The present study investigated the effect of the medicinal plant Salviae miltiorrhizae radix (SMR) on dopaminergic neurotransmission in comparison with amphetamine. The effect of SM (0.1 g/ml) on K+ (20 mM)-stimulated dopamine (DA) release from rat striatal slices was compared with amphetamine (10−4 M). Amphetamine and SMR significantly increased K+-stimulated DA release (P<0.001) from rat striatal slices when compared with K+-stimulated alone. On the other hand, to examine whether in vitro SMR treatment induces DA release in PC12 cells, the role of protein kinases has been investigated in the induction of the SMR-mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A (PKA). PKC inhibitors chelerythrine (50 and 100 nM), Ro31-8220 (100 nM) and the MAP kinase inhibitor, PD98059 (20 μM) inhibited the ability of SMR to elicit the SMR-stimulated DA release. The direct-acting PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA, 100 nM) mimicked the ability of SMR to elicit DA release. On the contrary, a selective PKA inhibitor, 50 μM Rp-8-Br-cAMP, blocked the development of SMR-stimulated DA release. The results demonstrated that SMR may stimulate DA release and that SMR-induced increases in MAP kinase and PKC are important for induction of the enhancement in transporter-mediated DA release and PKA was also required for the enhancement in SMR-stimulated DA release. SMR treatment (0.1–10 μg/ml) to the hydrogen peroxide (H2O2)-treated PC12 cells activated the enzyme activities such as catalase, superoxide dismutase and glutathione peroxidase, and decreased the malondialdehyde level, indicating that SMR has also protective effects against free radical-induced cell toxicity. Therefore, the mechanism by which SMR induces the enhancement in SMR-stimulated DA release is apparent. It remains to be determined whether the effect of SMR on DA function is important in its therapeutic use in the treatment of drug addiction.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- SMR:
-
Salviae miltiorrahizae radix extract
- H2O2:
-
Hydrogenperoxide
- MDA:
-
malondialdehyde
- AD:
-
Alzheimer’s disease
- Aβ:
-
β-amyloide peptide
- SOD:
-
superoxide dismutase
- GSH-Px:
-
glutathione peroxidase
- GST:
-
glutathione-S-transferase
- AChE:
-
acetylcholinesterse
- PBS:
-
phosphate-buffered saline
- LDH:
-
lactate dehydrogenase
- MTT:
-
(3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide
References
Jiangsu New Medical College (ed.), 1977. Dictionary of Chinese Materia Medica. Shanghai: Science and Technology Press of Shanghai.
S. Yu P. Kuang T. Kanazawa K. Onodera H. Metoki Y. Oike (1998) ArticleTitleThe effects of radix Salviae miltiorrhizae on lipid accumulation of peroxidized low density lipoprotein in mouse peritoneal macrophages-lipid analysis and morphological studies J. Tradit. Chin. Med. 18 IssueID4 292–299 Occurrence Handle1:STN:280:DyaK1Mzot12ktA%3D%3D Occurrence Handle10453600
L. Kantor M. E. Gnegy (1998a) ArticleTitleEnhanced AMPH-mediated DA release in AMPH-pretreated rats depends on Ca2+ and CaM-dependent protein kinase II FASEB J. 12 A159
M. Nakafuku Y. Kaziro (1993) ArticleTitleEpidermal growth factor and transforming growth factor-alpha can induce neuronal differentiation of rat pheochromocytoma PC12 cells under particular culture conditions FEBS Lett. 315 227–232 Occurrence Handle10.1016/0014-5793(93)81169-Z Occurrence Handle1:CAS:528:DyaK3sXpsFSrug%3D%3D Occurrence Handle8422911
C. H. Kim Y. G. Park S. H. Noh Y. K. Kim (2005) ArticleTitlePGE(2) induces the gene expression of bone matrix metalloproteinase-1 in mouse osteoblasts by cAMP-PKA signaling pathway Int. J. Biochem. Cell. Biol. 37 IssueID2 375–385 Occurrence Handle10.1016/j.biocel.2004.07.013 Occurrence Handle1:CAS:528:DC%2BD2cXotlCntbY%3D Occurrence Handle15474982
H. Hug T. F. Sarre (1993) ArticleTitleProtein kinase C isoenzymes: Divergence in signal transduction Biochem. J. 291 329–343 Occurrence Handle1:CAS:528:DyaK3sXisFShsrw%3D Occurrence Handle8484714
S. C. Licata R. C. Pierce (2003) ArticleTitleThe roles of calcium/calmodulin-dependent and Ras/mitogen-activated protein kinases in the development of psychostimulant-induced behavioral sensitization J. Neurochem. 85 14–22 Occurrence Handle1:CAS:528:DC%2BD3sXislOltLk%3D Occurrence Handle12641723
D. W. Self L. M. Genova B. T. Hope W. J. Barnhart J. J. Spencer E. J. Nestler (1998) ArticleTitleInvolvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior J. Neurosci. 18 1848–1859 Occurrence Handle1:CAS:528:DyaK1cXht12ju7s%3D Occurrence Handle9465009
T. O. Hansen J. F. Rehfeld F. C. Nielsen (2000) ArticleTitleCyclic AMP-induced neuronal differentiation via activation of p38 mitogen-activated protein kinase J. Neurochem. 75 1870–1877 Occurrence Handle1:CAS:528:DC%2BD3cXns1ejtb4%3D Occurrence Handle11032876
U. Jessen V. Novitskaya N. Pedersen P. Serup V. Berezin E. Bock (2001) ArticleTitleThe transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells J. Neurochem. 79 1149–1160 Occurrence Handle10.1046/j.1471-4159.2001.00636.x Occurrence Handle1:CAS:528:DC%2BD38XivFCqsA%3D%3D Occurrence Handle11752056
P. Borgatti M. Mazzoni C. Carini L. M. Neri M. Marchisio L. Bertolaso M. Previati G. Zauli S. Capitani (1996) ArticleTitleChanges of nuclear protein kinase C activity and isotype composition in PC12 cell proliferation and differentiation Exp. Cell Res. 224 72–78 Occurrence Handle10.1006/excr.1996.0112 Occurrence Handle1:CAS:528:DyaK28Xit1ehuro%3D Occurrence Handle8612693
N. Masaki M. E. Kyle J. L. Farber (1989) ArticleTitleMitochondrial damage as a mechanism of cell injury in the killing of cultured hepatocytes by tert-butyl hydroperoxide Arch. Biochem. Biophys. 270 672–680 Occurrence Handle10.1016/0003-9861(89)90550-X Occurrence Handle1:CAS:528:DyaL1MXhs1Okt78%3D Occurrence Handle2705785
Y. Sun (1990) ArticleTitleFree radicals, antioxidant enzymes and carcinogenesis J. Free Radical Biol. Med. 8 583–599 Occurrence Handle1:CAS:528:DyaK3MXkvVKrsLk%3D
B. Halliwell (1994) ArticleTitleFree radical, antioxidant and human disease: curiosity, cause, or consequence? Lancet 344 721–724 Occurrence Handle10.1016/S0140-6736(94)92211-X Occurrence Handle1:CAS:528:DyaK2cXmsFamurg%3D Occurrence Handle7915779
H. B. Li J. P. Lai Y. Jiang F. Chen (2002) ArticleTitlePreparative isolation and purification of salvianolic acid B from the Chinese medicinal plant Salvia miltiorrhiza by high-speed counter-current chromatography J. Chromatogr. A 943 235–239 Occurrence Handle10.1016/S0021-9673(01)01441-8 Occurrence Handle1:CAS:528:DC%2BD38Xhs1yl Occurrence Handle11833643
J. Liu H. M. Shen C. N. Ong (2001) ArticleTitleRole of intracellular thiol depletion, mitochondrial function and reactive oxygen species in Salvia miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells Life Sci. 69 1833–1850 Occurrence Handle1:CAS:528:DC%2BD3MXmvV2htr8%3D Occurrence Handle11693264
Kim, K. O. 2004. Salviae miltiorrhizae radix used in the treatment of addiction mimics the action of amphetamine on in vitro rat striatal dopamine release and activates the dopamine release in rat pheochromocytoma PC12 cells. Ph.D. Thesis. Dongguk University Graduate School, Kyungju, Korea.
G. W. Bennett T. Sharp C. A. Marsden T. L. Parker (1983) ArticleTitleA manually-operated brain tissue slicer suitable for neurotransmitter release studies J. Neurosci. Meth. 7 107–115 Occurrence Handle1:STN:280:BiyC28rmsF0%3D
W. Thongsaard D. A. Kendall G. W. Bennett C. A. Marsden (1997) ArticleTitleA simple method for measuring DA release from rat brain slices J. Pharmacol. Toxicol. Meth. 37 143–148 Occurrence Handle10.1016/S1056-8719(97)00010-5 Occurrence Handle1:CAS:528:DyaK2sXkvFeqsbg%3D
R. P. Ebstein K. Seamon C. R. Crevelling J. W. Daly (1982) ArticleTitleRelease of norepinephrine from brain vesicular preparations: Effects of an adenylate cyclase activator, forskolin and a phosphodiesterase inhibitor Cell. Mol. Neurobiol. 2 179–192 Occurrence Handle1:CAS:528:DyaL3sXosVSjsQ%3D%3D Occurrence Handle6891616
L. Kantor Y. H. Park K. K. W. Wang M. E. Gnegy (2002) ArticleTitleEnhanced amphetamine-mediated dopamine release develops in PC12 cells after repeated amphetamine treatment Eur. J. Pharmacol. 451 27–35 Occurrence Handle10.1016/S0014-2999(02)02190-8 Occurrence Handle1:CAS:528:DC%2BD38XmvVCrs7c%3D Occurrence Handle12223225
H. J. Kim W. H. Lee C. H. Yoon J. C. Jeong K. S. Nam H. M. Kim Y. K. Choo M. C. Lee C. H. Kim (2001) ArticleTitleBombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes Pharmacol. Res. 43 11–16 Occurrence Handle1:STN:280:DC%2BD3MzitFOrug%3D%3D Occurrence Handle11207060
M. B. Hansen S. E. Nielsen K. Berg (1989) ArticleTitleRe-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill J. Immunol. Meth. 119 203–210 Occurrence Handle10.1016/0022-1759(89)90397-9 Occurrence Handle1:STN:280:BiaB2MnntFI%3D
G. C. Mills (1959) ArticleTitleThe purification and properties of glutathione peroxidase of erythrocytes J. Biol. Chem. 234 502–506 Occurrence Handle1:CAS:528:DyaG1MXmtlGluw%3D%3D Occurrence Handle13641249
R. F. Beers I. W. Sizer (1952) ArticleTitleA spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase J. Biol. Chem. 195 133–140 Occurrence Handle1:CAS:528:DyaG38Xjt12juw%3D%3D Occurrence Handle14938361
K. A. Yagi (1976) ArticleTitleSimple fluorometric assay for lipoperoxide in blood plasma Biochem. Med. 15 212–216 Occurrence Handle10.1016/0006-2944(76)90049-1 Occurrence Handle1:CAS:528:DyaE28XltVKhsrk%3D Occurrence Handle962904
R. A. Shafer B. Levant (1998) ArticleTitleThe D3 dopamine receptor in cellular and organismal function Psychopharmacology (Berlin) 135 1–16 Occurrence Handle10.1007/s002130050479 Occurrence Handle1:CAS:528:DyaK1cXpsVShtQ%3D%3D
A. I. Leshner G. F. Koob (1999) ArticleTitleDrugs of abuse and the brain Proc. Assoc. Am. Physicians 111 99–108 Occurrence Handle10.1046/j.1525-1381.1999.09218.x Occurrence Handle1:CAS:528:DyaK1MXit1Wnu7k%3D Occurrence Handle10220804
J. W. Kim (1998) ArticleTitleEffects of Magnesium Lithospermate B from Salvia miltiorrhiza on Hepatic Antioxidant System in Senescence Accelerated Mouse (SAM-R/I) Kor. J. Gerotol. 8 IssueID1 83–89
B. Y. Ahn (1999) ArticleTitleMutagenic effect of Tansen (Salvia miltiorrhiza Bge) Kor. J. Appl. Microbiol 27 IssueID3 197–202
S. B. Kim (1998) ArticleTitleProtective effect of Salviae-radix extraction in H2O2 induced renal cell injury J. Kor. Oriental Med. Soc. 19 38–48
J. Sun (2002) ArticleTitleEffect of natural products on ischemic heart diseases and cardiovascular system Acta Pharmacol. Sin. 23 IssueID12 1142–1151 Occurrence Handle1:CAS:528:DC%2BD38Xps1eisb0%3D Occurrence Handle12466052
E. H. Cao X. Q. Liu J. J. Wang N. F. Xu (1996) ArticleTitleEffect of natural antioxidant tanshinone II-A on DNA damage by lipid peroxidation in liver cells Free Radic. Biol. Med. 20 IssueID6 801–806 Occurrence Handle10.1016/0891-5849(95)02211-2 Occurrence Handle1:CAS:528:DyaK28XisFCrsr4%3D Occurrence Handle8728027
S. Yu P. Kuang T. Kanazawa K. Onodera H. Metoki Y. Oike (1998) ArticleTitleThe effects of radix Salviae miltiorrhizae on lipid accumulation of peroxidized low density lipoprotein in mouse peritoneal macrophages-lipid analysis and morphological studies J. Trad. Chin. Med. 18 IssueID4 292–299 Occurrence Handle1:STN:280:DyaK1Mzot12ktA%3D%3D
B. L. Zhao W. Jiang Y. Zhao J. W. Hou W. J. Xin (1996) ArticleTitleScavenging effects of Salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury Biochem. Mol. Biol. Int. 38 IssueID6 1171–1182 Occurrence Handle8739039
P. Kuang Y. Tao Y. Tian (1996) ArticleTitleRadix Salviae miltiorrhizae treatment results in decreased lipid peroxidation in reperfusion injury J. Trad. Chin. Med. 16 IssueID2 138–142 Occurrence Handle1:STN:280:DyaK1c%2FltVGhtQ%3D%3D
H. B. Li J. P. Lai Y. Jiang F. Chen (2002) ArticleTitlePreparative isolation and purification of salvianolic acid B from the Chinese medicinal plant Salvia miltiorrhiza by high-speed counter-current chromatography J. Chromatogr. A 943 235–239 Occurrence Handle10.1016/S0021-9673(01)01441-8 Occurrence Handle1:CAS:528:DC%2BD38Xhs1yl Occurrence Handle11833643
J. Liu H. M. Shen C. N. Ong (2001) ArticleTitleRole of intracellular thiol depletion, mitochondrial function and reactive oxygen species in Salvia miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells Life Sci. 69 1833–1850 Occurrence Handle1:CAS:528:DC%2BD3MXmvV2htr8%3D Occurrence Handle11693264
M. T. Hsieh W. H. Peng C. R. Wu W. H. Wang (2000) ArticleTitleThe ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats Phytother. Res. 14 375–377 Occurrence Handle10.1002/1099-1573(200008)14:5<375::AID-PTR593>3.0.CO;2-5 Occurrence Handle1:STN:280:DC%2BD3M%2FhtVCgtg%3D%3D Occurrence Handle10925408
X. Y. Jie B. K. Tan Y. Z. Zhu (2000) ArticleTitleSalvia miltiorrhiza and ischemic diseases Acta Pharmacol. Sin. 21 1089–1094
B. S. Koo T. S. Kwon Y. C. Lee H. M. Kim C. H. Kim (2004) ArticleTitleSalviae miltiorrhizae Radix inhibits superoxide generation by activated rat microglias and mimics the action of amphetamine on in vitro rat striatal dopamine release Neurochem. Res. 29 IssueID10 1837–1845 Occurrence Handle10.1023/B:NERE.0000042210.72927.ec Occurrence Handle1:CAS:528:DC%2BD2cXnslSmtLY%3D Occurrence Handle15532539
C. A. Rice-Evans N. J. Miller G. Paganga (1996) ArticleTitleStructure–antioxidant activity relationship of flavonoids and phenolic acids Free Radic. Biol. Med. 20 933 Occurrence Handle10.1016/0891-5849(95)02227-9 Occurrence Handle1:CAS:528:DyaK28XjsVChu7g%3D Occurrence Handle8743980
S. D. Glick I. M. Maisonneuve (2000) ArticleTitleDevelopment of novel medications for drug addiction. The legacy of an African Shrub Ann. New York Acad. Sci. 909 88–103 Occurrence Handle1:CAS:528:DC%2BD3cXlsVOjtLs%3D
R. B. Roothman G. I. Elmer T. S. Shippenberg W. Rea M. H. Baumann (1998) ArticleTitlePhentermine and fenfluramine. Preclinical studies in animal models of cocaine addiction Ann. New York Acad. Sci. 844 59–74
C. Routledge L. Thorn T. Ashmeade S. Taylor (1996) ArticleTitleElucidation of D3 receptor function in vivo: do D3 receptors mediate inhibition of dopamine neuronal activity? Biochem. Soc. Trans. 24 199–201 Occurrence Handle1:CAS:528:DyaK28Xht1Smtbk%3D Occurrence Handle8674661
M. D. Wood I. Boyfield D. J. Nash F. R. Jewitt K. Y. Avenell G. J. Riley (2000) ArticleTitleEvidence for antagonist activity of the dopamine D3 receptor partial agonist, BP 897, at human dopamine D3 receptor Eur. J. Pharmacol. 407 47–51 Occurrence Handle10.1016/S0014-2999(00)00732-9 Occurrence Handle1:CAS:528:DC%2BD3cXnsFWqt7s%3D Occurrence Handle11050289
M. E. Gotz G. Kunig P. Riederer M. B. Youdim (1997) ArticleTitleOxidative stress: Free radical production in neuronal degeneration Pharmacol. Ther. 63 37–122
B. Chance H. Sies A. Boveris (1979) ArticleTitleHydroperoxide metabolism in mammalian organs Physiol. Rev. 59 527–605 Occurrence Handle1:CAS:528:DyaE1MXltVGmtLc%3D Occurrence Handle37532
C. Ip C. Hayes R. M. Budnick H. E. Ganther (1991) ArticleTitleChemical form of selenium, critical metabolites, and cancer prevention Cancer Res. 51 595–600 Occurrence Handle1:CAS:528:DyaK3MXhtlGltL0%3D Occurrence Handle1824684
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chung, TW., Koo, BS., Kim, KO. et al. Salviae Miltiorrhizae BGE Radix Increases Rat Striatal K+-Stimulated Dopamine Release and Activates the Dopamine Release with Protection Against Hydrogen Peroxide-Induced Injury in Rat Pheochromocytoma PC12 Cells. Neurochem Res 31, 109–120 (2006). https://doi.org/10.1007/s11064-005-9264-3
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11064-005-9264-3