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Context: Icariin (ICA) is the main active ingredient of Epimedium brevicornu Maxim (Berberidaceae), which is used in the immune, reproductive, neuroendocrine systems, and anti-aging.

Objective: To evaluate the effect of ICA on natural aging rat.

Materials and Methods: 16-month-old Sprague-Dawley (SD) rats were randomly divided into aging, low and high-dose ICA groups ( n = 8); 6-month-old rats were taken as the adult control ( n = 8). Rats were fed regular feed (aging and adult control) or feed containing ICA (ICA 2 and 6 mg/kg group) for 4 months. HE and Nissl staining were used to assess pathological changes. Western blot was used to test the expression of autophagy (LC3B, p62, Atg5, Beclin1) and p-AMPK, p-mTOR and p-ULK1 (ser 757). Immunofluorescence was used to detect the co-localization of LC3 and neurons.

Results: ICA improved neuronal degeneration associated with aging and increased the staining of Nissl bodies. Western blot showed that ICA up-regulated autophagy-related proteins LC3B (595%), Beclin1 (73.5%), p-AMPK (464%) protein ( p < 0.05 vs. 20 M) in the cortex and hippocampus of aging rats, down-regulated the expression of p62 (56.9%), p-mTOR (53%) and p-ULK1 (ser 757) (65.4%) protein ( p < 0.05 vs. 20 M). Immunofluorescence showed that the fluorescence intensity of LC3 decreased in the aging rat brain, but increased and mainly co-localized with neurons after ICA intervention.

Conclusions: Further research needs to verify the expression changes of AMPK/mTOR/ULK1 and the improvement effect of ICA in elderly. These results will further accelerate the applications of ICA and the treatment for senescence.

Titel:	Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway.
Autor/in / Beteiligte Person:	Zheng, J ; Hu, S ; Wang, J ; Zhang, X ; Yuan, D ; Zhang, C ; Liu, C ; Wang, T ; Zhou, Z
Link:	Zum Volltext
Zeitschrift:	Pharmaceutical biology, Jg. 59 (2021-12-01), Heft 1, S. 183
Veröffentlichung:	[London] : Taylor & Francis ; <i>Original Publication</i>: Lisse, the Netherlands : Swets & Zeitlinger, c1998-, 2021
Medientyp:	academicJournal
ISSN:	1744-5116 (electronic)
DOI:	10.1080/13880209.2021.1878238
Schlagwort:	AMP-Activated Protein Kinases metabolism Aging physiology Animals Autophagy-Related Protein-1 Homolog metabolism Brain pathology Dose-Response Relationship, Drug Epimedium chemistry Flavonoids administration & dosage Flavonoids isolation & purification Neurons pathology Rats Rats, Sprague-Dawley TOR Serine-Threonine Kinases metabolism Autophagy drug effects Brain drug effects Flavonoids pharmacology Neurons drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Comparative Study; Journal Article Language: English [Pharm Biol] 2021 Dec; Vol. 59 (1), pp. 183-191. MeSH Terms: Autophagy / drug effects ; Brain / drug effects ; Flavonoids / pharmacology ; Neurons / drug effects ; AMP-Activated Protein Kinases / metabolism ; Aging / physiology ; Animals ; Autophagy-Related Protein-1 Homolog / metabolism ; Brain / pathology ; Dose-Response Relationship, Drug ; Epimedium / chemistry ; Flavonoids / administration & dosage ; Flavonoids / isolation & purification ; Neurons / pathology ; Rats ; Rats, Sprague-Dawley ; TOR Serine-Threonine Kinases / metabolism References: J Cell Sci. 2015 Apr 1;128(7):1259-67. (PMID: 25829512) ; Behav Brain Res. 2017 Jan 15;317:374-381. (PMID: 27702637) ; J Neurosci. 2016 Mar 9;36(10):3049-63. (PMID: 26961958) ; Nature. 2006 Jun 15;441(7095):880-4. (PMID: 16625205) ; Chin J Integr Med. 2018 May;24(5):366-371. (PMID: 29327125) ; Aging (Albany NY). 2020 Apr 22;12(8):6852-6864. (PMID: 32320382) ; J Biol Chem. 2010 Mar 19;285(12):9100-13. (PMID: 20080969) ; CNS Neurosci Ther. 2016 Jan;22(1):63-73. (PMID: 26584824) ; eNeuro. 2016 May 23;3(2):. (PMID: 27257626) ; Cell Death Dis. 2017 Jun 29;8(6):e2911. (PMID: 28661473) ; Acta Pharmacol Sin. 2013 May;34(5):605-11. (PMID: 23416930) ; Metab Brain Dis. 2014 Mar;29(1):47-58. (PMID: 24435937) ; Nat Commun. 2019 Mar 21;10(1):1318. (PMID: 30899013) ; Cell Prolif. 2020 Feb;53(2):e12743. (PMID: 31943455) ; Nat Rev Drug Discov. 2010 Mar;9(3):237-48. (PMID: 20190788) ; Autophagy. 2018;14(7):1276-1277. (PMID: 29806784) ; Autophagy. 2013 Feb 1;9(2):124-37. (PMID: 23295650) ; Trends Neurosci. 2016 Mar;39(3):146-157. (PMID: 26899735) ; Am J Transl Res. 2016 May 15;8(5):2127-37. (PMID: 27347320) ; Cell Death Dis. 2017 Jul 6;8(7):e2912. (PMID: 28682313) ; Phytother Res. 2010 Nov;24(11):1658-63. (PMID: 21031624) ; Food Funct. 2018 Jan 24;9(1):371-378. (PMID: 29214257) ; J Pharmacol Exp Ther. 2019 Apr;369(1):121-128. (PMID: 30837279) ; Mol Cell. 2008 Apr 25;30(2):214-26. (PMID: 18439900) ; Nat Cell Biol. 2011 Feb;13(2):132-41. (PMID: 21258367) ; Aging (Albany NY). 2020 Apr 8;12(7):6401-6414. (PMID: 32268299) ; Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364. (PMID: 29618831) ; J Neuroinflammation. 2019 Apr 22;16(1):92. (PMID: 31010422) ; Int J Environ Res Public Health. 2019 Aug 09;16(16):. (PMID: 31404951) ; Nat Med. 2013 Aug;19(8):983-97. (PMID: 23921753) ; Int J Clin Exp Med. 2015 Jul 15;8(7):11843-53. (PMID: 26380026) ; J Neurochem. 2012 Feb;120(4):564-73. (PMID: 21950964) ; Acta Neuropathol. 2011 Feb;121(2):183-91. (PMID: 21076961) ; Nat Neurosci. 2013 Oct;16(10):1453-60. (PMID: 23995066) ; Int J Neuropsychopharmacol. 2016 Sep 21;19(9):. (PMID: 27207919) ; Environ Pollut. 2019 Aug;251:328-337. (PMID: 31091496) ; Adv Nutr. 2017 Nov 15;8(6):804-811. (PMID: 29141966) ; Mol Aspects Med. 2006 Oct-Dec;27(5-6):403-10. (PMID: 16973211) ; J Biol Chem. 2017 May 12;292(19):7888-7903. (PMID: 28330873) ; Front Pharmacol. 2020 Jun 09;11:880. (PMID: 32581820) ; Cell Metab. 2010 May 5;11(5):390-401. (PMID: 20444419) ; Acta Neuropathol. 2015 Mar;129(3):337-62. (PMID: 25367385) ; Front Mol Neurosci. 2018 Jan 09;10:441. (PMID: 29375304) ; Autophagy. 2011 Aug;7(8):924-6. (PMID: 21521945) ; Diabetes. 2006 Aug;55(8):2180-91. (PMID: 16873680) ; Immunology. 2018 Jun;154(2):204-219. (PMID: 29513402) ; FASEB J. 2017 Jan;31(1):5-10. (PMID: 28049155) ; Neuroscientist. 2012 Feb;18(1):82-97. (PMID: 21531985) ; Subcell Biochem. 2018;90:25-47. (PMID: 30779005) ; Biomed Res Int. 2017;2017:7464872. (PMID: 29057264) ; Sports Med. 2017 Apr;47(4):583-598. (PMID: 27459861) ; Int J Mol Med. 2020 Mar;45(3):715-730. (PMID: 31922237) ; Prog Brain Res. 2002;136:39-65. (PMID: 12143397) ; Mol Biol Cell. 2009 Apr;20(7):1981-91. (PMID: 19211835) ; Autophagy. 2008 Feb;4(2):176-84. (PMID: 18059160) ; Nature. 2018 Jun;558(7708):136-140. (PMID: 29849149) Contributed Indexing: Keywords: Epimedium brevicornu Maxim; Senescence; macroautophagy; neurodegenerative diseases Substance Nomenclature: 0 (Flavonoids) ; EC 2.7.1.1 (mTOR protein, rat) ; EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) ; EC 2.7.11.1 (TOR Serine-Threonine Kinases) ; EC 2.7.11.1 (ULK1 protein, rat) ; EC 2.7.11.31 (AMP-Activated Protein Kinases) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210208 Date Completed: 20210920 Latest Revision: 20220301 Update Code: 20231215 PubMed Central ID: PMC8871627

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Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway.