Objective: To observe the effect of Liuwei Dihuang pills on the learning and memory ability of the Aβ transgenic Caenorhabditis elegans model, and to explore its mechanism by metabolomics. Methods: The wild-type C. elegans was used as the blank control, and the CL2355 type transfected with human APP gene was used as the Alzheimer disease model. The extract of Liuwei Dihuang pills was administered (1.0 mg·mL-1) as a group, another metformin positive drug (50 mmol·L-1) group was set up as a positive group. The effect of Liuwei Dihuang pills on the learning and memory ability of AD model nematodes was verified by chemotaxis test; metabolomics method was used to screen the differential metabolites between Liuwei Dihuang pills treatment group and model group and enrich the metabolic pathways to explore Liuwei Dihuang pills Mechanism of action in the treatment of AD. Results: Compared with the blank group, the model group significantly reduced the tropism index of NaCl, and significantly inhibited the associative learning behavior(P<0.01). Compared with the model group, the tropism index of Nematode NaCl in the positive drug group and the Liuwei Dihuang pills group was significantly increased, and the associative learning behavior was repaired. In this study, nine differential metabolites were detected in AD model nematode tissue samples, namely galactosylhydroxylysine, lysophosphatidylcholine [18∶4(9Z, 12Z, 15Z),14∶1(9Z), 16∶1(9Z)], α-piperazole-5α-phosphate, tributyrate, L-leucine, lysophosphatidylethanolamine (0∶0/14∶0), N-acetyl-L-histidine, involved in glycerophospholipid metabolism, valine, leucine and isoleucine metabolism.Conclusion: The improvement of learning and memory impairment in AD model nematodes by Liuwei Dihuang pills is closely related to the regulation of glycerophospholipid, valine, leucine and isoleucine pathways.
ZUO Kun, TONG Yu-lang, SUN Ting, GUAN Yu-jia, WANG Di, WANG Yan, ZHANG Ning, LEI Xia
. A metabolomic study on the therapeutic effect and mechanism of Liuwei Dihuang pills on Caenorhabditis elegans transgenic AD model[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(8)
: 1360
-1368
.
DOI: 10.16155/j.0254-1793.2023.08.12
[1] 张力,李方玲,马丽.六味地黄丸联合西药治疗轻、中度阿尔茨海默病的临床观察[J].世界中医药,2017,12(11):2659
ZHANG L, LI FL, MA L. Clinical observation of Liuwei Dihuang pills combined with western medicine in the treatment of mild and moderate Alzheimer's disease [J].World Chin Med, 2017, 12(11):2659
[2] HOBERT O. Behavioral plasticity in C. elegans: paradigms, circuits, genes[J].Neurobiol, 2003, 54(1):203
[3] JOHNSON CH, IVANISEVIC J, SIUZDAK G. Metabolomics: beyond biomarkers and towards mechanisms[J].Nat Rev. Mol Cell Biol, 2016, 17(7):451
[4] ZHANG J, CAI W, ZHOU Y, et al. Profiling and identification of the metabolites of baicalin and study on their tissue distribution in rats by ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer [J].Chromatogr B Analyt Technol Biomed Life Sci, 2015,985:91
[5] 周文卷,高德岷,耿馨悦,等.基于拟靶标代谢组学考察不同煎煮方式对大黄功效组分煎出的影响[J].中草药,2020,51(10):2755
ZHOU WJ, GAO DM, GENG XY, et al.Influence of different decoction methods on the decoction of rhubarb functional components based on pseudo-target metabolomics[J].Chin Herb Med, 2020, 51(10):2755
[6] ZHANG G, LI Y, WEI W, et al. Metabolomics combined with multivariate statistical analysis for screening of chemical markers between Gentiana scabra and Gentiana rigescens[J].Molecules, 2020, 25(5):1228
[7] 佟玉良. 六味地黄丸对秀丽隐杆线虫AD模型线粒体功能的保护作用[D].哈尔滨:黑龙江中医药大学,2021
TONG YL. Protective effect of Liuwei Dihuang Pills on Mitochondrial Function in Caenorhabditis elegans AD Model[D].Haerbin:Heilongjiang University of Traditional Chinese Medicine, 2021
[8] TASLIMIFAR M, FALTYS M, KURTCUOGLU V, et al. Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, BAT2 and yLAT1 functional cooperation[J].Cereb Blood Flow Metab, 2022, 42(1):90
[9] YANAGISAWA H, ISHII T, ENDO K, et al. L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human niemann-pick type C disease[J].Sci Rep, 2017, 7(1):15944
[10] XU B, LEE KK, ZHANG L, et al. Stimulation of mTORC1 with L-leucine rescues defects associated with roberts syndrome [J].PLoS Genet, 2013, 9(10):e1003857
[11] ANASTASI A, CORREALE P, ERSPAMER V. Occurrence of N-acetylhistidine in the central nervous system and the eye of Rana esculenta[J].Neurochem, 1964, 11:63
[12] KURODA Y, IKOMA T. N-acetylhistidine isolated from frog heart[J].Science, 1966, 152(3726):1241
[13] LIU MT, LIU X, WANG HP, et al. Metabolomics study on the effects of Buchang Naoxintong capsules for treating cerebral ischemia in rats using UPLC-Q/TOF-MS[J].J Ethnopharmacol, 2016, 180:1
[14] WANG C, CAO S, SHEN Z, et al. Effects of dietary tributyrin on intestinal mucosa development, mitochondrial function and AMPK-mTOR pathway in weaned pigs[J].Anim Sci Biotechnol, 2019, 25(10):93
[15] SEMBA RD, ZHANG P, ADELNIA F, et al. Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the baltimore longitudinal study of aging[J].Aging Cell, 2019,18(2):e12915
[16] LLANO DA, DEVANARAYAN V. Alzheimer's disease neuroimaging initiative. serum phosphatidylethanolamine and lysophosphatidylethanolamine levels differentiate Alzheimer's disease from controls and predict progression from mild cognitive impairment[J].Alzheimers Dis, 2021, 80(1):311
[18] 杨昕. 用秀丽隐杆线虫模型研究亚精胺对神经变性疾病的保护作用及其机制[D].杭州:浙江大学,2020
YANG X. The Protective Effect and Mechanism of Spermidine on Neurodegenerative Diseases Were Studied by The Model of Caenorhabditis elegans[D].Hangzhou: Zhejiang University, 2020
