Yifei Xuanfei Jiangzhuo formula, a Chinese herbal decoction, improves memory impairment through inhibiting apoptosis and enhancing PKA/CREB signal transduction in rats with cerebral ischemia/reperfusion

Wu,Lin; Zhao,Qing-Shan; Li,Tian-Wei; Li,Hai-Yuan; Wang,Qing‑Bi; Bi,Xin-Ya; Cai,Xin-Kun; Tang,Nong

doi:10.3892/mmr.2015.3962

Yifei Xuanfei Jiangzhuo formula, a Chinese herbal decoction, improves memory impairment through inhibiting apoptosis and enhancing PKA/CREB signal transduction in rats with cerebral ischemia/reperfusion

Authors:
- Lin Wu
- Qing-Shan Zhao
- Tian-Wei Li
- Hai-Yuan Li
- Qing‑Bi Wang
- Xin-Ya Bi
- Xin-Kun Cai
- Nong Tang
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Affiliations: Guangxi Scientific Experimental Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China, Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China
Published online on: June 18, 2015 https://doi.org/10.3892/mmr.2015.3962
Pages: 4273-4283
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Apoptosis and the dysfunction of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway have a key role in memory impairment in vascular dementia (VaD), a challenging clinical problem. Yifei Xuanfei Jiangzhuo formula (YXJF), a Chinese herbal decoction, has been used to treat VaD in clinical practice and has produced positive outcomes; however, convincing evidence is currently lacking. The present study aimed to investigate the effects of YXJF on memory impairment in rats with cerebral ischemia/reperfusion and to explore the underlying mechanism. YXJF ameliorated memory impairment in rats with cerebral ischemia/reperfusion, inhibited hippocampal apoptosis in a dose-dependent manner and attenuated increases in the protein expression of B-cell lymphoma 2 (Bcl-2)-associated X protein as well as c-Jun and a reduction in Bcl-2 protein expression in the hippocampal tissue of the rats. Furthermore, administration of YXJF significantly increased the protein expression of PKA C-α and CREB, and promoted CREB phosphorylation. The results indicated that YXJF improves memory impairment through inhibiting apoptosis and enhancing PKA/CREB signal transduction in rats with cerebral ischemia/reperfusion.

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1	Román GC: Vascular dementia may be the most common form of dementia in the elderly. J Neurol Sci. 203–204:7–10. 2002. View Article : Google Scholar
2	Iemolo F, Duro G, Rizzo C, Castiglia L, Hachinski V and Caruso C: Pathophysiology of vascular dementia. Immun Ageing. 6:132009. View Article : Google Scholar : PubMed/NCBI
3	Zekry D, Herrmann FR, Graf CE, Giannelli S, Michel JP, Gold G and Krause KH: Mild cognitive impairment, degenerative and vascular dementia as predictors of intra-hospital, short- and long-term mortality in the oldest old. Aging Clin Exp Res. 23:60–66. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ekonomou A, Ballard CG, Pathmanaban ON, Perry RH, Perry EK, Kalaria RN and Minger SL: Increased neural progenitors in vascular dementia. Neurobiol Aging. 32:2152–2161. 2011. View Article : Google Scholar
5	Poels MM, Ikram MA, van der Lugt A, Hofman A, Niessen WJ, Krestin GP, Breteler MM and Vernooij MW: Cerebral micro-bleeds are associated with worse cognitive function: The Rotterdam Scan Study. Neurology. 78:326–333. 2012. View Article : Google Scholar : PubMed/NCBI
6	Wu CX, Liu R, Gao M, Zhao G, Wu S, Wu CF and Du GH: Pinocembrin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress induced apoptosis. Neurosci Lett. 546:57–62. 2013. View Article : Google Scholar : PubMed/NCBI
7	Nishio K, Ihara M, Yamasaki N, Kalaria RN, Maki T, Fujita Y, Ito H, Oishi N, Fukuyama H, Miyakawa T, et al: A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke. 41:1278–1284. 2010. View Article : Google Scholar : PubMed/NCBI
8	Chen CH, Jiang Z, Yan JH, Yang L, Wang K, Chen YY, Han JY, Zhang JH and Zhou CM: The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury. CNS Neurosci Ther. 19:566–576. 2013. View Article : Google Scholar : PubMed/NCBI
9	Eberspächer E, Werner C, Engelhard K, Pape M, Gelb A, Hutzler P, Henke J and Kochs E: The effect of hypothermia on the expression of the apoptosis-regulating protein Bax after incomplete cerebral ischemia and reperfusion in rats. J Neurosurg Anesthesiol. 15:200–208. 2003. View Article : Google Scholar : PubMed/NCBI
10	Bernabeu R, Bevilaqua L, Ardenghi P, Bromberg E, Schmitz P, Bianchin M, Izquierdo I and Medina JH: Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. Proc Natl Acad Sci USA. 94:7041–7046. 1997. View Article : Google Scholar : PubMed/NCBI
11	Abel T, Nguyen PV, Barad M, Deuel TA, Kandel ER and Bourtchouladze R: Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell. 88:615–626. 1997. View Article : Google Scholar : PubMed/NCBI
12	Hagiwara M, Brindle P, Harootunian A, Armstrong R, Rivier J, Vale W, Tsien R and Montminy MR: Coupling of hormonal stimulation and transcription via the cyclic AMP-reponsive factor CREB is rate limited by nucluear entry of protein kinase A. Mol Cell Biol. 13:4852–4859. 1993.PubMed/NCBI
13	Chutae DL, Villiger JW and Kirton NF: Testing cyclic AMP mediation of memory: Reversal of alpha-methyl-p-tyrosine-induced amnesia. Psychopharmacology (Berl). 74:129–131. 1981. View Article : Google Scholar
14	Zhao WQ, Polya GM, Wang BH, Gibbs ME, Sedman GL and Ng KT: Inhibitors of cAMP-dependent protein kinase impair long-term memory formation in day-old chicks. Neurobiol Learn Mem. 64:106–118. 1995. View Article : Google Scholar : PubMed/NCBI
15	Guzowski JF and McGaugh JL: Antisense oligodeoxynu-cleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. Proc Natl Acad Sci USA. 94:2693–2698. 1997. View Article : Google Scholar
16	Nagakura A, Niimura M and Takeo S: Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism-induced defects in memory function and cerebral cyclic AMP signal transduction system in rats. Br J Pharmacol. 135:1783–1793. 2002. View Article : Google Scholar : PubMed/NCBI
17	Takeo S, Niimura M, Miyake-Takagi K, Nagakura A, Fukatsu T, Ando T, Takagi N, Tanonaka K and Hara J: A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats. Br J Pharmacol. 138:642–654. 2003. View Article : Google Scholar : PubMed/NCBI
18	Li TW, Tang N and Zhao QS: Clinical observation of Yifei Xuanfei Jiangzhuo Formula treated vascular dementia. Guangxi J Trad Chin Med. 37:105–107. 2014.In Chinese.
19	Leung KS, Bian ZX, Moher D, Dagenais S, Li YP, Liu L, Wu TX and Miao JX: Improving the quality of randomized controlled trials in Chinese herbal medicine, part III: Quality control of Chinese herbal medicine used in randomized controlled trials. J Chin Integr Med. 4:225–232. 2006. View Article : Google Scholar
20	Alipanahzadeh H, Soleimani M, Soleimani Asl S, Pourheydar B, Nikkhah A and Mehdizadeh M: Transforming growth factor-α improves memory impairment and neurogenesis following ischemia reperfusion. Cell J. 16:315–324. 2014.PubMed/NCBI
21	Wu YY, Wu WY, Gong HL, Li WZ and Yin YY: Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury. Mol Med Rep. 9:1319–1324. 2014.PubMed/NCBI
22	Langdon KD, Granter-Button S, Harley CW, Moody-Corbett F, Peeling J and Corbett D: Cognitive rehabilitation reduces cognitive impairment and normalizes hippocampal CA1 architecture in a rat model of vascular dementia. J Cereb Blood Flow Metab. 33:872–879. 2013. View Article : Google Scholar : PubMed/NCBI
23	Li H and Xin X: Nitrogen dioxide (NO(2)) pollution as a potential risk factor for developing vascular dementia and its synaptic mechanisms. Chemosphere. 92:52–58. 2013. View Article : Google Scholar : PubMed/NCBI
24	Zhang S, Qi Y, Xu Y, Han X, Peng J, Liu K and Sun CK: Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of apoptosis and inflammation. Neurochem Int. 63:522–532. 2013. View Article : Google Scholar : PubMed/NCBI
25	Feng XT, Wang TZ, Chen Y, Liu JB, Liu Y and Wang WJ: Pollen Typhae total flavone improves insulin-induced glucose uptake through the β-arrestin-2-mediated signaling in C2C12 myotubes. Int J Mol Med. 30:914–922. 2012.PubMed/NCBI
26	Zekry D: Is it possible to treat vascular dementia? Front Neurol Neurosci. 24:95–106. 2009. View Article : Google Scholar : PubMed/NCBI
27	Baskys A and Hou AC: Vascular dementia: Pharmacological treatment approaches and perspectives. Clin Interv Aging. 2:327–335. 2007.PubMed/NCBI
28	Malykh AG and Sadaie MR: Piracetam and piracetam-like drugs: From basic science to novel clinical applications to CNS disorders. Drugs. 70:287–312. 2010. View Article : Google Scholar : PubMed/NCBI
29	Hartman RE, Lee JM, Zipfel GJ and Wozniak DF: Characterizing learning deficits and hippocampal neuron loss following transient global cerebral ischemia in rats. Brain Res. 1043:48–56. 2005. View Article : Google Scholar : PubMed/NCBI
30	Xing SH, Zhu CX, Zhang R and An L: Huperzine a in the treatment of Alzheimer's disease and vascular dementia: A meta-analysis. Evid Based Complement Alternat Med. 2014:3639852014. View Article : Google Scholar : PubMed/NCBI
31	He Z, Liao Y, Zheng M, Zeng FD and Guo LJ: Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats. Cell Mol Neurobiol. 28:613–627. 2008. View Article : Google Scholar
32	Lee JY, Lee HE, Kang SR, Choi HY, Ryu JH and Yune TY: Fluoxetine inhibits transient global ischemia-induced hippo-campal neuronal death and memory impairment by preventing blood-brain barrier disruption. Neuropharmacology. 79:161–171. 2014. View Article : Google Scholar
33	Carson DA and Ribeiro JM: Apoptosis and disease. Lancet. 341:1251–1254. 1993. View Article : Google Scholar : PubMed/NCBI
34	O'Reilly LA and Strasser A: Apoptosis and autoimmune disease. Inflamm Res. 48:5–21. 1999. View Article : Google Scholar : PubMed/NCBI
35	Fang M, Li J, Tiu SC, Zhang L, Wang M and Yew DT: N-methyl-D-aspartate receptor and apoptosis in Alzheimer's disease and multiinfarct dementia. J Neurosci Res. 81:269–274. 2005. View Article : Google Scholar : PubMed/NCBI
36	Espinosa-García C, Vigueras-Villaseñor RM, Rojas-Castañeda JC, Aguilar-Hernández A, Monfil T, Cervantes M and Moralí G: Post-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia. Neurosci Lett. 550:98–103. 2013. View Article : Google Scholar : PubMed/NCBI
37	Zhou J and Tang XC: Huperzine A attenuates apoptosis and mitochondria-dependent caspase-3 in rat cortical neurons. FEBS Lett. 526:21–25. 2002. View Article : Google Scholar : PubMed/NCBI
38	Gabryel B, Adamek M, Pudełko A, Małecki A and Trzeciak HI: Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxy-genation. Neurotoxicology. 23:19–31. 2002. View Article : Google Scholar : PubMed/NCBI
39	Murphy KM, Ranganathan V, Farnsworth ML, Kavallaris M and Lock RB: Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ. 7:102–111. 2000. View Article : Google Scholar : PubMed/NCBI
40	Jürgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D and Reed JC: Bax directly induces release of cytochrome C from isolated mitochondria. Proc Natl Acad Sci USA. 95:4997–5002. 1998. View Article : Google Scholar : PubMed/NCBI
41	Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H and Tsujimoto Y: Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci USA. 95:14681–14686. 1998. View Article : Google Scholar : PubMed/NCBI
42	Shaulian E and Karin M: AP-1 as a regulator of cell life and death. Nat Cell Biol. 4:E131–E136. 2002. View Article : Google Scholar : PubMed/NCBI
43	Yang S, Zhou G, Liu H, Zhang B, Li J, Cui R and Du Y: Protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a rat model of vascular dementia. Biomed Res Int. 2013:2157982013. View Article : Google Scholar
44	Sun ZK, Ma XR, Jia YJ, Liu YR, Zhang JW and Zhang BA: Effects of resveratrol on apoptosis in a rat model of vascular dementia. Exp Ther Med. 7:843–848. 2014.PubMed/NCBI
45	Zhang TL, Fu JL, Geng Z, Yang JJ and Sun XJ: The neuroprotective effect of losartan through inhibiting AT1/ASK1/MKK4/JNK3 pathway following cerebral I/R in rat hippocampal CA1 region. CNS Neurosci Ther. 18:981–987. 2012. View Article : Google Scholar : PubMed/NCBI
46	Wang R, Zhang HY and Tang XC: Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat. Eur J Pharmacol. 421:149–156. 2001. View Article : Google Scholar : PubMed/NCBI
47	He Z, Hu M, Zha YH, Li ZC, Zhao B, Yu LL, Yu M and Qian Y: Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax. Cell Mol Neurobiol. 34:539–547. 2014. View Article : Google Scholar : PubMed/NCBI
48	Gonzalez GA and Montminy MR: Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 59:675–680. 1989. View Article : Google Scholar : PubMed/NCBI
49	Weth G: The influence of piracetam on the cyclic adenosine monophosphate (cAMP) concentration in the brain and colon of guinea pigs. Arzneimittelforschung. 33:812–814. 1983.PubMed/NCBI
50	Yao H, Gu LJ and Guo JY: Study on effect of astragali radix polysaccharides in improving learning and memory functions in aged rats and its mechanism. China J Chin Mater Med. 39:2071–2075. 2014.In Chinese.