Investigation on the Mechanism of Lemai Granules in the Treatment of Vascular Dementia Based on Network Pharmacology and Molecular Docking

Abstract

Abstract:

Objective： To investigate the mechanism of Lemai Granules in the treatment of vascular dementia（VD） using network pharmacology and molecular docking. Methods： The active ingredients and targets of Lemai Granules were screened from the TCMSP database， and the relevant targets of VD were obtained from GeneCard， OMIM， DrugBank and other databases. The intersection targets were obtained after merging and deduplication. Cytoscape 3.9.0 software was used for visual analysis of the "drug-active ingredient-target" network and protein-protein interaction network to obtain core active ingredients and targets. R 4.2.1 software was used for GO analysis and KEGG pathway enrichment analysis of intersection targets， and AutoDock Vina 1.5.6 software was used for molecular docking. Results： Quercetin， luteolin， and kaempferol may be the core active ingredients for the treatment of VD by Lemai Granules， and core targets included AKT1， PTGS2， and TNF. GO analysis was mainly related to peptide response and cellular responses to chemical stress. KEGG mainly involved lipid and atherosclerosis， PI3K-Akt signaling pathway， and other pathways. The molecular docking results showed that the binding activity between core active ingredients and core targets was strong. Conclusion： Lemai Granules can exert their therapeutic effects on VD through multiple targets and pathways， mainly involving the suppression of inflammatory reaction and the regulation of neuronal apoptosis.

Key words:

"> font-size:10.5pt, ">Lemai Granules, vascular dementia, network pharmacology, molecular docking, mechanism of action

CLC Number:

Wang Jinyu, Zhou Longlong, Wang Xuechang, Li Xiaodong, Geng Shuqiong, Xia Conglong.

Investigation on the Mechanism of Lemai Granules in the Treatment of Vascular Dementia Based on Network Pharmacology and Molecular Docking [J]. Journal of Dali University, 2023, 8(4): 13-21.

References

〔1〕 MICELI V， RUSSELLI G， IANNOLO G， et al. Role of Non-Coding RNAs in Age-Related Vascular Cognitive Impairment： An Overview on Diagnostic/Prognostic Ｖalue in Vascular Dementia and Vascular Parkinsonism〔J〕. Mech Ageing Dev， 2020， 191： 111332.

〔2〕 GOLD G. Diagnosis and Treatment of Vascular Dementia〔J〕. Praxis， 2004， 93（33）： 1311-1316.

〔3〕 ZHOU D A， DING J， YA J， et al. Efficacy of Remote Ischemic Conditioning on Improving WMHs and Cognition in Very Elderly Patients with Intracranial Atherosclerotic Stenosis〔J〕.Aging （Albany NY）， 2019， 11（2）： 634-648.

〔4〕 VENKAT P， CHOPP M， CHEN J. Models and Mechanisms of Vascular Dementia〔J〕. Exp Neurol， 2015， 272： 97-108.

〔5〕杨红彦，张颖，陈盼盼，等. 不同抗痴呆药物治疗血管性痴呆的网状meta分析〔J〕. 现代医药卫生， 2020，36（19）：3085-3090.

〔6〕史梦龙，赵敏，张杰，等. 口服中成药辅助治疗血管性痴呆的网状Meta分析〔J〕. 中草药，2021，52（13）： 3994-4006.

〔7〕曹建伟，樊振梅，石素芳，等. 乐脉颗粒对局灶性脑缺血再灌注大鼠侧支循环形成的影响及机制研究〔J〕. 武警后勤学院学报（医学版）， 2019， 28（5）： 7-11.

〔8〕徐波，姜绪防，钟忠辉，等. 乐脉颗粒治疗28例血管性痴呆伴发行为—心理症状的疗效〔J〕. 华西药学杂志，2007， 22（5）： 594.

〔9〕曹雄彬，宫丽，戴军，等. 奥拉西坦联合乐脉颗粒辨证治疗血管性痴呆临床研究〔J〕. 中国实用神经疾病杂志，2015， 18（3）： 60-61.

〔10〕 YANG L， XU H， CHEN Y， et al. Melatonin： Multi-Target Mechanism against Diminished Ovarian Reserve Based on Network Pharmacology〔J〕. Front Endocrinol（Lausanne）， 2021， 12： 630504.

〔11〕 TAN Z， YANG G， QIU J， et al. Quercetin Alleviates Demyelination through Regulating Microglial Phenotype Transformation to Mitigate Neuropsychiatric Symptoms in Mice with Vascular Dementia〔J〕. Mol Neurobiol， 2022， 59（5）： 3140-3158.

〔12〕 KOU J J， SHI J Z， HE Y Y， et al. Luteolin Alleviates Cognitive Impairment in Alzheimer's Disease Mouse Model via Inhibiting Endoplasmic Reticulum Stress-Dependent Neuroinflammation〔J〕. Acta Pharmacol Sin， 2022， 43（4）： 840-849.

〔13〕 IMRAN M， RAUF A， SHAH Z A， et al. Chemo-Preventive and Therapeutic Effect of the Dietary Flavonoid Kaempferol： A Comprehensive Review〔J〕. Phytother Res， 2019， 33（2）： 263-275.

〔14〕 YANG S， LIU W， LU S， et al. A Novel Multifunctional Compound Camellikaempferoside B Decreases Aβ Produ-ction， Interferes with Aβ Aggregation， and Prohibits Aβ-Mediated Neurotoxicity and Neuroinflammation〔J〕. ACS Chem Neurosci， 2016， 7（4）： 505-518.

〔15〕 YE J Y， LI L， HAO Q M， et al. β-Sitosterol Treatment Attenuates Cognitive Deficits and Prevents Amyloid Plaque Deposition in Amyloid Protein Precursor/Presenilin 1 Mice〔J〕. Korean J Physiol Pharmacol， 2020，

24（1）： 39-46.

〔16〕 GOULAY R， MENA ROMO L， HOL E M， et al. From Stroke to Dementia： A Comprehensive Review Exposing Tight Interactions between Stroke and Amyloid-β Formation〔J〕. Transl Stroke Res，2020，11（4）： 601-614.

〔17〕 KONG D， LUO J， SHI S， et al. Efficacy of Tanshinone ⅡA and Mesenchymal Stem Cell Treatment of Learning and Memory Impairment in a Rat Model of Vascular Dementia〔J〕. J Tradit Chin Med， 2021，41（1）：133-139.

〔18〕 KAUR D， SHARMA V， DESHMUKH R. Activation of Microglia and Astrocytes： A Roadway to Neuroinflam-mation and Alzheimer's Disease〔J〕. Inflammopharmacology， 2019， 27（4）： 663-677.

〔19〕 MAUSBACH B T， DECASTRO G， VARA-GARCIA C， et al. The Relationship between Circulating Interleukin-6 Levels and Future Health Service Use in Dementia Caregivers〔J〕. Psychosom Med， 2019， 81（7）： 668-674.

〔20〕 DESAI S J， PRICKRIL B， RASOOLY A. Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 （COX-2） and Inflammation Related to Cancer〔J〕. Nutr Cancer， 2018， 70（3）： 350-375.

〔21〕 CHAUHAN G， ROY K， KUMAR G， et al. Distinct Influence of COX-1 and COX-2 on Neuroinflammatory Response and Associated Cognitive Deficits during High Altitude Hypoxia〔J〕. Neuropharmacology， 2019， 146： 138-148.

〔22〕 LEE M Y， GAMEZ-MENDEZ A， ZHANG J， et al. Endothelial Cell Autonomous Role of Akt1： Regulation of Vascular Tone and Ischemia-Induced Arteriogene-sis〔J〕. Arterioscler Thromb Vasc Biol， 2018， 38（4）： 870-879.

〔23〕 CHANG C Y， CHEN Y W， WANG T W， et al. Akting up in the GABA Hypothesis of Schizophrenia： Akt1 Deficiency Modulates GABAergic Functions and Hippocampus-Dependent Functions〔J〕. Sci Rep， 2016， 6： 33095.

〔24〕 YANG J， PAN Y， LI X， et al. Atorvastatin Attenuates Cognitive Deficits through Akt1/Caspase-3 Signaling Pathway in Ischemic Stroke〔J〕. Brain Res， 2015， 1629： 231-239.

〔25〕 EDGINGTON-MITCHELL L E， BOGYO M. Detection of Active Caspases during Apoptosis Using Fluorescent Activity-Based Probes〔M〕. New York： Humana Press，2016.

〔26〕 ZHANG Y， LI Y， WANG Y， et al. Effects of Resveratrol on Learning and Memory in Rats with Vascular Demen-tia〔J〕. Mol Med Rep， 2019， 20（5）： 4587-4593.

〔27〕 ZHANG Y， YANG X， GE X， et al. Puerarin Attenuates Neurological Deficits via Bcl-2/Bax/Cleaved Caspase-3 and Sirt3/SOD2 Apoptotic Pathways in Subarachnoid Hemorrhage Mice〔J〕. Biomed Pharmacother， 2019， 109： 726-733.

〔28〕 DUONG M T， NASRALLAH I M， WOLK D A， et al. Cholesterol， Atherosclerosis， and APOE in Vascular Contributions to Cognitive Impairment and Dementia （VCID）： Potential Mechanisms and Therapy〔J〕. Front Aging Neurosci， 2021， 13： 647990.

〔29〕李龙春，李晓晔，杜小华. 针刺通过调控PI3K/Akt/mTOR通路改善血管性痴呆大鼠认知功能的机制研究〔J〕.针刺研究， 2021， 46（10）： 851-856.

〔30〕 WU X， LIU Y， ZHU L， et al. Cerebroprotein Hydrolysate-I Inhibits Hippocampal Neuronal Apoptosis by Activating PI3K/Akt Signaling Pathway in Vascular Dementia Mice〔J〕. Neuropsychiatr Dis Treat， 2021， 17： 2359–2368.

〔31〕 YU X D， ZHANG D， XIAO C L， et al. P-Coumaric Acid Reverses Depression-Like Behavior and Memory Deficit via Inhibiting AGE-RAGE-Mediated Neuro-inflammation〔J〕. Cells， 2022， 11（10）： 1594.

〔32〕吴德，潘娜娜，王莉莉，等. 人巨细胞病毒先天性感染大鼠海马空间学习记忆功能受损〔J〕. 中华围产医学杂志， 2015，18（1）： 30-34.

[1]	Xiong Kai, Xiao Tianbao, Zeng Lian, Luo Zicheng, Yang Tao, Yang Shengbang. Therapeutic Effect of Miao Medicine Rubus pluribracteatus on Mice with Ulcerative Colitis [J]. Journal of Dali University, 2023, 8(4): 1-6.
[2]	Meng Dong, Li Ya, Wang Chongjuan, Tian Yong, Tian Yuncai, Wu Mingyi. Content Determination and Methodological Validation of Snail Glycosaminoglycan [J]. Journal of Dali University, 2023, 8(4): 7-12.
[3]	Huang Shan, Jin Liquan, Yu Yu, Huang Ji, Zhang Junhua, Chen Yiming. Expression of SOX9 in the Directed Differentiation of Mouse Hepatic Oval Cell into Biliary Epithelial Cells [J]. Journal of Dali University, 2023, 8(4): 22-27.
[4]	Zhao Chunjing, Chen Weiguo, Bai li, Wu Youcong. Effects of Periplaneta americana Extract CⅡ-3 on the Biofilm Formation of Candida albicans [J]. Journal of Dali University, 2023, 8(4): 28-33.
[5]	Bai Zongkai, Lü Neng, Liu Runhua, Luo Yuanxi, Wu Qiuyue, Xu Jing, Wu Youcong. Investigation on the Carrier Rate and Antifungal Susceptibility of Yeast Species Isolated from External Urethral Meatus of Healthy College Students [J]. Journal of Dali University, 2023, 8(4): 34-38.
[6]	Gao Wenyu, Zeng Rong, Xu Mengna, Zhang Yuanyuan. Study on the Correlation between Polymorphism of EPAS1 Gene rs1868092 and High Altitude Polycythemia in Tibetan Population [J]. Journal of Dali University, 2023, 8(4): 39-42.
[7]	Liu Ruai, Yang Xueqian, Wang Boyong, Mei Wen, Zhou Jinghua, Xiong Wei. Research on the Point Mutation of K-ras Gene in Human Malignant Pleural Mesothelioma [J]. Journal of Dali University, 2023, 8(4): 43-49.
[8]	Yan Qixing, Zhao Lini, Tang Wenjun, Chen Jinfang, Fang Cao. Correlation between MMP-9 Gene Polymorphism and the Short-Ｔerm Efficacy of TP Regimen in Patients with Ovarian Cancer [J]. Journal of Dali University, 2023, 8(4): 50-53.
[9]	Zhang Qian, Chang Aying, Yang Zhengchun, Liu Liru. Analysis of the Effect of Using Low Calcium Dialysate and Standard Calcium Dialysate in Segmented Citrate Anticoagulant Hemodialysis [J]. Journal of Dali University, 2023, 8(4): 54-59.
[10]	Yang Sili, Luo Wanxun, Wang Jianping. Application of Temporary Occlusion of Bilateral Internal Iliac Artery Balloon in Cesarean Section of Complete Placenta Previa [J]. Journal of Dali University, 2023, 8(4): 60-63.
[11]	Gao Guoxi, Hu Jianhua, Yang Zhao, Zhang Jun, Zhang Chao. Clinical Analysis of the Therapeutic Effect of Baylor Plaster Immobilization in the Treatment of Legg-Calve-Perthes Disease in Children [J]. Journal of Dali University, 2023, 8(4): 64-68.
[12]	Chen Wenqiu, Pang Qin, Zhao Yu, Li Tao, Lin Xianghong, Sun Sujiao. Clinical Effect of ELOS Technique Combined with Human-Like Collagen Repair Dressing in the Treatment of Patients with Facial Sensitive Skin [J]. Journal of Dali University, 2023, 8(4): 69-72.
[13]	Zhang Guohui, Cheng Yan, Liang Qiuyue, Yuan Shengxing, Xiao Benlong, Gao Qiuxia, Ding Yunchuan. Clinical Application of Percutaneous Puncture Biopsy of Peripheral Lung Lesions Guided by Contrast-Enhanced Ultrasound [J]. Journal of Dali University, 2023, 8(4): 73-77.
[14]	Xiao Min, Xiong Miaomiao, Fan Yujuan, Cheng Mingjing, Wang Li, Zhao Weidong. The Predictive Value of NLR for the Severity of Acute Pancreatitis [J]. Journal of Dali University, 2023, 8(4): 78-82.
[15]	Dong Liwen, Li Xi, Li Feiyan, Yi Changqing. Analysis of Fecal Occult Blood Test in a Second Class A Hospital in Kunming City [J]. Journal of Dali University, 2023, 8(4): 83-85.