Effects of Andrographolide on Related Neurotransmitters and HMGB1/RAGE/TLR4 Signaling Pathway in Depressed Rats

This study aimed to investigate the effects of Andr (andrographolide) on related neurotransmitters and HMGB1/RAGE/TLR4 signaling pathway in depressed rats. The rats were randomly divided into Control group, Model group, Andr low-dose (Andr-L) group, Andr high-dose (Andr-H) group, Andr-H+rHMGB1 (HMGB1 recombinant protein) group. Depressive behavior and cognitive function of rats were evaluated. The levels of TNF-α, IL-1β, IL-6 and NGF in the serum, as well as the levels of NE (norepinephrine), DA (dopamine) and 5-HT (serotonin) in the hippocampal tissue were detected. The morphology of hippocampus was observed. The neuronal apoptosis in hippocampus was detected. Expression levels of Cleaved caspase-3, BDNF, and HMGB1/RAGE/TLR4 pathways were detected. Compared with Control group, the hippocampal tissue in Model group was significantly damaged, and the number of standing episodes, sucrose water consumption, serum NGF level, hippocampal NE, DA and 5-HT levels, as well as BDNF protein expression level were decreased. Swimming immobility time, serum TNF-α, IL-1β and IL-6 levels, hippocampal neuronal apoptosis rate, and protein expression levels of Cleaved caspase-3, HMGB1, RAGE and TLR4 were increased (P<0.05). Compared with Model group, the hippocampal tissue morphology of Andr-L and Andr-H groups was significantly improved, and the number of standing times, sucrose water consumption, serum NGF level, hippocampus NE, DA and 5-HT levels, as well as BDNF protein expression level were increased. Swimming immobile time, serum TNF-α, IL-1β and IL-6 levels, hippocampal neuron apoptosis rate, and protein expression levels of Cleaved caspase-3, HMGB1, RAGE and TLR4 were decreased (P<0.05). rHMGB1 could reverse the ameliorating effect of Andr on the neurotransmitter levels in depressed rats (P<0.05). Andr can increase the levels of neurotransmitters in rats with depression, improve depressive behaviors, and this may be related to the inhibition of the HMGB1/RAGE/TLR4 signaling pathway

CSTR: 10.11844/cjcb.2026.02.0011