Salvia miltiorrhizacompounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells

Abstract

Context: Salvia miltiorrhiza Bunge is a traditional Asian medicine used to treat cerebral and cardiac ischemia. However, the effects of the active compounds of S. miltiorrhiza on liver damage are unclear. Objective: In this study, we tested the effects on acute liver injury of crude S. miltiorrhiza extracts from roots as well as neotanshinone B, dehydromiltirone, tanshinol A, tanshinone I, dihydrotanshinono I, neotanshinone A, cryptanshinono, tanshinone II A, and salvianolie acid B from purified S. miltiorrhiza extracts. Materials and methods: Various compounds or ethanol extract of S. miltiorrhiza (50, 100, and 200 mg/kg, p.o.) were administered to rats for five consecutive days. After acute carbon tetrachloride (CCl 4 )-induced liver injury by treatment of rats with a single dose of CCl 4 (0.75 mL/kg, p.o), rat liver function was tested by measuring serum biochemical parameters. Serum cytokine concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). Expression of p38 and NFkB was evaluated by western blot. Results: All S. miltiorrhiza components showed their effects on liver function from the dose from 50 to 200 mg/kg. At the dose of 200 mg/kg, they reduced serum levels of alkaline phosphatase (ALP) by 34-77%, alanine aminotransferase (ALT) by 30-57%, aspartate aminotransferase (AST) by 43-72%, creatine total bilirubin (BIL-T) by 33-81%, albumin (ALB) by 37-67%, indicating that S. miltiorrhiza extracts protected liver from CCl 4 -induced damage. Moreover, S. miltiorrhiza extracts at 200 mg/kg reduced the increase in the proinflammatory cytokines tumor necrosis factor-a (TNF-a) by 25-82%, interleukin-1 (IL-1) by 42-74% and interleukin-6 (IL-6) by 67-83%, indicating an effect on alleviating liver inflammation. Furthermore, in vitro, S. miltiorrhiza extracts inhibited p38 and NFkB signaling in Kupffer cells. This effect could be a main mechanism by which S. miltiorrhiza protects against acute liver toxicity. Discussion and conclusion: Active compounds of S. miltiorrhiza protected the liver from CCl 4 -induced injury. Protection might have been due to inhibition of p38 and NFkB signaling in Kupffer cells, which subsequently reduced inflammation in the liver.

Five‐descriptor model to predict the chromatographic sequence of natural compounds

“…The case of Radix Salvia miltiorrhiza was used for demonstrating the potential application of this method. Substantial evidence has shown that Tanshinone IIA is one of the main pharmacologically active ingredients in Radix Salvia miltiorrhiza . Our radar chart analysis suggests that Tanshinone IIA is a typical strong retention compound in the C 18 column (Supporting Information Fig.…”

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

“…Active ingredients of Salvia miltiorrhiza Bunge can also exert hepatoprotective effect from CCl 4 -induced liver injury in rats. The protective effect may be due to inhibition of NF-kB and p38 signaling in liver Kupffer cells [ 52 ]. Treatment of chronic iron-overloaded mice with Salvia miltiorrhiza Bunge will improve the hepatic morphology, decreasing iron deposition as well as inhibiting the expression of type I and type III collagen, TGF-beta mRNA, and increase the expression of matrix metalloprotein-9 (MMP-9) mRNA in the liver.…”

Phytochemical and biological research of Salvia medicinal resources

“…Sm compounds protect the liver from acute injury by the regulation of p38 and NF-kB signaling in Kupffer cells (Yue et al, 2014). S. plebeia suppresses atopic dermatitis-like skin lesions .…”