Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

Preliminary Studies on Anti-Inflammatory and Analgesic Activities of Optimized Liushen Wan(CNZ) / 中药新药与临床药理

Objective To observe the anti-inflammatory and analgesic effects of CNZ,an optimized prescrition of Liushen Wan based on our previous studies,so as to provide some pharmacological evidence for its further clinical use. Methods Both acetic-acid-induced increased mouse vascular permeability and carrageenan-induced mouse footpad edema were used to study the anti-inflammatory activity of CNZ.Meanwhile,its analgesic activity was evaluated in mice model of pain induced by thermal stimulus and acetic acid.The above activities were compared with those of Liushen Wan.Results CNZ significantly reduced acetic-acid-induced dye leakage at the doses of 16,32 and 64mg/kg after single oral administration.Meanwhile,CNZ at the two higher doses also markedly inhibited carrageenan-induced foot- pad edema,which exerted the strongest effect at 3 hours after carrageenan injection,and lasted over 5 hours.On the other hand,CNZ remarkably suppressed acetic-acid-induced writhing response at low,moderate-and high-doses, and significantly prolonged pain threshold in hot plate assay at moderate-and high-doses 0.5 hour after oral adminis- tration,lasting over 3 hours.Overall,its potency was similar to that of Liushen Wan.Conclusion CNZ has significant anti-inflammatory and analgesic activities.