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Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

General Research Article

New Tiaoxin Recipe Alleviates Energy Metabolism Disorders in an APPswe/PS1DE9 Mouse Model of Alzheimer’s Disease

Author(s): Yiran Hu, Sanli Xing*, Yan Huang, Chuan Chen, Dingzhu Shen and Jiulin Chen

Volume 27, Issue 4, 2024

Published on: 23 May, 2023

Page: [621 - 631] Pages: 11

DOI: 10.2174/1386207326666230428112358

Price: $65


Background: Alzheimer's disease (AD) is a typical neurodegenerative disease with a complex etiology. Until now, there has been no effective treatment available for AD; however, improving energy dysmetabolism, the key pathological event in the early stage of AD, can effectively delay the progression of AD.

Objective: This paper aims to investigate the therapeutic effect and potential mechanism of the new Tiaoxin recipe on early AD.

Methods: APP/PS1 mice were divided into a model group, a new Tiaoxin recipe group, and a donepezil group, and C57/BL mice were used for the control group. Mouse cognitive and learning abilities were tested using the Morris water maze test and a new object-recognition experiment. The 42 amino acid form of amyloid β peptide (Aβ1–42) content was detected by enzyme-linked immunosorbent assay, the senile plaque area was detected by thioflavin S staining, and the senescence- associated β-galactosidase (SA-β-gal)–positive area was detected by chemical staining. Also, the adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+), and nicotinamide adenine dinucleotide hydride (NADH) contents were detected using a biochemical method, and the cluster of differentiation 38 (CD38) and silent mating–type information regulation 2 homolog 3 (SIRT3) protein expression levels were detected by immunofluorescence and Western blot analysis.

Results: Compared with those of the control group, the learning and memory abilities of the model group were impaired; the senile plaque deposition, Aβ1–42 content, and SA-βgal–positive staining area were increased; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were decreased; the CD38 protein expression level was increased; and the SIRT3 protein expression level was decreased. Following intervention with the new Tiaoxin recipe, the learning and memory abilities were improved; the senile plaque deposition, Aβ1–42 content, and SA-βgal–positive area were reduced; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were increased; CD38 protein expression was decreased, and SIRT3 protein expression was increased.

Conclusion: This study shows that the new Tiaoxin Recipe can improve cognitive ability and reduce the Aβ1-42 content and senile plaque deposition in APP/PS1 mice, which may occur through the downregulation of CD38 protein expression, upregulation of SIRT3 protein expression, restoration of the NAD+ level, promotion of ATP synthesis, mitigation of energy metabolism disorders.

Keywords: Alzheimer’s disease, energy dysmetabolism, new tiaoxin recipe, NAD+, CD38, neurodegenerative disease.

Graphical Abstract
Ransohoff, R.M. Specks of insight into Alzheimer’s disease. Natur, 2017, 552(7685), 342-343.
A Armstrong, R. Risk factors for Alzheimer’s disease. Folia Neuropathol., 2019, 57(2), 87-105.
[] [PMID: 31556570]
Aprahamian, I.; Stella, F.; Forlenza, O.V. New treatment strategies for Alzheimer’s disease: Is there a hope? Indian J. Med. Res., 2013, 138(4), 449-460.
[PMID: 24434253]
Cunnane, S.C.; Trushina, E.; Morland, C.; Prigione, A.; Casadesus, G.; Andrews, Z.B.; Beal, M.F.; Bergersen, L.H.; Brinton, R.D.; de la Monte, S.; Eckert, A.; Harvey, J.; Jeggo, R.; Jhamandas, J.H.; Kann, O.; la Cour, C.M.; Martin, W.F.; Mithieux, G.; Moreira, P.I.; Murphy, M.P.; Nave, K.A.; Nuriel, T.; Oliet, S.H.R.; Saudou, F.; Mattson, M.P.; Swerdlow, R.H.; Millan, M.J. Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing. Nat. Rev. Drug Discov., 2020, 19(9), 609-633.
[] [PMID: 32709961]
Yin, F.; Sancheti, H.; Patil, I.; Cadenas, E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic. Biol. Med., 2016, 100, 108-122.
[] [PMID: 27154981]
Xie, N.; Zhang, L.; Gao, W.; Huang, C.; Huber, P.E.; Zhou, X.; Li, C.; Shen, G.; Zou, B. NAD+ metabolism: Pathophysiologic mechanisms and therapeutic potential. Signal Transduct. Target. Ther., 2020, 5(1), 227-263.
[] [PMID: 33028824]
Nikiforov, A.; Kulikova, V.; Ziegler, M. The human NAD metabolome: Functions, metabolism and compartmentalization. Crit. Rev. Biochem. Mol. Biol., 2015, 50(4), 284-297.
[] [PMID: 25837229]
Rajman, L.; Chwalek, K.; Sinclair, D.A. Therapeutic potential of NAD-boosting molecules: The in vivo evidence. Cell Metab., 2018, 27(3), 529-547.
[] [PMID: 29514064]
Katsyuba, E.; Auwerx, J. Modulating NAD+ metabolism, from bench to bedside. EMBO J., 2017, 36(18), 2670-2683.
[] [PMID: 28784597]
Ting, K.Y.; Leung, C.F.P.; Graeff, R.M.; Lee, H.C.; Hao, Q.; Kotaka, M. Porcine CD38 exhibits prominent secondary NAD + cyclase activity. Protein Sci., 2016, 25(3), 650-661.
[] [PMID: 26660500]
Blacher, E.; Dadali, T.; Bespalko, A.; Haupenthal, V.J.; Grimm, M.O.W.; Hartmann, T.; Lund, F.E.; Stein, R.; Levy, A. Alzheimer’s disease pathology is attenuated in a CD38-deficient mouse model. Ann. Neurol., 2015, 78(1), 88-103.
[] [PMID: 25893674]
Jin, G.Q.; Qiu, H.; Sun, Q.; Zhang, X.L.; Dai, W.W.; Zhao, W.K.; Lin, S.M. Effects of tiaoxin recipe on respiratory chain oxidase activity and amino acid transmitters content in brain tissue of ad model mice. J. Shang. Uni. Tradit. Chin. Med., 2003, 3, 39-41.
Sun, Q.; Jin, G.; Zhao, W.K.; Lin, S.M.; Zhang, X.L.; Dai, W.W. The effect of Tiaoxin Recipe on the anti-oxidation ability of brain tissue in AD rats. J. Tradit. Chin., 2003, 3, 273-274.
Kang, X.P.; Jin, G.Q.; Zhao, W.K.; Lin, S.M. The effect of TX0201. The effective part of Tiaoxin recipe. on the oxidative damage and energy metabolism of AD rats induced by Aβ25-35. Pharmacol. Clin. Chin. Materia Medica., 2005, 2, 23-26.
Hubin, E.; van Nuland, N.A.J.; Broersen, K.; Pauwels, K. Transient dynamics of Aβ contribute to toxicity in Alzheimer’s disease. Cell. Mol. Life Sci., 2014, 71(18), 3507-3521.
[] [PMID: 24803005]
Kurz, D.J.; Decary, S.; Hong, Y.; Erusalimsky, J.D. Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J. Cell Sci., 2000, 113(20), 3613-3622.
[] [PMID: 11017877]
Rijpma, A.; van der Graaf, M.; Meulenbroek, O.; Olde Rikkert, M.G.M.; Heerschap, A. Altered brain high-energy phosphate metabolism in mild Alzheimer’s disease: A 3-dimensional 31P MR spectroscopic imaging study. Neuroimage Clin., 2018, 18, 254-261.
[] [PMID: 29876246]
Braidy, N.; Berg, J.; Clement, J.; Khorshidi, F.; Poljak, A.; Jayasena, T.; Grant, R.; Sachdev, P. Role of nicotinamide adenine dinucleotide and related precursors as therapeutic targets for agerelated degenerative diseases: Rationale, biochemistry, pharmacokinetics, and outcomes. Antioxid. Redox Signal., 2019, 30(2), 251-294.
[] [PMID: 29634344]
Bagul, P.; Katare, P.; Bugga, P.; Dinda, A.; Banerjee, S.K. SIRT-3 modulation by resveratrol improves mitochondrial oxidative phosphorylation in diabetic heart through deacetylation of TFAM. Cells, 2018, 7(12), 235-248.
[] [PMID: 30487434]
Swerdlow, R.H. Mitochondria and mitochondrial cascades in Alzheimer’s Disease. J. Alzheimers Dis., 2018, 62(3), 1403-1416.
[] [PMID: 29036828]
Bradshaw, P. Cytoplasmic and mitochondrial NADPH-coupled redox systems in the regulation of aging. Nutrients, 2019, 11(3), 504-512.
[] [PMID: 30818813]
Katsyuba, E.; Mottis, A.; Zietak, M.; De Franco, F.; van der Velpen, V.; Gariani, K.; Ryu, D.; Cialabrini, L.; Matilainen, O.; Liscio, P.; Giacchè, N.; Stokar-Regenscheit, N.; Legouis, D.; de Seigneux, S.; Ivanisevic, J.; Raffaelli, N.; Schoonjans, K.; Pellicciari, R.; Auwerx, J. De novo NAD+ synthesis enhances mitochondrial function and improves health. Natur, 2018, 563(7731), 354-359.
[] [PMID: 30356218]
Hou, Y.; Lautrup, S.; Cordonnier, S.; Wang, Y.; Croteau, D.L.; Zavala, E.; Zhang, Y.; Moritoh, K.; O’Connell, J.F.; Baptiste, B.A.; Stevnsner, T.V.; Mattson, M.P.; Bohr, V.A. NAD + supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc. Natl. Acad. Sci., 2018, 115(8), E1876-E1885.
[] [PMID: 29432159]
Selkoe, D.J. Treatments for Alzheimer’s disease emerge. Science, 2021, 373(6555), 624-626.
[] [PMID: 34353940]
Ma, Y.Y.; Zhang, M.; Ma, S.H.; Wang, Y.M.; Gao, J.H.; Wang, H.X.; Yu, C.X. Study on the new mechanism of traditional chinese medicine for invigorating Qi in treating heart failure -- regulating myocardial energy metabolism. Zhongguo Zhongyao Zazhi, 2011, 36, 3210-3212.
[PMID: 22375410]
Chen, W.W. Discussion on the essence of Qi in traditional chinese medicine from the perspective of bioenergetics. J. Beijing Univ. Trad. Chin. Med., 1994, 12, 7-9.
Song, Z.X. The essence of Qi from the perspective of biological ability. Hubei J. Trad. Chin. Med., 1980, 5, 44-46.
Kim, H.J.; Moon, K.D.; Lee, D.S.; Lee, S.H. Ethyl ether fraction of Gastrodia elata Blume protects amyloid β peptide-induced cell death. J. Ethnopharmacol., 2003, 84(1), 95-98.
[] [PMID: 12499082]
Kim, D.S.H.L.; Kim, J.Y.; Han, Y.S. Alzheimer’s disease drug discovery from herbs: Neuroprotectivity from beta-amyloid (1-42) insult. J. Altern. Complement. Med., 2007, 13(3), 333-340.
[] [PMID: 17480132]
Huang, Y.C.; Tsay, H.J.; Lu, M.K.; Lin, C.H.; Yeh, C.W.; Liu, H.K.; Shiao, Y.J. Astragalus membranaceus-polysaccharides ameliorates obesity, hepatic steatosis, neuroinflammation and cognition impairment without affecting amyloid deposition in metabolically stressed APPswe/PS1dE9 Mice. Int. J. Mol. Sci., 2017, 18(12), 2746-2763.
[] [PMID: 29258283]
Wei, G.; Xu, X.; Tong, H.; Wang, X.; Chen, Y.; Ding, Y.; Zhang, S.; Ju, W.; Fu, C.; Li, Z.; Zeng, L.; Xu, K.; Qiao, J. Salidroside inhibits platelet function and thrombus formation through AKT/GSK3β signaling pathway. Aging, 2020, 12(9), 8151-8166.
[] [PMID: 32352928]
Wang, X.; Zhang, D.; Song, W.; Cai, C.; Zhou, Z.; Fu, Q.; Yan, X.; Cao, Y.; Fang, M. Neuroprotective effects of the aerial parts of Polygala tenuifolia Willd extract on scopolamine induced learning and memory impairments in mice. Biomed. Rep., 2020, 13(5), 1.
[] [PMID: 32874571]
Chang, W.L.; Chen, J.C.; Chung, W.Y.; Hsiao, C.Y.; Wong, R.; Vasilakos, A.V. Quantum speedup and mathematical solutions of implementing bio-molecular solutions for the independent set problem on IBM quantum computers. IEEE Trans. Nanobiosci., 2021, 20(3), 354-376.
[] [PMID: 33900920]
Wong, R.; Chang, W.L. Fast quantum algorithm for protein structure prediction in hydrophobic-hydrophilic model. J. Parallel Distrib. Comput., 2022, 164, 178-190.
Chang, W.L.; Chung, W.Y.; Hsiao, C.Y.; Wong, R.; Chen, J.C.; Feng, M.; Vasilakos, A.V. Quantum speedup for inferring the value of each bit of a solution state in unsorted databases using a bio-molecular algorithm on IBM quantum’s computers. IEEE Trans. Nanobiosci., 2022, 21(2), 286-293.
[] [PMID: 34822331]
Wong, R.; Chang, W.L. Quantum speedup for protein structure prediction. IEEE Trans. Nanobiosci., 2021, 20(3), 323-330.
[] [PMID: 33690123]

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