1.Traditional Chinese Medicine Intervention in Parkinson's Disease Based on Keap1/Nrf2/ARE Signaling Pathway: A Review
Liuping YUE ; Yongkang SUN ; Fangbiao XU ; Yanbo SONG ; Yijun WU ; Huan YU ; Xinzhi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):307-317
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra, abnormal aggregation of alpha-Synuclein (α-Syn), and the formation of Lewy bodies. However, the exact mechanisms remain unclear. In recent years, the PD incidence has gradually increased, while current treatment methods are limited to symptom alleviation, incapable of halting disease progression, and prone to adverse effects, thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is closely related to oxidative stress, neuroinflammation, apoptosis, ferroptosis, and mitochondrial dysfunction, playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine (TCM) can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages, such as multiple targets, multiple pathways, and fewer adverse reactions, TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD, while summarizing the latest research on PD intervention by TCM monomers, active ingredients, and compounds, as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway, aiming to provide a reference for clinical medicine development to prevent and treat PD.
2.Mechanism of Yishen Qubi Tongluo Formula (益肾祛痹通络方) in the Treatment of Rheumatoid Arthritis:Based on Network Pharmacology,Molecular Docking and Experimental Verification
Liuping XU ; Canyu YANG ; Ying LU ; Lisha MO ; Qiang CHI ; Yuan XIA ; Shuijuan LIU ; Mingliang QIU
Journal of Traditional Chinese Medicine 2026;67(5):557-566
ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula (益肾祛痹通络方, YQTF) in the treatment of rheumatoid arthritis(RA). MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP, BATMAN, ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed, and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group, model group, methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum, while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α (TNF-α) for 24 h to establish the RA cell model. On this basis, the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L, and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention, the levels of TNF-α and interleukin-17A(IL-17A)contents in cell supernatants were detected by enzyme-linked immunosorbent assay (ELISA), and mRNA expressions of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT) and mammalian target of rapamycin(mTOR) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF, as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin,β-sitosterol, kaempferol, stigmasterol and luteolin were the core active components of YQTF for the treatment of RA, while matrix metalloproteinase-9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2), Toll-like receptor 4 (TLR4), tumor protein p53 (TP53) and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses, PI3K-AKT signaling pathway and Toll-like receptor (TLR) signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin, β-sitosterol, kaempferol, stigmasterol and luteolin; TLR4 exhibited high binding activities with β-sitosterol, stigmasterol and luteolin; and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group, the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased (P<0.05 or P<0.01). Compared with the model group, all the above indicators significantly decreased in the YQTF group, while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group (P<0.05 or P<0.01). ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.
3.Study on the similarities and differences of orthostatic hypotension in patients with Parkinson′s disease and multiple system atrophy
Ningxiao LI ; Fubo ZHOU ; Erhe XU ; Hongxiu CHEN ; Liuping CUI ; Yingqi XING
Chinese Journal of Neurology 2024;57(1):61-69
Objective:To summarize and compare the characteristics of orthostatic hypotension (OH) in patients with Parkinson′s disease and multiple system atrophy (MSA).Methods:The active standing test data of 210 Parkinson′s disease patients (Parkinson′s disease group) and 85 MSA patients (MSA group) admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2021 to March 2022 were retrospectively analyzed. Demographic information, clinical data, Hoehn-Yahr staging, and Unified Parkinson′s Disease Rating Scale (UPDRS), Non-Motor Symptoms Questionnaire (NMSQ), Montreal Cognitive Assessment Scale and Mini-Mental State Examination scores were collected. The comparative analysis of OH was conducted according to the changes of heart rate and blood pressure during the active standing test.Results:Among the 85 patients with MSA, 52 were found with MSA parkinsonism variant (MSA-P) and 33 with MSA cerebellar variant (MSA-C). The 210 Parkinson′s disease patients were aged (61.5±11.0) years, with 116 males (55.2%). The 85 MSA patients were aged (60.1±6.8) years, with 44 males (51.8%). Compared with the Parkinson′s disease group, the Hoehn-Yahr staging [2.0(2.0, 3.0) vs 3.0(2.0, 3.0), Z=-5.278, P<0.001], NMSQ[ 25.0(11.0,46.5) vs 45.0(24.0,70.0), Z=-3.632, P<0.001] and UPDRS scores [50.0(32.0,68.0) vs 65.5(44.5,78.5), Z=-3.073, P=0.003] in the MSA group were higher. The incidence of OH in the MSA group was higher than that in the Parkinson′s disease group [63.5% (54/85) vs 25.7%(54/210), χ 2= 37.284, P<0.001], but there was no statistically significant difference between the MSA-P and MSA-C groups . Compared with the Parkinson′s disease group, the MSA group had a higher incidence of classical OH [54.1%(46/85) vs 12.9%(27/210), χ 2=55.316, P<0.001] and neurogenic OH [36.5%(31/85) vs 9.0%(19/210), χ 2=32.326, P<0.001],but there was no statistically significant difference in the incidence of initial OH and delayed OH between the two groups. The incidence of severe OH in the MSA group was also higher than that in the Parkinson′s disease group [57.6%(49/85) vs 16.7%(35/210), χ 2=49.894, P<0.001], but there was no statistically significant difference in the incidence of pre-clinical OH and mild OH between the two groups. Conclusions:The incidence, time change, severity and pathophysiological basis of OH in Parkinson′s disease and MSA patients are different. Different types of OH may help to distinguish MSA from Parkinson′s disease.
4.Regulation of Alzheimer's Disease by Chinese Medicine Based on BDNF/TrkB Signaling Pathway: A Review
Liuping YUE ; Yongkang SUN ; Fangbiao XU ; Yanbo SONG ; Xinzhi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):274-282
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by the progressive loss of cognitive and memory functions. Its pathological features mainly include neurofibrillary tangles formed by the aggregation of hyperphosphorylated tau proteins and amyloid plaques formed by the accumulation of β-amyloid. The exact pathogenesis of AD has not been fully elucidated, and there are currently no effective specific drugs or radical treatments available in clinical practice. In recent years, the incidence of AD has been on the rise, severely affecting life and health, making the search for effective drugs and therapeutic components for AD treatment crucial. Modern medical research has found that the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway is closely related to neurogenesis, apoptosis, neuroinflammation, synaptic plasticity, and oxidative stress, playing a vital role in the pathophysiological development of AD. Additionally, Chinese medicine has a long history of treating neurodegenerative diseases with few adverse reactions and features a multi-target, multi-link, and multi-pathway approach to treatment. Therefore, the author reviewed the latest research reports in China and abroad to elaborate on the role of the BDNF/TrkB signaling pathway in the onset and progression of AD, and summarized the research progress on the regulation of the BDNF/TrkB pathway by Chinese medicine compounds and monomers in AD intervention. This study is expected to provide references for the development of clinical drugs for the prevention and treatment of AD and to broaden the perspective on Chinese medicine treatment of AD.
5.Understanding the excellent use of Chaihu Guizhi Decoction from xiang thinking
Yilong SUN ; Fangbiao XU ; Yanbo SONG ; Yuhe HU ; Yongkang SUN ; Wenbo LIU ; Liuping YUE ; Xinzhi WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1512-1519
Chaihu Guizhi Decoction is an excellent prescription of ZHANG Zhongjing;however,nowadays the application of Chaihu Guizhi Decoction is primarily derived from the text.The xiang thinking is the source of traditional Chinese medicine thinking.Understanding Chaihu Guizhi Decoction from the xiang thinking,it is easy to perceive the true meaning of ZHANG Zhongjing,and grasp the location of the disease and the patient's overall qi,so as to make better use of this formula.This article discusses the understanding of Chaihu Guizhi Decoction from five perspectives:firstly,it gives an overview of the xiang thinking,pointing out the source and essential value of the xiang thinking;secondly,it analyses the disease position and the patient's qi of Chaihu Guizhi Decoction under the perspective of the xiang thinking as a whole;thirdly,it discusses the disease position and the patient's qi of the original text of Chaihu Guizhi Decoction from the xiang thinking;fourthly,it discusses how to understand the principle of formula formation and the main and minor parts of Chaihu Guizhi Decoction by xiang thinking;finally,it analyses the primary medicines in Chaihu Guizhi Decoction by using xiang thinking based on the records of Shennong Bencao Jing.Based on these five points,we hope to reveal the traditional Chinese medicine thinking behind Chaihu Guizhi Decoction,and provide new ideas for the clinical application of Chaihu Guizhi Decoction.

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