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Network-based biomarkers for cold coagulation blood stasis syndrome and the therapeutic effects of shaofu zhuyu decoction in rats.

Su S, Duan J, Cui W, Shang E, Liu P, Bai G, Guo S, Qian D, Tang Y - Evid Based Complement Alternat Med (2013)

Bottom Line: Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05).The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions.In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China.

ABSTRACT
In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

No MeSH data available.


Related in: MedlinePlus

PLS-DA model results and loadings plots for the plasma and urine samples obtained from the normal, model, and treatment groups and analyzed in positive ion mode (Plasma: (a) 2-D plot and (b) 3-D plot; Urine: (c) 2-D plot and (d) 3-D plot).
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fig6: PLS-DA model results and loadings plots for the plasma and urine samples obtained from the normal, model, and treatment groups and analyzed in positive ion mode (Plasma: (a) 2-D plot and (b) 3-D plot; Urine: (c) 2-D plot and (d) 3-D plot).

Mentions: To more clearly characterize the effects of SFZYD on CCBS model rats, a PCA analysis was carried out to determine the changes before and after SFZYD treatment. The results revealed variations between the plasma and urine metabolic profiles of the model group, normal group, and SFZYD group (Figures 6(a), 6(b), 6(c), and 6(d)). To better understand the time-dependent effect of SFZYD, a PCA model was constructed to analyze all the data acquired from the normal group, predose group and treatment group at days 1, 3, 5, 7, and 10 in both positive and negative ion modes (Figures 7(a) and 7(b)). The spot observed in the treatment group at days 1–5 is close to that of the model group, indicating that the cold coagulation and blood stasis syndrome state is dominant. The spots observed in the treatment group at day 7 clustered near the center of the plot with a shift back toward the normal group, which might be an indication of the accumulated effect of SFZYD. The spot observed in the treatment group at days 8 and 10 ultimately approached the normal state, suggesting that SFZYD treatment had a positive therapeutic effect on the rats. Furthermore, the relative concentrations of 6 endogenous metabolites in the plasma and 5 endogenous metabolites in the urine were significantly affected by SFZYD (P < 0.05). All of these metabolites returned to normal levels after SFZYD treatment (Figures 8(a) and 8(b)). Thus, the efficient regulation of these potential biomarkers may account for the effects of SFZYD in model rats.


Network-based biomarkers for cold coagulation blood stasis syndrome and the therapeutic effects of shaofu zhuyu decoction in rats.

Su S, Duan J, Cui W, Shang E, Liu P, Bai G, Guo S, Qian D, Tang Y - Evid Based Complement Alternat Med (2013)

PLS-DA model results and loadings plots for the plasma and urine samples obtained from the normal, model, and treatment groups and analyzed in positive ion mode (Plasma: (a) 2-D plot and (b) 3-D plot; Urine: (c) 2-D plot and (d) 3-D plot).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818846&req=5

fig6: PLS-DA model results and loadings plots for the plasma and urine samples obtained from the normal, model, and treatment groups and analyzed in positive ion mode (Plasma: (a) 2-D plot and (b) 3-D plot; Urine: (c) 2-D plot and (d) 3-D plot).
Mentions: To more clearly characterize the effects of SFZYD on CCBS model rats, a PCA analysis was carried out to determine the changes before and after SFZYD treatment. The results revealed variations between the plasma and urine metabolic profiles of the model group, normal group, and SFZYD group (Figures 6(a), 6(b), 6(c), and 6(d)). To better understand the time-dependent effect of SFZYD, a PCA model was constructed to analyze all the data acquired from the normal group, predose group and treatment group at days 1, 3, 5, 7, and 10 in both positive and negative ion modes (Figures 7(a) and 7(b)). The spot observed in the treatment group at days 1–5 is close to that of the model group, indicating that the cold coagulation and blood stasis syndrome state is dominant. The spots observed in the treatment group at day 7 clustered near the center of the plot with a shift back toward the normal group, which might be an indication of the accumulated effect of SFZYD. The spot observed in the treatment group at days 8 and 10 ultimately approached the normal state, suggesting that SFZYD treatment had a positive therapeutic effect on the rats. Furthermore, the relative concentrations of 6 endogenous metabolites in the plasma and 5 endogenous metabolites in the urine were significantly affected by SFZYD (P < 0.05). All of these metabolites returned to normal levels after SFZYD treatment (Figures 8(a) and 8(b)). Thus, the efficient regulation of these potential biomarkers may account for the effects of SFZYD in model rats.

Bottom Line: Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05).The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions.In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China.

ABSTRACT
In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

No MeSH data available.


Related in: MedlinePlus