Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Huatuo Zaizao pill promotes functional recovery and neurogenesis after cerebral ischemia-reperfusion in rats

Authors: Sijin Duan, Tian Wang, Jianqiao Zhang, Minmin Li, Chengwen Lu, Lijie Wang, Yan Zou, Fenghua Fu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. Huatuo Zaizao pill (HT), a traditional Chinese medicine, has been used clinically in China to promote the rehabilitation after stroke, but the underlying mechanism of action was still unclear. This study is to investigate the effects of HT on the functional recovery in a rat model of cerebral ischemia-reperfusion (I/R) injury, and the potential molecular mechanisms.

Methods

Rats were randomly divided into sham, model with cerebral I/R injury, or HT-treated groups, then administered orally with vehicle (for the sham and model group) or HT (0.5, 1.0, or 2.0 mg/kg) respectively, for 3 or 7 days. Functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Neurogenesis was investigated by double immunofluorescence staining for 5-ethynyl-2-deoxyuridine (EdU) and neuronal nuclear protein (NeuN). The proteins of kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were assayed by western blotting. The level of BDNF mRNA was evaluated by RT-PCR.

Results

Compared with the model group, treatment with HT significantly promoted functional recovery in I/R injured rats (p < 0.05 or p < 0.01). The generation of new neurons was increased in the HT groups. HT treatment for 3 days increased the level of BDNF mRNA in I/R injured rats. Expression of PKA, phosphorylated CREB, and BDNF were significantly (p < 0.05) increased with the 7-day HT treatment.

Conclusions

These results indicated that HT treatment could promote functional recovery after stroke. HT enhanced the expression of BDNF and increased the level of neurogenesis in cerebral I/R animal, which might be associated with the functional recovery.
Literature
1.
Lin Y, Zhang JC, Fu J, Chen F, Wang J, Wu ZL, Yuan SY. Hyperforin attenuates brain damage induced by transient middle cerebral artery occlusion (MCAO) in rats via inhibition of TRPC6 channels degradation. J Cereb Blood Flow Metab. 2013;33(2):253–62.CrossRefPubMed
2.
Kim DH, Lee HE, Kwon KJ, Park SJ, Heo H, Lee Y, Choi JW, Shin CY, Ryu JH. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus. Neuroscience. 2014;284C:42–54.
3.
Nehlig A. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br J Clin Pharmacol. 2013;75(3):716–27.PubMedPubMedCentral
4.
Iguchi H, Mitsui T, Ishida M, Kanba S, Arita J. cAMP response element-binding protein (CREB) is required for epidermal growth factor (EGF)-induced cell proliferation and serum response element activation in neural stem cells isolated from the forebrain subventricular zone of adult mice. Endocr J. 2011;58(9):747–59.CrossRefPubMed
5.
6.
Liu JG, Li Z, Xu HM, Xu X. Huatuo Zaizao pill prevents thrombosis and microcirculation disorders in experimental animals. Guangdong Med J. 2000;21:368–70.
7.
Liu Y, Luo ZM, Ji L, Gao L, Zhang Z, Zeng Z. The protective effect of Huatuo Zaizao Pills against neuronal injury of focal cerebral ischemia in rats. West China J Pharm Sci. 2004;19:103–5.
8.
Xia W, Lu Y, Yuan D, Kong D, Qi W, Kang F. Efficacy of Huatuo Zaizao pills for ischemic stroke. Eval Anal Drug-use Hosp China. 2012;12(9):772–5.
9.
Zheng F. Clinical efficacy of Hua Tuo’s pill in the treatment of cerebral infarction. China Heal Stands Manageme. 2015;6(20):122–3.
10.
Cai Y, Xu Y, Guo J, Zhang X, Li W, Liang W, Huang Y. A systematic review and meta-analysis to assess the efficacy of Huatuo Zaizao pill for the treatment of ischemic stroke. Chinese Tradi Herb Drug. 2007;38(4):581–4.
11.
Du JP, Zhang J. The clinical efficacy of Huatuo Zaizao pill to improve the rehabilitation of patients with stroke. Chengdu Med J. 2003;29:155–6.
12.
Wei JL, Shao NF. To study the effects of Huatuo Zaizao Pill on the ischemic stoke paients. Chin J Tradit Med Sci Technol. 1999;6:142–3.
13.
Xia W, Lu YJ, Yuan DC, Kong DZ, Qi WC, Kang F. Efficacy of Huatuo Zaizao Pills for ischemic stroke. Eval Anal Drug Hospit China. 2012;12:772–5.
14.
Cai YF, Xu Y, Guo JW, Zhang XC, Li WF, Liang WX, Huang Y. The meta-analysis about the clinical efficacy of Huatuo Zaizao pills on ischemic stroke. Chin Tradit Herb Drug. 2007;4:581–4.
15.
Ahmed ME, Tucker D, Dong Y, Lu Y, Zhao N, Wang R, Zhang Q. Methylene Blue promotes cortical neurogenesis and ameliorates behavioral deficit after photothrombotic stroke in rats. Neuroscience. 2016;336:39–48.CrossRefPubMed
16.
Zhao Y, Guan YF, Zhou XM, Li GQ, Li ZY, Zhou CC, Wang P, Miao CY. Regenerative neurogenesis after ischemic stroke promoted by nicotinamide phosphoribosyltransferase-nicotinamide adenine dinucleotide cascade. Stroke. 2015;46(7):1966–74.CrossRefPubMed
17.
Pereira BM, Weinstein PR, Zea-Longa E, el-Fiki M. Effect of blood flow rate and donor vessel diameter on the patency of carotid venous bypass grafts in dogs. Surg Neurol. 1989;31(3):195–9.CrossRefPubMed
18.
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91.CrossRefPubMed
19.
Shi GX, Yang CY, Wu MM, Guan LP, Wang LP, Liu CZ. Muscle hypertonia after permanent focal cerebral ischemia in rats: a qualitative and quantitative behavioral and electrophysiological study. Int J Neurosci. 2013;123(8):575–81.CrossRefPubMed
20.
Lin B, Levy S, Raval AP, Perez-Pinzon MA, Defazio RA. Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats. Cardiovasc Psychiatry Neurol. 2010;2010:506952.CrossRefPubMedPubMedCentral
21.
Schallert T, Upchurch M, Wilcox RE, Vaughn DM. Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum. Pharmacol Biochem Behav. 1983;18(5):753–9.CrossRefPubMed
22.
Liu X, Zhu Z, Kalyani M, Janik JM, Shi H. Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats. Physiol Behav. 2014;130:99–107.CrossRefPubMedPubMedCentral
23.
Porritt MJ, Andersson HC, Hou L, Nilsson A, Pekna M, Pekny M, Nilsson M. Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane. PLoS One. 2012;7(7):e41090.CrossRefPubMedPubMedCentral
24.
Qu H, Zhao M, Zhao S, Xiao T, Tang X, Zhao D, Jolkkonen J, Zhao C. Forced limb-use enhances brain plasticity through the cAMP/PKA/CREB signal transduction pathway after stroke in adult rats. Restor Neurol Neurosci. 2014;32(5):597–609.PubMed
25.
Chehrehasa F, Meedeniya AC, Dwyer P, Abrahamsen G, Mackay-Sim A. EdU, a new thymidine analogue for labelling proliferating cells in the nervous system. J Neurosci Methods. 2009;177(1):122–30.CrossRefPubMed
26.
Zeng C, Pan F, Jones LA, Lim MM, Griffin EA, Sheline YI, Mintun MA, Holtzman DM, Mach RH. Evaluation of 5-ethynyl-2'-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system. Brain Res. 2010;1319:21–32.CrossRefPubMed
27.
Satoh J, Tabunoki H, Arima K. Molecular network analysis suggests aberrant CREB-mediated gene regulation in the Alzheimer disease hippocampus. Dis Markers. 2009;27(5):239–52.CrossRefPubMedPubMedCentral
28.
Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD. Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science. 1999;286(5448):2358–61.CrossRefPubMed
29.
Yamamoto KK, Gonzalez GA, Biggs 3rd WH, Montminy MR. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature. 1988;334(6182):494–8.CrossRefPubMed
30.
Tanaka K, Nogawa S, Nagata E, Suzuki S, Dembo T, Kosakai A, Fukuuchi Y. Temporal profile of CREB phosphorylation after focal ischemia in rat brain. Neuroreport. 1999;10(11):2245–50.CrossRefPubMed
31.
Choi Y, Kang SG, Kam KY. Changes in the BDNF-immunopositive cell population of neocortical layers I and II/III after focal cerebral ischemia in rats. Brain Res. 2015;1605:76–82.CrossRefPubMed
32.
Mu J, Ostrowski RP, Soejima Y, Rolland WB, Krafft PR, Tang J, Zhang JH. Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury. Neurobiol Dis. 2013;51:133–43.CrossRefPubMed
33.
Kokaia Z, Nawa H, Uchino H, Elmer E, Kokaia M, Carnahan J, Smith ML, Siesjo BK, Lindvall O. Regional brain-derived neurotrophic factor mRNA and protein levels following transient forebrain ischemia in the rat. Brain Res Mol Brain Res. 1996;38(1):139–44.CrossRefPubMed
34.
Yang JT, Chang CN, Lee TH, Hsu JC, Lin TN, Hsu YH, Hsieh WJ. Effect of dexamethasone on the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids after forebrain ischemia in the rat. Crit Care Med. 2002;30(4):913–8.CrossRefPubMed
35.
Lee TH, Kato H, Chen ST, Kogure K, Itoyama Y. Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons. Neuroreport. 2002;13(17):2271–5.CrossRefPubMed
36.
Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227–32.PubMedPubMedCentral
37.
Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke. 2007;38(11):3032–9.CrossRefPubMed
38.
Krupinski J, Kaluza J, Kumar P, Kumar S, Wang JM. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke. 1994;25(9):1794–8.CrossRefPubMed
Metadata
Title
Huatuo Zaizao pill promotes functional recovery and neurogenesis after cerebral ischemia-reperfusion in rats
Authors
Sijin Duan
Tian Wang
Jianqiao Zhang
Minmin Li
Chengwen Lu
Lijie Wang
Yan Zou
Fenghua Fu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1516-z

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Effects of phenolic constituents of daylily flowers on corticosterone- and glutamate-treated PC12 cells

Research article

Comparison of chemical profiles between the root and aerial parts from three Bupleurum species based on a UHPLC-QTOF-MS metabolomics approach

Research article

Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial

Research article

A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome: results from a randomized double-blind placebo-controlled pilot trial

Research article

Evidence based anti-osteoporosis effects of Periplaneta americana L on osteoblasts, osteoclasts, vascular endothelial cells and bone marrow derived mesenchymal stem cells

Research article

Fungal endophytes associated with Viola odorata Linn. as bioresource for pancreatic lipase inhibitors