中药提取物调控铁死亡改善阿尔茨海默病的研究新进展

doi:10.12114/j.issn.1007-9572.2024.0295

摘要/Abstract

摘要： 阿尔茨海默病（AD）是一种老年人群中常见的神经退行性疾病，其典型临床表现是进行性记忆障碍。铁死亡是近些年新兴起的潜在的生物学机制研究方向，是一种铁依赖性程序性细胞死亡方式，大量证据表明AD与大脑中的铁死亡密切相关，然而其参与AD的确切机制尚不清楚，其可能由铁代谢紊乱、脂质过氧化和氨基酸代谢诱导，从而影响大脑中铁离子的沉积。迄今为止，部分中药有效化学成分已被深入研究，例如红景天、远志、银杏、茯苓等，这些中药在靶向铁死亡治疗AD的过程中展现出了显著的效果。在此背景下，本综述系统阐述了大脑中铁的代谢、铁死亡的特点，并重点关注铁死亡代谢调控机制。同时，本文还讨论了铁死亡和AD的联系，并同时列举了中药的有效成分通过抑制铁死亡改善AD的药物，以期为今后铁死亡抑制剂的开发研究提供参考信息。

关键词: 阿尔茨海默病, 中药, 铁死亡, 作用机制, 综述

Abstract:

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly population. It's typical clinical manifestation is progressive memory impairment. Ferroptosis, rising as a new research direction on AD biological mechanism in recent years, mainly studies on iron-dependent programmed cell death. A large amount of evidence has shown that AD is closely related to ferroptosis in the brain. However, the exact mechanism of the role ferroptosis has played in AD is still unclear. One of the most popular research results indicates that AD might be induced by iron metabolism disorders, lipid peroxidation, and amino acid metabolism, thereby affecting the deposition of iron ions in the brain. So far, some effective chemical components of traditional Chinese herbs as cures of AD have been studied in depth, such as rhodiola rosea, polygala root, ginkgo biloba, poria cocos, etc. These traditional Chinese herbs have shown remarkable effects in the treatment of AD by means of targeting ferroptosis. In this context, this review systematically elaborates on the metabolism of iron in the brain, the characteristics of ferroptosis, and focuses on the metabolic regulation mechanism of ferroptosis. Meanwhile, this review also discusses the connection between ferroptosis and AD. Furthermore, it lists the effective compositions in traditional Chinese herbs that can improve AD by inhibiting ferroptosis, so as to provide reference information for the development and research of ferroptosis inhibitors in the future.

Key words: Alzheimer's disease, Traditional Chinese drugs, Ferroptosis, Mechanism of action, Review

中图分类号:

R 745.7

裴金英,宋金洲,马到丰,等. 中药提取物调控铁死亡改善阿尔茨海默病的研究新进展[J]. 中国全科医学, 2025, 28(05): 639-648. DOI: 10.12114/j.issn.1007-9572.2024.0295.
PEI Jinying,SONG Jinzhou,MA Daofeng, et al. Research Progress in the Study of Traditional Chinese Herbal Medicine Extracts Regulating Ferroptosis thus Improving the Symptom of Alzheimer's Disease[J]. Chinese General Practice, 2025, 28(05): 639-648. DOI: 10.12114/j.issn.1007-9572.2024.0295.

图/表 1

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有效成分	模型	剂量	靶点
红景天苷	SAMP8小鼠	30 mg/kg	Aβ1-42、铁沉积、MDA、IL-1β、IFN-γ、TNF-α、ACSL4、TFR1↓、GSH、SOD、IL-10、GPX4、SLC7A11、SLC3A2、FTH1、Fpn1、Nrf2、HO-1↑
红景天苷	Nrf2基因敲除小鼠、C57BL/6小鼠	50 mg/kg	MDA↓、SOD↑、GSH/GSSG↑、GPX4↑、SLC7A11↑、HO-1↑、ROS↓、Nrf2↑、Fe²⁺↓、PTGS2↓
连翘酯苷A	APP/PS1小鼠	30 mg/kg	MDA↓、MMP，Aβ1-42、p-tau、NO↓、IL-4↑、IL-10↑、IL-1β↓、IL-6↓、Fe、GPX4↑、xCT↑、FTL↑、Fpn↑、DRD1↑、CREB↑、BDNF↑、TrkB↑、PI3K、p-AKT、GNAL↑、Adcy5↑、cAMP↑、p-Fyn↓、p-GSK-3β↑、Nrf2↑、TFRC↓、DMT1↓、FTH↑、Iba1↓、GFAP↓、TGF-β↑、MCP-1↓、ALOX5↓、CD33↓、iNOS↓、TNF-α↓、IKK↓
芍药苷	C57BL/6小鼠、APP/PS1小鼠	10 mg/kg	Fe³⁺↓、SOD↑、MDA↓、JC-1↑、P53↓、STAT3、GPX4↑、GAPDH、ΔΨm
淫羊藿苷	APP/PS1小鼠、C57BL/6小鼠	5、10 mg/kg	MDA↓、SOD↑、MDM2、GSH-Px↑、LDH↓、GSH↑、caspase-3↓、Fe↓、p53↓、Aβ25-35↓、p-Tau
何首乌苷	APP/PS1小鼠、C57BL/6小鼠	60、120、180 mg/kg	Aβ↓、GSS、SOD1、SOD2、Prdx1、8-OHdG↓、Nrf2↑、Keap1↑、HO-1↑、NQO1↑、GCLC↑、GCLM↑、NLRP3↓、TXNIP↓、TXNRD1↓、iNOS↓、GPX4↑、xCT、GPX4↑、GPX1↑、FTH1↑、xCT↑、CD98↑、DMT1↓、ACSL4↓、NCOA4↓、FTH↓、FTL↓
远志皂苷元	Aβ25-35诱导的PC12细胞	15、30、60、120、240 μmol/L	ACSL4↓、PEBP1↓、GPX4↑、ROS↓、MDA、GAPDH
细叶远志皂苷	C57BL/6小鼠	10 mg/kg	AKT、STAT3、CASP3、BDNF↑、PSD95↑、p-TrkB↑、Actin、p-Akt↑、mRNA↑、Ca²⁺↓、m-calpain↓、calpastatin↑、MDA↓、GSH↑、SOD↑、CAT↑、ROS↓、MFI↓、ACSL4↓、GPX4↑、SLC7A11↑、SYN
银杏内酯B	SAMR1小鼠、SAMP8小鼠	20、30、40 mg/kg	GFAP、Iba-1、TNF-a、IL-1b、IL-6、SOD↑、GSH↑、MDA↓、NO↓、ROS↓、GPX4↑、Fe²⁺↓、TFR1、NCOA4、FTH1↑、Nrf2↑、RSL3、GAPDH、Lamin B1、DAPI
	Aβ1-42诱导的N2a细胞	100 μmol/L	FTH1↑、SPP1↓、ROS↓、SOD↑、MDA↓、SLC7A11↓、Psen2、Fn1↑、Ftl1↑、Syn1↓、Apom↓
小檗碱	3×Tg-AD小鼠、WT小鼠	50 mg/kg	APP↓、Bace1↓、Aβ1-42↓、ADAM10↑、P-tau↓、Fe³⁺、Fe²⁺、FTH1、TFR、GSH↑、MDA↓、GPX4↑、SLC7A11↑、ACSL4↓、Nrf2、Keap1、4HNE↓、Fpn1、
番泻苷A	C57BL/6小鼠、APP/PS1小鼠	7.5、15、30 mg/kg	caspase-3↓、PARP-1↓、GSH↑、MDA↓、ROS、IL-1β↓、IL-6↓、TNF-α↓、TRAF6↓、p-P65↓
旋覆花内酯	5xFAD小鼠、C57BL6小鼠	20 mg/kg	TNF-α↓、PGE2↓、IL-10↑、Arg-1↑、iNOS↓、COX-2↓、GPx4、GSH↑、MDA↓、T-SOD↓、BACE1↓、Aβ↓、p-Tau↓、GFAP↓、Iba-1↓
圣草酚	APP/PS1小鼠	50 mg/kg	Aβ↓、p-Tau↓、TfRC↓、FTH↓、Fpn↑、MDA↓、GPX4↑、ROS、mRNA↑、p-Nrf2↑、VDR、HO-1↑
表没食子儿茶素没食子酸酯	DNL细胞、CHO细胞	1~10 μmol/L	TfR↑、β-actin、Aβ↓、holo-APP↓、IRPs、APP、sAPPα↑、mRNA
仙茅苷	ICR小鼠	50、100 mg/kg	GPX4↑、SLC7A11↓、MDA↓、Fe↓、GSH↑、GSH/GSSG↑、GAPDH、GCLM↑、GCLC↑、ROS↓、LIP、Aβ1-42↓、ACSL4↓、p-BECN1↑、p-Tau↓、FPN↑、STEAP3、DMT1
大黄酚	SD大鼠（D-半乳糖造模）	0.036 mg/mL	GPx↑、GSH↑、GPX4↑、ROS↓、GAPDH、Aβ
麝香水提物	HT22细胞	330 μg/mL、60 μg/mL	MDA↓、GSH↑、ROS↓、GPX4↑、SLC7A11↑、TFRC↓、Fpn1↑、FTH1↑、Fe²⁺、Nrf2、Keap1↓、HO-1、FTH1
茯苓酸	SD大鼠（Aβ25-35诱导）	50 mg/kg	Nrf2、SLC7A11、GPX4↑、GSH↑、MDA↓、Fe²⁺↓

有效成分	模型	剂量	靶点
红景天苷	SAMP8小鼠	30 mg/kg	Aβ1-42、铁沉积、MDA、IL-1β、IFN-γ、TNF-α、ACSL4、TFR1↓、GSH、SOD、IL-10、GPX4、SLC7A11、SLC3A2、FTH1、Fpn1、Nrf2、HO-1↑
红景天苷	Nrf2基因敲除小鼠、C57BL/6小鼠	50 mg/kg	MDA↓、SOD↑、GSH/GSSG↑、GPX4↑、SLC7A11↑、HO-1↑、ROS↓、Nrf2↑、Fe²⁺↓、PTGS2↓
连翘酯苷A	APP/PS1小鼠	30 mg/kg	MDA↓、MMP，Aβ1-42、p-tau、NO↓、IL-4↑、IL-10↑、IL-1β↓、IL-6↓、Fe、GPX4↑、xCT↑、FTL↑、Fpn↑、DRD1↑、CREB↑、BDNF↑、TrkB↑、PI3K、p-AKT、GNAL↑、Adcy5↑、cAMP↑、p-Fyn↓、p-GSK-3β↑、Nrf2↑、TFRC↓、DMT1↓、FTH↑、Iba1↓、GFAP↓、TGF-β↑、MCP-1↓、ALOX5↓、CD33↓、iNOS↓、TNF-α↓、IKK↓
芍药苷	C57BL/6小鼠、APP/PS1小鼠	10 mg/kg	Fe³⁺↓、SOD↑、MDA↓、JC-1↑、P53↓、STAT3、GPX4↑、GAPDH、ΔΨm
淫羊藿苷	APP/PS1小鼠、C57BL/6小鼠	5、10 mg/kg	MDA↓、SOD↑、MDM2、GSH-Px↑、LDH↓、GSH↑、caspase-3↓、Fe↓、p53↓、Aβ25-35↓、p-Tau
何首乌苷	APP/PS1小鼠、C57BL/6小鼠	60、120、180 mg/kg	Aβ↓、GSS、SOD1、SOD2、Prdx1、8-OHdG↓、Nrf2↑、Keap1↑、HO-1↑、NQO1↑、GCLC↑、GCLM↑、NLRP3↓、TXNIP↓、TXNRD1↓、iNOS↓、GPX4↑、xCT、GPX4↑、GPX1↑、FTH1↑、xCT↑、CD98↑、DMT1↓、ACSL4↓、NCOA4↓、FTH↓、FTL↓
远志皂苷元	Aβ25-35诱导的PC12细胞	15、30、60、120、240 μmol/L	ACSL4↓、PEBP1↓、GPX4↑、ROS↓、MDA、GAPDH
细叶远志皂苷	C57BL/6小鼠	10 mg/kg	AKT、STAT3、CASP3、BDNF↑、PSD95↑、p-TrkB↑、Actin、p-Akt↑、mRNA↑、Ca²⁺↓、m-calpain↓、calpastatin↑、MDA↓、GSH↑、SOD↑、CAT↑、ROS↓、MFI↓、ACSL4↓、GPX4↑、SLC7A11↑、SYN
银杏内酯B	SAMR1小鼠、SAMP8小鼠	20、30、40 mg/kg	GFAP、Iba-1、TNF-a、IL-1b、IL-6、SOD↑、GSH↑、MDA↓、NO↓、ROS↓、GPX4↑、Fe²⁺↓、TFR1、NCOA4、FTH1↑、Nrf2↑、RSL3、GAPDH、Lamin B1、DAPI
	Aβ1-42诱导的N2a细胞	100 μmol/L	FTH1↑、SPP1↓、ROS↓、SOD↑、MDA↓、SLC7A11↓、Psen2、Fn1↑、Ftl1↑、Syn1↓、Apom↓
小檗碱	3×Tg-AD小鼠、WT小鼠	50 mg/kg	APP↓、Bace1↓、Aβ1-42↓、ADAM10↑、P-tau↓、Fe³⁺、Fe²⁺、FTH1、TFR、GSH↑、MDA↓、GPX4↑、SLC7A11↑、ACSL4↓、Nrf2、Keap1、4HNE↓、Fpn1、
番泻苷A	C57BL/6小鼠、APP/PS1小鼠	7.5、15、30 mg/kg	caspase-3↓、PARP-1↓、GSH↑、MDA↓、ROS、IL-1β↓、IL-6↓、TNF-α↓、TRAF6↓、p-P65↓
旋覆花内酯	5xFAD小鼠、C57BL6小鼠	20 mg/kg	TNF-α↓、PGE2↓、IL-10↑、Arg-1↑、iNOS↓、COX-2↓、GPx4、GSH↑、MDA↓、T-SOD↓、BACE1↓、Aβ↓、p-Tau↓、GFAP↓、Iba-1↓
圣草酚	APP/PS1小鼠	50 mg/kg	Aβ↓、p-Tau↓、TfRC↓、FTH↓、Fpn↑、MDA↓、GPX4↑、ROS、mRNA↑、p-Nrf2↑、VDR、HO-1↑
表没食子儿茶素没食子酸酯	DNL细胞、CHO细胞	1~10 μmol/L	TfR↑、β-actin、Aβ↓、holo-APP↓、IRPs、APP、sAPPα↑、mRNA
仙茅苷	ICR小鼠	50、100 mg/kg	GPX4↑、SLC7A11↓、MDA↓、Fe↓、GSH↑、GSH/GSSG↑、GAPDH、GCLM↑、GCLC↑、ROS↓、LIP、Aβ1-42↓、ACSL4↓、p-BECN1↑、p-Tau↓、FPN↑、STEAP3、DMT1
大黄酚	SD大鼠（D-半乳糖造模）	0.036 mg/mL	GPx↑、GSH↑、GPX4↑、ROS↓、GAPDH、Aβ
麝香水提物	HT22细胞	330 μg/mL、60 μg/mL	MDA↓、GSH↑、ROS↓、GPX4↑、SLC7A11↑、TFRC↓、Fpn1↑、FTH1↑、Fe²⁺、Nrf2、Keap1↓、HO-1、FTH1
茯苓酸	SD大鼠（Aβ25-35诱导）	50 mg/kg	Nrf2、SLC7A11、GPX4↑、GSH↑、MDA↓、Fe²⁺↓