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Background: Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect., Methods: After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined., Results: The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926., Conclusions: Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

Ethnopharmacological Relevance: Flos Chrysanthemi is used in a variety of diseases in traditional Chinese medicine including hypertension, and the total flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is known to modulate vascular functions and reduce the blood pressure. However, the active flavonoids and their synergistic effects on anti-hypertension are still unclear. To investigate the combined anti-hypertension effects of LUT and BUD enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti-hypertensive mechanism of LUT&BUD mixture., Materials and Methods: CODA Mouse & Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET, PGI2 and TXB2 were investigated by ELASA. Serum NO concentration was measured by the method of Nitric acid reductase., Results: A single administration of LUT, BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and 15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30 days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group, respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels of ANG, ALD and ET, but increased serum NO concentration., Conclusion: This study shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The effects of LBM on blood pressure are associated with RAAS and endothelial system. Thus, our experiments suggest that the combination of luteolin and buddleoside from Flos Chrysanthemi are potentially useful for the therapeutic treatments for hypertension., (© 2013 Elsevier Ireland Ltd. All rights reserved.)