Ginsenoside Rb1 Prevents MPP⁺-Induced Apoptosis in PC12 Cells by Stimulating Estrogen Receptors with Consequent Activation of ERK1/2, Akt and Inhibition of SAPK/JNK, p38 MAPK

Abstract

Ginsenoside Rb1 shows neuroprotective effects in various neurons, including dopaminergic cells. However, the precise mechanisms of action are uncertain. In this paper, we examine whether Rb1 has a neuroprotective effect on MPP+-induced apoptosis and attempt to clarify the signaling pathway in PC12 cells. Apoptosis of PC12 cells was determined by DNA fragmentation assay, the activation of caspase-3, or by the inactivation of Bcl-xL. Rb1 inhibited MPP+-induced caspase-3 activation and DNA fragmentation and activated Bcl-xL in MPP+-treated PC12 cells. These antiapoptotic effect was abrogated in PC12 cells transfected with estrogen receptor siRNA. Levels of DNA fragmentation were increased by wortmannin or PD 98059, while they were decreased by SB 203580 or SP 600125 in MPP+-treated PC12 cells. Rb1 increased phosphorylation levels of ERK1/2 or Akt in MPP+-treated PC12 cells, while it reduced phosphorylated p38 or SAPK/JNK. The increased phosphorylation of ERK/1/2 or Akt by Rb1 was abrogated by estrogen receptor siRNA. Rb1-induced inhibition of SAPK/JNK or p38 phosphorylation was also abolished by estrogen receptor siRNA. These results suggest that ginsenoside Rb1 protects PC12 cells from caspase-3-dependent apoptosis through stimulation of estrogen receptor with consequent activation of ERK1/2 and Akt and inhibition of SAPK/JNK and p38.

Shengmai injection attenuates the cerebral ischemia/reperfusion induced autophagy via modulation of the AMPK, mTOR and JNK pathways

“…Many compounds in SMI have been reported to exhibit various potential neuroprotective effects, including the antioxidant effects of Ginsenoside Rg1 , the anti-inflammatory effects of Ginsenoside Re (Lee et al 2012), the anti-apoptotic and anti-autophagic effects of Ginsenoside Rb1 (Chen et al 2010;Lu et al 2011;Hashimoto et al 2012) and the anti-excitotoxic effects of schizandrin (Cheng et al 2008). Previously, we confirmed that SMI inhibited cerebral ischemia/reperfusioninduced brain injury and the expression of tissue factors ).…”

Ginsenoside Rb1 prevents interleukin-1 beta induced inflammation and apoptosis in human articular chondrocytes

“…A previous study has shown that Rb1 can exert a suppressive effect on local inflammation in rats with cerebral ischemia [9]. Furthermore, Rb1 protects PC12 cells from apoptosis through stimulation of the oestrogen receptor [10]. However, no data yet has been reported concerning the effect of Rb1 on apoptosis and inflammation in chondrocytes or its therapeutic role in OA.…”

Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat mesenteric venules by intervening in both trans- and paracellular pathway

“…As one of the most active ingredients of ginseng, Rb1 has been reported to have a variety of pharmacological effects, including anti-inflammation, anti-apoptosis, anti-oxidation, increasing endothelial cell nitric oxide production, and inhibiting angiogenesis, mainly through asso-ciation to androgen or estrogen receptors (5,14,17,23,43). Our previous study has shown that Rb1 pretreatment inhibits LPS-induced leukocyte adhesion to microvascular wall and interstitial mast cell degranulation (39), which are implicated in vascular hyperpermeability (19,38), suggesting a protective role of Rb1 against vascular protein leakage.…”