Salvia miltiorrhiza stems and leaves total phenolic acids combination with tanshinone protect against DSS-induced ulcerative colitis through inhibiting TLR4/PI3K/AKT/mTOR signaling pathway in mice

Ethnopharmacological relevance: Salvia miltiorrhiza Bge. as a traditional Asian medicinal plant, roots and rhizomes (Danshen) are used to treat chronic hepatitis and coronary heart disease. In recent years, the medicinal value of S. miltiorrhiza stems and leaves total phenolic acids extract (JF) similar to roots and rhizomes has received increasing attention. S. miltiorrhiza roots and rhizome tanshinone extract (DT) has a good anti-inflammatory effect. We investigated therapeutic effects of JF alone or in combination with DT against inflammatory bowel disease and its mechanisms.

Aim of the study: To explore the anti-inflammatory effect and its molecular mechanisms of JF and DT alone or in combination on dextran sulfate sodium (DSS)-induced colitis mice.

Materials and methods: Colitis was induced by received 2% DSS in drinking water for 7 consecutive days. Then mice were administered orally for 7 days. Disease activity index (DAI) scores were recorded daily. After the end of the experiment, colon was removed and length was measured and histopathological analysis was performed. Inflammatory factors expression was determined by ELISA, its mRNA expression was detected by real-time quantitative PCR, and the expression of related proteins on TLR4/PI3K/AKT/mTOR signal was analyzed by Western blot.

Results: Treatment with JF and DT alone or in combination reduced DAI scores, improved colonic shortening, and decreased colon histology scores. In addition, the expression level of inflammatory factors was inhibited. The combination of JF and DT has a better inhibitory effect on inflammatory factors compared to JF or DT alone. We also found that the combination of JF and DT inhibits TLR4/PI3K/AKT/mTOR signaling-related proteins expression level (including TLR, p- PI3K p110α/PI3K p110α, p-AKT (ser473)/AKT, mTOR, p-mTOR, NF-κB p65), it shows an effective anti-inflammatory effect.

Conclusions: We demonstrated for the first time that, combination with JF and DT effectively ameliorated DSS-induced ulcerative colitis in mice by inhibiting the TLR4/PI3K/AKT/mTOR signaling pathway.

Keywords: Colitis; DSS; Inflammation; Salvia miltiorrhiza; TLR4/PI3K/AKT/mTOR signaling pathway.