Evaluation of the anti-inflammatory activities of tanshinones isolated from Salvia miltiorrhiza var. alba roots in THP-1 macrophages

Abstract

Ethnopharmacological relevance: Salvia miltiorrhiza var. alba roots are used as the Chinese traditional medicine Danshen for the treatment of cardiovascular diseases in local clinical practice. Tanshinones are the major effective constituents of S. miltiorrhiza var. alba roots, but only tanshinone IIA, tanshinone I, cryptotanshinone, and 15,16-dihydrotanshinone have been investigated for their anti-inflammatory activities.

Materials and methods: Eleven known compounds were isolated from S. miltiorrhiza var. alba roots, and the structures of all compounds were elucidated by spectroscopic analysis and comparisons with reported data. Immune anti-inflammatory activities were assessed by the ability to inhibit the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin (IL)-8 using enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was also used to compare the inhibitory effects of the compounds on TNF-α, IL-1β, and IL-8 mRNA expression with that of tanshinone IIA in lipopolysaccharide-stimulated THP-1 macrophages.

Results: All tanshinones, except for compound 5, significantly inhibited the mRNA and protein expression of TNF-α, IL-1β, and IL-8, and their anti-inflammatory activities were stronger than that of tanshinone IIA. Compound 9 (5μM) showed the highest inhibitory effects for TNF-α, IL-1β, and IL-8, at 56.3%, 67.6%, and 51.7%, respectively.

Conclusions: Ten of the 11 tanshinones were shown to have anti-inflammatory properties superior to those of TSIIA, and which significantly inhibited the expression of TNF-α, IL-1β, and IL-8. The present results provided a referential basis for explaining the use of S. miltiorrhiza var. alba root as a Chinese folk medicine for treating cardiovascular diseases associated with inflammation, and show the importance of trace constituents of this herb.

Keywords: 1,2,6,7,8,9-hexahydro-1,6,6- trimethyl-3,11-dioxanaphtho [2,1-e] azulene-10,12-dione (PubChem CID: 14609845); 2-isopropyl-8-methylphenanthrene-3,4-dione (PubChem CID: 135872); Anti-inflammatory activity; Atherosclerosis; Bioactivity evaluation; Pro-inflammatory cytokines; Tanshinones; arucadiol (PubChem CID: 11011966); danshenol A (PubChem CID: 3083514); sugiol (PubChem CID: 275529); tanshindiol C (PubChem CID: 5321620); tanshinone IIA (PubChem CID: 164676); tanshinone IIB (PubChem CID: 318797).