Abstract
Inflammation is a complex protective response of body tissues to harmful stimuli. Acute inflammation can progress to chronic inflammation, which can lead to severe disease. Therefore, this research focuses on the development of anti-inflammatory drugs, and natural extracts have been explored as potential agents. No study has yet examined the inflammation-associated pharmacological activity of Potentilla glabra Var. mandshurica (Maxim.) Hand.-Mazz ethanol extract (Pg-EE). To examine the mechanisms by which Pg-EE exerts anti-inflammatory effects, we studied its activities in lipopolysaccharide (LPS)-treated murine macrophage RAW264.7 cells and an HCl/EtOH-induced gastritis model. LPS-triggered nitric oxide (NO) release and mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in RAW264.7 cells were suppressed by Pg-EE in a dose-dependent manner. Using a luciferase assay and western blot assay, we found that the NF-κB pathway was inhibited by Pg-EE, particularly by the decreased level of phosphorylated proteins of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunits (p65 and p50), inhibitor of kappa B alpha (IκBα), p85, and Src. Using an overexpression strategy, cellular thermal shift assay, and immunoprecipitation analysis, we determined that the anti-inflammatory effect of Pg-EE was mediated by the inhibition of Src. Pg-EE further showed anti-inflammatory effects in vivo in the HCl/EtOH-induced gastritis mouse model. In conclusion, Pg-EE exerts anti-inflammatory activities by targeting Src in the NF-κB pathway, and these results suggest that Pg-EE could be used as an anti-inflammatory herbal medicine.
Highlights
Inflammation is a type of immune response to stimuli such as a pathogen and injury [1,2]
Proteins were degraded as the temperature increased to 61 ◦C, but the degradation level in the Pg-EE-treated group was lower than that in the control group (Figure 4B). These results indicate that the binding of Pg-EE and Src leads to the increased thermostabilization of Src and confirms that Pg-EE binds with Src
Through the experiments presented in this paper, we have demonstrated that Pg-EE interacts with Src, and further immunoprecipitation inhibited the activation of p85 as a downstream protein of Src (Figure 4F)
Summary
Inflammation is a type of immune response to stimuli such as a pathogen and injury [1,2]. Various immune cells are involved in the inflammation response, and they try to remove the stimuli to relieve inflammatory symptoms, such as pain, redness, swelling, heat, and loss of function [3]. The immune system can be divided into two types: innate immunity and adaptive immunity. Innate immunity is a non-specific immune response and mostly occurs at early infection. Macrophages, epithelial cells, and natural killer cells are involved in this type of immunity [6]. The non-specific response of innate immunity involves the interaction of pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). PRRs are receptors that recognize PAMPs, which are present according to the type of pathogen [7]
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