Progress of Chinese medicine intervention in HMGB1 pathway to improve type 2 diabetes mellitus and its complications

doi:10.12092/j.issn.1009-2501.2026.06.012

Abstract

Abstract:

The development of type2 diabetes mellitus (T2DM) is closely related to insulin resistance and pancreatic β-cell dysfunction, and high mobility group box 1 (HMGB1) and its related receptors and signaling pathways play an important role in the development of T2DM and its complications. HMGB1 is a core regulator of inflammatory response, widely found in various tissues and organs such as liver, adipose, skeletal muscle, and pancreatic islets, and affects the course of T2DM by enhancing inflammatory response and exacerbating insulin resistance. In recent years, a variety of traditional Chinese medicines (TCM) have been shown to slow down the progression of T2DM and its complications by regulating the expression of HMGB1 and its related receptors and signaling pathways. Therefore, the article discusses the current status of domestic and international research on the intervention of Chinese medicines in the HMGB1 pathway to improve T2DM and its complications, with the aim of providing medication ideas for the future use of Chinese medicines in the treatment of T2DM and its related complications.

Key words: high mobility group protein B1, type 2 diabetes mellitus, traditional Chinese medicine, pathway, mechanism

CLC Number:

R587.1
R28

Ailin LU, Mengrui YUAN, Yongqing WU, Hongyi LIU. Progress of Chinese medicine intervention in HMGB1 pathway to improve type 2 diabetes mellitus and its complications[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 827-835.

Figures/Tables 5

References 60

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中药活性成分	来源	疾病类别	实验对象	作用机制与靶点	参考文献
茯苓酸	茯苓	IR	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE、p-NF-κBp65↓， FINS、HOMA-IR、TNF-α、IL-1β↓	[5]
红景天苷	红景天	IR	db/db小鼠	抑制HMGB1/RAGE/NF-κB信号通路	[6]
栀子苷	栀子	IR	GDM大鼠	抑制HMGB1/RAGE信号，HMGB1、RAGE↓，FPG、FINS、IRITC、 TG、LDL-C↓，HDL-C、CTRP3、GLUT4↑	[7]
欧前胡素	蛇床子	DR	HRMECs	抑制HMGB1/RAGE/NF-κB信号通路，IL-6、TNF-α、IL-1β、MDA↓	[9]
芸香苷	槐花	DR	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、miR-155↓	[10]
甘草甜素	甘草	DR	C57BL/6小鼠	HMGB1、RAGE↓，IL-6、IL-1β↓	[11]
		DCM	H9c2细胞	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、IL-1β、TNF-α、ROS↓，细胞凋亡率、Bax、LC3、Beclin-1↓	[13]
		DKD	SD大鼠、RSC96细胞	HMGBI、RAGE↓，抑制NF-κB易位，ERK、p38MAPK磷酸化↓	[16]
		DPN	SD大鼠、RSC96细胞	阻断HMGB1及抑制RAGE/p38MAPK/NF-κBp65信号通路，NGF、 neuritin-1、caspase-3↓，促进坐骨神经恢复	[22]
青蒿素	青蒿	DCM	SD大鼠	调节AGE-RAGE/HMGB1信号通路，IL-1β↓	[14]
槲皮素	银杏叶	DKD	SD大鼠	抑制HMGB1/RAGE/NF-κB信号通路，IL-1β、IL-6、TNF-α↓，Bax、 Caspase-3↓，Bcl-2↑	[17]
川芎嗪	川芎	DKD	SD大鼠	抑制HMGB1/RAGEs信号通路，RAGEs、Cr、BUN↓	[18]
穿心莲内酯	穿心莲	DPN	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE、NF-κBp65、MDA、氧化应激↓，SOD↑	[21]
连翘苷	连翘	DPN	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、IL-6、TNF-a、 ROS、MDA、FPG、HbAlc↓，MBP、SOD↑	[23]

中药活性成分	来源	疾病类别	实验对象	作用机制与靶点	参考文献
茯苓酸	茯苓	IR	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE、p-NF-κBp65↓， FINS、HOMA-IR、TNF-α、IL-1β↓	[5]
红景天苷	红景天	IR	db/db小鼠	抑制HMGB1/RAGE/NF-κB信号通路	[6]
栀子苷	栀子	IR	GDM大鼠	抑制HMGB1/RAGE信号，HMGB1、RAGE↓，FPG、FINS、IRITC、 TG、LDL-C↓，HDL-C、CTRP3、GLUT4↑	[7]
欧前胡素	蛇床子	DR	HRMECs	抑制HMGB1/RAGE/NF-κB信号通路，IL-6、TNF-α、IL-1β、MDA↓	[9]
芸香苷	槐花	DR	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、miR-155↓	[10]
甘草甜素	甘草	DR	C57BL/6小鼠	HMGB1、RAGE↓，IL-6、IL-1β↓	[11]
		DCM	H9c2细胞	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、IL-1β、TNF-α、ROS↓，细胞凋亡率、Bax、LC3、Beclin-1↓	[13]
		DKD	SD大鼠、RSC96细胞	HMGBI、RAGE↓，抑制NF-κB易位，ERK、p38MAPK磷酸化↓	[16]
		DPN	SD大鼠、RSC96细胞	阻断HMGB1及抑制RAGE/p38MAPK/NF-κBp65信号通路，NGF、 neuritin-1、caspase-3↓，促进坐骨神经恢复	[22]
青蒿素	青蒿	DCM	SD大鼠	调节AGE-RAGE/HMGB1信号通路，IL-1β↓	[14]
槲皮素	银杏叶	DKD	SD大鼠	抑制HMGB1/RAGE/NF-κB信号通路，IL-1β、IL-6、TNF-α↓，Bax、 Caspase-3↓，Bcl-2↑	[17]
川芎嗪	川芎	DKD	SD大鼠	抑制HMGB1/RAGEs信号通路，RAGEs、Cr、BUN↓	[18]
穿心莲内酯	穿心莲	DPN	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE、NF-κBp65、MDA、氧化应激↓，SOD↑	[21]
连翘苷	连翘	DPN	SD大鼠	抑制HMGB1/RAGE信号通路，HMGB1、RAGE mRNA、IL-6、TNF-a、 ROS、MDA、FPG、HbAlc↓，MBP、SOD↑	[23]

中药活性成分	来源	疾病类别	实验对象	作用机制与靶点	参考文献
红景天苷	红景天	IR	db/db小鼠	抑制HMGB1/TLR4/NLRP3信号通路	[6]
大黄素	大黄	IR	PCOS小鼠	抑制HMGB1/TLR4/NF-κB通路，GLUT4、IRS2、INSR↑	[25]
西红花苷	红花	DR	SD大鼠	抑制HMGB1/TLR4/MyD88/NF-κB通路和NF-κB核转位， TNF-α、IL-1β、IL-8、sICAM-1↓	[28]
银杏二萜内酯	银杏叶	DR	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，IL-1β、TNF-α、IL-6、IL-8↓	[29]
芍药苷	芍药	DR	CD-1小鼠	抑制HMGB1/TLR4/NF-κB和HSP70/TLR4/NF-κB信号通路， SOCS3↑，MMP-9↓	[30]
甘草甜素	甘草	DR	C57BL/6小鼠	HMGB1、TLR4↓，IL-6、IL-1β↓	[11]
		DKD	SD大鼠、RSC96细胞	HMGBI、TLR4↓，抑制NF-κB易位，ERK、p38MAPK磷酸化↓	[17]
桂皮醛	桂皮	DCM	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，FPG、LVEDD、LVESD、CVF↓，IL-6、IL-1β、TNF-α↓	[32]
牛磺酸	牛胆汁	DKD	C57BL/6小鼠	抑制HMGB1/TLR4信号通路，IL-6、TNF-α、IL-1β↓、NF-κBp65、MyD88、CD68、MCP-1↓	[36]
鞣花酸	石榴皮	DKD	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，IRAK4、TRAF6、IKK-β、 NF-κBp65↓	[37]
五味子乙素	五味子	DKD	SD大鼠	抑制HMGB1/TLR4信号通路，HMGB1、TLR4、IL-1β、TNF-α、 IL-6↓，Scr、Cys-c、ALT、↓，Ucr、Ccr↑	[38]
柴胡多糖	柴胡	DKD	SD大鼠	抑制HMGB1/TLR4信号，TNF-α、IL-6↓，ColIV、FN、α-SMA↓	[39]
红芪多糖	红芪	DPN	SD大鼠	调控HMGB1/TLR4信号通路，NF-κB、IL-1、mRNA↓	[40]

中药活性成分	来源	疾病类别	实验对象	作用机制与靶点	参考文献
红景天苷	红景天	IR	db/db小鼠	抑制HMGB1/TLR4/NLRP3信号通路	[6]
大黄素	大黄	IR	PCOS小鼠	抑制HMGB1/TLR4/NF-κB通路，GLUT4、IRS2、INSR↑	[25]
西红花苷	红花	DR	SD大鼠	抑制HMGB1/TLR4/MyD88/NF-κB通路和NF-κB核转位， TNF-α、IL-1β、IL-8、sICAM-1↓	[28]
银杏二萜内酯	银杏叶	DR	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，IL-1β、TNF-α、IL-6、IL-8↓	[29]
芍药苷	芍药	DR	CD-1小鼠	抑制HMGB1/TLR4/NF-κB和HSP70/TLR4/NF-κB信号通路， SOCS3↑，MMP-9↓	[30]
甘草甜素	甘草	DR	C57BL/6小鼠	HMGB1、TLR4↓，IL-6、IL-1β↓	[11]
		DKD	SD大鼠、RSC96细胞	HMGBI、TLR4↓，抑制NF-κB易位，ERK、p38MAPK磷酸化↓	[17]
桂皮醛	桂皮	DCM	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，FPG、LVEDD、LVESD、CVF↓，IL-6、IL-1β、TNF-α↓	[32]
牛磺酸	牛胆汁	DKD	C57BL/6小鼠	抑制HMGB1/TLR4信号通路，IL-6、TNF-α、IL-1β↓、NF-κBp65、MyD88、CD68、MCP-1↓	[36]
鞣花酸	石榴皮	DKD	SD大鼠	抑制HMGB1/TLR4/NF-κB信号通路，IRAK4、TRAF6、IKK-β、 NF-κBp65↓	[37]
五味子乙素	五味子	DKD	SD大鼠	抑制HMGB1/TLR4信号通路，HMGB1、TLR4、IL-1β、TNF-α、 IL-6↓，Scr、Cys-c、ALT、↓，Ucr、Ccr↑	[38]
柴胡多糖	柴胡	DKD	SD大鼠	抑制HMGB1/TLR4信号，TNF-α、IL-6↓，ColIV、FN、α-SMA↓	[39]
红芪多糖	红芪	DPN	SD大鼠	调控HMGB1/TLR4信号通路，NF-κB、IL-1、mRNA↓	[40]

中药活性成分	来源	疾病类别	实验对象	作用机制与靶点	参考文献
香青兰总黄酮	薄荷	IR	SD大鼠	HMGB1、IAA、TNF-α、IL-1β、IL-6、IL-18、CRP、LP↓，INS、ADPN↑	[42]
姜黄素	姜黄	IR	db/db小鼠、 H9c2细胞	抑制HMGB1/NLRP3/NF-κB信号通路，IL-1β、TNF-α、IL-6、 TGF-β↓	[43]
荞麦黄酮	荞麦	DR	HRMECs	HMGB1、IL-6、TNF-α↓，IL-10↑	[45]
芒果苷	芒果叶	DR	SD大鼠	抑制Nrf-2/HO-1/HMGB1/NF-κB信号通路，IL-1β、IL-6、TNF-α、 MDA↓	[46]
葛花总黄酮	葛根	DR	C57BL/6小鼠	抑制HMGB1信号通路，VEGF、NF-κB、TNF-α↓	[47]
白藜芦醇	虎杖	DR	HRMECs	抑制SIRT-1/HMGB1信号通路，VEGF↓	[48]
二氢杨梅素	地榆	DCM	SD大鼠	HMGB1、NF-κBp65磷酸化↓，EF、FS、SV↑，LVIDd、LVIDs、心脏肥厚指数↓	[53]
姜黄素	姜黄	DCM	db/db小鼠、 H9c2细胞	抑制HMGB1/NLRP3/NF-κB信号通路，IL-1β、TNF-α、IL-6、TGF-β↓	[43]
黄芪甲苷	黄芪	DKD	DN细胞	抑制HMGB1/AGEs/NF-κB信号通路	[56]
毛蕊花糖苷	夏枯草	DKD	C57BL/6小鼠	HMGB1、NF-κB↓，24hUP、BUN、Cr↓	[57]