Emodin enhances cholesterol efflux by activating peroxisome proliferator-activated receptor-γ in oxidized low density lipoprotein-loaded THP1 macrophages.

Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear receptor involved in the regulation of lipid metabolism. In the present study, we sought to investigate the effects of emodin, an anthraquinone derivative isolated from the roots of Rheum palmatum, on PPARγ signalling and cholesterol efflux in macrophage foam cells. Oxidized low-density lipoprotein (oxLDL)-stimulated THP1 macrophages were incubated with different concentrations of emodin (0-10 µmol/L) for 18 h. Western blot analysis and semiquantitative reverse transcription-polymerase chain reaction were used to assess the expression of key genes involved in cholesterol efflux, namely PPARγ, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG1. In addition, apolipoprotein (apo) A-I-mediated cholesterol efflux in emodin-treated cells was measured. Expresssion of PPARγ mRNA and protein was increased in emodin-treated cells in a time- and dose-dependent manner. Emodin treatment also concentration-dependently induced LXRα, ABCA1 and ABCG1 expression. Moreover, emodin promoted apoA-I-mediated cholesterol efflux from oxLDL-loaded THP1 macrophages, which was significantly abolished by pretreatment with the PPARγ-selective antagonist GW9662 or the specific small interfering RNA for PPARγ. Together, the results demonstrate that emodin promotes cholesterol efflux from THP1 macrophages via activation of the PPARγ signalling pathway and may represent a potential anti-atherosclerotic drug.

Characteristics of emodin on modulating the contractility of jejunal smooth muscle.

Emodin is traditionally used as a laxative and is found to increase or decrease the contractility of intestinal smooth muscle in low doses and high doses, respectively. In this study, we propose that bidirectional regulation (BR) on the contractility of jejunal smooth muscle (CJSM) is inducible by emodin in the absence of control by the central nervous system. The results indicated that emodin-induced BR had the following characteristics. A stimulatory effect on CJSM was induced by emodin at 7 low contractile states, and an inhibitory effect was induced on CJSM at 7 high contractile states. Emodin-induced BR on myosin phosphorylation was also observed. BR was not observed in the presence of tetrodotoxin, suggesting that enteric nervous system is required for producing BR. The stimulatory effect of emodin on CJSM was abolished by atropine and diphenhydramine, respectively, suggesting that BR was correlated with cholinergic and histamine system while jejunal smooth muscle was at low contractile state. The inhibitory effect of emodin on CJSM was abolished by phentolamine, propranolol, and L-NG-nitroarginine (L-NNA), respectively, suggesting that BR was related to adrenergic hyperactivity and with a nitric oxide relaxing mechanism while jejunal smooth muscle was in a high contractile state. The exact mechanism, however, needs further investigation.

The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine.

Anthraquinone stimulant cathartics, such as emodin, are believed to increase the rate of contraction of ileum tissue in vitro via multiple mechanisms. The aim of this study was to probe the effects of emodin on acetylcholine (ACh)-induced contraction of the rat isolated ileum preparation. 2 Ileal sections were incubated in Tyrode's solution and responses to methacholine, ACh and emodin obtained in the absence and presence of the muscarinic antagonist atropine and the choline uptake inhibitor hemicholinium (HC-3). Depletion of endogenous ACh in the presence of HC-3 was achieved by construction of an ACh dose-response curve, using exogenous ACh, prior to re-testing the effects of emodin in the presence of HC-3. 3 Emodin caused dose-dependent tissue contraction that was abolished by inclusion of atropine (1 microM) in the buffer. Atropine (1 microM) antagonized the response caused by methacholine. Incubation of tissues with HC-3 (1 and 10 microM) reduced the maximum response caused by emodin by 45% and 71% respectively, but had no effect on ACh-induced tissue contraction. These data suggest that, emodin causes contraction of the ileum by triggering the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation.

[Role of cyclin kinase inhibitor p27 in inhibition of emodin on mesangial cell proliferation induced by tumor necrosis factor-alpha].

OBJECTIVE: To investigate the role of p27 in the inhibition of emodin on the mesangial cell (MC) proliferation induced by tumor necrosis factor-alpha(TNF-alpha). METHODS: p27 protein of MC was detected with western blotting analysis. The degree of MC proliferation was estimated through [(3)H] thymidine ([(3)H] TdR) incorporation. Different dosage of emodin (50 mg/L,100 mg/L) was added into MC stimulated by TNF-alpha. RESULTS: TNF-alpha (200 kU/L) decreased p27 level of MC cultured in serum-free DMEM for 24 hours and increased[(3)H] TdR incorporation. Emodin increased p27 level of MC stimulated by TNF-alpha and decreased [(3)H] TdR incorporation. The more the emodin was added, the greater the above-mentioned effect of emodin. CONCLUSION: The increment of p27 level maybe play an important role in the inhibition of emodin on MC proliferation induced by TNF-alpha.