Application of GC/MS-Based Metabonomic Profiling in Studying the Therapeutic Effects of Aconitum carmichaeli with Ampelopsis japonica Extract on Collagen-Induced Arthritis in Rats.

Hua Jin,Lili Song,Xin Li,Ningning Ma,Maojuan Guo,Mingqin Kang

doi:10.3390/molecules24101934

Abstract

Aconitum carmichaeli with Ampelopsis japonica (AA) is a classical traditional Chinese medicine (TCM) formula. There are a lot of examples showing that AA can be used to treat rheumatoid arthritis, but its mechanism of action is still not completely clear. In this research, collagen-induced arthritis (CIA) was chosen as a rheumatoid arthritis (RA) model. Rats of treated groups were continuously administered Aconitum carmichaeli (AC), Ampelopsis japonica (AJ) and Aconitum carmichaeli + Ampelopsis japonica (AA) orally once a day from the day after the onset of arthritis (day 7) until day 42. The results showed that AA not only significantly reduced paw swelling, but also improved the levels of TNF-α and IL-6 in serum. GC-MS-based urine metabonomics was established to analysis metabolic profiles and 21 biomarkers of RA rats were identified by the Partial Least Squares Discriminant Analysis (PLS-DA) and Support Vector Machine (SVM) methods. The prediction rate of the SVM method for the 21 biomarkers was 100%. Twenty of 21 biomarkers, including D-galactose, inositol and glycerol, gradually returned to normal levels after administration of AA. Metabolomic Pathway Analysis (MetPA) generated three related metabolic pathways—galactose metabolism, glycerolipid metabolism and inositol phosphate metabolism—which explain the mechanism of AA treatment of rheumatoid arthritis. This research provides a better understanding of the therapeutic effects and possible therapeutic mechanism of action of a complex TCM (AA) on rheumatoid arthritis.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of people worldwide [1]
Studies have shown that liver X receptor can be oxidized by lipid molecules, such as fatty acid oxidation products and metabolites of arachidonic acid [41]. These potential activators derive from unsaturated fatty acids, cholesterol and its metabolites in some basic metabolic processes, especially triglycerides, as the balance of triglycerides in the body and the conversion between glycerol esters and fatty acids have a great relationship. These results suggest that the reason glycerol is increased in the RA inflammatory group is the destroyed mutual transformation between glycerol and fatty acids, leading to lipid metabolism disorders, reducing the liver X receptor expression, whereas Ampelopsis japonica (AA) can reduce the content of glycerol, rebalancing the fatty acid glycerides and mutual transformation balance, and causing liver X receptor upregulation in order which results in an anti-inflammatory effect
The GC-MS technique was used to explore the metabonomic effects of AA extract on collagen-induced arthritis in rats

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of people worldwide [1]. Environmental factors, such as smoking, and genetic factors are the causes of rheumatoid arthritis. The genetic factors are reported to be the main cause of rheumatoid arthritis, accounting for 50% [2]. The joints of RA patients are swollen and gradually become stiff, affecting the action and causing inconvenience [6]. With the gradual development of modern medicine, treatments for RA have been studied [7]. A more effective treatment of RA is still an urgent necessity for modern medicine [8,9]

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