Preventive effect of Imperatorin on acute lung injury induced by lipopolysaccharide in mice.
ABSTRACT Imperatorin, a linear furanocoumarin, has many pharmacological effects such as antibacterial, anti-inflammatory and antiviral effects. The purpose of this study was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1h before LPS challenge. We found that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level of interleukin-10 (IL-10) was up-regulated 8h after Imperatorin treatment. Pretreatment with Imperatorin (15 or 30mg/kg) decreased lung wet-to-dry weight (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO) activities. Additionally, Imperatorin attenuated lung histopathological changes and significantly inhibited the phosphorylation of IκB, JNK, ERK and p38/MAPK. These findings demonstrate that Imperatorin protects against LPS-induced ALI in mice.
- [Show abstract] [Hide abstract]
ABSTRACT: OW1 is a novel imperatorin derivative that exhibits vasodilative activity. In the present study the antihypertensive effect and inhibition effect on vascular remodeling of OW1 were investigated in 2K1C renovascular hypertensive rats. OW1-induced vasodilatation in rat mesenteric arteries and renal arteries was evaluated in vitro. 2K1C renovascular hypertensive rats were developed and treated with OW1 (40 and 80 mg/kg/day) for 8 weeks. Blood pressure of rats was measured in conscious. Concentration of microalbumin (mALB) and total protein (U-TP) of urine and the levels of angiotensin II (Ang II), calcitonin gene-related peptide (CGRP), and angiotensin-converting enzyme 1 (ACE) of plasma were detected. The unclipped kidney was stained with hematoxylin and eosin (H&E) and Masson trichrome. The sectioned aortas were stained with Masson trichrome. Immunohistochemical analysis was used to quantify the collagen I and III. OW1 relaxed the rat mesenteric and renal arterial rings in vitro. Treatment of 2K1C hypertensive rats with OW1 (40 and 80 mg/kg/day) for 8 weeks significantly decreased blood pressure Besides, OW1 reduced the Ang II and ACE concentration and raised the CGRP concentration in rat plasma. High doses of OW1 decreased the levels of blood urea nitrogen, mALB and U-TP. Histology results demonstrated that OW1 reduced renal arteriolar thickness and relieved the structural hypertrophic arteries. Moreover, OW1 caused an inhibition effect on vascular remodeling and renal lesions in hypertensive rats. In summary, the results suggested that OW1 could be a potential novel candidate for hypertension intervention.This article is protected by copyright. All rights reserved.Clinical and Experimental Pharmacology and Physiology 05/2014; · 2.41 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The 2-kidney, 1-clip (2K,1C) model of hypertension was used to investigate the potential antihypertensive and antioxidant effect of imperatorin extracted from the root of radix angelicae. After 10 weeks treatment of imperatorin, mean blood pressure (MBP) of 2K,1C hypertensive rats was obtained, and superoxide dismutase (SOD), nitric oxide (NO) and nitric oxide synthase (NOS) were measured. Malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CATA), xanthine oxidase (XOD), angiotensinII (Ang II) and endothelin (ET) levels of kidney were evaluated with commercial kits. Nicotinamide adenine dinucleotidephosphate (NADPH) oxidase subunits of the renal cortial tissues were determined by RT-PCR and Western blot. 8-Iso-prostaglandin F2α (8-iso-PGF2α) of 24h urinary excretion was also measured by ELISA. MBP was significantly reduced by treatment with IMP (6.25, 12.5 and 25mg/kg/day, i.g.) in 2K,1C hypertensive rats. Meanwhile, we found that renal CATA and XOD activities, GSH levels, plasma NO and NOS contents were significantly increased in IMP-treated groups. Plasma ET, renal Ang II levels, MDA and the 24h urinary excretion of 8-iso-PGF2α in the IMP treated group were lower than control SD group. After that, we found the mRNA expressions and protein levels of NADPH oxidase subunits in the clipped kidney were markedly reduced after IMP treated in 2K,1C hypertensive rats. IMP showed antihypertensive and antioxidant effects in the renal injury of renovascular hypertensive rats, suggesting that IMP could be of therapeutic use in preventing renal injury related hypertension.Phytomedicine: international journal of phytotherapy and phytopharmacology 06/2013; · 2.97 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background Imperatorin (IMP) is an active furocoumarin in the traditional Chinese medicine Angelica Dahurica, and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of IMP on blood pressure (BP) and antioxidant effects in Spontaneously Hypertensive Rats (SHR) and HEK293 cells. Methods and Results SHR were administered IMP (6.25, 12.5 and 25 mg/kg/day) or tempol (18 mg/kg/day) daily by gavage for 12 weeks. Thiobarbituric acid-reactive substances (TBARS), proteinuria levels and superoxide dismutase (SOD) activity were evaluated with commercial kits. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits of the renal cortial tissues were determined by RT-PCR and Western blot. 24 h urinary 8-Iso-prostaglandin F2α (8-iso-PGF2α) was measured by ELISA. Systolic blood pressure and diastolic blood pressure were significantly reduced by treatment with IMP (6.25, 12.5 and 25 mg/kg/day) in SHR. Meanwhile, we found that renal cortical SOD activities were significantly increased in IMP-treated groups. Renal cortical and urinary TBARS levels, the 24 h urinary excretion of 8-iso-PGF2α and proteinuria in the IMP treated group were lower than SHR group. After that, we found the mRNA expressions and protein levels of NADPH oxidase subunits were markedly reduced after IMP treated in SHR. IMP also reduced the phosphorylation of Akt, ERK1/2, p38MAPK and JNK in renal cortical in SHR. In addition, H2O2-induced ROS production in HEK293 cells was markedly attenuated by IMP. H2O2-induced activation of MAPK, AKT and expression of NADPH oxidase were also attenuated by pretreatment of IMP. Conclusions In summary, IMP showed antihypertensive effect via preventing of renal injury not only by reducing NADPH oxidase but also by inhibiting of MAPK pathway.Journal of the American Society of Hypertension 08/2014; · 2.84 Impact Factor