Ginsenosides with a few exceptions share a similar basic structure, consisting of a saturated 1, 2-cyclopentanoperhydrophenanthrene (sterane or gonane) steroid nucleus [18
]. The potential health effects of ginsenosides include anticarcinogenic, immunomodulatory, anti-inflammatory, antiallergic, antiatherosclerotic, antihypertensive, and antidiabetic effects, as well as antistress activity and effects on the central nervous system [18
]. Although the extracts from fresh or processed P. ginseng
have been extensively tested for their pharmacological effects, the precise biological functions and underlying action mechanisms of pure molecules from ginseng
extract are still largely unknown [19
In this paper we have demonstrated that purified ginsenoside Rb1 has a neuroprotective effect on MPP+-induced apoptosis. Ginsenoside Rb1 inhibited MPP+-induced caspase-3 activation and cell DNA fragmentation. It also activated Bcl-xL in MPP+-treated PC12 cells.
Interestingly, the antiapoptotic effect by ginsenoside Rb1 was abolished by ER siRNA but not by AR siRNA.
Ginsenosides (except Ro) belong to a family of steroids named steroidal saponins [20
]. It has been demonstrated that ginsenoside Rb1 acts both as phytoestrogen [21
] and as phytoandrogen [24
]. The brain is a highly estrogen responsive tissue where estrogens induce several beneficial actions [25
]. Our data indicates that ginsenoside Rb1 possesses estrogenic properties in PC12 cells, suggesting that ginsenoside Rb1 acts as a phytoestrogen in neural tissue.
Accumulating reports provide the evidence that phosphorylation of SAPK/JNK, p38 MAPK serves as a proapoptotic factor and phosphorylation of ERK1/2, Akt acts as a cell survival factor [6
]. In this paper, we have demonstrated that the ginsenoside Rb1-induced neuroprotective effects were mediated through the reduction in phosphorylated SAPK/JNK, p38 MAPK and the increase in phosphorylated protein of Akt, ERK1/2. The increased phosphorylation of ERK/1/2 or Akt was abrogated by ER alpha or beta siRNA but was not affected by AR siRNA. Ginsenoside Rb1-induced inhibition of SAPK/JNK or p38 MAPK phosphorylation was also abolished by ER alpha or beta siRNA but not by AR siRNA. Taken together, our findings suggest that ginsenoside Rb1 protects PC12 cells from caspase-3-dependent apoptosis induced by MPP+
through stimulation estrogen receptor alpha and beta with the consequent activation of ERK1/2 or Akt and the inhibition of SAPK/JNK or p38 MAPK.
In this study, we have used both DNA fragmentation and caspase activity for measurements of apoptotic cell death, however other specific assays including Terminal deoxynucleotidyl transferase dUTP nick end labeling assay would be required further to confirm the conclusions.
Liu et al. previously demonstrated the absorption and disposition of ginsenosides after oral administration of Panax notoginseng
extract to rats [30
]. According to their reports, the maximal plasma concentrations of the ginsenoside Rb1 were 1000 to 1200
nM after oral administration of Panax notoginseng
extract within 6 to 10 hours. In our studies, ginsenoside Rb1 showed significant neuroprotective effects at concentrations of 10−6
M. Plasma concentration of 10−6
M ginsenoside Rb1 has been retained after usual dose of ginseng in human, suggesting a possible mechanism of action by which ginseng has exerted its pharmacological effects in traditional Chinese medicine [1