Objective To analyze the endogenous metabolic biomarkers and pathways in serum involving acupuncture-induced improvement of symptoms of patients with rheumatoid arthritis(RA) by using metabolomics technique.Methods A total of 30 RA patients who were treated in the Department of Acupuncture and Moxibustion of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine(from January 2018 to October 2018) were selected in the present study. They were randomly and equally divided into acupuncture group and medication group. Acupuncture(lifting-thrusting reinforcing and uniform reducing-reinforcing methods) was applied to bilateral Fengchi(GB20)

Yangchi(TE4)

Quchi(LI11)

Yingu(KI10)

Taixi(KI3)

Xuehai(SP10)

Guanyuan(CV4)

Yanglingquan(GB34) and Ashi-points for 20 min every time

once daily for 3 months. Patients of the medication group were asked to take Tripterygium Wilfordii Polyglycoside tablets(a positive drug for RA

one tablet per time

3 times a day) for 3 months. Other 10 healthy volunteers were selected as the normal control group. The tenderness scale(0-4 points) and swelling scale(0-3 points) and morning stiffness time were recorded

and serum rheumatoid factor(RF)

C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR) were detected for analyzing pharmacodynamic effects. Serum samples were captured for profiling and quantifying metabolite biomarkers by using GC-MS(gas chromatography-mass spectrometry) technique. The acquired metabolite profiles were processed(multivariable data analysis) by using ProteoWizard package

XCMS Online software and SIMCA 13.0 software

respectively

followed by screening differential metabolites according to variable importance projection(VIP) and by constructing metabolic pathways with MetaboAnalyst 4.0.Results After acupuncture treatment

the tenderness score

swelling score

morning stiffness time

serum RF and CRP contents were significantly decreased in both acupuncture and medication groups in comparison with their own pretreatment(P<0.05). No significant differences were found between acupuncture and medication groups in the levels of tenderness score

swelling score

morning stiffness time

serum RF and CRP contents(P>0.05). A total of 14 differential metabolites including citrate

creatine

3-hydroxybutyrate arachidonic acid

arachidonic acid

valine

lactic acid and palmitic acid(up-regulated)

and tryptophan

arginine

L-phenylalanine

glucose

glycine

glutamine

aspartic acid and(down-regulated) which mainly involve metabolic pathways of alanine

aspartic acid and glutamate; metabolism of phenylalanine

tyrosine and tryptophan; metabolism of glycine

serine and threonine; glyoxalic acid dicarboxylic acid metabolism; metabolism of starch and sucrose; and metabolism of phenylalanine and arachidonic acid

respectively.Citrate

creatine

arachidonic acid

valine and glucose was positively correlated with tenderness index

swelling index

morning stiff time

RF

CRF and ESR. Glycine

L-phenylalanine

glutamine was negatively correlated with efficacy indicators.Conclusion Acupuncture can relieve symptoms of patients with RA

which may be related to its effects in improving amino acid metabolism and glucose metabolism.