Kaempferol Inhibits P. intermedia Lipopolysaccharide‐Induced Production of Nitric Oxide Through Translational Regulation in Murine Macrophages: Critical Role of Heme Oxygenase‐1‐Mediated ROS Reduction

Abstract

Background: Nitric oxide (NO) could be a potential target for the development of new therapeutic approaches to the treatment of periodontal disease because this molecule plays a significant role in the tissue destruction observed in periodontitis. In this study, the authors investigate the effect of kaempferol on the production of NO by murine macrophage‐like RAW264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease, and try to determine the underlying mechanisms of action.Methods: NO production was assayed by measuring the accumulation of nitrite in culture supernatants. Real‐time polymerase chain reaction was performed to quantify inducible NO synthase (iNOS) and heme oxygenase‐1 (HO‐1) mRNA expression. iNOS and HO‐1 protein expression and phosphorylation of c‐Jun N‐terminal kinase and p38 were characterized via immunoblot analysis. Reactive oxygen species (ROS) production was measured using the redox‐sensitive fluorescent probe 2′,7′‐dichlorodihydrofluorescein diacetate.Results: Kaempferol significantly inhibited NO production and expression of iNOS protein in P. intermedia LPS‐stimulated RAW246.7 cells without affecting iNOS mRNA expression. Kaempferol upregulated HO‐1 expression in LPS‐activated cells. Inhibition of HO‐1 activity by tin protoporphyrin IX (SnPP) abolished the suppressive effect of kaempferol on NO production. In addition, kaempferol significantly attenuated P. intermedia LPS‐induced increase of intracellular ROS, and SnPP blocked this reduction. Treatment with antioxidants downregulated the production of LPS‐induced NO.Conclusions: Kaempferol inhibits NO production and iNOS protein expression in P. intermedia LPS‐stimulated RAW264.7 cells at the translational level via HO‐1‐mediated ROS reduction and could be an efficient modulator of host response in the treatment of periodontal disease.

Effect of Tanshinone IIA in an In Vitro Model of Graves' Orbitopathy

“…occurred together with ROS reduction. This is consistent with the finding that induction of HO-1 by isorhamnetin, a 3 0 -Omethylated metabolite of quercetin, 40 flavonoid kaempferol, 41 and curcumin, an anti-inflammatory agent extracted from Curcuma longae, 42 leads to a reduction in ROS production in RAW 264.7 cells. Curcumin also was found to reduce ROS levels by upregulating HO-1 expression in human retinal pigment epithelial cells.…”

Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

“…Then, an integrated in silico approach was applied to decipher the 42 targets for these active ingredients related to BSS including 27 common targets, which distinctly explained the action modes and biological processes that active ingredients achieve their synergistic and complementary curative effects. It is worth mentioning that the results from several compound-target interaction experiments by us and other groups indicated the reasonability of our integrated in silico approach4546474849505173. Subsequently, 20 signaling pathways associated with BSS treatment and prophylaxis by Danggui-Honghua were retrieved.…”

“…For example, in animal models, increased expression of HMOX1 has been shown to protect tissues and cells against ischemia-reperfusion injury, oxidative stress, inflammation and hypoxia-induced vascular stasis47. The protein HMOX1 was found to have interactions with 9 ingredients, and senkyunolide A, kaempferol and eriodictyol synergistically increase HMOX1 expression484950. In addition, the neurotoxic proinflammatory mediator PTGS2 was also connected with several active ingredients.…”

The influenc of hydrolyzed and non-hydrolyzed linden inflorescence (<i>Tilia cordata</i>) extract on metabolic and transcriptomic profile in rat liver

“…Liu et al (2012) have suggested that quercetin attenuates ethanol-induced oxidative stress through a pathway which HO-1 upregulation. The second most abundant active substance in linden inflorescence, namely kaempferol, inhibits nitric oxide production and nitric oxide synthase protein expression via HO-1-mediated ROS reduction in murine macrophages (Choi et al, 2012). Although in our study the administration of hydrolyzed and non-hydrolyzed linden extract did not influenced the HO-1 gene expression we were able to identify the 18 genes which were expression targets of HO-1 (Table 4).…”