Lipid‐soluble Extracts from Salvia miltiorrhiza Inhibit Production of LPS‐induced Inflammatory Mediators via NF‐κB Modulation in RAW 264.7 Cells and Perform Antiinflammatory Effects In Vivo

Abstract

Salvia miltiorrhiza, a traditional Chinese herbal medicine, is used to treat various inflammatory diseases. In the present study, the antiinflammatory effects of S. miltiorrhiza lipid-soluble extracts (SMLE) were demonstrated in vitro and in vivo, along with its underlying mechanism of action. SMLE significantly inhibited the production of NO, TNF-α, IL-1β and IL-6 in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. SMLE also inhibited the LPS-induced degradation of IκB-α in the cytoplasm and the translocation of p65 to the nucleus in RAW 264.7 cells. In addition, SMLE inhibited the production of intracellular reactive oxygen species (ROS) and the surface expression of CD14 induced by LPS. In animal models, intraperitoneal administration of SMLE increased the survival rate of endotoxemia and sepsis in mice. The topical administration of SMLE significantly inhibited ear edema induced by PMA. It was found that SMLE inhibits the LPS-induced gene and protein expression of iNOS, TNF-α, IL-1β and IL-6 in macrophages by blocking NF-κB activation, and these effects are mediated, at least in part, through the inhibition of intracellular ROS generation and the surface expression of CD14. The results suggest a possible therapeutic application of SMLE in inflammatory diseases and provide scientific evidence in support of the traditional Chinese medical practice of treatment with S. miltiorrhiza.

Synergistic Effects of Danshen (Salvia Miltiorrhiza Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells

“…The anti-inflammatory activities of tanshinones reported in this study are compatible with the findings of previous studies. It was demonstrated that lipid-soluble extracts of Danshen were capable of inhibiting the LPS-induced gene and protein expression of iNOS, TNF, IL-1 β , and IL-6 in macrophages via blocking NF- κ B activation [18, 19]. It was also previously reported that CT downregulated the expression of proinflammatory enzymes, including COX-2 and iNOS [18].…”

“…For example, a clinical study in patients with hypercholesterolaemia revealed that a Danshen extract produced protective effects in endothelial progenitor cells (EPCs) at least partially via reducing the expression of IL-6 and TNF, highlighting its anti-inflammatory activity [16]. Results from previous studies in LPS-stimulated macrophage cells have shown that lipid-soluble compounds of Danshen including tanshinone I (T1), cryptotanshinone I (CT), dihydrotanshinone I (DT), and tanshinone IIA (TIIA) reduce iNOS-induced NO, TNF, IL-1 β , PGE 2 , and MCP-1 levels [17–19]. Panax notoginseng saponins (PNS) have been shown to exert antiatherogenic effect through their anti-inflammatory activity in an apolipoprotein E- (apoE-) deficient mouse model and to produce dose-dependent inhibition of MCP-1 mRNA expressions in a high-fat and chronically inflamed induced atherosclerotic rabbit model [20, 21].…”

Genkwanin Inhibits Proinflammatory Mediators Mainly through the Regulation of miR-101/MKP-1/MAPK Pathway in LPS-Activated Macrophages

“…The cells were pretreated with genkwanin at the indicated concentrations for 2 h and then exposed to LPS (10 ng/mL) for 4 h. The RNA extraction and RT- q PCR assays for the mRNA levels of iNOS, TNF-α, IL-1β and IL-6 were performed as we previously described [21]. RT- q PCR assay for the miR-101 level was performed according to the manufacturer's protocol.…”

“…The western blot assay was performed as we previously described [21]. Proteins in nucleus or cytoplasm were extracted and separated by SDS-PAGE and transferred to polyvinylidene difluoride membranes.…”

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis

“…Although Danshen injection had been found to ameliorate fibrosis by downregulating the expression of ECM in DN [17], the mechanism is still elusive. Recent pharmacological studies reported that the lipidsoluble extract from Danshen showed significant inhibitory effects on drug-induced inflammatory mediators via NF-κB modulation in an inflammation model [18,19]. However, there is no report about the anti-inflammatory effect of Danshen injection in DN.…”