Skip to main content
Top
Published in: Chinese Medicine 1/2017

Open Access 01-12-2017 | Research

Danggui Buxue Tang, a simple Chinese formula containing Astragali Radix and Angelicae Sinensis Radix, stimulates the expressions of neurotrophic factors in cultured SH-SY5Y cells

Authors: Amy G. W. Gong, Huai Y. Wang, Tina T. X. Dong, Karl W. K. Tsim, Y. Z. Zheng

Published in: Chinese Medicine | Issue 1/2017

Login to get access

Abstract

Background

Danggui Buxue Tang (DBT), a phytoestrogen-enriched Chinese herbal formula, serves as dietary supplement in stimulating the “Blood” functions of menopausal women. In traditional Chinese medicine (TCM) theory, “Blood” has a strong relationship with brain activities. Previous studies supported that some ingredients of DBT possessed neuronal beneficial functions. Therefore, the neurotrophic function and the mechanistic action of DBT were systematically evaluated in cultured human neuroblastoma SH-SY5Y cells.

Methods

The DBT-triggered protein expressions were analyzed by western blotting, while the transcriptional activities of promoters coding for related genes were revealed by luciferase assays. For mechanistic analysis of DBT, Erk1/2 and its inhibitor U0126 were analyzed.

Results

The application of DBT in cultured neuroblastoma cells showed the efficacies in: (1) up-regulation of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF); (2) activation of transcriptional activities of promoters coding for NGF, BDNF, GDNF; (3) activation of Erk1/2 and CREB; and (4) attenuation of the neurotrophic factor expression by the treatment of an Erk1/2 inhibitor.

Conclusions

Our study supports that MAPK/Erk pathway acts as fundamental role in monitoring DBT-induced expression of neurotrophic factors in cultured human neuroblastoma cell. These results shed light in developing the working mechanism of this ancient herbal decoction for its neuronal function.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dong TTX, Zhao KJ, Gao QT, Ji ZN, Zhu TT, Li J, et al. Chemical and biological assessment of a Chinese herbal decoction containing Radix. Astragali and Radix Angelicae Sinensis: determination of drug ratio in having optimized properties. J Agric Food Chem. 2006;54:2767–74.CrossRefPubMed Dong TTX, Zhao KJ, Gao QT, Ji ZN, Zhu TT, Li J, et al. Chemical and biological assessment of a Chinese herbal decoction containing Radix. Astragali and Radix Angelicae Sinensis: determination of drug ratio in having optimized properties. J Agric Food Chem. 2006;54:2767–74.CrossRefPubMed
2.
go back to reference Gong AGW, Li N, Lau KM, Lee PSC, Yan L, Xu ML, et al. Calycosin orchestrates the functions of Danggui Buxue Tang, a Chinese herbal decoction composing of Astragali Radix and Angelica Sinensis Radix: an evaluation by using calycosin-knock out herbal extract. J Ethnopharmacol. 2015;16:150–7.CrossRef Gong AGW, Li N, Lau KM, Lee PSC, Yan L, Xu ML, et al. Calycosin orchestrates the functions of Danggui Buxue Tang, a Chinese herbal decoction composing of Astragali Radix and Angelica Sinensis Radix: an evaluation by using calycosin-knock out herbal extract. J Ethnopharmacol. 2015;16:150–7.CrossRef
3.
go back to reference Gao QT, Choi RC, Cheung AW, Zhu JT, Li J, Chu GK, et al. Danggui Buxue Tang—a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells. FEBS Lett. 2007;581:233–40.CrossRefPubMed Gao QT, Choi RC, Cheung AW, Zhu JT, Li J, Chu GK, et al. Danggui Buxue Tang—a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells. FEBS Lett. 2007;581:233–40.CrossRefPubMed
4.
go back to reference Lin HQ, Gong AG, Wang HY, Duan R, Dong TT, Zhao KJ, et al. Danggui Buxue Tang (Astragali Radix and Angelicae Sinensis Radix) for menopausal symptoms: a review. J Ethnopharmacol. 2017;199:205–10.CrossRefPubMed Lin HQ, Gong AG, Wang HY, Duan R, Dong TT, Zhao KJ, et al. Danggui Buxue Tang (Astragali Radix and Angelicae Sinensis Radix) for menopausal symptoms: a review. J Ethnopharmacol. 2017;199:205–10.CrossRefPubMed
5.
go back to reference Ning L, Chen CX, Jin RM, Wu YP, Zhang HG, Sun CL, et al. Effect of components of dang-gui- bu-xue decoction on hematopenia. Zhongguo Zhong Yao Za Zhi. 2002;27:50–3.PubMed Ning L, Chen CX, Jin RM, Wu YP, Zhang HG, Sun CL, et al. Effect of components of dang-gui- bu-xue decoction on hematopenia. Zhongguo Zhong Yao Za Zhi. 2002;27:50–3.PubMed
6.
go back to reference Zierau O, Zheng KY, Papke A, Dong TT, Tsim KW, Vollmer G. Functions of Danggui Buxue Tang, a Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix, in uterus and liver are both estrogen receptor-dependent and -independent. Evid Based Complement Alternat Med. 2014. doi:10.1155/2014/438531. Zierau O, Zheng KY, Papke A, Dong TT, Tsim KW, Vollmer G. Functions of Danggui Buxue Tang, a Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix, in uterus and liver are both estrogen receptor-dependent and -independent. Evid Based Complement Alternat Med. 2014. doi:10.​1155/​2014/​438531.
7.
go back to reference Wang WL, Sheu SY, Chen YS, Kao ST, Fu YT, Kuo TF, et al. Enhanced bone tissue regeneration by porous gelatin composites loaded with the Chinese herbal decoction Danggui Buxue Tang. PLoS ONE. 2015;10:e0131999.CrossRefPubMedPubMedCentral Wang WL, Sheu SY, Chen YS, Kao ST, Fu YT, Kuo TF, et al. Enhanced bone tissue regeneration by porous gelatin composites loaded with the Chinese herbal decoction Danggui Buxue Tang. PLoS ONE. 2015;10:e0131999.CrossRefPubMedPubMedCentral
8.
go back to reference Yang X, Huang CG, Du SY, Yang SP, Zhang X, Liu JY, et al. Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow proliferation mice. Phytomedicine. 2014;21:640–6.CrossRefPubMed Yang X, Huang CG, Du SY, Yang SP, Zhang X, Liu JY, et al. Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow proliferation mice. Phytomedicine. 2014;21:640–6.CrossRefPubMed
9.
go back to reference Lv J, Zhao Z, Chen Y, Wang Q, Tao Y, Yang L, et al. The Chinese herbal decoction Danggui Buxue Tang inhibits angiogenesis in a rat model of liver fibrosis. Evid Based Complement Alternat Med. 2012. doi:10.1155/2012/284963. Lv J, Zhao Z, Chen Y, Wang Q, Tao Y, Yang L, et al. The Chinese herbal decoction Danggui Buxue Tang inhibits angiogenesis in a rat model of liver fibrosis. Evid Based Complement Alternat Med. 2012. doi:10.​1155/​2012/​284963.
10.
go back to reference Zheng KYZ, Choi RC, Guo AJ, Bi CW, Zhu KY, Du CY, et al. The membrane permeability of Astragali Radix-derived formononetin and calycosin is increased by Angelicae Sinensis Radix in Caco-2 cells: a synergistic action of an ancient herbal decoction Danggui Buxue Tang. J Pharm Biomed Anal. 2012;70:671–9.CrossRefPubMed Zheng KYZ, Choi RC, Guo AJ, Bi CW, Zhu KY, Du CY, et al. The membrane permeability of Astragali Radix-derived formononetin and calycosin is increased by Angelicae Sinensis Radix in Caco-2 cells: a synergistic action of an ancient herbal decoction Danggui Buxue Tang. J Pharm Biomed Anal. 2012;70:671–9.CrossRefPubMed
11.
go back to reference Zhang L, Gong AG, Riaz K, Ho CM, Lin HQ, Dong TT, et al. A novel combination of four flavonoids derived from Astragali Radix relieves the symptoms of cyclophosphamide-induced anemic rats. FEBS Open Bio. 2017;7:318–23.CrossRefPubMedPubMedCentral Zhang L, Gong AG, Riaz K, Ho CM, Lin HQ, Dong TT, et al. A novel combination of four flavonoids derived from Astragali Radix relieves the symptoms of cyclophosphamide-induced anemic rats. FEBS Open Bio. 2017;7:318–23.CrossRefPubMedPubMedCentral
12.
go back to reference Xu SL, Zhu KY, Bi CW, Yan L, Men SW, Dong TT, et al. Flavonoids, derived from traditional Chinese medicines, show roles in the differentiation of neurons: possible targets in developing health food products. Birth Defects Res C Embryo Today. 2013;99:292–9.CrossRefPubMed Xu SL, Zhu KY, Bi CW, Yan L, Men SW, Dong TT, et al. Flavonoids, derived from traditional Chinese medicines, show roles in the differentiation of neurons: possible targets in developing health food products. Birth Defects Res C Embryo Today. 2013;99:292–9.CrossRefPubMed
13.
go back to reference Espinet C, Gonzalo H, Fleitas C, Menal MJ, Egea J. Oxidative stress and neurodegenerative diseases: a neurotrophic approach. Curr Drug Targets. 2015;16:20–30.CrossRefPubMed Espinet C, Gonzalo H, Fleitas C, Menal MJ, Egea J. Oxidative stress and neurodegenerative diseases: a neurotrophic approach. Curr Drug Targets. 2015;16:20–30.CrossRefPubMed
14.
go back to reference Murray B, Alessandrini A, Cole AJ, Yee AG, Furshpan EJ. Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity. Proc Natl Acad Sci. 1998;95:11975–80.CrossRefPubMedPubMedCentral Murray B, Alessandrini A, Cole AJ, Yee AG, Furshpan EJ. Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity. Proc Natl Acad Sci. 1998;95:11975–80.CrossRefPubMedPubMedCentral
15.
go back to reference Satoh T, Nakatsuka D, Watanabe Y, Nagata I, Kikuchi H, Namura S. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neurosci Lett. 2000;288:163–6.CrossRefPubMed Satoh T, Nakatsuka D, Watanabe Y, Nagata I, Kikuchi H, Namura S. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neurosci Lett. 2000;288:163–6.CrossRefPubMed
16.
go back to reference Gong AG, Lau KM, Xu ML, Lin HQ, Dong TT, Zheng KY, et al. The estrogenic properties of Danggui Buxue Tang, a Chinese herbal decoction, are triggered predominantly by calycosin in MCF-7 cells. J Ethnopharmacol. 2016;189:81–9.CrossRefPubMed Gong AG, Lau KM, Xu ML, Lin HQ, Dong TT, Zheng KY, et al. The estrogenic properties of Danggui Buxue Tang, a Chinese herbal decoction, are triggered predominantly by calycosin in MCF-7 cells. J Ethnopharmacol. 2016;189:81–9.CrossRefPubMed
17.
go back to reference Yang Q, Feng B, Zhang K, Guo YY, Liu SB, Wu YM, et al. Excessive astrocyte-derived neurotrophin-3 contributes to the abnormal neuronal dendritic development in a mouse model of fragile X syndrome. PLoS Genet. 2012;8:e1003172.CrossRefPubMedPubMedCentral Yang Q, Feng B, Zhang K, Guo YY, Liu SB, Wu YM, et al. Excessive astrocyte-derived neurotrophin-3 contributes to the abnormal neuronal dendritic development in a mouse model of fragile X syndrome. PLoS Genet. 2012;8:e1003172.CrossRefPubMedPubMedCentral
18.
go back to reference Yan L, Xu SL, Zhu KY, Lam KY, Xin G, Maiwulanjiang M, et al. Optimizing the compatibility of paired-herb in an ancient Chinese herbal decoction Kai-Xin-San in activating neurofilament expression in cultured PC12 cells. J Ethnopharmacol. 2015;162:155–62.CrossRefPubMed Yan L, Xu SL, Zhu KY, Lam KY, Xin G, Maiwulanjiang M, et al. Optimizing the compatibility of paired-herb in an ancient Chinese herbal decoction Kai-Xin-San in activating neurofilament expression in cultured PC12 cells. J Ethnopharmacol. 2015;162:155–62.CrossRefPubMed
19.
go back to reference Pan SY, Chen SB, Dong HG, Yu ZL, Dong JC, Long ZX, et al. New perspectives on Chinese herbal medicine (Zhong-Yao) research and development. Evid Based Complement Alternat Med. 2011. doi:10.1093/ecam/neq056. Pan SY, Chen SB, Dong HG, Yu ZL, Dong JC, Long ZX, et al. New perspectives on Chinese herbal medicine (Zhong-Yao) research and development. Evid Based Complement Alternat Med. 2011. doi:10.​1093/​ecam/​neq056.
20.
go back to reference Tohda C, Tamura T, Matsuyama S, Komatsu K. Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus. Br J Pharmacol. 2006;149:532–41.CrossRefPubMedPubMedCentral Tohda C, Tamura T, Matsuyama S, Komatsu K. Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus. Br J Pharmacol. 2006;149:532–41.CrossRefPubMedPubMedCentral
21.
go back to reference Sajad M, Zargan J, Zargar MA, Sharma J, Umar S, Arora R, et al. Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): implications on CNS regeneration. Neurotoxicology. 2013;36:24–33.CrossRefPubMed Sajad M, Zargan J, Zargar MA, Sharma J, Umar S, Arora R, et al. Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): implications on CNS regeneration. Neurotoxicology. 2013;36:24–33.CrossRefPubMed
22.
go back to reference Oh SB, Park HR, Jang YJ, Choi SY, Son TG, Lee J. Baicalein attenuates impaired hippocampal neurogenesis and the neurocognitive deficits induced by ã-ray radiation. Br J Pharmacol. 2013;168:421–31.CrossRefPubMed Oh SB, Park HR, Jang YJ, Choi SY, Son TG, Lee J. Baicalein attenuates impaired hippocampal neurogenesis and the neurocognitive deficits induced by ã-ray radiation. Br J Pharmacol. 2013;168:421–31.CrossRefPubMed
23.
go back to reference Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem. 2003;85:180–92.CrossRefPubMed Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem. 2003;85:180–92.CrossRefPubMed
24.
go back to reference Guo X, Chen ZH, Wang HL, Liu ZC, Wang XP, Zhou BH, et al. WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling. Mol Med Rep. 2015;11:2927–34.PubMed Guo X, Chen ZH, Wang HL, Liu ZC, Wang XP, Zhou BH, et al. WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling. Mol Med Rep. 2015;11:2927–34.PubMed
25.
go back to reference An L, Zhang YZ, Yu NJ, Liu XM, Zhao N, Yuan L, et al. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1484–90.CrossRefPubMed An L, Zhang YZ, Yu NJ, Liu XM, Zhao N, Yuan L, et al. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1484–90.CrossRefPubMed
26.
go back to reference Xing H, Zhang K, Zhang R, Shi H, Bi K, Chen X. Anti-depressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress. Phytomedicine. 2015;22:1178–85.CrossRefPubMed Xing H, Zhang K, Zhang R, Shi H, Bi K, Chen X. Anti-depressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress. Phytomedicine. 2015;22:1178–85.CrossRefPubMed
27.
go back to reference Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis. 2015;6:331–41.CrossRefPubMedPubMedCentral Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis. 2015;6:331–41.CrossRefPubMedPubMedCentral
28.
go back to reference Farrand AQ, Gregory RA, Scofield MD, Helke KL, Boger HA. Effects of aging on glutamate neurotransmission in the substantia nigra of GDNF heterozygous mice. Neurobiol Aging. 2015;36:1569–76.CrossRefPubMed Farrand AQ, Gregory RA, Scofield MD, Helke KL, Boger HA. Effects of aging on glutamate neurotransmission in the substantia nigra of GDNF heterozygous mice. Neurobiol Aging. 2015;36:1569–76.CrossRefPubMed
29.
go back to reference Ferreira D, Westman E, Eyjolfsdottir H, Almqvist P, Lind G, Linderoth B, et al. Brain changes in Alzheimer’s disease patients with implanted encapsulated cells releasing nerve growth factor. J. Alzheimers Dis. 2015;43:1059–72.PubMed Ferreira D, Westman E, Eyjolfsdottir H, Almqvist P, Lind G, Linderoth B, et al. Brain changes in Alzheimer’s disease patients with implanted encapsulated cells releasing nerve growth factor. J. Alzheimers Dis. 2015;43:1059–72.PubMed
30.
go back to reference Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010;1802:396–405.CrossRefPubMed Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010;1802:396–405.CrossRefPubMed
31.
go back to reference Villalba M, Bockaert J, Journot L. Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J Neurosci. 1997;17:83–90.PubMed Villalba M, Bockaert J, Journot L. Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J Neurosci. 1997;17:83–90.PubMed
32.
go back to reference Cao R, Lee B, Cho HY, Saklayen S, Obrietan K. Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock. Mol Cell Neurosci. 2008;38:312–24.CrossRefPubMedPubMedCentral Cao R, Lee B, Cho HY, Saklayen S, Obrietan K. Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock. Mol Cell Neurosci. 2008;38:312–24.CrossRefPubMedPubMedCentral
Metadata
Title
Danggui Buxue Tang, a simple Chinese formula containing Astragali Radix and Angelicae Sinensis Radix, stimulates the expressions of neurotrophic factors in cultured SH-SY5Y cells
Authors
Amy G. W. Gong
Huai Y. Wang
Tina T. X. Dong
Karl W. K. Tsim
Y. Z. Zheng
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2017
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-017-0144-y

Other articles of this Issue 1/2017

Chinese Medicine 1/2017 Go to the issue