J Ethnopharmacol:黄芩汤通过抑制TLR4/NF-κB/NLRP3通路减轻高脂饮食诱导的大鼠肝脏炎症

2022-12-18 紫菀款冬 MedSci原创 发表于北京

评估黄芩汤(HQD)对高脂饮食(HFD)诱导的非酒精性脂肪肝(NAFLD)的疗效并阐明其相关机制。

背景:非酒精性脂肪肝(NAFLD)已成为全球最常见的慢性肝病,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。黄芩汤(HQD)是一种在临床上使用了数千年的中药配方,具有明显的抗炎作用。然而,HQD抗NAFLD炎症的作用和机制仍不明确。

目的:评估HQD对高脂饮食(HFD)诱导的NAFLD的疗效并阐明其相关机制。

方法:首先采用高效液相色谱法分析HQD的主要化学成分。通过对大鼠进行16周HFD,诱导NAFLD模型,并从第8-16周口服HQD(400和800 mg/kg)或多烯卵磷脂胆碱(PLC,8 mg/kg)。

评估药效学指标,包括体重、肝脏重量、肝脏指数以及生化和组织学参数。在机制探索方面,研究了TLR4/NF-κB/NLRP3通路的表达以及HQD主要植物化学物质与TLR4/NNF-κB/NLRP 3通路关键靶点之间的分子对接

结果:HPLC分析揭示了HQD的七种主要单体成分。HQD可以有效减轻NAFLD大鼠的体重、肝脏重量和肝脏指数,挽救血清转氨酶和脂质谱的紊乱,纠正肝脏组织学异常,减少吞噬细胞向肝脏的浸润和促炎细胞因子的释放。

机制研究发现,HQD对TLR4/NF-κB/NLRP3通路调节的肝脏炎症具有抑制作用。进一步的研究发现,HQD中的七种植物化学物质与TLR4/NF-κB/NLRP3途径表现出更好的结合模式,其中黄芩素、黄芩苷和甘草苷分别对蛋白TLR4、NF-κB和NLRP3表现出最高的亲和力和对接分数

结论:这些发现证实了HQD通过阻断TLR4/NF-κB/NLRP3通路,以多组分和多靶点的作用模式改善了NAFLD大鼠的肝脏炎症

 

文献来源:

Yan BF, Wang Y, Wang WB, et al. Huangqin decoction mitigates hepatic inflammation in high-fat diet-challenged rats by inhibiting TLR4/NF-κB/NLRP3 pathway [published online ahead of print, 2022 Dec 9]. J Ethnopharmacol. 2022;303:115999. doi:10.1016/j.jep.2022.115999

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  1. [GetPortalCommentsPageByObjectIdResponse(id=2131090, encodeId=afa82131090fe, content=<a href='/topic/show?id=85d999e268a' target=_blank style='color:#2F92EE;'>#非酒精性脂肪肝#</a>(NAFLD)已成为全球最常见的<a href='/topic/show?id=779a5362677' target=_blank style='color:#2F92EE;'>#慢性肝病#</a>,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。<a href='/topic/show?id=0f96104699ef' target=_blank style='color:#2F92EE;'>#黄芩汤#</a>(HQD)是一种在临床上使用了数千年的<a href='/topic/show?id=57db225208f' target=_blank style='color:#2F92EE;'>#中药配方#</a>,具有明显的<a href='/topic/show?id=98c0553894c' target=_blank style='color:#2F92EE;'>#抗炎#</a>作用。<a href='/topic/show?id=2cf1103194ef' target=_blank style='color:#2F92EE;'>#黄芩素#</a>、<a href='/topic/show?id=daab103195b7' target=_blank style='color:#2F92EE;'>#黄芩苷#</a>和<a href='/topic/show?id=8eca68835dc' target=_blank style='color:#2F92EE;'>#甘草苷#</a>分别对蛋白<a href='/topic/show?id=2de31e53537' target=_blank style='color:#2F92EE;'>#TLR4#</a>、NF-κB和<a href='/topic/show?id=93341286ee6' target=_blank style='color:#2F92EE;'>#NLRP3#</a>表现出最高的亲和力和对接分数。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99726, encryptionId=85d999e268a, topicName=非酒精性脂肪肝), TopicDto(id=53626, encryptionId=779a5362677, topicName=慢性肝病), TopicDto(id=104699, encryptionId=0f96104699ef, topicName=黄芩汤), TopicDto(id=22520, encryptionId=57db225208f, topicName=中药配方), TopicDto(id=55389, encryptionId=98c0553894c, topicName=抗炎), TopicDto(id=103194, encryptionId=2cf1103194ef, topicName=黄芩素), TopicDto(id=103195, encryptionId=daab103195b7, topicName=黄芩苷), TopicDto(id=68835, encryptionId=8eca68835dc, topicName=甘草苷), TopicDto(id=17535, encryptionId=2de31e53537, topicName=TLR4), TopicDto(id=12867, encryptionId=93341286ee6, topicName=NLRP3)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Tue May 09 06:43:53 CST 2023, time=2023-05-09, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=2106567, encodeId=516f210656ea3, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Sun Dec 18 13:14:00 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106592, encodeId=c4582106592e1, content=中药复方作用机制研究 可以借鉴!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 17:01:45 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106591, encodeId=dcfa2106591b5, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 16:59:44 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省)]
    2023-05-09 侠胆医心 来自上海

    #非酒精性脂肪肝#(NAFLD)已成为全球最常见的#慢性肝病#,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。#黄芩汤#(HQD)是一种在临床上使用了数千年的#中药配方#,具有明显的#抗炎#作用。#黄芩素##黄芩苷##甘草苷#分别对蛋白#TLR4#、NF-κB和#NLRP3#表现出最高的亲和力和对接分数。

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2131090, encodeId=afa82131090fe, content=<a href='/topic/show?id=85d999e268a' target=_blank style='color:#2F92EE;'>#非酒精性脂肪肝#</a>(NAFLD)已成为全球最常见的<a href='/topic/show?id=779a5362677' target=_blank style='color:#2F92EE;'>#慢性肝病#</a>,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。<a href='/topic/show?id=0f96104699ef' target=_blank style='color:#2F92EE;'>#黄芩汤#</a>(HQD)是一种在临床上使用了数千年的<a href='/topic/show?id=57db225208f' target=_blank style='color:#2F92EE;'>#中药配方#</a>,具有明显的<a href='/topic/show?id=98c0553894c' target=_blank style='color:#2F92EE;'>#抗炎#</a>作用。<a href='/topic/show?id=2cf1103194ef' target=_blank style='color:#2F92EE;'>#黄芩素#</a>、<a href='/topic/show?id=daab103195b7' target=_blank style='color:#2F92EE;'>#黄芩苷#</a>和<a href='/topic/show?id=8eca68835dc' target=_blank style='color:#2F92EE;'>#甘草苷#</a>分别对蛋白<a href='/topic/show?id=2de31e53537' target=_blank style='color:#2F92EE;'>#TLR4#</a>、NF-κB和<a href='/topic/show?id=93341286ee6' target=_blank style='color:#2F92EE;'>#NLRP3#</a>表现出最高的亲和力和对接分数。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99726, encryptionId=85d999e268a, topicName=非酒精性脂肪肝), TopicDto(id=53626, encryptionId=779a5362677, topicName=慢性肝病), TopicDto(id=104699, encryptionId=0f96104699ef, topicName=黄芩汤), TopicDto(id=22520, encryptionId=57db225208f, topicName=中药配方), TopicDto(id=55389, encryptionId=98c0553894c, topicName=抗炎), TopicDto(id=103194, encryptionId=2cf1103194ef, topicName=黄芩素), TopicDto(id=103195, encryptionId=daab103195b7, topicName=黄芩苷), TopicDto(id=68835, encryptionId=8eca68835dc, topicName=甘草苷), TopicDto(id=17535, encryptionId=2de31e53537, topicName=TLR4), TopicDto(id=12867, encryptionId=93341286ee6, topicName=NLRP3)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Tue May 09 06:43:53 CST 2023, time=2023-05-09, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=2106567, encodeId=516f210656ea3, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Sun Dec 18 13:14:00 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106592, encodeId=c4582106592e1, content=中药复方作用机制研究 可以借鉴!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 17:01:45 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106591, encodeId=dcfa2106591b5, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 16:59:44 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省)]
    2022-12-18 yangchou 来自浙江省

    好文章,谢谢分享。

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2131090, encodeId=afa82131090fe, content=<a href='/topic/show?id=85d999e268a' target=_blank style='color:#2F92EE;'>#非酒精性脂肪肝#</a>(NAFLD)已成为全球最常见的<a href='/topic/show?id=779a5362677' target=_blank style='color:#2F92EE;'>#慢性肝病#</a>,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。<a href='/topic/show?id=0f96104699ef' target=_blank style='color:#2F92EE;'>#黄芩汤#</a>(HQD)是一种在临床上使用了数千年的<a href='/topic/show?id=57db225208f' target=_blank style='color:#2F92EE;'>#中药配方#</a>,具有明显的<a href='/topic/show?id=98c0553894c' target=_blank style='color:#2F92EE;'>#抗炎#</a>作用。<a href='/topic/show?id=2cf1103194ef' target=_blank style='color:#2F92EE;'>#黄芩素#</a>、<a href='/topic/show?id=daab103195b7' target=_blank style='color:#2F92EE;'>#黄芩苷#</a>和<a href='/topic/show?id=8eca68835dc' target=_blank style='color:#2F92EE;'>#甘草苷#</a>分别对蛋白<a href='/topic/show?id=2de31e53537' target=_blank style='color:#2F92EE;'>#TLR4#</a>、NF-κB和<a href='/topic/show?id=93341286ee6' target=_blank style='color:#2F92EE;'>#NLRP3#</a>表现出最高的亲和力和对接分数。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99726, encryptionId=85d999e268a, topicName=非酒精性脂肪肝), TopicDto(id=53626, encryptionId=779a5362677, topicName=慢性肝病), TopicDto(id=104699, encryptionId=0f96104699ef, topicName=黄芩汤), TopicDto(id=22520, encryptionId=57db225208f, topicName=中药配方), TopicDto(id=55389, encryptionId=98c0553894c, topicName=抗炎), TopicDto(id=103194, encryptionId=2cf1103194ef, topicName=黄芩素), TopicDto(id=103195, encryptionId=daab103195b7, topicName=黄芩苷), TopicDto(id=68835, encryptionId=8eca68835dc, topicName=甘草苷), TopicDto(id=17535, encryptionId=2de31e53537, topicName=TLR4), TopicDto(id=12867, encryptionId=93341286ee6, topicName=NLRP3)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Tue May 09 06:43:53 CST 2023, time=2023-05-09, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=2106567, encodeId=516f210656ea3, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Sun Dec 18 13:14:00 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106592, encodeId=c4582106592e1, content=中药复方作用机制研究 可以借鉴!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 17:01:45 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106591, encodeId=dcfa2106591b5, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 16:59:44 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省)]
    2022-12-18 msJackie 来自浙江省

    中药复方作用机制研究 可以借鉴!

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2131090, encodeId=afa82131090fe, content=<a href='/topic/show?id=85d999e268a' target=_blank style='color:#2F92EE;'>#非酒精性脂肪肝#</a>(NAFLD)已成为全球最常见的<a href='/topic/show?id=779a5362677' target=_blank style='color:#2F92EE;'>#慢性肝病#</a>,其中异位脂肪变性(5%)和肝脏炎症浸润是主要临床特征。<a href='/topic/show?id=0f96104699ef' target=_blank style='color:#2F92EE;'>#黄芩汤#</a>(HQD)是一种在临床上使用了数千年的<a href='/topic/show?id=57db225208f' target=_blank style='color:#2F92EE;'>#中药配方#</a>,具有明显的<a href='/topic/show?id=98c0553894c' target=_blank style='color:#2F92EE;'>#抗炎#</a>作用。<a href='/topic/show?id=2cf1103194ef' target=_blank style='color:#2F92EE;'>#黄芩素#</a>、<a href='/topic/show?id=daab103195b7' target=_blank style='color:#2F92EE;'>#黄芩苷#</a>和<a href='/topic/show?id=8eca68835dc' target=_blank style='color:#2F92EE;'>#甘草苷#</a>分别对蛋白<a href='/topic/show?id=2de31e53537' target=_blank style='color:#2F92EE;'>#TLR4#</a>、NF-κB和<a href='/topic/show?id=93341286ee6' target=_blank style='color:#2F92EE;'>#NLRP3#</a>表现出最高的亲和力和对接分数。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99726, encryptionId=85d999e268a, topicName=非酒精性脂肪肝), TopicDto(id=53626, encryptionId=779a5362677, topicName=慢性肝病), TopicDto(id=104699, encryptionId=0f96104699ef, topicName=黄芩汤), TopicDto(id=22520, encryptionId=57db225208f, topicName=中药配方), TopicDto(id=55389, encryptionId=98c0553894c, topicName=抗炎), TopicDto(id=103194, encryptionId=2cf1103194ef, topicName=黄芩素), TopicDto(id=103195, encryptionId=daab103195b7, topicName=黄芩苷), TopicDto(id=68835, encryptionId=8eca68835dc, topicName=甘草苷), TopicDto(id=17535, encryptionId=2de31e53537, topicName=TLR4), TopicDto(id=12867, encryptionId=93341286ee6, topicName=NLRP3)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Tue May 09 06:43:53 CST 2023, time=2023-05-09, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=2106567, encodeId=516f210656ea3, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Sun Dec 18 13:14:00 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106592, encodeId=c4582106592e1, content=中药复方作用机制研究 可以借鉴!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 17:01:45 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2106591, encodeId=dcfa2106591b5, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=306a6407285, createdName=msJackie, createdTime=Sun Dec 18 16:59:44 CST 2022, time=2022-12-18, status=1, ipAttribution=浙江省)]
    2022-12-18 msJackie 来自浙江省

    不错

    0

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既往研究发现,牙周病与非酒精性脂肪肝(NAFLD)有关。牙周病致病菌,主要是牙龈卟啉单胞菌,可能与非酒精性脂肪肝患者的纤维化严重程度有关。

European Radiology:CCTA的斑块进展与非酒精性脂肪肝疾病及心血管事件相关

冠状动脉CT血管造影(CCTA)为准确评估管腔狭窄和斑块特征的非侵入性成像方式。

Diabetes Care:卡格列净和格列美脲能在小程度上改善非酒精性脂肪肝的进展!

托格列净和格列美脲在较小程度上改善了2型糖尿病和NAFLD患者的肝脏组织学和代谢,且两种药物之间没有显著差异。

J Hepatol:MRG15可能是非酒精性脂肪肝炎的新潜在靶点

在肝脏中敲除MRG15后可以显著减缓小鼠NASH发展进程,该研究为NASH治疗提供了潜在的靶点。