Attenuation of Neuropathic Pain by Saikosaponin a in a Rat Model of Chronic Constriction Injury

Abstract

Despite immense advances in the treatment strategies, the effective treatment of patients suffering from neuropathic pain remains challenging. Saikosaponin a possesses anti-inflammatory activity. However, the role of saikosaponin a in neuropathic pain is still unclear. Therefore, the objective of this study was to investigate the effects of saikosaponin a on neuropathic pain. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After CCI, rats were administered saikosaponin a (6.25, 12.50 and 25.00 mg/kg intraperitoneal, once daily) for 14 days. Mechanical withdrawal threshold and thermal withdrawal latency were assessed before surgery and on days 1, 3, 7, and 14 after CCI. Our results showed that CCI significantly decreased mechanical withdrawal threshold and thermal withdrawal latency on days 1, 3, 7 and 14, as compared with sham groups, however, saikosaponin a reversed this effects. In addition, saikosaponin a inhibited CCI-induced the levels of TNF-α, IL-1β, IL-2 in spinal cord. Western blot analysis demonstrated that saikosaponin a reduced the elevated expression of p-p38 mitogen-activated protein kinase (MAPK) and NF-κB in the spinal cord induced by CCI. These results suggest that saikosaponin a could effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38 MAPK and NF-κB signaling pathways in spinal cord.

Identification and characterization of saikosaponins as antagonists of transient receptor potential A1 channel

“…They contribute significantly to the pharmacological activities of B. falcatum in vitro and in vivo , including anti‐inflammatory, immunomodulatory, anti‐tumor and hepatoprotection activities. In addition, in line with our results, saikosaponin A was shown to alleviate mechanical hypersensitivity in an animal model of chronic constriction injury (CCI)‐induced neuropathic pain (Zhou et al, ). Although the authors suggested that the reduced mechanical hypersensitivity is likely to be attributable, in part, to the anti‐inflammatory effects of saikosaponin A, we cannot exclude the possibility that TRPA1 antagonism by saikosaponin A also contributes to reducing CCI‐induced neuropathic pain.…”

Saikosaponin a attenuates hyperlipidemic pancreatitis in rats via the PPAR‑γ/NF‑κB signaling pathway

“…Another study also found that NLRP3 mitigated injury to the pancreas and lungs, the inflammatory response and neutrophil infiltration in NLRP3 -/-SAP mice (45). Similar results were observed in a rat model of chronic constriction injury, where SSa inhibited the levels of TNF-α, IL-1β and IL-2 and reduced the elevated expression of MAPK and NF-κB in the spinal cord, thus attenuating neuropathic pain (46).…”

A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications

“…It inhibits the activation of p38 MAPK, NF- κ B signaling pathways to attenuate neuropathic pain (Zhou et al. 2014 ), and activates γ -aminobutyric acid (GABA) receptor B to attenuate cocaine-reinforced behavior (Yoon et al. 2012 , 2013 ) and drug addiction (Maccioni et al.…”

“… 2014 ), and neuromodulation activities (Zhou et al. 2014 ). All of these potent effects are due to its various secondary metabolites, especially saikosaponins, the content of which is up to 7% of the total dry weight of Radix Bupleuri roots (Ashour & Wink 2011 ).…”