Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats

Abstract

Microgravity experienced during space flight is known to exert several negative effects on the learning ability and memory of astronauts. Few effective strategies are currently available to counteract these effects. Rg1 and Rb1, the major steroidal components of ginseng, have shown potent neuroprotective effects with a high safety profile. The present study aimed to investigate the effects of Rg1 and Rb1 on simulated microgravity-induced learning and memory dysfunction and its underlying mechanism in the hindlimb suspension (HLS) rat model. Administration of Rg1 (30 and 60 μmol/kg) and Rb1 (30 and 60 μmol/kg) for 2 weeks resulted in a significant amelioration of impaired spatial and associative learning and memory caused by 4-week HLS exposure, measured using the Morris water maze and Reward operating conditioning reflex (ROCR) tests, respectively. Furthermore, Rg1 and Rb1 administration alleviated reactive oxygen species production and enhanced antioxidant enzyme activities in the prefrontal cortex (PFC). Rg1 and Rb1 also assisted in the recovery of mitochondrial complex I (NADH dehydrogenase) activities, increased the expression of Mfn2 and decreased the fission marker dynamin-related protein (Drp)-1expression. Additionally, Rg1 and Rb1 treatment increased the SYN, and PSD95 protein expressions and decreased the ratio of Bax:Bcl-2 and reduced the expression of cleaved caspase-3 and cytochrome C. Besides these, the BDNF-TrkB/PI3K-Akt pathway was also activated by Rg1 and Rb1 treatment. Altogether, Rg1 and Rb1 treatment attenuated cognitive deficits induced by HLS, mitigated mitochondrial dysfunction, attenuated oxidative stress, inhibited apoptosis, increased synaptic plasticity, and restored BDNF-TrkB/PI3K-Akt signaling.

Trolox and recombinant Irisin as a potential strategy to prevent neuronal damage induced by random positioning machine exposure in differentiated HT22 cells

“…Furthermore, Jiang et al recently evaluated the efficacy of some steroid components of ginseng in preserving memory in a simulated microgravity model. Specifically, the authors administered diol-type ginseng saponin (Rb1) and triol-type ginseng saponin (Rg1) to rats subjected to limb unloading and observed a reduction in ROS in the prefrontal cortex, concomitant with a reduction in markers of apoptosis and an increase in BDNF expression compared to untreated rats [ 60 ]. This evidence confirms the responsibility of oxidative stress in microgravity-induced neuronal death and suggests the existence of a worrying alteration in the mechanisms underlying memory and learning processes.…”

Progress of Ginsenoside Rb1 in neurological disorders

“…GsRb1 has been shown to possess a diverse array of biological activities, including the capacity to cross the blood-brain barrier and produce neuroprotective effects, such as anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagic effects ( Figure 4 ; Table 1 ) ( Lin et al, 2022 ; Zhang M. et al, 2023 ; Hu et al, 2023 ; Jiang et al, 2023 ).…”

“…GsRb1 exerted anti-neuroinflammatory effects and corrected the loss of learning and memory skills in a rat (Male Wistar rats weighing 250–300 g and aged 3–4 months old were used to create Alzheimer’s disease rat models through intracerebroventricular injection of Amyloid beta 1–42.) model of AD ( Wang et al, 2011 ; Jiang et al, 2023 ). Currently, GsRb1 can protect the nerves, enhance cognitive function, and be applied in preclinical and clinical studies of AD through several administration methods.…”

Structural Characters and Pharmacological Activity of Protopanaxadiol‐Type Saponins and Protopanaxatriol‐Type Saponins from Ginseng

“…Rd could improve learning and memory ability and exhibit neuroprotective effects in model mice, probably through inhibiting the transcription activity of NF- κ B, reducing proinflammatory cytokines, and generating protective factors [ 120 ]. Rb1 and Rg1 improved the cognitive impairment induced by simulated microgravity in rats; the protective effects of Rb1 are superior to Rg1 in some parameters, such as escape latency, SOD, MDA, GSH-x, cleaved-Cas3 expression of prefrontal cortices [ 121 ].…”