The Experts below are selected from a list of 2709 Experts worldwide ranked by ideXlab platform
Deng-hai Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway
Canadian Journal of Diabetes, 2019Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Georges Uzan, Bin Peng, Xiao-cheng Xue, Jun You, Deng-hai ZhangAbstract:OBJECTIVES: The natural triterpenoid compound Celastrol ameliorates insulin resistance (IR) in animal models, but the underlying molecular mechanism is unclear. In this study, we investigated how Celastrol regulates IR. METHODS: The HepG2 cellular IR model was initially established with palmitic acid (PA). The expression and activity of glucose transporter 4 (GLUT4), insulin receptor substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, -150, -223 and -370) were detected before and after Celastrol treatment using the PA-induced HepG2 IR model. RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM Celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM Celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of Celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent Celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished Celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that Celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of Celastrol in treating IR-related disorders.
-
Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA
Journal of Cellular Physiology, 2018Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound Celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for Celastrol is still unclear. As Celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for Celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: Celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both Celastrol and PA could bind MD2, and that Celastrol could expel PA from cells. Finally, Celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that Celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2.
-
Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:AbstractBackgroundCelastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention.Methods and ResultsHere, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not.ConclusionsFor the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
Bin Peng - One of the best experts on this subject based on the ideXlab platform.
-
Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway
Canadian Journal of Diabetes, 2019Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Georges Uzan, Bin Peng, Xiao-cheng Xue, Jun You, Deng-hai ZhangAbstract:OBJECTIVES: The natural triterpenoid compound Celastrol ameliorates insulin resistance (IR) in animal models, but the underlying molecular mechanism is unclear. In this study, we investigated how Celastrol regulates IR. METHODS: The HepG2 cellular IR model was initially established with palmitic acid (PA). The expression and activity of glucose transporter 4 (GLUT4), insulin receptor substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, -150, -223 and -370) were detected before and after Celastrol treatment using the PA-induced HepG2 IR model. RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM Celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM Celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of Celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent Celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished Celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that Celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of Celastrol in treating IR-related disorders.
-
Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA
Journal of Cellular Physiology, 2018Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound Celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for Celastrol is still unclear. As Celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for Celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: Celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both Celastrol and PA could bind MD2, and that Celastrol could expel PA from cells. Finally, Celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that Celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2.
-
Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:AbstractBackgroundCelastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention.Methods and ResultsHere, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not.ConclusionsFor the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
-
inhibiting inducible mir 223 further reduces viable cells in human cancer cell lines mcf 7 and pc3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin PengAbstract:Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention. Here, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not. For the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
Xue Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway
Canadian Journal of Diabetes, 2019Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Georges Uzan, Bin Peng, Xiao-cheng Xue, Jun You, Deng-hai ZhangAbstract:OBJECTIVES: The natural triterpenoid compound Celastrol ameliorates insulin resistance (IR) in animal models, but the underlying molecular mechanism is unclear. In this study, we investigated how Celastrol regulates IR. METHODS: The HepG2 cellular IR model was initially established with palmitic acid (PA). The expression and activity of glucose transporter 4 (GLUT4), insulin receptor substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, -150, -223 and -370) were detected before and after Celastrol treatment using the PA-induced HepG2 IR model. RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM Celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM Celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of Celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent Celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished Celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that Celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of Celastrol in treating IR-related disorders.
-
Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA
Journal of Cellular Physiology, 2018Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound Celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for Celastrol is still unclear. As Celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for Celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: Celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both Celastrol and PA could bind MD2, and that Celastrol could expel PA from cells. Finally, Celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that Celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2.
-
Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:AbstractBackgroundCelastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention.Methods and ResultsHere, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not.ConclusionsFor the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
-
inhibiting inducible mir 223 further reduces viable cells in human cancer cell lines mcf 7 and pc3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin PengAbstract:Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention. Here, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not. For the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
Georges Uzan - One of the best experts on this subject based on the ideXlab platform.
-
Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway
Canadian Journal of Diabetes, 2019Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Georges Uzan, Bin Peng, Xiao-cheng Xue, Jun You, Deng-hai ZhangAbstract:OBJECTIVES: The natural triterpenoid compound Celastrol ameliorates insulin resistance (IR) in animal models, but the underlying molecular mechanism is unclear. In this study, we investigated how Celastrol regulates IR. METHODS: The HepG2 cellular IR model was initially established with palmitic acid (PA). The expression and activity of glucose transporter 4 (GLUT4), insulin receptor substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, -150, -223 and -370) were detected before and after Celastrol treatment using the PA-induced HepG2 IR model. RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM Celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM Celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of Celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent Celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished Celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that Celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of Celastrol in treating IR-related disorders.
-
Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA
Journal of Cellular Physiology, 2018Co-Authors: Xue Zhang, Fanfan Cao, Ying Wang, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound Celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for Celastrol is still unclear. As Celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for Celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: Celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both Celastrol and PA could bind MD2, and that Celastrol could expel PA from cells. Finally, Celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that Celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2.
-
Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin Peng, Deng-hai ZhangAbstract:AbstractBackgroundCelastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention.Methods and ResultsHere, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not.ConclusionsFor the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
-
inhibiting inducible mir 223 further reduces viable cells in human cancer cell lines mcf 7 and pc3 treated by Celastrol
BMC Cancer, 2015Co-Authors: Lu Cao, Xue Zhang, Fanfan Cao, Ying Wang, Yufan Shen, Chunxin Yang, Georges Uzan, Bin PengAbstract:Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of Celastrol has attracted much research attention. Here, we report that Celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by Celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol’s miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in Celastrol-treated cells. NF-κB inhibitor, like Celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or Celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with Celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of Celastrol or not. For the first time, we disclose that Celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in Celastrol-treated cancer cell lines. We thus provide a novel way to increase Celastrol’s anti-cancer effects.
Kamal D. Moudgil - One of the best experts on this subject based on the ideXlab platform.
-
Celastrol and Its Role in Controlling Chronic Diseases
Advances in experimental medicine and biology, 2016Co-Authors: Shivaprasad H. Venkatesha, Kamal D. MoudgilAbstract:Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer. Celastrol modulates intricate cellular pathways and networks associated with disease pathology, and it interrupts or redirects the aberrant cellular and molecular events so as to limit disease progression and facilitate recovery, where feasible. The major cell signaling pathways modulated by Celastrol include the NF-kB pathway, MAPK pathway, JAK/STAT pathway, PI3K/Akt/mTOR pathway, and antioxidant defense mechanisms. Furthermore, Celastrol modulates cell proliferation, apoptosis, proteasome activity, heat-shock protein response, innate and adaptive immune responses, angiogenesis, and bone remodeling. Current understanding of the mechanisms of action of Celastrol and information about its disease-modulating activities in experimental models have set the stage for testing Celastrol in clinical studies as a therapeutic agent for several chronic human diseases.
-
Control of autoimmune inflammation by Celastrol, a natural triterpenoid.
Pathogens and disease, 2016Co-Authors: Shivaprasad H. Venkatesha, Steven Dudics, Brian Astry, Kamal D. MoudgilAbstract:Celastrol is a bioactive compound derived from traditional Chinese medicinal herbs of the Celastraceae family. Celastrol is known to possess anti-inflammatory and anti-oxidant activities. Our studies have highlighted the immunomodulatory attributes of Celastrol in adjuvant-induced arthritis (AA), an experimental model of human rheumatoid arthritis (RA). RA is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joints, leading eventually to tissue damage and deformities. Identification of the molecular targets of Celastrol such as the NF-κB pathway, MAPK pathway, JAK/STAT pathway and RANKL/OPG pathway has unraveled its strategic checkpoints in controlling arthritic inflammation and tissue damage in AA. The pathological events that are targeted and rectified by Celastrol include increased production of pro-inflammatory cytokines; an imbalance between pathogenic T helper 17 and regulatory T cells; enhanced production of chemokines coupled with increased migration of immune cells into the joints; and increased release of mediators of osteoclastic bone damage. Accordingly, Celastrol is a promising candidate for further testing in the clinic for RA therapy. Furthermore, the results of other preclinical studies suggest that Celastrol might also be beneficial for the treatment of a few other autoimmune diseases besides arthritis.
-
Suppression of autoimmune arthritis by Celastrus-derived Celastrol through modulation of pro-inflammatory chemokines.
Bioorganic & medicinal chemistry, 2012Co-Authors: Shivaprasad H. Venkatesha, Brian Astry, Siddaraju M. Nanjundaiah, Kamal D. MoudgilAbstract:Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints, deformities, and disability. The prolonged use of conventional anti-inflammatory drugs is associated with severe adverse effects. Therefore, there is an urgent need for safer and less expensive therapeutic products. Celastrol is a bioactive component of Celastrus, a traditional Chinese medicine, and it possesses anti-arthritic activity. However, the mechanism of action of Celastrol remains to be fully defined. In this study based on the rat adjuvant-induced arthritis (AA) model of RA, we examined the effect of Celastrol on two of the key mediators of arthritic inflammation, namely chemokines and their receptors, and related pro-inflammatory cytokines. We treated arthritic Lewis rats with Celastrol (200μg/rat) or its vehicle by daily intraperitoneal (ip) injection beginning at the onset of AA. At the peak phase of AA, the sera, the draining lymph node cells, spleen adherent cells, and synovial-infiltrating cells of these rats were harvested and tested. Celastrol-treated rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC) as well as cytokines (TNF-α and IL-1β) that induce them, compared to the vehicle-treated rats. However, Celastrol did not have much effect on cellular expression of chemokine receptors except for an increase in CCR1. Further, Celastrol inhibited the migration of spleen adherent cells in vitro. Thus, Celastrol-induced suppression of various chemokines that mediate cellular infiltration into the joints might contribute to its anti-arthritic activity. Our results suggest that Celastrol might offer a promising alternative/adjunct treatment for RA.