Salviae miltiorrhizae radix increases dopamine release of rat and pheochromocytoma PC12 cells

• Published in: Phytotherapy research Vol. 20; no. 3; pp. 191 - 199
• Main Authors: Kim, C.H, Koo, B.S, Kim, K.O, Kim, J.K, Chang, Y.C, Lee, I.S
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2006; Wiley
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Alkaloids; Amphetamine - pharmacology; Animals; Benzophenanthridines; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cell Survival - drug effects; dopamine; Dopamine - analysis; Dopamine - metabolism; Dopamine Agents - pharmacology; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; General pharmacology; Inhibitory Concentration 50; Male; Medical sciences; Organic Chemicals - chemistry; PC12 Cells; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phenanthridines - pharmacology; pheochromocytoma PC12 cells; Plant Extracts - pharmacology; Plant Stems - chemistry; Potassium - pharmacology; rat; Rats; Salvia miltiorrhiza; Salviae miltiorrhizae radix; Thionucleotides - pharmacology; Time Factors; Water - chemistry; Endocrinopathy; Salviae miltiorrhizae radix; Dopamine; Pheochromocytoma; Rat; Pharmacognosy; Rodentia; Catecholamine; In vitro; Medicinal plant; Secretory tumor; Vertebrata; pheochromocytoma PC12 cells; Mammalia; Animal; Plant origin; Neurotransmitter
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.1833

The Radix of Salvia miltiorrhiza Bunge (Labiatae) (SMR), an eminent herb, is often included as an ingredient in various herbal remedies recommended for vascular circulation therapies. The present study investigated the effect of SMR on dopaminergic neurotransmission. Various extracts prepared from the stems of SMR were tested for cytotoxic activity on pheochromocytoma PC12 cells using the XTT assay method. The ethanol extract (IC50 > 100 µg/mL), water extract (IC50 > 100 µg/mL) and chloroform (IC50 = 90 µg/mL) fraction exhibited weak cytotoxic activity. However, the butanol (IC50 = 80 µg/mL) and ethyl acetate (EtOAc; IC50 = 70 µg/mL) fractions exhibited strong cytotoxic activity. Also, the extracts and fractions were investigated for dopamine release effects. The EtOAc fraction showed a stronger stimulatory effect on dopamine release activity than the other fractions. The effect of the crude EtOAc fraction (50 µg/mL) of SMR on K+ (20 mm)‐stimulated dopamine (DA) release from rat striatal slices was compared with amphetamine (10−4 m) using high‐performance liquid chromatography with electrochemical detection to measure endogenous DA. The EtOAc fraction significantly increased K+‐stimulated DA release (p < 0.001) from rat striatal slices when compared with K+‐stimulated alone. The EtOAc fraction potentiated the effect of amphetamine on K+‐stimulated DA release (p < 0.001) when compared with amphetamine alone. To examine whether in vitro the EtOAc fraction treatment induces DA release in PC12 cells, the role of protein kinases was investigated in the induction of the EtOAc fraction‐mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A (PKA). The PKC inhibitors chelerythrine (50 nm and 100 nm) and Ro31‐8220 (100 nm) and the MAP kinase kinase inhibitor, PD98059 (20 µm), inhibited the ability of the EtOAc fraction of SMR to elicit the EtOAc fraction‐stimulated DA release. The PKC activator, 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA, 100 nm) mimicked the ability of the EtOAc fraction of SMR to elicit DA release. In contrast, a selective PKA inhibitor, 50 µm Rp‐8‐Br‐cAMP, blocked the development of EtOAc fraction‐stimulated DA release. It was demonstrated that the EtOAc fraction of SMR stimulated DA release. Therefore the mechanism by which the EtOAc fraction of SMR induced the enhancement in EtOAc fraction‐stimulated DA release is apparent. Copyright © 2006 John Wiley & Sons, Ltd.