Anti-ulcer effect and potential mechanism of licoflavone by regulating inflammation mediators and amino acid metabolism.
BACKGROUND
Glycyrrhiza is the dry root and rhizome of the leguminous plant, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., which was firstly cited in Shennong's Herbal Classic in Han dynasty and was officially listed in the Chinese Pharmacopoeia, has been widely used in China during the past millennia. Licoflavone is the major component of Glycyrrhiza with anti-ulcer activity. The present study is based on clarifying the anti-ulcer effect of licoflavone, aiming at elucidating the possible molecule mechanisms of its action for treating gastric ulcer rats induced by acetic acid.


METHODS
Rats were divided into 7 groups, and drugs were administered from on the day after the onset of gastric ulcer (day 3) until day 11 of the experiment once daily continuously. The plasma were analyzed by high-performance liquid chromatography combined with time-of-flight mass spectrometry (HPLC/ESI-TOF-MS), significant different metabolites were investigated to explain its therapeutic mechanism. Furthermore, quantitative real time polymerase chain reaction (RT-PCR) analysis was performed to detect the expression of RNA in stomach tissue for verifying the above results.


RESULTS
Licoflavone can effectively cure the gastric ulcer, particularly the middle dose group. According to the statistical analysis of the plasma different metabolites from each groups and the expression of genes in tissues, sixteen significant different metabolites, including histamine, tryptophan, arachidonic acid, phingosine-1-phosphate etc., contributing to the treatment of gastric ulcer were discovered and identified. In RT-PCR analysis, the results of the expression of RNA were corresponded with what we discovered.


CONCLUSIONS
Our study indicated licoflavone plays the role of treating gastric ulcer by regulating inflammation mediators and amino acid metabolism. We demonstrated that metabolomics technology combined with gene technology is a useful tool to search different metabolites and to dissect the potential mechanisms of traditional Chinese medicine (TCM) in treating gastric ulcer.
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: yy741412697@163.com.
Yi
Y
Yang
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China; Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, China; Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, China; Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, PR China. Electronic address: christina8673028@126.com.
Shuai
S
Wang
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China; Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, China; Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, China; Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, PR China. Electronic address: byr1026@163.com.
Yong-Rui
YR
Bao
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China; Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, China; Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, China; Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, PR China. Electronic address: 1229130655@qq.com.
Tian-Jiao
TJ
Li
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: studiomx2006@126.com.
Guan-Lin
GL
Yang
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: cx19900312@163.com.
Xin
X
Chang
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China; Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, China; Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, China; Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, PR China. Electronic address: mxsvvv@163.com.
Xian-Sheng
XS
Meng
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D029882:Glycyrrhiza uralensis; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
D000596:Amino Acids; D000897:Anti-Ulcer Agents; D004365:Drugs, Chinese Herbal; D047309:Flavones; D018836:Inflammation Mediators
(+/-)14,15-EpETrE (PubChem CID: 5353279); Amino acid metabolism; Arachidonic acid (PubChem CID: 444899); Gastric ulcer; Glycoursodeoxycholic acid (PubChem CID: 12310288); Histidine (PubChem CID: 6274); Inflammation mediators; Licoflavone; Lysine (PubChem CID: 5962); Pantothenic Acid (PubChem CID: 6613); Pyruvic acid (PubChem CID: 1060); Sphingosine-1-phosphate (PubChem CID: 5283560); Stearic acid (PubChem CID: 5281); Tryptamine (PubChem CID: 1150)