Volume 13 Issue 10
Oct.  2023
Turn off MathJax
Article Contents
Article Navigation >  Journal of Pharmaceutical Analysis  > 2023  >  13(10): 1153-1167
Zhang Mao, Haochen Hui, Xuerong Zhao, Lina Xu, Yan Qi, Lianhong Yin, Liping Qu, Lan Han, Jinyong Peng. Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1153-1167. doi: 10.1016/j.jpha.2023.06.007
Citation: Zhang Mao, Haochen Hui, Xuerong Zhao, Lina Xu, Yan Qi, Lianhong Yin, Liping Qu, Lan Han, Jinyong Peng. Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1153-1167. doi: 10.1016/j.jpha.2023.06.007
shu

Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

doi: 10.1016/j.jpha.2023.06.007

  • a. Department of Pharmaceutical Analysis, College of Pharmacy, Dalian Medical University, Dalian, Shenyang, 116044, China;

  • b. Innovation Materials Research and Development Center, Botanee Research Institute, Yunnan Botanee Bio-technology Group Co., Ltd., Kunming, 650106, China;

  • c. Department of Traditional Chinese Medicine Pharmacology, School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China;

  • d. Department of Pharmacology, School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, China

Funds:

The authors gratefully acknowledge funding from the Spring City Plan: The High-Level Talent Promotion and Training Project of Kunming and the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory (Grant No.: 2022YKZY001).

  • Received Date: Feb. 15, 2023
  • Accepted Date: Jun. 13, 2023
  • Rev Recd Date: May 30, 2023
  • Publish Date: Oct. 30, 2023
    Abstract
  • It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.
    • FullText(HTML)
  • loading
    • References(72)
  • Y. Chandrasekhar, G. Phani Kumar, E.M. Ramya, et al., Gallic acid protects 6-OHDA induced neurotoxicity by attenuating oxidative stress in human dopaminergic cell line, Neurochem. Res. 43 (2018) 1150-1160.
    P. Gan, L. Ding, G. Hang, et al., Oxymatrine attenuates dopaminergic neuronal damage and microglia-mediated neuroinflammation through cathepsin D-dependent HMGB1/TLR4/NF-κB pathway in Parkinson’s disease, Front. Pharmacol. 11 (2020) 776-776.
    S. Peng, B. Zhang, J. Yao, et al., Dual protection of hydroxytyrosol, an olive oil polyphenol, against oxidative damage in PC12 cells, Food Funct. 6 (2015) 2091-2100.
    J.L. Ilkiw, L.C. Kmita, A.D.S. Targa, et al., Dopaminergic lesion in the olfactory bulb restores olfaction and induces depressive-like behaviors in a 6-OHDA model of Parkinson’s disease, Mol. Neurobiol. 56 (2019) 1082-1095.
    J. Lee, K. Song, E. Huh, et al., Neuroprotection against 6-OHDA toxicity in PC12 cells and mice through the Nrf2 pathway by a sesquiterpenoid from Tussilago farfara, Redox Biol. 18 (2018) 6-15.
    H. Li, Z. Tang, P. Chu, et al., Neuroprotective effect of phosphocreatine on oxidative stress and mitochondrial dysfunction induced apoptosis in vitro and in vivo: Involvement of dual PI3K/Akt and Nrf2/HO-1 pathways, Free Radic. Biol. Med. 120 (2018) 228-238.
    C. Zhang, C. Li, S. Chen, et al., Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways, Redox Biol. 11 (2017) 1-11.
    C. van der Merwe, H.C. van Dyk, L. Engelbrecht, et al., Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson’s disease from mitochondrial dysfunction and cell death, Mol. Neurobiol. 54 (2017) 2752-2762.
    M.R. de Oliveira, A. Peres, G.C. Ferreira, et al., Carnosic acid protects mitochondria of human neuroblastoma SH-SY5Y cells exposed to paraquat through activation of the Nrf2/HO-1 axis, Mol. Neurobiol. 54 (2017) 5961-5972.
    A. Romero, E. Ramos, I. Ares, et al., Oxidative stress and gene expression profiling of cell death pathways in alpha-cypermethrin-treated SH-SY5Y cells, Arch. Toxicol. 91 (2017) 2151-2164.
    C. Qiao, Q. Zhang, Q. Jiang, et al., Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating systemic inflammation in a MPTP/p mouse model of Parkinson’s disease, J. Neuroinflammation 15 (2018) 193-193.
    J.R. Bedarf, F. Hildebrand, L.P. Coelho, et al., Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naive Parkinson’s disease patients, Genome Med. 9 (2017), 39.
    E.M. Hill-Burns, J.W. Debelius, J.T. Morton, et al., Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome, Mov. Disord. 32 (2017) 739-749.
    M.M. Unger, J. Spiegel, K.U. Dillmann, et al., Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls, Parkinsonism Relat. Disord. 32 (2016) 66-72.
    X. Qi, C. Yun, L. Sun, et al., Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome, Nat. Med. 25 (2019) 1225-1233.
    Z. Song, Y. Cai, X. Lao, et al., Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome, Microbiome 7 (2019), 9.
    A. Luxenburger, H. Clemmens, C. Hastings,et al., 3α,7-Dihydroxy-14(13→12)abeo-5β, 12α(H),13β(H)-cholan-24-oic acids display neuroprotective properties in common forms of Parkinson’s disease, Biomolecules 13 (2022), 76.
    W.J. Griffiths, J. Abdel-Khalik, E. Yutuc, et al., Concentrations of bile acid precursors in cerebrospinal fluid of Alzheimer’s disease patients, Free Radic. Biol. Med. 134 (2019) 42-52.
    A. Heinken, D.A. Ravcheev, F. Baldini, et al., Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease, Microbiome 7 (2019), 75.
    N.F. Abdelkader, M.M. Safar, H.A. Salem, Ursodeoxycholic acid ameliorates apoptotic cascade in the rotenone model of Parkinson’s disease: Modulation of mitochondrial perturbations, Mol. Neurobiol. 53 (2016) 810-817.
    M. Castro-Caldas, A.N. Carvalho, E. Rodrigues, et al., Tauroursodeoxycholic acid prevents MPTP-induced dopaminergic cell death in a mouse model of Parkinson’s disease, Mol. Neurobiol. 46 (2012) 475-486.
    F. Reimann, A.M. Habib, G. Tolhurst, et al., Glucose sensing in L cells: A primary cell study, Cell Metab. 8 (2008) 532-539.
    S. Fukuda, S. Nakagawa, R. Tatsumi, et al., Glucagon-like peptide-1 strengthens the barrier integrity in primary cultures of rat brain endothelial cells under basal and hyperglycemia conditions, J. Mol. Neurosci. 59 (2016) 211-219.
    W. Liu, J. Jalewa, M. Sharma, et al., Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine mouse model of Parkinson’s disease, Neuroscience 303 (2015) 42-50.
    G. Yoon, Y.K. Kim, J. Song, Glucagon-like peptide-1 suppresses neuroinflammation and improves neural structure, Pharmacol. Res. 152 (2019), 104615.
    S.L. Wu, C.C. Zhang, J.J. Chen, et al., Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor, Fitoterapia 163 (2022), 105336.
    R.G. Abdel-Latif, G.H. Heeba, A. Taye, et al., Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats, Naunyn Schmiedebergs Arch. Pharmacol. 391 (2018) 705-717.
    M. Mohammed El Tabaa, A. Anis, R. Mohamed Elgharabawy, et al., GLP-1 mediates the neuroprotective action of crocin against cigarette smoking-induced cognitive disorders via suppressing HMGB1-RAGE/TLR4-NF-kappaB pathway, Int. Immunopharmacol. 110 (2022), 108995.
    H. Chen, L. Xu, L. Yin, et al., iTRAQ-based proteomic analysis of dioscin on human HCT-116 colon cancer cells, Proteomics 14 (2014) 51-73.
    L. Lv, L. Zheng, D. Dong, et al., Dioscin, a natural steroid saponin, induces apoptosis and DNA damage through reactive oxygen species: A potential new drug for treatment of glioblastoma multiforme, Food Chem. Toxicol. 59 (2013) 657-669.
    X. Tao, X. Wan, Y. Xu, et al., Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis, Transplantation 98 (2014) 604-611.
    X. Tao, X. Sun, L. Yin, et al., Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition, Free Radic. Biol. Med. 84 (2015) 103-115.
    Y. Qi, R. Li, L. Xu, et al., Neuroprotective effect of dioscin on the aging brain, Molecules 24 (2019), 1247.
    A.C.V. de Guzman, M.A. Razzak, B. Purevdulam, et al., Anti-Parkinson’s disease function of Dioscin-Zein-Carboxymethyl cellulose nanocomplex in caenorhabditis elegans, Biotechnol. J. 15 (2020), 2000080.
    K. Li, Y. Tang, J.P. Fawcett, et al., Characterization of the pharmacokinetics of dioscin in rat, Steroids 70 (2005) 525-530.
    S. Jin, T. Guan, S. Wang, et al., Dioscin alleviates cisplatin-induced mucositis in rats by modulating gut microbiota, enhancing intestinal barrier function and attenuating TLR4/NF-κB signaling cascade, Int. J. Mol. Sci. 23 (2022), 4431.
    B. Ren, S. Fu, Y. Liu, et al., Dioscin ameliorates slow transit constipation in mice by up-regulation of the BMP2 secreted by muscularis macrophages, Iran. J. Basic Med. Sci. 25 (2022) 1132-1140.
    Y. Liu, K. Chen, F. Li, et al., Probiotic lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice, Hepatology 71 (2020) 2050-2066.
    J. Sun, J. Xu, Y. Ling, et al., Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice, Transl. Psychiat. 9 (2019) 189-189.
    W.B. Dunn, D. Broadhurst, P. Begley, et al., Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry, Nat Protoc. 6 (2011) 1060-1083.
    T. Kind, G. Wohlgemuth, D.Y. Lee, et al., FiehnLib: Mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry, Anal. Chem. 81 (2009) 10038-10048.
    C.A. Smith, E.J. Want, G. O’Maille, et al., XCMS: Processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification, Anal. Chem. 78 (2006) 779-787.
    S. Kapoor, M. Fitzpatrick, E. Clay, et al., Metabolomics in the Analysis of Inflammatory Diseases, in: U. Roessner (Ed.) Metabolomics, InTech, Rijeka (HR), 2012.
    R.M. Uppu, D. Woods, N.L. Parinandi, Measurement of Oxidative Stress Status in Human Populations: A Critical Need for a Metabolomic Profiling, in: L.J. Berliner, N.L. Parinandi (Eds.) Measuring Oxidants and Oxidative Stress in Biological Systems, Springer Nature Switzerland AG., Cham (CH), 2020, pp. 123-131.
    J. Wang, T. Zhang, X. Shen, et al., Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS, Metabolomics 12 (2016), 116.
    K.E.W. Vendrik, R.E. Ooijevaar, P.R.C. de Jong, et al., Fecal microbiota transplantation in neurological disorders, Front. Cell. Infect. Microbiol. 10 (2020), 98.
    C.S. Chuang, J.C. Chang, F.C. Cheng, et al., Modulation of mitochondrial dynamics by treadmill training to improve gait and mitochondrial deficiency in a rat model of Parkinson’s disease, Life Sci. 191 (2017) 236-244.
    M. Shah, S. Rajagopalan, L. Xu, et al., The high-affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of Parkinson’s disease, J. Neurochem. 131 (2014) 74-85.
    C.S. Chuang, H.L. Su, F.C. Cheng, et al., Quantitative evaluation of motor function before and after engraftment of dopaminergic neurons in a rat model of Parkinson’s disease, J. Biomed. Sci. 17 (2010), 9.
    A.R. Tsang, N. Rajakumar, M.S. Jog, Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model, Acta Physiol. 226 (2019), e13230.
    Y. Qian, X. Yang, S. Xu, et al., Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease, Brain Behav. Immun. 70 (2018) 194-202.
    H. Xiao, M. Li, J. Cai, et al., Selective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats, Neurosci. Lett. 659 (2017) 92-98.
    X. Yang, Y. Qian, S. Xu, et al., Longitudinal analysis of fecal microbiome and pathologic processes in a rotenone induced mice model of Parkinson’s disease, Front. Aging Neurosci. 9 (2017), 441.
    M.F. Sun, Y.L. Zhu, Z.L. Zhou, et al., Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway, Brain Behav. Immun. 70 (2018) 48-60.
    Z.L. Zhou, X.B. Jia, M.F. Sun, et al., Neuroprotection of fasting mimicking diet on MPTP-Induced Parkinson’s disease mice via gut microbiota and metabolites, Neurotherapeutics 16 (2019) 741-760.
    K.L. Mertens, A. Kalsbeek, M.R. Soeters, et al., Bile acid signaling pathways from the enterohepatic circulation to the central nervous system, Front. Neurosci. 11 (2017) 617-617.
    J. Hertel, A.C. Harms, A. Heinken, et al., Integrated analyses of microbiome and longitudinal metabolome data reveal microbial-host interactions on sulfur metabolism in Parkinson’s disease, Cell Rep. 29 (2019) 1767-1777.
    F. Huang, X. Zheng, X. Ma, et al., Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism, Nat. Commun. 10 (2019), 4971.
    Z. Araya, K. Wikvall, 6α-Hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes, BBA-Mol. Cell Biol. Lipids 1438 (1999) 47-54.
    Y.N. Tang, Y.X. Pang, X.C. He, et al., UPLC-QTOF-MS identification of metabolites in rat biosamples after oral administration of Dioscorea saponins: A comparative study, J. Ethnopharmacol. 165 (2015) 127-140.
    V.K. Manda, B. Avula, Z. Ali, et al., Characterization of in vitro ADME properties of diosgenin and dioscin from Dioscorea villosa, Planta Med. 79 (2013) 1421-1428.
    H. Zhu, J.-D. Xu, Q. Mao, et al., Metabolic profiles of dioscin in rats revealed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, Biomed. Chromatogr. 29 (2015) 1415-1421.
    N. Yanguas-Casas, M.A. Barreda-Manso, M. Nieto-Sampedro, et al., TUDCA: An agonist of the bile acid receptor GPBAR1/TGR5 with anti-inflammatory effects in microglial cells, J. Cell Physiol. 232 (2017) 2231-2245.
    T.D. Muller, B. Finan, S.R. Bloom, et al., Glucagon-like peptide 1 (GLP-1), Mol. Metab. 30 (2019) 72-130.
    X. Zheng, T. Chen, R. Jiang, et al., Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism, Cell Metab. 33 (2021) 791-803.
    J. Sun, H. Li, Y. Jin, et al., Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson’s disease via gut microbiota-GLP-1 pathway, Brain Behav. Immun. 91 (2021) 703-715.
    G.N. Salles, M.L. Calio, C. Holscher, et al., Neuroprotective and restorative properties of the GLP-1/GIP dual agonist DA-JC1 compared with a GLP-1 single agonist in Alzheimer’s disease, Neuropharmacology 162 (2020), 107813.
    J.K. Sterling, M.O. Adetunji, S. Guttha, et al., GLP-1 receptor agonist NLY01 reduces retinal inflammation and neuron death secondary to ocular hypertension, Cell Rep. 33 (2020), 108271.
    M.K. Mahapatra, M. Karuppasamy, B.M. Sahoo, Therapeutic potential of semaglutide, a newer GLP-1 receptor agonist, in abating obesity, non-alcoholic steatohepatitis and neurodegenerative diseases: A narrative review, Pharm. Res. 39 (2022) 1233-1248.
    S. Bandopadhyay, U. Anand, V.S. Gadekar, et al., Dioscin: A review on pharmacological properties and therapeutic values, Biofactors 48 (2022) 22-55.
    X. Zhang, M. Jin, N. Tadesse, et al., Dioscorea zingiberensis C. H. Wright: An overview on its traditional use, phytochemistry, pharmacology, clinical applications, quality control, and toxicity, J. Ethnopharmacol. 220 (2018) 283-293.
    L. Yang, S. Ren, F. Xu, et al., Recent advances in the pharmacological activities of Dioscin, Biomed Res. Int. 2019 (2019), 5763602.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (212) PDF downloads(31) Cited by()
    Proportional views
    Related

    Copyright © Journal of Pharmaceutical Analysis

    E-mail: jpa2011@126.com;  jpasubmit@126.com;  jpaeditor@xjtu.edu.cn   Tel:+86-029-88960092

    Address: Western China Science and Technology Innovation Harbour, Xixian New Area, Xi’an, 712000, China

    Email alert RSS

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return