Plasma metabolomic profiling to reveal antipyretic mechanism of Shuang-huang-lian injection on yeast-induced pyrexia rats - PubMed (original) (raw)

Plasma metabolomic profiling to reveal antipyretic mechanism of Shuang-huang-lian injection on yeast-induced pyrexia rats

Xiaoyan Gao et al. PLoS One. 2014.

Abstract

Shuang-huang-lian injection (SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. The existing randomized controlled trial (RCT) studies suggested that SHLI could afford a certain anti-febrile action. However, seldom does research concern the pharmacological mechanisms of SHLI. In the current study, we explored plasma metabolomic profiling technique and selected potential metabolic markers to reveal the antipyretic mechanism of SHLI on yeast-induced pyrexia rat model using UPLC-Q-TOF/MS coupled with multivariate statistical analysis and pattern recognition techniques. We discovered a significant perturbance of metabolic profile in the plasma of fever rats and obvious reversion in SHLI-administered rats. Eight potential biomarkers, i.e. 1) 3-hydeoxybutyric acid, 2) leucine, 3) 16:0 LPC, 4) allocholic acid, 5) vitamin B2, 6) Cys-Lys-His, 7) 18:2 LPC, and 8) 3-hydroxychola-7, 22-dien-24-oic acid, were screened out by OPLS-DA approach. Five potential perturbed metabolic pathways, i.e. 1) valine, leucine, and isoleucine biosynthesis, 2) glycerophospholipid metabolism, 3) ketone bodies synthesis and degradation, 4) bile acid biosynthesis, and 5) riboflavin metabolism, were revealed to relate to the antipyretic mechanisms of SHLI. Overall, we investigated antipyretic mechanisms of SHLI at metabolomic level for the first time, and the obtained results highlights the necessity of adopting metabolomics as a reliable tool for understanding the holism and synergism of Chinese patent drug.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors declared that they have no competing interests. Though Xu Bai and Yingxin Wang, the co-authors, were from a company, they definitely did not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. The changing trend of rectal temperatures in NC, M and SHLI treatment group.

Data was expressed as mean ± SD. ### P<0.001 vs., NC group; **P<0.01 vs., M group.

Figure 2

Figure 2. Typical base peak intensity (BPI) chromatograms ofplasma samples from each groups.

(A) NC at positive ion mode. (B) M at positive ion mode (C) SHLI treatment at positive mode (Blue arrows show drug induced components).

Figure 3

Figure 3. The results of multiple pattern recognition of plasma metabolites (PCA scores).

(A) At positive ion mode. (B) At negative ion mode. Note: NC (▴), M (•) and SHLI (▪).

Figure 4

Figure 4. The results of S-plots of OPLS-DA models.

(A) At positive ion mode. (B) At negative ion mode. Note: NC (▴), M (•) and SHLI (▪).

Figure 5

Figure 5. The results of relative integral levels of metabolites among NC, M and SHLI treatment groups.

(A) At positive ion mode. (B) At negative ion mode. a P<0.05 or P<0.01 among NC, M, and SHLI treatment group.

Figure 6

Figure 6. Summary of pathway analysis with MetPA.

Note: 1. Valine, leucine and isoleucine biosynthesis. 2. Glycerophospholipid metabolism. 3. Synthesis and degradation of ketone bodies. 4. Riboflavin metabolism. 5. Butanoate metabolism. 6. Valine, leucine and isoleucine degradation. 7. Aminoacyl-tRNA biosynthesis.

Figure 7

Figure 7. The profile of metabolic network.

The map was gained by analyzing the known metabolic pathways.

References

    1. Glossary of terms for thermal physiology. Second edition. Revised by The Commission for Thermal Physiology of the International Union of Physiological Sciences (IUPS Thermal Commission). Pflugers Arch 410: 567–587. - PubMed
    1. Polderman KH (2008) Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 371: 1955–1969. - PubMed
    1. Duncker DJ, Klassen CL, Ishibashi Y, Herrlinger SH, Pavek TJ, et al. (1996) Effect of temperature on myocardial infarction in swine. Am J Physiol 270: H1189–1199. - PubMed
    1. Rice P, Martin E, He JR, Frank M, DeTolla L, et al. (2005) Febrile-range hyperthermia augments neutrophil accumulation and enhances lung injury in experimental gram-negative bacterial pneumonia. J Immunol 174: 3676–3685. - PubMed
    1. Launey Y, Nesseler N, Malledant Y, Seguin P (2011) Clinical review: fever in septic ICU patients–friend or foe? Crit Care 15: 222. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources