Network pharmacology analysis and experimental study of Shufeng Huoluo Pill in the treatment of rheu-matoid arthritis
OBJECTIVE To explore the potential mechanism of Shufeng Huoluo Pill(SHP)in treating rheumatoid arthritis(RA).METHODS Compounds in SHP were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the relevant literature for establishing a chemical composition database.The databases of Swis-sTargetPrediction and PharmMapper were utilized for harvesting potential targets for comparing RA-related targets from the data-bases of DisGeNET and GeneCards.A protein-protein interaction(PPI)network was constructed with the overlapping targets for topological analysis.GO/KEGG enrichment analyses were performed and a"Compound-Target-Pathway"network was estab-lished.Forty mice were randomized into four groups of control,positive control(dexamethasone 1.289 6 mg·kg-1),low-dose SHP(422.5 mg·kg-1)and high-dose SHP(845 mg·kg-1).After 4-day oral dosing,acetic acid writhing test was utilized for observing analgesic effects.One week later,xylene-induced auricular edema was employed for observing anti-inflammatory effects.Auricular thickness and weight were measured.And auricular histopathological changes were assessed by hematoxylin-eosin(HE)stain.Serum levels of IL-1β,IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression levels of IL-1 β,IL-6 and TNF-α in auricular tissues were evaluated by immunohistochemistry while those of PI3K,AKT and MAPK by immunofluorescence.RESULTS Among 1 352 chemical components of SHP,184 active compo-nents were selected by specific criteria.There were 1 514 identified targets for bioactive components.And 5 211 targets were cor related with RA with an overlap of 858 targets.PPI network analysis revealed 291 core targets,including such prominent ones as TNF,CTNNB1 and EGFR.GO/KEGG analyses indicated the involvement of signaling pathways of PI3K-Akt,MAPK and Ras.As compared with control,low/high-dose SHP blunted acetic acid-induced visceral pain(P＜0.01).High-dose dosing could significantly alleviate auricular edema(P＜0.05).Pathological changes of thickening and neutrophil aggregation in auricular dermis were mitigated by high-dose dosing.No significant change of serum levels of IL-1β,IL-6 and TNF-α occurred in any group(P＞0.05).Low/high-dose SHP could blunt the over-expressions of IL-1β and IL-6 in auricular tissues(P＜0.05)and arrest the up-regulations of PI3K,AKT and MAPK(P＜0.05).CONCLUSION SHP may exert its therapeutic effects on RA through modulating the signaling pathways of PI3K-Akt,MAPK and Ras,highlighting the multi-component,multi-target and multi-pathway approach of traditional Chinese medicine.
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