Study on mechanism of analgesic active constituents from Piper wallichii based on network pharmacology and experimental verification
AIM To investigate the analgesic mechanism of the active constituents of Piper wallichii.METHODS The core targets related to analgesia of Piper wallichii were screened by network pharmacology,and GO functional enrichment and KEGG pathway enrichment analyses were carried out by DAVID database.The cationic elution site of Shinan vine was eluted by a silica gel column with a gradient(95:5-50:50)of petroleum ether-ethyl acetate separation system system to isolate the wallwort alkaloids,and the purity was determined by HPLC.Selected ICR mice were randomly divided into a blank group,positive control(aspirin 120 mg·kg-1)group,a model group,and low,medium,and high dose(150,300,and 600 mg·kg-1)pellitorine groups(all n=8),and were administered continuously for 7 d.After the last administration,each group was injected intraperitoneally with 0.1 mL of 0.7％acetic acid for every 10 g of body weight except the blank group.The number of twisting responses and latency period in each group were examined.Serum levels of tumour necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β were detected by ELISA,and the concentrations of choline acetyltransferase(ChAT),acetylcholine(ACh),and acetylcholinesterase(AChE)were examined in brain tissues.RESULTS The network pharmacological results showed that Piper wallichii screened out the core components such as pellitorine and futoamide,and the key pathways such as nerve signalling pathway and cholinergic synaptic pathway.The purity of isolated pellitorine was 90.42％.Animal experiments showed that,compared with the model group,the number of twisting in the low,medium and high dose pellitorine groups was significantly reduced(P＜0.05),and the content of TNF-α,IL-6 and IL-1β in serum was significantly reduced(P＜0.01).ChAT in the brain tissues of the three dose pellitorine groups were significantly higher(P＜0.01),and the concentration of ACh in the medium and high dose pellitorine groups were significantly higher(P＜0.01),and the AChE concentration of low,middle and high dose pellitorine groups were significantly decreased(P＜0.05).CONCLUSION The key active constituent in the analgesic effect of Piper wallichii is pellitorine,which is involved in the cholinergic synaptic pathway by up-regulating the activities of ChAT and ACh,and down-regulating AChE,thus reducing pain.
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