Orengedokuto and San'oshashinto Improve Memory Deficits by Inhibiting Aging-dependent Activation of Glycogen Synthase Kinase-3β

Overview

Journal J Tradit Complement Med

Specialty Rehabilitation Medicine

Date 2019 Aug 28

PMID 31453129

Citations 3

Authors

Hironori Fujiwara

Jun Yoshida

Dya Fita Dibwe

Suresh Awale

Haruka Hoshino

Hiroshi Kohama

Hiroyuki Arai

Yukitsuka Kudo

Kinzo Matsumoto

Affiliations

Soon will be listed here.

Abstract

Background And Aim: The aging-dependent activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be important in the onset of dementia. To discover novel therapeutic Kampo medicines for dementia, we examined the effects of orengedokuto (OGT; huáng lián jiědú tāng) and san'oshashinto (SST; sān huáng xiè xīn tāng) on memory deficits and GSK-3β activity in senescence-accelerated prone mice (SAMP8).

Experimental Procedure: The object recognition test (ORT) and conditioned fear memory test (CFT) were employed to elucidate short-term working memory and long-term fear memory. The activity of GSK-3β and the phosphorylation of related molecules were measured using a kinase assay and Western blotting.

Results And Conclusion: OGT and SST attenuated memory deficits in SAMP8 in ORT, but not in CFT. In experiments, cortical GSK-3β activity was significantly stronger in SAMP8 than in SAMR1. The enhanced cortical GSK-3β activity in SAMP8 was accompanied by a significant increase in the level of phosphorylated collapsin response mediator protein-2 (CRMP2), an important factor that is involved in the regulation of microtubule stability. OGT and SST attenuated not only increases in cortical GSK-3β activity, but also the levels of phosphorylated CRMP2 in SAMP8. In vitro experiments, flavonoids contained in these kampo medicines, inhibited GSK-3β activity in concentration-dependent manners. These results suggest that OGT and SST prevent aging-induced short-term working memory deficits by inhibiting aging-dependent elevations in the cortical GSK-3β activity and subsequent CRMP2 phosphorylation.

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References

Gu Y, Hamajima N, Ihara Y . Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry. 2000; 39(15):4267-75. DOI: 10.1021/bi992323h. View

Hardy J, Selkoe D . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-6. DOI: 10.1126/science.1072994. View

Charrier E, Reibel S, Rogemond V, Aguera M, Thomasset N, Honnorat J . Collapsin response mediator proteins (CRMPs): involvement in nervous system development and adult neurodegenerative disorders. Mol Neurobiol. 2003; 28(1):51-64. DOI: 10.1385/MN:28:1:51. View

Iwasaki K, Kobayashi S, Chimura Y, Taguchi M, Inoue K, Cho S . A randomized, double-blind, placebo-controlled clinical trial of the Chinese herbal medicine "ba wei di huang wan" in the treatment of dementia. J Am Geriatr Soc. 2004; 52(9):1518-21. DOI: 10.1111/j.1532-5415.2004.52415.x. View

Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K . GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell. 2005; 120(1):137-49. DOI: 10.1016/j.cell.2004.11.012. View

Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N . A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry. 2005; 66(2):248-52. DOI: 10.4088/jcp.v66n0214. View

Bertaina-Anglade V, Enjuanes E, Morillon D, la Rochelle C . The object recognition task in rats and mice: a simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity. J Pharmacol Toxicol Methods. 2006; 54(2):99-105. DOI: 10.1016/j.vascn.2006.04.001. View

Plattner F, Angelo M, Giese K . The roles of cyclin-dependent kinase 5 and glycogen synthase kinase 3 in tau hyperphosphorylation. J Biol Chem. 2006; 281(35):25457-65. DOI: 10.1074/jbc.M603469200. View

Inestrosa N, Varela-Nallar L, Grabowski C, Colombres M . Synaptotoxicity in Alzheimer's disease: the Wnt signaling pathway as a molecular target. IUBMB Life. 2007; 59(4-5):316-21. DOI: 10.1080/15216540701242490. View

10.

Ye X, Zerlanko B, Kennedy A, Banumathy G, Zhang R, Adams P . Downregulation of Wnt signaling is a trigger for formation of facultative heterochromatin and onset of cell senescence in primary human cells. Mol Cell. 2007; 27(2):183-196. PMC: 2698096. DOI: 10.1016/j.molcel.2007.05.034. View

11.

Cole A, Noble W, van Aalten L, Plattner F, Meimaridou R, Hogan D . Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer's disease progression. J Neurochem. 2007; 103(3):1132-44. DOI: 10.1111/j.1471-4159.2007.04829.x. View

12.

Saunders N, Summers M . Attention and working memory deficits in mild cognitive impairment. J Clin Exp Neuropsychol. 2009; 32(4):350-7. DOI: 10.1080/13803390903042379. View

13.

Lim Y, Yoon S, Choi J, Kim S, Lee H, Choe H . Maintained activity of glycogen synthase kinase-3beta despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model. Biochem Biophys Res Commun. 2010; 395(2):207-12. DOI: 10.1016/j.bbrc.2010.03.163. View

14.

Hensley K, Venkova K, Christov A, Gunning W, Park J . Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications. Mol Neurobiol. 2011; 43(3):180-91. DOI: 10.1007/s12035-011-8166-4. View

15.

Fujiwara H, Takayama S, Iwasaki K, Tabuchi M, Yamaguchi T, Sekiguchi K . Yokukansan, a traditional Japanese medicine, ameliorates memory disturbance and abnormal social interaction with anti-aggregation effect of cerebral amyloid β proteins in amyloid precursor protein transgenic mice. Neuroscience. 2011; 180:305-13. DOI: 10.1016/j.neuroscience.2011.01.064. View

16.

Trivedi M, Stoub T, Murphy C, George S, deToledo-Morrell L, Shah R . Entorhinal cortex volume is associated with episodic memory related brain activation in normal aging and amnesic mild cognitive impairment. Brain Imaging Behav. 2011; 5(2):126-36. PMC: 3164997. DOI: 10.1007/s11682-011-9117-4. View

17.

Yamada M, Hayashida M, Zhao Q, Shibahara N, Tanaka K, Miyata T . Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice. J Ethnopharmacol. 2011; 135(3):737-46. DOI: 10.1016/j.jep.2011.04.010. View

18.

Zhao Q, Yokozawa T, Tsuneyama K, Tanaka K, Miyata T, Shibahara N . Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence-accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic factors and neuroplasticity systems in the brain. Chin Med. 2011; 6:33. PMC: 3189182. DOI: 10.1186/1749-8546-6-33. View

19.

Zhao Q, Matsumoto K, Tsuneyama K, Tanaka K, Li F, Shibahara N . Diabetes-induced central cholinergic neuronal loss and cognitive deficit are attenuated by tacrine and a Chinese herbal prescription, kangen-karyu: elucidation in type 2 diabetes db/db mice. J Pharmacol Sci. 2011; 117(4):230-42. DOI: 10.1254/jphs.11115fp. View

20.

Serrano-Pozo A, Frosch M, Masliah E, Hyman B . Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2012; 1(1):a006189. PMC: 3234452. DOI: 10.1101/cshperspect.a006189. View