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Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin.

Im DS, Nah SY - Acta Pharmacol. Sin. (2013)

Bottom Line: However, the effects of ginseng are not fully explained by ginsenosides.This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics.Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.

View Article: PubMed Central - PubMed

Affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 609-735, Korea.

ABSTRACT
Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic mediator. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.

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Schematic diagram of gintonin-mediated signal transduction pathways. For the desensitization, gintonin activates LPA GPCRs, which leads to activation of GRK2. The activated GRK2 phosphorylates the LPA GPCRs and then β-arrestin I is recruited. The recruited β-arrestin I inhibits GPCR-G protein coupling. For cellular responses, gintonin activates LPA GPCRs, which leads to activation of phospholipase C (PLC). The activated PLC produces IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC), which phosphorylates Ca2+ channels. IP3 mobilizes Ca2+ from internal Ca2+ stores through IP3 receptors. The increased Ca2+ levels activate many kinases.
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fig2: Schematic diagram of gintonin-mediated signal transduction pathways. For the desensitization, gintonin activates LPA GPCRs, which leads to activation of GRK2. The activated GRK2 phosphorylates the LPA GPCRs and then β-arrestin I is recruited. The recruited β-arrestin I inhibits GPCR-G protein coupling. For cellular responses, gintonin activates LPA GPCRs, which leads to activation of phospholipase C (PLC). The activated PLC produces IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC), which phosphorylates Ca2+ channels. IP3 mobilizes Ca2+ from internal Ca2+ stores through IP3 receptors. The increased Ca2+ levels activate many kinases.

Mentions: The crude ginseng total saponin (cGTS) fraction contains approximately 50% ginsenosides by weight. Furthermore, the cGTS fraction increases intracellular Ca2+ in mammalian cells and activates endogenous Ca2+-activated Cl− channels in Xenopus oocytes, whereas ginsenosides do not. These data imply that some unidentified ginseng component(s) is responsible for the Ca2+ increase7. In addition, the cGTS fraction-induced Ca2+ increases are both reversible and transient. Precise and continuing studies over the past twenty years have elucidated a signaling pathway downstream of cGTS in oocytes, namely the unknown membrane target protein-Gq/11-PLCβ3-IP3-Ca2+ release38. Later, homologous desensitization by cGTS was shown to be mediated through GRK2 and β-arrestin I in oocytes, strongly implying GPCR involvement (Figure 2)39.


Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin.

Im DS, Nah SY - Acta Pharmacol. Sin. (2013)

Schematic diagram of gintonin-mediated signal transduction pathways. For the desensitization, gintonin activates LPA GPCRs, which leads to activation of GRK2. The activated GRK2 phosphorylates the LPA GPCRs and then β-arrestin I is recruited. The recruited β-arrestin I inhibits GPCR-G protein coupling. For cellular responses, gintonin activates LPA GPCRs, which leads to activation of phospholipase C (PLC). The activated PLC produces IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC), which phosphorylates Ca2+ channels. IP3 mobilizes Ca2+ from internal Ca2+ stores through IP3 receptors. The increased Ca2+ levels activate many kinases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818586&req=5

fig2: Schematic diagram of gintonin-mediated signal transduction pathways. For the desensitization, gintonin activates LPA GPCRs, which leads to activation of GRK2. The activated GRK2 phosphorylates the LPA GPCRs and then β-arrestin I is recruited. The recruited β-arrestin I inhibits GPCR-G protein coupling. For cellular responses, gintonin activates LPA GPCRs, which leads to activation of phospholipase C (PLC). The activated PLC produces IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC), which phosphorylates Ca2+ channels. IP3 mobilizes Ca2+ from internal Ca2+ stores through IP3 receptors. The increased Ca2+ levels activate many kinases.
Mentions: The crude ginseng total saponin (cGTS) fraction contains approximately 50% ginsenosides by weight. Furthermore, the cGTS fraction increases intracellular Ca2+ in mammalian cells and activates endogenous Ca2+-activated Cl− channels in Xenopus oocytes, whereas ginsenosides do not. These data imply that some unidentified ginseng component(s) is responsible for the Ca2+ increase7. In addition, the cGTS fraction-induced Ca2+ increases are both reversible and transient. Precise and continuing studies over the past twenty years have elucidated a signaling pathway downstream of cGTS in oocytes, namely the unknown membrane target protein-Gq/11-PLCβ3-IP3-Ca2+ release38. Later, homologous desensitization by cGTS was shown to be mediated through GRK2 and β-arrestin I in oocytes, strongly implying GPCR involvement (Figure 2)39.

Bottom Line: However, the effects of ginseng are not fully explained by ginsenosides.This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics.Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.

View Article: PubMed Central - PubMed

Affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 609-735, Korea.

ABSTRACT
Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic mediator. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.

Show MeSH