Postoperative cognitive dysfunction (POCD) is common in elderly patients.
Senegenin, an active component of extracts from Polygala tenuifolia root, a
traditional Chinese medicine, has neuroprotective and neuroregenerative effects. However, the mechanism underlying the effects of
senegenin against postoperative
cognitive impairment in elderly individuals has yet to be elucidated. The aim of this study was to investigate the protective effects of
senegenin on the cognitive functions of elderly rats with
splenectomy-induced POCD. Results from a Morris water maze test suggested that
splenectomy induced a transient cognitive deficiency in the elderly rats; however, when the rats were treated with
senegenin, the
cognitive impairment was notably attenuated. Further experiments showed that
senegenin significantly inhibited the
mRNA and
protein expression of several key pro-inflammatory
cytokines, specifically,
tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β),
IL-6 and
IL-8, in the hippocampal tissues of elderly rats following
splenectomy. In order to investigate the molecular mechanism involved, the expression and activity of the
Toll-like receptor 4 (TLR4) signaling pathway was assessed. On day 1 postoperatively, it was observed that
senegenin markedly suppressed the
mRNA and
protein expression of TLR4,
myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor-inducing
interferon-β (TRIF). Furthermore, the phosphorylation levels of nuclear factor-κB (NF-κB) p65 and inhibitor of NF-κB (IκBα) were also decreased following
senegenin treatment on the first day subsequent to surgery. These results suggest that
senegenin suppressed
splenectomy-induced transient
cognitive impairment in elderly rats, possibly by downregulating two signaling pathways involved in
inflammation, TLR4/MyD88/NF-κB and TLR4/TRIF/NF-κB, to further inhibit the expression of key pro-inflammatory
cytokines, specifically, TNF-α, IL-1β,
IL-6 and
IL-8, and ultimately the
neuroinflammation in the hippocampal tissues. In conclusion, the present study revealed that
senegenin exhibited
neuroprotective effects against
splenectomy-induced transient
cognitive impairment in elderly rats, which indicated that
senegenin may be a promising agent for the treatment of POCD.