Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury

Abstract

Abstract. Trimethyltin (TMT) is a potent neurotoxicant that affects various regions within the central nervous system, including the neocortex, cerebellum, and hippocampus. In the present study, ginsenoside Rd was investigated as a candidate neuroprotective agent in a primary hippocampal neuron culture and mouse models. TMT induced neurotoxicity in a seven-day primary hippocampal neuron culture in a dose-dependent manner (2.5-10 µM). However, pre-treatment with 20 µg/ml ginsenoside Rd for 24 h reversed the toxic action. ICR mice were administered a single injection of 2 mg/kg body weight TMT. Apparent tremor seizure and impaired passive avoidance tests demonstrated significant differences when compared with a saline treated control group. Nissl staining was performed to evaluate the neuronal loss in the hippocampus. In addition, immunostaining of glial fibrillary acidic protein characterized the features of astroglial activation. These results demonstrated that TMT markedly induced Cornu Ammonis 1 subregion neuronal loss and reactive astrocytes in the hippocampus, indicating disrupted hippocampal function. Notably, ginsenoside Rd attenuated the tremor seizures and cognitive decline in behavioral tests. Additionally, significantly reduced neuronal loss (P=0.018) and active astroglials (P=0.003) were observed in the ginsenoside Rd treated group. Ginsenoside Rd prevented TMT-induced cell apoptosis via regulation of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 and caspase-3. These results demonstrate that ginsenoside may be developed as a neuroprotective agent to prevent TMT-induced neurotoxicity.

Integrated metabolomic and transcriptomic analyses revealed the distribution of saponins in Panax notoginseng

“…Triterpenoids possess important pharmacological effects, such as hypoglycemic activity (Rg1) 27 , antioxidant activity (Re) 28 , neuroprotection activity (Rb1) 29 , improvement in learning and memory abilities (Rd) 30 , immunity activity (Rb2) 31 , and anti-inflammatory activity (Rc) 32 . Notoginsenoside R1 and ginsenoside ( i.e.…”

Ginsenoside Rg3 and Rh2 protect trimethyltin‐induced neurotoxicity via prevention on neuronal apoptosis and neuroinflammation

“…A passive avoidance test was employed 48 hr after TMT treatment to access the passive avoidance response, as described previously (Hou et al, ). Two compartments were separated by a guillotine door, and it allows the animals to move freely from one side to the other.…”

“…In the investigation into TMT‐induced neurotoxicity, ginsenoside Re protects against activation of IL‐6‐mediated phosphoinositol 3‐kinase/Akt signaling (Tu et al, ) and mountain‐cultivated ginseng alleviates neurotoxicity via IL‐6 dependent JAK2/STA3/ERK signaling (Tu et al, ). Our preliminary experiments revealed that ginsenoside Rd prevents trimethyltin injury by inhibiting apoptosis in vitro and suppressing neuron loss and activation of astrocytes (Hou, Xue, Lee, & Sung, ). However, ginsenoside as well‐known neuroprotective agent, the mechanism by which it prevents or attenuates TMT‐induced neurotoxicity, has yet to be fully elucidated.…”

Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study

“…Notably, Rd attenuated the tremor seizures and cognitive decline in behavioral tests and significantly reduced neuronal loss ( P =0.018) and active astroglials ( P =0.003) compared with the negative control group. The mechanism involved in prevention of TMT-induced cell apoptosis by Rd treatment is the regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax) and caspase-3 [ 76 ]. Moreover, Rd may promote neurite outgrowth in PC12 cells by upregulating growth-associated protein-43 expression through both extracellular signal-regulated kinase (ERK)- and adhesion related kinase-dependent signaling pathways [ 77 ].…”