Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Participate in Anti-inflammatory Activity of Imperatorin from Glehnia littoralis

Abstract

In this study, we have investigated the anti-inflammatory effects of imperatorin, a compound isolated from the roots of Glehnia littoralis, using a lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) in vitro and a carrageenan (Carr)-induced mouse paw edema model in vivo. When RAW264.7 macrophages were treated with imperatorin together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that imperatorin blocked the protein expression of iNOS and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages significantly. In the anti-inflammatory test, imperatorin decreased the paw edema at 4 and 5 h after Carr administration and increased the activities of catalase, superoxide dismutase, and glutathione peroxidase in paw edema. We also demonstrated that imperatorin significantly attenuated the malondialdehyde level in the edema paw at the fifth hour after Carr injection. Imperatorin decreased the NO and tumor necrosis factor and prostaglandin E2 levels on serum at 5 h after Carr injection. Western blotting revealed that imperatorin decreased Carr-induced iNOS and COX-2 expressions at 5 h in edema paw. An intraperitoneal injection treatment with imperatorin also diminished neutrophil infiltration into sites of inflammation as did indomethacin. The results suggested that imperatorin had anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and Carr-injected mice, respectively. In addition, inhibition of elevated iNOS and COX-2 protein expression as well as neutrophil infiltration of Carr-injected paws may be involved in the beneficial effects of imperatorin.

Preventive effect of Imperatorin on acute lung injury induced by lipopolysaccharide in mice

“…In our experiment, we used LPS intranasal instillation to develop an ALI model. The in vitro anti-inflammatory effect of Imperatorin has been reported [14]. To the best of our knowledge, this study is the first to investigate the effects of Imperatorin on LPS-induced ALI in mice.…”

“…It has been reported that Imperatorin can prevent cardiac hypertrophy, inhibit periplasmic copper, zinc super oxide dismutase of Shigella dysenteriae and depress vasoconstriction [8,12,13]. Previous studies have reported that Imperatorin can decrease the protein expression of iNOS and cyclooxygenase-2 in both LPS-stimulated RAW 264.7 cells and Carr-injected mice [14]. However, there is a little information on whether Imperatorin protects against LPS-induced ALI.…”

New coumarins from the roots of Angelica dahurica var. formosana cv. Chuanbaizhi and their inhibition on NO production in LPS-activated RAW264.7 cells

“…Among them, coumarins were considered as the dominant chemical constituents. It was reported that coumarins possessed various pharmacological effects, such as imperatorin, which had the antihypertensive, antioxidant [5], anti-inflammatory [6], anti-cancer [7], anticonvulsant [8], vasodilatation [9], and anti-HIV-1 [10] activities, and the prevention on lipopolysaccharide (LPS)-induced acute lung injury [11], cerebral ischemia [12], cardiac hypertrophy and heart failure [13]. Isoimperatorin was found to have the anti-Mycobacterium tuberculosis [14] and anti-inflammatory [15] activities, as well as prevention on aflatoxin B 1 -inducible cytotoxicity [16].…”

“…Insert Table 3 Previous study on compound 4 suggested that it had anti-inflammatory effects in LPS-activated RAW264.7 cells via inhibition of elevated iNOS [6]. In order to elucidate the mechanism of compounds 2, 5-8 on inhibiting NO production in LPS-activated RAW264.7 cells, the expression level of the iNOS mRNA was detected by RT-PCR analysis.…”

The Optimum Extraction Process for Radix glycyrrhizae and Angelica dahurica (Fisch.) Benth.et Hook with Orthogonal Design

“…The combination extract taken liquiritin and imperatorin as representatives from Radix glycyrrhizae and Angelica dahurica (Fisch.) Benth.et Hook, which showed significant activity of anti-inflammatory and analgesic, 14,15,16 played an important role in the Fengshiding dropping pill. Furthermore, recent studies have indicated that the extraction of salicin 17,18,19 from Alangium chinense has the antinociceptive and anti-inflammatory activity, and steam distillation of paeonol 20,21,22 from Cynanchum paniculatum has suppressed swelling, inflammatory reaction and cell impairment.…”