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Liu P, Zhao Z, Zhang H, Xiao C, Wang M, Yang C, Liu YE, Wang L, He H, Ge Y, Fu Y, Zhou T, You Z, Zhang J. A comprehensive pharmacology study reveals the molecular mechanisms underlying the antidepressant effects of Gastrodiae Rhizoma. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 142:156761. [PMID: 40279969 DOI: 10.1016/j.phymed.2025.156761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 02/26/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Gastrodiae Rhizoma (GR) and its extract have been widely used in the treatment of depression, but the underlying mechanism of its antidepressant effects is unclear due to its numerous components. PURPOSE Revealing the cellular and molecular mechanisms underlying the antidepressant effects of GR through a comprehensive pharmacology-based in vivo and in vitro investigation. METHODS A mouse model of depression was established using chronic mild stress (CMS) procedure, and the antidepressant effects of GR were evaluated using systematic behavior. Metabolites in GR decoction and in mouse brain were identified by UPLC-QTOF-MS technology. Core components and targets of GR against MDD were screened based on network pharmacology analysis and molecular docking. The mechanism through which GR mitigated MDD was explored using transcriptome analysis, immunohistochemistry and western blotting in vitro and in vivo. RESULTS A total of 273 components were identified in the GR decoction, out of which 15 were detected in the brain of depressed mice treated with the GR decoction. We further identified nine key active ingredients, six essential targets, and fifth signaling pathways associated with the therapeutic effects of GR against MDD. We confirmed that the active ingredients of GR can target the neural stem/precursor cells (NSPCs) in the hippocampus of depressed mice to promote neurogenesis, as evidenced by a significant increase in the numbers of DCX+ cells, BrdU+ cells, BrdU+-DCX+ cells, and BrdU+-NeuN+ cells within the hippocampus of GR-treated mice compared to salinetreated mice under CMS exposure. Moreover, we have identified that the key active constituents of GR, namely gastrodin and parishin C, exert a targeted effect on EGFR to activate PI3K-Akt signaling in NSPCs, thereby facilitating proliferation and differentiation of NSPCs. CONCLUSION The antidepressant effect of GR involves the facilitation of PI3K/Akt-mediated neurogenesis through gastrodin and parishin C targeting EGFR in NSPCs.
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Affiliation(s)
- Pei Liu
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Zhihuang Zhao
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Haili Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Chenghong Xiao
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Meidan Wang
- Faculty of Biology, University of Freiburg, Freiburg, 79104, Germany.
| | - Chengyan Yang
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Yu-E Liu
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Lulu Wang
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Hui He
- The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
| | - Yangyan Ge
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Yan Fu
- The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
| | - Tao Zhou
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
| | - Zili You
- The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
| | - Jinqiang Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
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Wang L, Li B, Tang Z, Wang Y, Peng Y, Sun T, Zhang A, Qi X. Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity. CNS Neurosci Ther 2025; 31:e70283. [PMID: 40119586 PMCID: PMC11928745 DOI: 10.1111/cns.70283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/11/2025] [Accepted: 02/03/2025] [Indexed: 03/24/2025] Open
Abstract
BACKGROUND The pathogenesis of Alzheimer's disease (AD) remains incompletely elucidated, and there is a notable deficiency in effective and safe therapeutic interventions. The influence of brain matrix viscoelasticity on the progression of AD has frequently been underestimated. It is imperative to elucidate these overlooked pathogenic factors and to innovate novel therapeutic strategies for AD. Gastrodin, a bioactive constituent derived from the traditional Chinese medicinal herb Gastrodia elata, exhibits a range of pharmacological properties, notably in the enhancement of neural function. Nevertheless, the underlying mechanisms of its action remain insufficiently elucidated. Consequently, this study seeks to examine the therapeutic effects and underlying mechanisms of gastrodin in the context of AD, with particular emphasis on its potential influence on the viscoelastic properties of the brain matrix. METHODS This study employs a range of methodologies, including the Morris water maze test, Y-maze spontaneous alternation test, atomic force microscopy (AFM), immunofluorescence, transmission electron microscopy, molecular docking, and Cellular Thermal Shift Assay (CETSA), to demonstrate that gastrodin mitigates tau pathology by modulating FERMT2, thereby reversing the deterioration of mechanical viscoelasticity in the brain. RESULTS Gastrodin administration via gavage has been demonstrated to mitigate cognitive decline associated with AD, attenuate the hyperphosphorylation of tau protein in the hippocampus and cortex, and ameliorate synaptic damage. Additionally, gastrodin was observed to counteract the reduction in brain matrix viscoelasticity in 3xTg-AD mice, as evidenced by the upregulation of extracellular matrix components pertinent to viscoelasticity, notably collagen types I and IV. Furthermore, molecular docking and CETSA revealed a strong binding affinity between gastrodin and FERMT2. Gastrodin treatment resulted in a reduction of FERMT2 fluorescence intensity, which is selectively expressed in astrocytes. Additionally, gastrodin contributed to the restoration of the blood-brain barrier (BBB) and modulated the expression levels of inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metallopeptidase 8 (MMP8). CONCLUSION Gastrodin treatment has the potential to mitigate tau pathology, thereby enhancing learning and memory in AD mouse models. This effect may be mediated through the modulation of cerebral mechanical viscoelasticity via the mechanosensor FERMT2, which facilitates the restoration of synaptic structure and function. This process is potentially linked to the maintenance of BBB integrity and the modulation of inflammatory factor release.
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Affiliation(s)
- Li Wang
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
- School of NursingGuizhou Medical UniversityGuiyangChina
| | - Bo Li
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
| | - Zhi Tang
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
| | - Yang Wang
- The Department of ImagingAffiliated Hospital of Guizhou Medical UniversityGuiyangChina
| | - Yaqian Peng
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
| | - Ting Sun
- School of NursingGuizhou Medical UniversityGuiyangChina
| | - Anni Zhang
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
- The Department of NeurologyAffiliated Hospital of Guizhou Medical UniversityGuiyangChina
| | - Xiaolan Qi
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou ProvinceKey Laboratory of Molecular Biology of Guizhou Medical UniversityGuiyangChina
- Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Constructed by the Province and MinistryGuiyangChina
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JIN H, WANG X, WANG R, LI J, YU J, ZHAO D, ZHAI L. Neuroprotective effect of Naochuxue prescription on intracerebral hemorrhage: inhibition of autophagy downregulating high mobility group box-1. J TRADIT CHIN MED 2024; 44:944-953. [PMID: 39380225 PMCID: PMC11462531 DOI: 10.19852/j.cnki.jtcm.20240515.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 09/05/2023] [Indexed: 10/10/2024]
Abstract
OBJECTIVE To determine the molecular mechanisms underlying the neuroprotective effects of Naochuxue prescription (,NCXP) in rats with intracerebral hemorrhage (ICH). METHODS Sprague-Dawley rats were injected with collagenase to generate ICH models, which were then randomly divided into six groups, including control, sham, model, and three intervention groups. The intervention groups received different doses of NCXP (0.13, 0.26, and 0.52 g/kg) daily for 10 d. High-performance liquid chromatography (HPLC) was used to analyze the chemical characteristics of NCXP. The neurobehavioral outcomes of the rats were evaluated using neurological deficit scores (Zea Longa 5) and the corner turn test. Pathomorphological changes in perihematomal tissues after ICH were observed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was used to detect the inflammation expression of interleukin 6 (IL-6) and toll-like receptor 4 (TLR4). High mobility group box-1 (HMGB1), Beclin1, microtubule-associated protein 1 light chain 3 beta (LC3), and sequestosome 1 (p62) were detected using real-time quantitative polymerase chain reaction and Western blotting in perihematomal tissues. RESULTS HPLC showed that the NCXP had good stability. Rats with ICH had severe neurological function deficits compared to the control group. IHC results showed that NCXP significantly downregulated the expression of the inflammatory proteins IL-6 and TLR4. ICH rats treated with NCXP showed less neurological injury than the model group, accompanied by a significantly decreased expression of HMGB1, Beclin1, and LC3 and an increased expression of p62. CONCLUSIONS The neuroprotective effect of NCXP alleviated inflammation and autophagy possibly by downregulating HMGB1 expression. However, further research on the signaling pathways is required to verify this hypothesis.
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Affiliation(s)
- Hong JIN
- 1 College of Chinese medicine, Changchun University of Chinese Medicine, Changchun 13000, China
| | - Xinna WANG
- 2 Department of Encephalopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, China
| | - Ruonan WANG
- 3 College of nursing, Changchun University of Chinese Medicine, Changchun 13000, China
| | - Jinjian LI
- 2 Department of Encephalopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, China
| | - Junchao YU
- 2 Department of Encephalopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, China
| | - Dexi ZHAO
- 2 Department of Encephalopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, China
| | - Lu ZHAI
- 4 Research Center of Traditional Chinese Medicine, the First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 13000, China
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Que C, Wei Y, Yin G, Zhou C, Liu Z, Lai X, Qin M, Xiong X, Zheng X, Dong X, Gao Y. Updated evidence of the Naoshuantong capsule against ischemic stroke: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2024; 15:1434764. [PMID: 39391695 PMCID: PMC11464442 DOI: 10.3389/fphar.2024.1434764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 09/11/2024] [Indexed: 10/12/2024] Open
Abstract
Background Stroke is a serious health issue that can result in death or disability, leading to a significant economic strain on society and families. A growing number of studies have shown that the Naoshuantong capsule (NSTC) is beneficial as a treatment for ischemic stroke (IS) in recent years. Our study aims to provide an update on the safety and efficacy of the NSTC in IS patients. Methods We thoroughly searched eight databases to identify suitable randomized controlled trials (RCTs) assessing the effectiveness of the NSTC in the treatment of IS. The National Institute of Health Stroke Scale (NIHSS) for an acute period and modified Rankin Scale (mRS) at 3 months for a non-acute period were considered the primary outcome, and secondary outcomes included the NIHSS for a non-acute period, mRS, Barthel Index (BI), modified Barthel Index (MBI), Stroke-specific Quality of life (SS-QOL), and the recurrence rate of cerebrovascular events. Subsequently, its quality was assessed using the Cochrane risk assessment scale. Statistical analysis was conducted using RevMan 5.3 and Stata 14.0. Results A total of 27 RCTs were included, which involved 3,139 patients. The results showed that the NSTC improved neurological function not only in the acute period (MD = -2.53; 95% CI: -2.91, -2.15; p < 0.00001) but also in the non-acute period (MD = -3.70; 95% CI: -5.82, -1.58; p = 0.0006) and improved the long-term functional outcomes with lower mRS scores (MD = -0.68; 95% CI: -1.09, -0.26; p = 0.001). At the same time, the NSTC decreased the risk of cerebrovascular disease recurrence (RR = 0.43; 95% CI: 0.27, 0.70; p = 0.0006) and increased the quality of life in the acute period (MD = 23.88; 95% CI: 16.63, 31.13; p < 0.00001). Significant disparities in the incidence of adverse events between the NSTC and control groups were not observed. The certainty of evidence was estimated as moderate to very low. Conclusion The NSTC emerges as a potentially efficacious and safe treatment option for IS. NSTC could improve neurological function in different period of IS, and it has certain clinical value in secondary prevention. As a result of the poor quality and heterogeneity of the included trials, larger and standardized RCTs are needed to validate NSTC in IS treatment. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=482981, identifier CRD42023482981.
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Affiliation(s)
- Cuilin Que
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yupeng Wei
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Guanxiang Yin
- Beijing University of Chinese Medicine, Beijing, China
| | - Congren Zhou
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Zhenhong Liu
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
| | - Xinxing Lai
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
| | - Mingzhen Qin
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xuejiao Xiong
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xiangyi Zheng
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xinglu Dong
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
| | - Ying Gao
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Chinese Medicine Key Research Room of Brain Disorders Syndrome and Treatment of the National Administration of Traditional Chinese Medicine, Beijing, China
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Li ZR, Wang YY, Wang ZH, Qin QL, Huang C, Shi GS, He HY, Deng YH, He XY, Zhao XM. The positive role of transforming growth factor-β1 in ischemic stroke. Cell Signal 2024; 121:111301. [PMID: 39019338 DOI: 10.1016/j.cellsig.2024.111301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/05/2024] [Accepted: 07/12/2024] [Indexed: 07/19/2024]
Abstract
Ischemic stroke is one of the most disabling and fatal diseases around the world. The damaged brain tissues will undergo excessive autophagy, vascular endothelial cells injury, blood-brain barrier (BBB) impairment and neuroinflammation after ischemic stroke. However, there is no unified viewpoint on the underlying mechanism of brain damage. Transforming growth factor-β1 (TGF-β1), as a multi-functional cytokine, plays a crucial role in the intricate pathological processes and helps maintain the physiological homeostasis of brain tissues through various signaling pathways after ischemic stroke. In this review, we summarize the protective role of TGF-β1 in autophagic flux, BBB, vascular remodeling, neuroinflammation and other aspects after ischemic stroke. Based on the review, we believe that TGF-β1 could serve as a key target for treating ischemic stroke.
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Affiliation(s)
- Zi-Rong Li
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Yong-Yan Wang
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Zi-Han Wang
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Qi-Lin Qin
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Cheng Huang
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Guang-Sen Shi
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Hong-Yun He
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China; Anning First People's Hospital Affiliated to Kunming University of Science and Technology, Kunming, China.
| | - Yi-Hao Deng
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China.
| | - Xiu-Ying He
- Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu, China.
| | - Xiao-Ming Zhao
- Faculty of Medicine, Kunming University of Science and Technology, Kunming, China; Anning First People's Hospital Affiliated to Kunming University of Science and Technology, Kunming, China.
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He Y, Li R, Yu Y, Huang C, Xu Z, Wang T, Chen M, Huang H, Qi Z. Human neural stem cells promote mitochondrial genesis to alleviate neuronal damage in MPTP-induced cynomolgus monkey models. Neurochem Int 2024; 175:105700. [PMID: 38417589 DOI: 10.1016/j.neuint.2024.105700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 02/14/2024] [Accepted: 02/18/2024] [Indexed: 03/01/2024]
Abstract
Currently, there is no effective treatment for Parkinson's disease (PD), and the regenerative treatment of neural stem cells (NSCs) is considered the most promising method. This study aimed to investigate the protective effect and mechanism of NSCs on neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced cynomolgus monkey (Macaca fascicularis) model of PD. We first found that injecting NSCs into the subarachnoid space relieved motor dysfunction in PD cynomolgus monkeys, as well as reduced dopaminergic neuron loss and neuronal damage in the substantia nigra (SN) and striatum. Besides, NSCs decreased 17-estradiol (E2) level, an estrogen, in the cerebrospinal fluid (CSF) of PD cynomolgus monkeys, which shows NSCs may provide neuro-protection by controlling estrogen levels in the CSF. Furthermore, NSCs elevated proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a), mitofusin 2 (MFN2), and optic atrophy 1 (OPA1) expression, three genes mediating mitochondrial biogenesis, in the SN and striatum of PD monkeys. In addition, NSCs suppress reactive oxygen species (ROS) production caused by MPTP, as well as mitochondrial autophagy, therefore preserving dopaminergic neurons. In summary, our findings show that NSCs may preserve dopaminergic and neuronal cells in an MPTP-induced PD cynomolgus monkey model. These protective benefits might be attributed to NSCs' ability of modulating estrogen balance, increasing mitochondrial biogenesis, and limiting oxidative stress and mitochondrial autophagy. These findings add to our understanding of the mechanism of NSC treatment and shed light on further clinical treatment options.
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Affiliation(s)
- Ying He
- Medical College, Guangxi University, Nanning, Guangxi, 530004, China; The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545007, China
| | - Ruicheng Li
- Medical College, Guangxi University, Nanning, Guangxi, 530004, China
| | - Yuxi Yu
- Medical College, Guangxi University, Nanning, Guangxi, 530004, China
| | - Chusheng Huang
- The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530004, China
| | - Zhiran Xu
- Translational Medicine Research Center, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China
| | - Tianbao Wang
- Medical College, Guangxi University, Nanning, Guangxi, 530004, China
| | - Ming Chen
- Jinjiang Municipal Hospital (Shanghai Sixth People's Hospital Fujian Campus), Quanzhou, Fujian, 362200, China
| | - Hongri Huang
- Guangxi Taimei Rensheng Biotechnology Co., Ltd., Nanning, Guangxi, 530011, China
| | - Zhongquan Qi
- Medical College, Guangxi University, Nanning, Guangxi, 530004, China.
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Li XN, Shang NY, Kang YY, Sheng N, Lan JQ, Tang JS, Wu L, Zhang JL, Peng Y. Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway. Acta Pharmacol Sin 2024; 45:248-267. [PMID: 37833536 PMCID: PMC10789749 DOI: 10.1038/s41401-023-01177-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023]
Abstract
There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.
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Affiliation(s)
- Xin-Nan Li
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Nian-Ying Shang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yu-Ying Kang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Ning Sheng
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jia-Qi Lan
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jing-Shu Tang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Lei Wu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jin-Lan Zhang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
| | - Ying Peng
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
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Yang F, Yan Y, Gu Y, Qi K, Chen J, Wang G. Multi-target mechanism of Naoshuantong capsule for treatment of Ischemic stroke based on network pharmacology and molecular docking. Medicine (Baltimore) 2023; 102:e35771. [PMID: 37933045 PMCID: PMC10627680 DOI: 10.1097/md.0000000000035771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/03/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND Naoshuantong capsule (NST capsule) is a classic Chinese patent medicine, which can treat ischemic stroke (IS) and has good clinical efficacy. However, its pharmacological mechanism remains to be further explored in the treatment of IS. METHODS The bio-active components and potential targets of NST Capsules were obtained by ETCM and TCMSP databases. In addition, the related targets of IS were collected by Genecard, OMIM, DrugBank, TTD and DisGeNET databases. NST-IS common target was obtained by Venn platform. PPI network of NST-IS common target and the composition - target network diagram of NST Capsule were constructed by Cytoscape3.8.1. Finally, AutoDock was used for molecular docking. RESULTS 265 targets were predicted from 32 active compounds in NST Capsule, 109 common targets were identified between NST Capsule and IS. The top 10 key targets of PPI network were ALB, TNF, TP53, VEGFA, CASP3, MYC, etc. Enrichment analysis showed that NST capsules treated IS mainly through lipid and atherosclerosis, fluid shear stress and atherosclerosis signaling pathways. CONCLUSION Through the methods of network pharmacology and molecular docking, this study clarified that NST capsules play a role in the treatment of IS, which is multi-target, multi-channel and multi-component regulation. This study further explored the pharmacological mechanism of NST capsule in the treatment of IS, which can provide some references for the subsequent research in the pharmacological mechanism of NST capsule.
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Affiliation(s)
- Fengjiao Yang
- College of Pharmacy, Dali University, Dali, PR China
| | - Ya Yan
- College of Pharmacy, Dali University, Dali, PR China
| | - Yun Gu
- College of Pharmacy, Dali University, Dali, PR China
| | - Kezhen Qi
- College of Pharmacy, Dali University, Dali, PR China
| | - Jianjie Chen
- School of Clinical Medicine, Dali University, Dali, PR China
| | - Guangming Wang
- School of Clinical Medicine, Dali University, Dali, PR China
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Du Y, Cai X. Therapeutic potential of natural compounds from herbs and nutraceuticals in spinal cord injury: Regulation of the mTOR signaling pathway. Biomed Pharmacother 2023; 163:114905. [PMID: 37207430 DOI: 10.1016/j.biopha.2023.114905] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/13/2023] [Accepted: 05/16/2023] [Indexed: 05/21/2023] Open
Abstract
Spinal cord injury (SCI) is a disease in which the spinal cord is subjected to various external forces that cause it to burst, shift, or, in severe cases, injure the spinal tissue, resulting in nerve injury. SCI includes not only acute primary injury but also delayed and persistent spinal tissue injury (i.e., secondary injury). The pathological changes post-SCI are complex, and effective clinical treatment strategies are lacking. The mammalian target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells in response to various nutrients and growth factors. The mTOR signaling pathway has multiple roles in the pathogenesis of SCI. There is evidence for the beneficial effects of natural compounds and nutraceuticals that regulate the mTOR signaling pathways in a variety of diseases. Therefore, the effects of natural compounds on the pathogenesis of SCI were evaluated by a comprehensive review using electronic databases, such as PubMed, Web of Science, Scopus, and Medline, combined with our expertise in neuropathology. In particular, we reviewed the pathogenesis of SCI, including the importance of secondary nerve injury after the primary mechanical injury, the roles of the mTOR signaling pathways, and the beneficial effects and mechanisms of natural compounds that regulate the mTOR signaling pathway on pathological changes post-SCI, including effects on inflammation, neuronal apoptosis, autophagy, nerve regeneration, and other pathways. This recent research highlights the value of natural compounds in regulating the mTOR pathway, providing a basis for developing novel therapeutic strategies for SCI.
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Affiliation(s)
- Yan Du
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China
| | - Xue Cai
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
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10
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Zhao S, Zhang P, Yan Y, Xu W, Li J, Wang L, Wang N, Huang Y. Network pharmacology-based prediction and validation of the active ingredients and potential mechanisms of the Huangxiong formula for treating ischemic stroke. JOURNAL OF ETHNOPHARMACOLOGY 2023; 312:116507. [PMID: 37080367 DOI: 10.1016/j.jep.2023.116507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/30/2023] [Accepted: 04/16/2023] [Indexed: 05/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huangxiong Formula (HXF) is composed of four herbs: Rheum palmatum L., Ligusticum striatum DC., Curcuma aromatica Salisb., and Acorus gramineus Aiton. HXF is clinically used for the treatment of ischemic stroke (IS). However, its molecular mechanism remains unclear. AIM OF THE STUDY A network pharmacology-based strategy combined with experimental study in vivo and in vitro to were used to investigate the bioactive components, potential targets, and molecular mechanisms of HXF in the treatment of IS. MATERIALS AND METHODS The components of HXF were detected by ultra-performance liquid chromatography (UPLC). The potential active ingredients of HXF were acquired from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, and corresponding targets were discerned through the Swiss TargetPrediction database. IS-related targets were obtained from Genecards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DisGeNET. The intersection of ingredient and disease targets was screened, and a herbal-compound-target network was constructed. A protein-protein interaction (PPI) network was created, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Based on these analyses, we established a compound-target-pathway (C-T-P) network. A cerebral ischemia-reperfusion (I/R) animal model was established, and the cerebral protective effect of HXF was assessed. The accuracy of the predicted targets was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Hippocampal neuronal injury cell model induced by oxygen-glucose deprivation and reperfusion (OGD/R) was used to evaluate the protective effect of α-Asarone. Furthermore, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to verify whether α-Asarone can bind to PI3K. RESULTS A total of 44 active ingredients and 795 gene targets were identified through network pharmacology. Network analysis showed that naringenin, eupatin, kaempferol, and α-Asarone were possible drug candidates. SRC, AKT1, TP53, MAPK3, STAT3, HRAS, CTNNB1, EGFR, VEGFA, PIK3R1 could serve as potential drug targets. KEGG analysis implied that the PI3K/AKT signaling pathway might play an important role in treating IS by HXF. Moreover, HXF significantly reduced neurological impairment, cerebral infarct volume, brain index, and brain histopathological damage in I/R rats. The mRNA expression of the top 10 potential targets was verified in the brain tissue. The C-T-P network and UPLC analysis suggested that α-Asarone might be an important component of HXF and can inhibit oxidative stress and apoptosis in HT22 cells by activating the PI3K/AKT signaling pathway. Molecular docking, DARTS, and CETSA assay analysis confirmed that there were direct interactions between α-Asarone and PI3K. CONCLUSION HXF had a therapeutic effect in IS with multi-component, multi-target, and multi-approach features. α-Asarone, identified as one of the major active components of HXF, could alleviate oxidative stress and apoptosis by targeting PI3K/AKT pathway.
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Affiliation(s)
- Saihong Zhao
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Pingping Zhang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Yonghuan Yan
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Weifang Xu
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Jiacheng Li
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Lei Wang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Ning Wang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China; Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei, China; Institute for the Evaluation of the Efficacy and Safety of Chinese Medicines, Anhui Academy of Chinese Medicine, Hefei, China.
| | - Yingying Huang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China; Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei, China; Institute for the Evaluation of the Efficacy and Safety of Chinese Medicines, Anhui Academy of Chinese Medicine, Hefei, China.
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11
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Liu H, An N, Wang L, Li Y, Song K, Sun Y, Gao Y. Protective effect of Xingnaojing injection on ferroptosis after cerebral ischemia injury in MCAO rats and SH-SY5Y cells. JOURNAL OF ETHNOPHARMACOLOGY 2023; 301:115836. [PMID: 36252877 DOI: 10.1016/j.jep.2022.115836] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Xingnaojing（XNJ）injection is a traditional Chinese medicine injection with neuroprotective effect, which has been widely used in the treatment of stroke for many years. AIM OF THE STUDY This study aimed to explore the potential mechanism of XNJ in cerebral ischemia mediated by ferroptosis using proteomics and in vivo and in vitro experiments. MATERIALS AND METHODS After the rat model of middle cerebral artery occlusion (MCAO) was successfully established, they were randomly divided into model, XNJ, and deferoxamine (DFO) group. Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin and eosin (H&E), and Nissl staining were used to observe the infarct area, pathological changes and the degree of neuronal apoptosis of rat brain. Proteins extracted from rat brain tissues were analyzed by quantitative proteomics using tandem mass tags (TMT). Western blotting and immunohistochemical assessment were used to measure the expression of ferroptosis-related proteins. In vitro, the SH-SY5Y cells were subjected to hypoxia (37°C/5% CO2/1% O2) for 24 h to observe the survival rate, and detect the reactive oxygen species (ROS) content and ferroptosis-related proteins. RESULTS In TTC and H&E experiments, we found that XNJ drug treatment reduced the infarct volume and brain tissue damage in MCAO rats. Nissl staining also showed that compared with MCAO group rats, the Nissl bodies of brain tissue after XNJ drug intervention were clear with a 3.54-fold increased times, suggesting that XNJ improved cerebral infraction, and neurological deficits in MCAO rats. Proteomics identified 101 intersected differentially expressed proteins (DEPs). According to the bioinformatics analysis, these DEPs were closely related to ferroptosis. Further research indicated that MCAO-induced cerebral ischemia was alleviated by upregulating recombinant glutathione peroxidase 4 (GPX4), ferroportin (FPN) expression, Heme oxygenase-1 (HO-1) expression, and downregulating cyclooxygenase-2 (COX-2), transferring receptor (TFR) and divalent metal transporter-1 (DMT1) expression after XNJ treatment. In addition, in vitro experiment indicated that XNJ improved the survival rate of hypoxia-damaged SH-SY5Y cells. XNJ increased the level of GPX4 and inhibited the protein expression of COX-2 and TFR after cell hypoxia. Moreover, different concentrations of XNJ (0.25%, 0.5%, 1%) reduced the ROS content of hypoxic cells, suggesting that XNJ could inhibit hypoxia-induced cell damage by regulating the expression of ferroptosis-related proteins and decreasing the production of ROS. CONCLUSIONS XNJ could promote the recovery of neurological function in MCAO rats and hypoxia SH-SY5Y cells by regulating ferroptosis.
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Affiliation(s)
- Haoqi Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Na An
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Liqin Wang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China; Baotou Mongolian Traditional Chinese Medicine Hospital, Inner Mongolia Municipality, Baotou, 014040, China.
| | - Yuanyuan Li
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Ke Song
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Yikun Sun
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Yonghong Gao
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China; Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China.
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Dong X, Feng L, Li T, Song Y, Li L, Wu S, Zhang C, Gao Y, ; For the VENUS Investigators. Vital real-world experience regarding Naoshuantong capsules for unselected ischemic stroke (VENUS): Rationale, design, and baseline of a prospective, multicenter, observational study. Front Pharmacol 2022; 13:933258. [PMID: 36278169 PMCID: PMC9579274 DOI: 10.3389/fphar.2022.933258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Naoshuantong capsules (NC) are commonly used for the treatment of ischemic stroke. Experimental research and small-sample clinical trials have demonstrated that NC is effective in improving neurological recovery. Yet, there is a substantial lack of high-quality evidence on the precision treatment population of NC and long-term safety when making real-world clinical decisions. The acquisition of prospective longitudinal data in the real-world setting is essential to fully characterize the effectiveness and safety profile of NC for patients with ischemic stroke. Methods: The Vital real-world Experience regarding Naoshuantong capsules for Unselected ischemic Stroke (VENUS) registry is a prospective, multicenter, observational study aiming to register 5,000 patients. Eligible adult patients diagnosed with ischemic stroke and newly treated with NC within 30 days of symptom onset will be consecutively registered from 84 participating sites across the Chinese mainland. Baseline data will be recorded at the patient registry, and all patients will be regularly followed up at 2, 4, 8, and 12 weeks after the initial patient registry, and 180 days after ischemic stroke onset. The primary outcome is the distribution of scores on the modified Rankin Scale at 12 weeks after initial patient registry. Adverse events will be recorded during the study for NC safety assessment. Results: A total of 4,185 patients with ischemic stroke were enrolled, among which 37.06% patients were female. The average age of all patients was 65.22 years. The proportion of patients whose course of ischemic stroke was less than 14 days accounted for 93.45%. Conclusion: The VENUS registry is designed to comprehensively document medical data regarding NC treatment for ischemic stroke in real-world settings. The findings of this study will provide valuable insights into the clinical management of patients with ischemic stroke and the subsequent outcomes of the use of NC when included in the best clinical practice. Study registration: This study was registered with the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/index.aspx, Unique identifier: ChiCTR1900025053).
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Affiliation(s)
- Xinglu Dong
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Luda Feng
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Tingting Li
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yuebo Song
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Lei Li
- Chinese-Western Medicine Research and Development Working Committee, China Association of Traditional Chinese Medicine, Beijing, China
| | - Shengxian Wu
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Office of State Drug Clinical Trial Institution, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Chi Zhang
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Ying Gao, ; Chi Zhang,
| | - Ying Gao
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Ying Gao, ; Chi Zhang,
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Sun L, Ye X, Wang L, Yu J, Wu Y, Wang M, Dai L. A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease. Front Neurosci 2022; 16:942188. [PMID: 35844225 PMCID: PMC9278698 DOI: 10.3389/fnins.2022.942188] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/02/2022] [Indexed: 11/13/2022] Open
Abstract
Cerebral small vessel disease (CSVD) is often referred to as “collaterals disease” in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.
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14
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Gastrodin and Vascular Dementia: Advances and Current Perspectives. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2563934. [PMID: 35463081 PMCID: PMC9019412 DOI: 10.1155/2022/2563934] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 02/08/2022] [Accepted: 03/16/2022] [Indexed: 12/15/2022]
Abstract
Gastrodia elata, a traditional Chinese medicine, has been widely used since ancient times to treat diseases such as dizziness, epilepsy, stroke, and memory loss. Gastrodin, one of the active components of Gastrodia elata, has been used in the treatment of migraine, epilepsy, Parkinson's disease, dementia, and depression in recent years. It can improve cognitive function and related neuropsychiatric symptoms through various effects and is considered as a promising treatment for dementia. Vascular dementia is a kind of severe cognitive impairment syndrome caused by vascular factors, and it is the dementia syndrome with the largest number of patients besides Alzheimer's disease. Although there is still a lack of evidence-based explorations, the paper reviewed the mechanism and methods of gastrodin in the treatment of vascular dementia, providing a reference for clinical therapy.
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Li J, Zhao X, Zhang Y, Wan H, He Y, Li X, Yu L, Jin W. Comparison of Traditional Chinese Medicine in the Long-Term Secondary Prevention for Patients with Ischemic Stroke: A Systematical Analysis. Front Pharmacol 2021; 12:722975. [PMID: 34867326 PMCID: PMC8637749 DOI: 10.3389/fphar.2021.722975] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 10/05/2021] [Indexed: 12/31/2022] Open
Abstract
Background: Keeping in view the high recurrence rate and risk of ischemic stroke, combinatorial therapy involving traditional Chinese medicine (TCM) with conventional Western medicine (WM) is receiving wider scientific attention. Thus, a systematical analysis was made to explore the efficacy of TCM+WM in the long-term secondary prevention for patients with ischemic stroke. Methods: Qualified inclusion and exclusion criteria were set up beforehand, and two researchers independently read the articles, extracted data, and evaluated the quality of included articles according to Cochrane Reviewer's Handbook 5.1 method. For the sake of comprehensive data acquisition, seven databases from the time of their establishment to May 5, 2021, have been searched completely. Additionally, pairwise meta-analysis was made to compare TCM+WM vs. WM, and network meta-analysis was conducted by frequentist random effects models for the comparison of different kinds of TCM+WM via indirect evidence. The primary outcomes defined were recurrent stroke and NIHSS. Secondary outcomes were fibrinogen (Fib) fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Safety outcomes were outlined as all-cause mortality and adverse events (AEs). Furthermore, Stata16.0 software was used to accomplish the systematical analysis and cluster analysis. Results: In total, 47 qualified randomized controlled trials (RCTs) including 10,732 patients were taken into consideration. Seven traditional Chinese medicines included in the study are Naoxintong capsule (NXT), Tongxinluo capsule (TXL), Buyang Huanwu decoction (BYHW), Naomaitai capsule (NMT), Dengzhan Shengmai capsule (DZSM), Naoshuantong capsule (NST), and Maixuekang capsule (MXK). With respect to their primary outcomes, all kinds of TCM+WM were significantly more effective than WM (e.g., NXT in recurrent stroke (OR=0.54, P<0.01), TXL in NIHSS (WM=-1.4, P<0.01)). Additionally, the outcomes of cluster analysis indicated that MXK+WM and NST+WM had relatively good preventive effects for recurrent stroke, NIHSS, and all-cause mortality. There was no significant difference in the comparisons of AEs; however, this may arise from the lack of sufficient data. Conclusion: According to our systematical analysis, MXK+WM and NST+WM had relatively good secondary prevention effects for patients with ischemic stroke regarding recurrent stroke, NIHSS, and all-cause mortality. Nevertheless, better, high-quality, large-sample randomized clinical trials (RCTs) are required to verify our conclusions in the future. Systematic Review Registration: [https://inplasy.com/inplasy-2021-5-0036/], identifier [INPLASY202150036].
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Affiliation(s)
- Jiali Li
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xixi Zhao
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yangyang Zhang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Haitong Wan
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yu He
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaohong Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li Yu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Weifeng Jin
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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