Ginsenoside Rf relieves mechanical hypersensitivity, depression‐like behavior, and inflammatory reactions in chronic constriction injury rats

Abstract

The aim of this study was to investigate whether ginsenoside Rf can effectively relieve pain hypersensitivity in a neuropathic pain rat model. Neuropathic pain was induced in rats by chronic constriction injury (CCI) to the right sciatic nerve. Ginsenoside Rf was administered intraperitoneally after CCI surgery. The von Frey filament test and forced swimming test were performed to examine pain hypersensitivity and depression-like behavior in rats. Western blot was used to measure the levels of inflammatory cytokines in the dorsal root ganglion (DRG) and the spinal cord. Pretreatment of ginsenoside Rf for 7 days did not affect the onset of mechanical allodynia in CCI rats; however, a single dose of ginsenoside Rf 1 day after surgery attenuated established mechanical allodynia in CCI rats. Additionally, chronic treatment of ginsenoside Rf 1 week before and 2 weeks after CCI surgery diminished mechanical allodynia and depression-like behavior without affecting spontaneous locomotor activity in CCI rats. Furthermore, in CCI rats, chronic ginsenoside Rf treatment partially reversed the upregulation of proinflammatory cytokines in the spinal cord and/or the DRG but elevated IL-10, an anti-inflammatory factor, in the DRG. Ginsenoside Rf alleviated neuropathic pain and its associated depression and restored the balance between proinflammatory and anti-inflammatory cytokines. Our results suggest that ginsenoside Rf may be a potential therapy for nerve injury-induced neuropathic pain.

Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

“…Expression levels of VEGF and inflammation-related iNOS, IL-6, IL-1β, and TNF-α were significantly downregulated in the ginsenoside Rf-treated group in a dose-dependent manner [22]. In a rat nerve injury-induced neuropathic pain model, chronic ginsenoside Rf treatment partially reversed the upregulation of pro-inflammatory cytokines in the spinal cord and/or the dorsal root ganglion, but elevated IL-10, an anti-inflammatory factor [23].…”

“…Expression levels of VEGF and inflammation-related iNOS, IL-6, IL-1β, and TNF-α were significantly downregulated in the ginsenoside Rf-treated group in a dose-dependent manner [22]. In a rat nerve injury-induced neuropathic pain model, chronic ginsenoside Rf treatment partially reversed the upregulation of pro-inflammatory cytokines in the spinal cord and/or the dorsal root ganglion, but elevated IL-10, an anti-inflammatory factor [23]. Ginsenoside Rg6, a rare ginsenoside from ginseng, was found to have a significant immunosuppressive function on TLR4-induced systemic inflammatory responses, i.e., LPS-induced septic shock, cecal ligation and puncture-induced sepsis [24].…”

“…Because exposure to IL-4, IL-10, or glucocorticoids could induce a type of M2-polarized macrophage [51,52], the previously reported induction of anti-inflammatory cytokine IL-10 by ginsenosides Rg6, Rb1, Rc, Rd, Re, Rf, Rg1, Rh1, Rh2, and Rp1, as well as compound K [14,23,24,41,[61][62][63][64][65][66][67], or activation of glucocorticoid receptors by compound K, ginsenosides Rg1, and Re [36][37][38][39] may imply that those ginsenosides could partly induce the resolution of inflammation through M2 polarization.…”

How to study anxiety and depression in rodent models of chronic pain?

“…Interestingly, in the SNI and CCI models a shift to an earlier development of depressive‐like behaviours can be observed. Indeed, over the 15 studies reporting an increase in immobility time in CCI, eight showed it at or even before 2 weeks post‐surgery (Fukuhara et al, 2012; Garg, Deshmukh, & Prasoon, 2017; Li et al, 2014; Li, Chen, Li, & Jiang, 2019; see also Table 1 and Figures 5 and 6). For the SNI, among the 17 studies presenting depressive‐like behaviour, 11 observed the development of deficits in active behaviour in this test before 2 weeks post‐surgery (Laumet et al, 2017; Pan et al, 2018; Stratinaki et al, 2013; Xu et al, 2017; Yang, Liu, et al, 2019; Zhou et al, 2015; see also Table 1 and Figures 5 and 6).…”

Taurine and Ginsenoside Rf Induce BDNF Expression in SH-SY5Y Cells: A Potential Role of BDNF in Corticosterone-Triggered Cellular Damage

“…For example, the ginsenoside Rb1 upregulates hippocampal BDNF expression to relieve stress in rats subjected to stressful conditions [29,30], and Rg1, Rg3, and Rg5 activate BDNF signaling to elicit antidepressant effects [26,[31][32][33]. Ginsenoside Rf also relieves depression-like behavior in rats with chronic constriction injury by alleviating neuropathic pain in the spinal cord [41]. Our work presented here shows that, similar to other ginsenosides, g-Rf upregulated BDNF expression and was able to reverse the CORT-mediated decreased of BDNF in SH-SY5Y cells, thereby mitigating cellular damage and the loss of viability.…”