Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-κB Pathway.

Seung A Kim,Haeyeop Kim,Chae Young Lee,Jin Kyoung Noh,Yong Deog Hong,Jae Youl Cho,Han Gyung Kim,Byoung Young Woo,Ankita Mitra,Dong-Keun Yi

doi:10.3390/plants10112335

Abstract

There is a growing need to develop anti-inflammatory drugs to regulate inflammatory responses. An extract of Huberia peruviana Cogn. had the best inhibitory effect on nitric oxide (NO) production in screening process undertaken in our laboratory. However, the anti-inflammatory effect of Huberia peruviana Cogn. methanol extract (Hp-ME) has not been studied. In this study, the anti-inflammatory effect of Hp-ME was assessed by using an NO assay, RT-PCR, luciferase reporter gene activity assay, western blotting assay, HCl/EtOH-induced acute gastritis model, and LPS-induced acute lung injury model. The phytochemical components of Hp-ME were determined through LC-MS/MS analysis. When RAW264.7 and HEK293T cells were treated with Hp-ME, NO production was decreased dose-dependently without cytotoxicity and the mRNA levels of iNOS, COX-2, and TNF-α were decreased. In a luciferase assay, the activity of transcription factors, NF-κB in TRIF or MyD88-overexpressing HEK293T cells was extremely reduced by Hp-ME. The western blotting analysis indicated that Hp-ME has anti-inflammatory effects by inhibiting the phosphorylation of Src. Hp-ME showed anti-inflammatory effects on in vivo models of HCl/EtOH-induced gastritis and LPS-induced acute lung injury. LC-MS/MS revealed that Hp-ME contains several anti-inflammatory flavonoids. The final findings of this study imply that Hp-ME could be used as an anti-inflammatory drug in several inflammatory diseases.

Highlights

The inflammatory response in humans is a part of the innate immune system
The cell viability was not decreased below 90% (even when RAW264.7 cells were treated with Huberia peruviana Cogn. methanol extract (Hp-ME) for 24 h (Figure 1b))
Compared with the normal group, the wet-to-dry weight increased about 1.2 times in the group with acute lung injury (ALI) induced by LPS

Summary

Introduction

The inflammatory response in humans is a part of the innate immune system. When body tissue senses exogenous and endogenous danger signals such as bacteria, fungi, viruses, etc., inflammation is initiated [1]. Innate immunity initiates the activation of macrophages and dendritic cells to manage an immune response against pathogens and to act as an effective line of defense in humans, especially in the early stage of infection [4,5]. Adaptor molecules can deliver signals by sequentially activating the kinase factors protooncogene tyrosine-protein kinase Src, IκB kinase α/β (IKKα/β), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), extracellular-signalregulated kinase (ERK), and c-Jun N-terminal kinase (JNK) When these signals are delivered to the transcription factors, activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) are present in the nucleus, and inflammation-related cytokines and enzymes are expressed [10]. A study for the control of excessive inflammatory reactions would be useful

Results

Discussion

Conclusion