix metalloproteinase 9 (MMP-9) could prevent the destruction of acinar tissue in the salivary glands of patients with Sjogren's syndrome (SS). The present study was undertaken to investigate the effect of Cepharanthine on the suppression of TNFα-induced MMP-9 production in NS-SV-AC, an SV40-immortalized normal human acinar cell clone. Methods After pretreatment with or without Cepharanthine, NS-SV-AC cells were treated with TNFα alone or with a combination of TNFα and Cepharanthine. The expression of MMP-9 was then examined at the protein and messenger RNA levels. In addition, the effect of Cepharanthine on the morphogenetic behavior of NS-SV-AC cells cultured on type IV collagen–coated dishes in the presence of TNFα was examined. Results Although TNFα induced the production of MMP-9 in NS-SV-AC cells, this production was greatly suppressed when cells were pretreated with Cepharanthine, followed by treatment with both TNFα and Cepharanthine. In addition, Cepharanthine suppressed the TNFα-stimulated NF-κB activity by partly preventing the degradation of IκBα protein in NS-SV-AC cells. When NS-SV-AC cells were seeded on type IV collagen–coated dishes in the presence of both TNFα and plasmin, type IV collagen interaction with the cells was lost and the cells entered apoptosis. However, pretreatment with Cepharanthine restored the aberrant in vitro morphogenesis of the NS-SV-AC cells. Conclusion These results may indicate a molecular mechanism by which Cepharanthine is able to protect against the destruction of the acinar structure in salivary glands from patients with SS.
Wenmin Zhao - One of the best experts on this subject based on the ideXlab platform.
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a molecular docking study Cepharanthine protects articular cartilage against arthritis by wnt pi3k tlr 3 signaling
Arabian Journal of Chemistry, 2021Co-Authors: Wenmin Zhao, Dongyun Yao, Ru Yang, Heshui Huo, Chenman Qin, Kai SunAbstract:Abstract Rheumatoid arthritis (RA) is an autoimmune disorder that causes joint inflammation and permanent disability in affected patients. This study investigated the protective effect of Cepharanthine treatment against Freund's adjuvant-induced RA in a rat model. RA was induced in rats by injection of incomplete Freund’s adjuvant (IFA) into the plantar surface on days 0 and 9. Cepharanthine at a dose of 10 or 20 mg/kg was administered intraperitoneally to separate groups of rats 12 days after the administration of IFA. The effects of Cepharanthine on RA were determined by measuring serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators. The expression levels of several proteins that regulate the Wnt/PI3K/Toll-like receptor (TLR)-3 pathway were measured via immunohistochemistry, western blotting and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assays. Molecular docking was performed to assess the interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. Our data revealed that Cepharanthine treatment attenuated serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators in RA rats. Analyses with qRT-PCR and western blotting revealed that the mRNA expression levels of Wnt/PI3K/TLR-3 pathway components were attenuated in Cepharanthine-treated RA rats. Cepharanthine also reduced chondrocyte apoptosis and autophagy. Molecular docking analysis revealed significant interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. In conclusion, the findings implied that Cepharanthine treatment attenuates chondrocyte autophagy, apoptosis and proliferation by regulating the Wnt/PI3K/TLR-3 pathway in RA rats.
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A molecular docking study: Cepharanthine protects articular cartilage against arthritis by Wnt/PI3K/TLR-3 signaling
Arabian Journal of Chemistry, 2021Co-Authors: Wenmin Zhao, Dongyun Yao, Ru Yang, Heshui Huo, Chenman Qin, Kai SunAbstract:Abstract Rheumatoid arthritis (RA) is an autoimmune disorder that causes joint inflammation and permanent disability in affected patients. This study investigated the protective effect of Cepharanthine treatment against Freund's adjuvant-induced RA in a rat model. RA was induced in rats by injection of incomplete Freund’s adjuvant (IFA) into the plantar surface on days 0 and 9. Cepharanthine at a dose of 10 or 20 mg/kg was administered intraperitoneally to separate groups of rats 12 days after the administration of IFA. The effects of Cepharanthine on RA were determined by measuring serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators. The expression levels of several proteins that regulate the Wnt/PI3K/Toll-like receptor (TLR)-3 pathway were measured via immunohistochemistry, western blotting and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assays. Molecular docking was performed to assess the interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. Our data revealed that Cepharanthine treatment attenuated serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators in RA rats. Analyses with qRT-PCR and western blotting revealed that the mRNA expression levels of Wnt/PI3K/TLR-3 pathway components were attenuated in Cepharanthine-treated RA rats. Cepharanthine also reduced chondrocyte apoptosis and autophagy. Molecular docking analysis revealed significant interactions of Cepharanthine with Wnt, PI3K and TLR-3 proteins. In conclusion, the findings implied that Cepharanthine treatment attenuates chondrocyte autophagy, apoptosis and proliferation by regulating the Wnt/PI3K/TLR-3 pathway in RA rats.
Chun Jen Huang - One of the best experts on this subject based on the ideXlab platform.
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Cepharanthine alleviates liver injury in a rodent model of limb ischemia reperfusion
Acta Anaesthesiologica Taiwanica, 2016Co-Authors: Yin Kuang Chang, Ming-chang Kao, Su Cheng Huang, Chun Jen HuangAbstract:Abstract Objectives Limb ischemia–reperfusion (I/R) causes remote organ injury (e.g., liver injury). Oxidation and inflammation are crucial mechanisms. We investigated the effects of Cepharanthine, a potent antioxidative and anti-inflammatory drug, on alleviating liver injury induced by limb I/R. Methods Twenty-four adult male Sprague-Dawley rats were randomized to receive sham operation (Sham), Sham plus Cepharanthine, I/R, or I/R plus Cepharanthine and designated as the Sham, Sham+Cep, I/R, or I/R+Cep group, respectively ( n = 6 in each group). I/R was induced by applying rubber band tourniquets high around each hind limb for 3 hours followed by reperfusion for 24 hours. Results The plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the Sham and Sham+Cep groups were low, and the levels of AST and ALT of the I/R group were significantly higher than those of the Sham group (both p p 2 (PGE 2 ) of the Sham and Sham+Cep groups were also low. As expected, the NO, MDA, MIP-2, IL-6, and COX-2/PGE 2 of the I/R group were significantly higher than those of the Sham group (all p 2 of the I/R+Cep group were significantly lower than those of the I/R group (all p Conclusion Cepharanthine alleviates liver injury in a rodent model of limb I/R. The mechanisms may involve reducing oxidation and inflammation.
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Cepharanthine alleviates liver injury in a rodent model of limb ischemia–reperfusion
Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists, 2015Co-Authors: Yin Kuang Chang, Ming-chang Kao, Su Cheng Huang, Chun Jen HuangAbstract:Abstract Objectives Limb ischemia–reperfusion (I/R) causes remote organ injury (e.g., liver injury). Oxidation and inflammation are crucial mechanisms. We investigated the effects of Cepharanthine, a potent antioxidative and anti-inflammatory drug, on alleviating liver injury induced by limb I/R. Methods Twenty-four adult male Sprague-Dawley rats were randomized to receive sham operation (Sham), Sham plus Cepharanthine, I/R, or I/R plus Cepharanthine and designated as the Sham, Sham+Cep, I/R, or I/R+Cep group, respectively ( n = 6 in each group). I/R was induced by applying rubber band tourniquets high around each hind limb for 3 hours followed by reperfusion for 24 hours. Results The plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the Sham and Sham+Cep groups were low, and the levels of AST and ALT of the I/R group were significantly higher than those of the Sham group (both p p 2 (PGE 2 ) of the Sham and Sham+Cep groups were also low. As expected, the NO, MDA, MIP-2, IL-6, and COX-2/PGE 2 of the I/R group were significantly higher than those of the Sham group (all p 2 of the I/R+Cep group were significantly lower than those of the I/R group (all p Conclusion Cepharanthine alleviates liver injury in a rodent model of limb I/R. The mechanisms may involve reducing oxidation and inflammation.
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Cepharanthine mitigates pro inflammatory cytokine response in lung injury induced by hemorrhagic shock resuscitation in rats
Cytokine, 2015Co-Authors: Ming-chang Kao, Chen Hsien Yang, Joen Rong Sheu, Chun Jen HuangAbstract:Abstract Background Cepharanthine possesses strong anti-inflammation capacity. We sought to clarify whether Cepharanthine could mitigate pro-inflammatory cytokine production in acute lung injury induced by hemorrhagic shock/resuscitation (HS/RES). The involvement of heme oxygenase-1 (HO-1) was also investigated. Methods Male Sprague Dawley rats were allocated to receive HS/RES, HS/RES plus iv Cepharanthine or HS/RES plus Cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP) and denoted as the HS/RES, HS/RES + CEP, and HS/RES + CEP + SnPP group, respectively. HS/RES was achieved by blood drawing to lower mean arterial pressure (40–45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5 h before sacrifice. Results Arterial blood gas, lung permeability and histologic assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced significant lung injury. Significant increases in pulmonary levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, prostaglandin E2 and cyclooxygenase-2 confirmed that HS/RES induced a significant inflammatory response in the lungs. Cepharanthine significantly attenuated the pulmonary pro-inflammatory cytokine production and lung injury induced by HS/RES. However, the protective effects of Cepharanthine were blocked by SnPP, the potent HO-1 activity inhibitor. Conclusion Cepharanthine significantly mitigates pro-inflammatory cytokine response in acute lung injury induced by HS/RES in rats. The mechanism may involve the HO-1 pathway.
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Salutary Effects of Cepharanthine against Skeletal Muscle and Kidney Injuries following Limb Ischemia/Reperfusion
Evidence-based complementary and alternative medicine : eCAM, 2015Co-Authors: Ming-chang Kao, Chih-yang Chung, Ya-ying Chang, Joen Rong Sheu, Chih Kung Lin, Chun Jen HuangAbstract:Limb ischemia/reperfusion (I/R) causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of Cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus Cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal) was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase) and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1). Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2) and reactive nitrogen species (nitric oxide) as well as lipid peroxidation (malondialdehyde). Of note, these effects of limb I/R could be mitigated by Cepharanthine. These data confirmed that Cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities.
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salutary effects of Cepharanthine against skeletal muscle and kidney injuries following limb ischemia reperfusion
Evidence-based Complementary and Alternative Medicine, 2015Co-Authors: Ming-chang Kao, Chih-yang Chung, Ya-ying Chang, Joen Rong Sheu, Chih Kung Lin, Chun Jen HuangAbstract:Limb ischemia/reperfusion (I/R) causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of Cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus Cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal) was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase) and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1). Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2) and reactive nitrogen species (nitric oxide) as well as lipid peroxidation (malondialdehyde). Of note, these effects of limb I/R could be mitigated by Cepharanthine. These data confirmed that Cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities.
M Hayama - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory effect of Cepharanthine on fibronectin production in growth factor-stimulated rat mesangial cells.
European journal of pharmacology, 2000Co-Authors: M Hayama, R Inoue, S Akiba, T SatoAbstract:We examined the effect of Cepharanthine, a biscoclaurine alkaloid, on extracellular matrix production in rat mesangial cells in response to platelet-derived growth factor (PDGF) or transforming growth factor-beta (TGF-beta). Stimulation of the cells with PDGF increased the amounts of fibronectin, one of extracellular matrix components. Pretreatment with Cepharanthine (0.1-2 microM) suppressed the PDGF-stimulated increase in fibronectin in a dose-dependent manner. At a concentration of 2 microM, the alkaloid almost completely suppressed the production. Under the conditions, the alkaloid inhibited tyrosine phosphorylation of several proteins including PDGF beta receptor in PDGF-stimulated cells, and also tyrosine kinase activity of the receptor prestimulated with PDGF in a cell-free assay system. Furthermore, Cepharanthine suppressed TGF-beta-stimulated fibronectin production at the same concentration ranges. Our results suggest that Cepharanthine inhibits fibronectin production induced by growth factors, probably through suppression of receptor autophosphorylation.
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Inhibitory effect of Cepharanthine on fibronectin production in growth factor-stimulated rat mesangial cells.
European Journal of Pharmacology, 2000Co-Authors: M Hayama, R Inoue, S Akiba, Takashi SatoAbstract:Abstract We examined the effect of Cepharanthine, a biscoclaurine alkaloid, on extracellular matrix production in rat mesangial cells in response to platelet-derived growth factor (PDGF) or transforming growth factor-β (TGF-β). Stimulation of the cells with PDGF increased the amounts of fibronectin, one of extracellular matrix components. Pretreatment with Cepharanthine (0.1–2 μM) suppressed the PDGF-stimulated increase in fibronectin in a dose-dependent manner. At a concentration of 2 μM, the alkaloid almost completely suppressed the production. Under the conditions, the alkaloid inhibited tyrosine phosphorylation of several proteins including PDGF β receptor in PDGF-stimulated cells, and also tyrosine kinase activity of the receptor prestimulated with PDGF in a cell-free assay system. Furthermore, Cepharanthine suppressed TGF-β-stimulated fibronectin production at the same concentration ranges. Our results suggest that Cepharanthine inhibits fibronectin production induced by growth factors, probably through suppression of receptor autophosphorylation.