Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6
Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory f...
Ausführliche Beschreibung
Autor*in: |
Di, Qianqian [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Pharmacological research - London : Academic Press, 2011, 164 |
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Übergeordnetes Werk: |
volume:164 |
DOI / URN: |
10.1016/j.phrs.2020.105386 |
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Katalog-ID: |
ELV005477131 |
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245 | 1 | 0 | |a Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
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520 | |a Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. | ||
650 | 4 | |a Cintelactone A | |
650 | 4 | |a LPS-induced inflammation | |
650 | 4 | |a TRAF6 | |
650 | 4 | |a Ubiquitination | |
650 | 4 | |a Sepsis | |
700 | 1 | |a Zhao, Xibao |4 oth | |
700 | 1 | |a Zhang, Ruihan |4 oth | |
700 | 1 | |a Ma, Xingyu |4 oth | |
700 | 1 | |a Liang, Xinxin |4 oth | |
700 | 1 | |a Li, Xiaoli |4 oth | |
700 | 1 | |a Gao, Junbo |4 oth | |
700 | 1 | |a Tang, Haimei |4 oth | |
700 | 1 | |a Chen, Weilin |4 oth | |
700 | 1 | |a Xiao, Weilie |4 oth | |
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10.1016/j.phrs.2020.105386 doi (DE-627)ELV005477131 (ELSEVIER)S1043-6618(20)31694-7 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Di, Qianqian verfasserin aut Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis Zhao, Xibao oth Zhang, Ruihan oth Ma, Xingyu oth Liang, Xinxin oth Li, Xiaoli oth Gao, Junbo oth Tang, Haimei oth Chen, Weilin oth Xiao, Weilie oth Enthalten in Pharmacological research London : Academic Press, 2011 164 (DE-627)268125872 (DE-600)1471456-5 109-61186 nnns volume:164 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 AR 164 |
spelling |
10.1016/j.phrs.2020.105386 doi (DE-627)ELV005477131 (ELSEVIER)S1043-6618(20)31694-7 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Di, Qianqian verfasserin aut Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis Zhao, Xibao oth Zhang, Ruihan oth Ma, Xingyu oth Liang, Xinxin oth Li, Xiaoli oth Gao, Junbo oth Tang, Haimei oth Chen, Weilin oth Xiao, Weilie oth Enthalten in Pharmacological research London : Academic Press, 2011 164 (DE-627)268125872 (DE-600)1471456-5 109-61186 nnns volume:164 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 AR 164 |
allfields_unstemmed |
10.1016/j.phrs.2020.105386 doi (DE-627)ELV005477131 (ELSEVIER)S1043-6618(20)31694-7 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Di, Qianqian verfasserin aut Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis Zhao, Xibao oth Zhang, Ruihan oth Ma, Xingyu oth Liang, Xinxin oth Li, Xiaoli oth Gao, Junbo oth Tang, Haimei oth Chen, Weilin oth Xiao, Weilie oth Enthalten in Pharmacological research London : Academic Press, 2011 164 (DE-627)268125872 (DE-600)1471456-5 109-61186 nnns volume:164 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 AR 164 |
allfieldsGer |
10.1016/j.phrs.2020.105386 doi (DE-627)ELV005477131 (ELSEVIER)S1043-6618(20)31694-7 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Di, Qianqian verfasserin aut Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis Zhao, Xibao oth Zhang, Ruihan oth Ma, Xingyu oth Liang, Xinxin oth Li, Xiaoli oth Gao, Junbo oth Tang, Haimei oth Chen, Weilin oth Xiao, Weilie oth Enthalten in Pharmacological research London : Academic Press, 2011 164 (DE-627)268125872 (DE-600)1471456-5 109-61186 nnns volume:164 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 AR 164 |
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10.1016/j.phrs.2020.105386 doi (DE-627)ELV005477131 (ELSEVIER)S1043-6618(20)31694-7 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Di, Qianqian verfasserin aut Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis Zhao, Xibao oth Zhang, Ruihan oth Ma, Xingyu oth Liang, Xinxin oth Li, Xiaoli oth Gao, Junbo oth Tang, Haimei oth Chen, Weilin oth Xiao, Weilie oth Enthalten in Pharmacological research London : Academic Press, 2011 164 (DE-627)268125872 (DE-600)1471456-5 109-61186 nnns volume:164 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 AR 164 |
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Enthalten in Pharmacological research 164 volume:164 |
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Enthalten in Pharmacological research 164 volume:164 |
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Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis |
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Di, Qianqian @@aut@@ Zhao, Xibao @@oth@@ Zhang, Ruihan @@oth@@ Ma, Xingyu @@oth@@ Liang, Xinxin @@oth@@ Li, Xiaoli @@oth@@ Gao, Junbo @@oth@@ Tang, Haimei @@oth@@ Chen, Weilin @@oth@@ Xiao, Weilie @@oth@@ |
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2020-01-01T00:00:00Z |
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Di, Qianqian ddc 610 ssgn 15,3 fid PHARM bkl 44.38 misc Cintelactone A misc LPS-induced inflammation misc TRAF6 misc Ubiquitination misc Sepsis Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
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610 DE-600 15,3 ssgn PHARM DE-84 fid 44.38 bkl Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 Cintelactone A LPS-induced inflammation TRAF6 Ubiquitination Sepsis |
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Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
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Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
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novel clerodane-type diterpenoid cintelactone a suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of traf6 |
title_auth |
Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
abstract |
Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. |
abstractGer |
Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. |
abstract_unstemmed |
Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases. |
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Novel clerodane-type diterpenoid Cintelactone A suppresses lipopolysaccharide -induced inflammation by promoting ubiquitination, proteasomal degradation of TRAF6 |
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Zhao, Xibao Zhang, Ruihan Ma, Xingyu Liang, Xinxin Li, Xiaoli Gao, Junbo Tang, Haimei Chen, Weilin Xiao, Weilie |
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|
score |
7.400692 |