钩藤及其单体干预中枢神经系统疾病的作用机制研究进展

doi:10.12092/j.issn.1009-2501.2026.08.012

摘要/Abstract

摘要：

中枢神经系统（central nervous system，CNS）疾病是全球热点关注疾病类型，已严重影响全球健康并造成巨大经济负担。中医药治疗CNS疾病具有理论及临床双重优势。钩藤作为应用千年的平肝息风药，能够通过多途径、多靶点在CNS疾病的治疗中发挥重要作用。研究表明，钩藤吲哚类生物碱是其主要活性成分，钩藤碱、异钩藤碱等是钩藤治疗CNS疾病的主要物质基础。其活性成分能够通过抗炎、抗氧化、抑制细胞凋亡、促进自噬、抑制β淀粉样蛋白沉积及Tau蛋白异常磷酸化等途径发挥作用。本文通过系统性总结钩藤及其单体干预阿尔茨海默病、帕金森病、癫痫及抑郁症等常见CNS疾病的作用机制，以期为钩藤在CNS疾病中的进一步研究及临床应用提供参考，为研究者了解钩藤治疗CNS疾病的研究进展及不足提供一定帮助。

关键词: 钩藤, 钩藤碱, 异钩藤碱, 中枢神经系统疾病, 阿尔茨海默病

Abstract:

Central nervous system diseases (CNSDs) have garnered global attention as a major category of illnesses, significantly impacting worldwide health and imposing a substantial economic burden. Traditional Chinese Medicine (TCM) demonstrates both theoretical and clinical advantages in treating CNSDs. Uncaria rhynchophylla (Gouteng), a herb used for millennia to pacify the liver and extinguish wind, plays an important role in the treatment of CNSDs through multiple pathways and targets. Research indicates that indole alkaloids are its primary active constituents, with rhynchophylline and isorhynchophylline serving as the main material basis for its therapeutic effects against CNSDs. These active components exert their actions through mechanisms such as anti-inflammatory and antioxidant effects, inhibition of apoptosis, promotion of autophagy, suppression of β-amyloid peptide deposition, and prevention of abnormal Tau protein phosphorylation. This article systematically reviews the mechanisms by which Uncaria rhynchophylla and its monomeric compounds intervene in four common CNSDs—Alzheimer^,s disease, Parkinson^,s disease, epilepsy, and depression—with the aim of providing a reference for further research and clinical application of Uncaria rhynchophylla in CNSDs, and to assist researchers in understanding both the progress and limitations of current studies on its therapeutic use.

Key words: uncaria rhynchophylla, rhynchophylline, isorhynchophylline, central nervous system diseases, Alzheimer^,s disease

中图分类号:

R285
R277.7

姚景曦, 魏钰舒, 袁文君, 魏星, 孙可馨, 尚菁, 史正刚. 钩藤及其单体干预中枢神经系统疾病的作用机制研究进展[J]. 中国临床药理学与治疗学, 2026, 31(8): 1112-1126.

Jingxi YAO, Yushu WEI, Wenjun YUAN, Xing WEI, Kexin SUN, Jing SHANG, Zhenggang SHI. Advances in the mechanisms of Uncaria rhynchophylla and its monomeric compounds against central nervous system diseases[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1112-1126.

图/表 6

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Disease	Intervention	Model	Mechanism	References
AD	Extract of Uncaria rhynchophylla	5XFAD mice (transgenic model)	Iba-1↓	[18]
AD	Uncaria rhynchophylla alkaloid extract	APP/PS1 (transgenic model) mice; splenic lymphocytes (ConA)	Aβ, p-tau, IFN-γ, IL-17, CD4? effector T cells, HK2, GLUT1, p-PI3K, p-Akt, p-mTOR↓; IL-10, TGF-β, Treg↑	[23]
AD	RN，IRN	N9 microglial cells (LPS)	TNF-α, IL-1β, NO, iNOS, ERK, MAPKs, IκBα↓	[26]
AD	RN	Primary microglia (LPS)	NO, PEG2, MCP-1, TNF-α, IL-1β, iNOS, COX2, p-IκBα, p-MAPKs↓	[27]
AD	Extract of Uncaria rhynchophylla	SD rats (STZ)	p-tau, IL-6, IL-1β, TNF-α↓; p-Akt, p-GSK-3β↑	[38]
AD	RN	TgCRND8 mice，5×FAD mice， 3×Tg-AD mice (transgenic models); BV-2 cells (Aβ42)	p-tau, p-APP, BACE1, APH1, FL-APP, IL-6, IL-1β, TNF-α, Galectin-3, C/EBPβ, AEP, HDAC2, AMPKα1↓; IDE, PINK1↑	[44]
PD	Hirsutine	SD rats (6-OHDA)	p-IκBα, NF-κB p65, IL-6, IL-1β, TNF-α↓; DA, TH↑	[22]
PD	Uncaria rhynchophylla alkaloid extract	C57BL/6J mice (MPTP); BV-2 cells, SH-SY5Y cells (LPS)	IL-1β, TNF-α, IL-6, TLR4, NLRP3, COX2↓; TH, IL-10↑	[36]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	Superoxide anion, NF-κB, AP-1, p-JNK↓	[29]
EP	Extract of Uncaria rhynchophylla	SD rats (kainic acid)	ED1, nNOS, iNOS↓	[30]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	MIF, CypA↑	[31]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	MAPK, p-JNK↓	[32]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	IL-1β, BDNF↓	[35]
EP	IRN	SD rats (Lithium-pilocarpine)	IL-6, IL-1β, TNF-α, Acetyl-p53/p53, cleaved caspase-3/caspase-3↓; SIRT1↑	[21]
DD	IRN	ICR mice (CUMS)	TNF-α, IL-6, NF-kB p-65↓; NGF, BDNF, p-GSK-3β, p-Akt↑	[19]
Cerebral Ischemia/ Reperfusion Injury	IRN	SD rats (MCAO)	GFAP, IBA-1, TNFα, IL-1β, CX3CR1, p-NF-κB p65↓; YM-1/2, IκB-α↑	[28]
ACI	IRN	SD rats (MCAO)	IL-6, TNF-α, STING, p-TBK1, p-IRF3↓; ZO-1, occludin↑	[41]

Disease	Intervention	Model	Mechanism	References
AD	Extract of Uncaria rhynchophylla	5XFAD mice (transgenic model)	Iba-1↓	[18]
AD	Uncaria rhynchophylla alkaloid extract	APP/PS1 (transgenic model) mice; splenic lymphocytes (ConA)	Aβ, p-tau, IFN-γ, IL-17, CD4? effector T cells, HK2, GLUT1, p-PI3K, p-Akt, p-mTOR↓; IL-10, TGF-β, Treg↑	[23]
AD	RN，IRN	N9 microglial cells (LPS)	TNF-α, IL-1β, NO, iNOS, ERK, MAPKs, IκBα↓	[26]
AD	RN	Primary microglia (LPS)	NO, PEG2, MCP-1, TNF-α, IL-1β, iNOS, COX2, p-IκBα, p-MAPKs↓	[27]
AD	Extract of Uncaria rhynchophylla	SD rats (STZ)	p-tau, IL-6, IL-1β, TNF-α↓; p-Akt, p-GSK-3β↑	[38]
AD	RN	TgCRND8 mice，5×FAD mice， 3×Tg-AD mice (transgenic models); BV-2 cells (Aβ42)	p-tau, p-APP, BACE1, APH1, FL-APP, IL-6, IL-1β, TNF-α, Galectin-3, C/EBPβ, AEP, HDAC2, AMPKα1↓; IDE, PINK1↑	[44]
PD	Hirsutine	SD rats (6-OHDA)	p-IκBα, NF-κB p65, IL-6, IL-1β, TNF-α↓; DA, TH↑	[22]
PD	Uncaria rhynchophylla alkaloid extract	C57BL/6J mice (MPTP); BV-2 cells, SH-SY5Y cells (LPS)	IL-1β, TNF-α, IL-6, TLR4, NLRP3, COX2↓; TH, IL-10↑	[36]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	Superoxide anion, NF-κB, AP-1, p-JNK↓	[29]
EP	Extract of Uncaria rhynchophylla	SD rats (kainic acid)	ED1, nNOS, iNOS↓	[30]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	MIF, CypA↑	[31]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	MAPK, p-JNK↓	[32]
EP	Extract of Uncaria rhynchophylla，RN	SD rats (kainic acid)	IL-1β, BDNF↓	[35]
EP	IRN	SD rats (Lithium-pilocarpine)	IL-6, IL-1β, TNF-α, Acetyl-p53/p53, cleaved caspase-3/caspase-3↓; SIRT1↑	[21]
DD	IRN	ICR mice (CUMS)	TNF-α, IL-6, NF-kB p-65↓; NGF, BDNF, p-GSK-3β, p-Akt↑	[19]
Cerebral Ischemia/ Reperfusion Injury	IRN	SD rats (MCAO)	GFAP, IBA-1, TNFα, IL-1β, CX3CR1, p-NF-κB p65↓; YM-1/2, IκB-α↑	[28]
ACI	IRN	SD rats (MCAO)	IL-6, TNF-α, STING, p-TBK1, p-IRF3↓; ZO-1, occludin↑	[41]

Disease	Intervention	Model	Mechanism	References
AD	Extract of Uncaria rhynchophylla	ICR mice(D-galactose)	ACh, GSH↑; AChE, MDA↓	[48]
AD	IRN	PC12 cells (Aβ25-35)	ROS, MDA↓; GSH↑	[49]
AD	Geissoschizine methyl ether	HT22 (H₂O₂)	ROS, p-ERK↓	[52]
AD	Extract of Uncaria rhynchophylla	SD rats (STZ)	Keap1↓; SOD, CAT, GPx, HO-1, Nrf2↑	[38]
AD	RN	Astrocytes (TNF-α)	IL-23, IL-6, MDA, p-mTOR, p-STAT3↓; NOS, NO, SOD↑	[57]
PD	Uncaria rhynchophylla alkaloid extract	C57BL/6J mice (MPTP); BV-2 cells, SH-SY5Ycells (LPS)	IL-1β, TNF-α, IL-6, LDH, MDA, TLR4, NLRP3, COX2↓; TH, IL-10, SOD, GSH, Nrf2, HO-1↑	[36]
DD	IRN	SD rats (CUMS)	MDA, p-JNK↓; SOD, GSH-Px↑	[54]

Disease	Intervention	Model	Mechanism	References
AD	Extract of Uncaria rhynchophylla	ICR mice(D-galactose)	ACh, GSH↑; AChE, MDA↓	[48]
AD	IRN	PC12 cells (Aβ25-35)	ROS, MDA↓; GSH↑	[49]
AD	Geissoschizine methyl ether	HT22 (H₂O₂)	ROS, p-ERK↓	[52]
AD	Extract of Uncaria rhynchophylla	SD rats (STZ)	Keap1↓; SOD, CAT, GPx, HO-1, Nrf2↑	[38]
AD	RN	Astrocytes (TNF-α)	IL-23, IL-6, MDA, p-mTOR, p-STAT3↓; NOS, NO, SOD↑	[57]
PD	Uncaria rhynchophylla alkaloid extract	C57BL/6J mice (MPTP); BV-2 cells, SH-SY5Ycells (LPS)	IL-1β, TNF-α, IL-6, LDH, MDA, TLR4, NLRP3, COX2↓; TH, IL-10, SOD, GSH, Nrf2, HO-1↑	[36]
DD	IRN	SD rats (CUMS)	MDA, p-JNK↓; SOD, GSH-Px↑	[54]

Disease	Intervention	Model	Mechanism	References
AD	IRN	SD rats (Aβ25-35)	caspase-3, caspase-9, GSK-3β↓; Bcl-2/Bax, Akt↑	[70]
AD	IRN	PC12 cells (Aβ25-35)	caspase-3↓; Bcl-2/Bax↑	[49]
AD	Extract of Uncaria rhynchophylla	SD rats (NMDA)	c-jun, p53, bax↓	[64]
PD	RN	Primary cerebellar granule neurons (MPP?)	Bax/Bcl-2↓; MEF2, MEF2D, p-GSK3β, p-Ser473-Akt↑	[66]
PD	RN	PC12 cells (MPP?)	LDH, Ca²⁺, ROS, caspase-3↓; Bcl-2/Bax, p-Akt↑	[67]
PD	Extract of Uncaria rhynchophylla	C57BL/6 mice (MPTP)	caspase-3↓; DA, HVA, DAT, TH, p-mTOR, p-Akt, Bcl-2/BAD↑	[68]
PD	Gastrodin, IRN	PC12 cells (MPP⁺)	caspase-3, LPO, ERK1/2, PI3K, GSK-3β↓; HO-1, NQO-1↑	[69]
DD	IRN	SD rats (CUMS)	level of apoptosis, Bax, Cleaved Caspase-3, p-JNK↓; Bcl-2↑	[54]