Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by regulating the eNOS/Nrf2/HO‑1 signaling pathway

Abstract

The present study aimed to investigate whether ginsenoside Rb1 (G-Rb1) attenuates spinal cord injury-associated oxidative stress in rats by regulating the endothelial nitric oxide synthase eNOS/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway. Sprague Dawley rats were randomly divided into the sham operation group (S group), spinal cord injury group (SCI group), G-Rb1 treatment group (G-Rb1 group) and SCI+G-Rb1+Inhibitor L-name group (L-name group). The posterior limb function was evaluated via the Basso, Beattie and Bresnahan scoring method. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) in serum were measured by ELISA. The pathological changes in the spinal cord were observed by H&E staining. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect eNOS, phosphorylated (p)-eNOS, heat shock protein (HSP)90, Nrf2 and NAD(P)H quinone dehydrogenase 1 (Nqo1) at the mRNA and protein level. Immunohistochemistry was used to detect the expression of Nrf2 and p-eNOS. Compared with the S group, the scores of spinal cord function in the SCI group were significantly lower, and the levels of MDA were significantly increased, while the levels of SOD, CAT and GSH protein in spinal cord were significantly decreased (P<0.05). The spinal cord tissue exhibited hemorrhage, neuronal degeneration/necrosis, as well as mononuclear cell and lymphocyte infiltration. The eNOS, HSP90, Nrf2, Nqo1 and HO-1 mRNA levels were decreased (P<0.05). Compared with those in the SCI group, the spinal cord function score in the G-Rb1 group were significantly higher and the serum MDA content was significantly decreased, while the activity of SOD, CAT and GSH was significantly increased (P<0.05). The degeneration/necrosis of spinal cord neurons was attenuated, inflammatory cell infiltration was significantly reduced and the levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly upregulated (P<0.05). In the group that was administered the eNOS inhibitor L-name, the levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly decreased. In conclusion, G-Rb1 attenuates oxidative stress in injured spinal cords. The mechanism may at least in part involve the eNOS/Nrf2/HO-1 pathway.

Alternative Exercise Intervention for Patients With Severe Peripheral Artery Disease ― Akt1-Induced Blood Flow Recovery ―

“…A possible mechanism is that VEGF receptor activation may lead to HO-1 upregulation through the Akt signaling pathway or eNOS/Nrf2/HO-1 pathway, or musclederived VEGF may directly augment HO-1 expression ( Figure). 14,15 Unfortunately, the findings from the present study were unable to explain how HO-1 simply induced angiogenesis and increased the formation of capillaries in the ischemic tissue, resulting in functional recovery. Although blood flow was significantly increased in the Akt1-TG mice compared with either wild type or Akt1-TG mice treated with HO-1 inhibitor, no difference was found in the capillary density at ischemic sites.…”

Ginsenoside Re Mitigates 6-Hydroxydopamine-Induced Oxidative Stress through Upregulation of GPX4

“…A number of ginsenosides upregulate multiple antioxidant genes including GPX1, GPX3, SOD, and heme oxygenase (HO)-1 [17,[37][38][39]. Ginsenoside Rb1 elicits an antioxidant effect by upregulating HO-1 and SOD [17,37]. A mixture of ginsenosides Rh1 and Rg2 upregulates GPX1 [38], while ginsenosides Rb1, Rc, and Re induce GPX3 [39].…”

“…Ginsenosides are active components found abundantly in ginseng [12,13]. Among their multiple biological activities, many ginsenosides (Figure 1), including Rg1, Rb1, Rb2, and Rd, have antioxidant properties [14][15][16][17][18][19]. In particular, ginsenoside Rb1 reduces cerebral ischemia-induced injuries and oxidative stress in mouse spinal cords and aged mice, respectively, by regulating antioxidant signaling pathways [16,17].…”

“…Among their multiple biological activities, many ginsenosides (Figure 1), including Rg1, Rb1, Rb2, and Rd, have antioxidant properties [14][15][16][17][18][19]. In particular, ginsenoside Rb1 reduces cerebral ischemia-induced injuries and oxidative stress in mouse spinal cords and aged mice, respectively, by regulating antioxidant signaling pathways [16,17]. Ginsenosides Rb2 and Rd attenuate oxidative stress and cell death triggered by glutamate and amyloid-β (Aβ) in hippocampal neuronal cells, respectively [18,19].…”

Effects of Red Ginseng on Neural Injuries with Reference to the Molecular Mechanisms

“…Shi et al indicated that gRb1 protected the brain from neural injury through Nrf2 activation, and that the knockdown of Nrf2 counteracted the neuroprotective effect of gRb1 [41]. Liu et al indicated that gRb1 protected the spinal cord from oxidative stress by activating the Nrf2/ARE signal pathway [42]. Taken together, the neuroprotection achieved by RG and its active ingredients, especially gRb1, is attributed to their anti-apoptotic, anti-inflammatory, and anti-oxidative actions.…”