Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Gang Li,Zhenhua Wang,Honglun Wang,Xiaowei Zhou,Yanhao He,Chen Yuan,Jian Ouyang,Yingjie Han,Wenna Zhou,Yu Han

doi:10.3390/ijms222112009

Abstract

Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways.

Highlights

Inflammation involves a series of abnormal pathological reactions in the body caused by the invasion of pathogenic microorganisms
We investigated the potential role of Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) (Figure 1) on inflammation induced by LPS in RAW264.7 cells
We found that OA, AA, and MA had small structural differences, but each compound had a certain extent of anti-inflammatory activity and could reduce inflammation

Summary

Introduction

Inflammation involves a series of abnormal pathological reactions in the body caused by the invasion of pathogenic microorganisms. The entire process is strictly regulated by inflammation-related signaling molecules, which are closely associated with the occurrence, maintenance, and regression of inflammation [1]. Screening anti-inflammatory compounds based on signaling molecules involved in the inflammation signaling pathways is an important approach. Nonsteroidal and steroidal anti-inflammatory drugs are commonly used in clinical practice. Long-term and frequent use may lead to adverse reactions. Natural medicines have the advantages of availability from a wide range of sources, low cost, and few side effects. The anti-inflammatory effect of some natural medicines has been recognized by increasing research [2]

Methods

Discussion

Conclusion