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Material basis of Chinese herbal formulas explored by combining pharmacokinetics with network pharmacology.

Pei L, Bao Y, Liu S, Zheng J, Chen X - PLoS ONE (2013)

Bottom Line: However, the bioactive compounds that account for their therapeutic effects remain unclear.Up to 12 compounds were detected in the BZ decoction, but only 5 could be analyzed using PK parameters.Combined PK results, network pharmacology analysis revealed that 4 compounds might serve as the material basis for BZ.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

ABSTRACT
The clinical application of Traditional Chinese medicine (TCM), using several herbs in combination (called formulas), has a history of more than one thousand years. However, the bioactive compounds that account for their therapeutic effects remain unclear. We hypothesized that the material basis of a formula are those compounds with a high content in the decoction that are maintained at a certain level in the system circulation. Network pharmacology provides new methodological insights for complicated system studies. In this study, we propose combining pharmacokinetic (PK) analysis with network pharmacology to explore the material basis of TCM formulas as exemplified by the Bushen Zhuanggu formula (BZ) composed of Psoralea corylifolia L., Aconitum carmichaeli Debx., and Cnidium monnieri (L.) Cuss. A sensitive and credible liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the simultaneous determination of 15 compounds present in the three herbs. The concentrations of these compounds in the BZ decoction and in rat plasma after oral BZ administration were determined. Up to 12 compounds were detected in the BZ decoction, but only 5 could be analyzed using PK parameters. Combined PK results, network pharmacology analysis revealed that 4 compounds might serve as the material basis for BZ. We concluded that a sensitive, reliable, and suitable LC-MS/MS method for both the composition and pharmacokinetic study of BZ has been established. The combination of PK with network pharmacology might be a potent method for exploring the material basis of TCM formulas.

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Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.
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pone-0057414-g003: Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.

Mentions: Although 12 compounds were detected in D7, 4 (aconitine, hypaconitine, mesaconitine, and benzoylaconitine) were not detected in rat plasma after D7 administration. Of the other 8 compounds detected, only psoralen (157.80 µg/rat), isopsoralen (242.80 µg/rat), xanthotoxin (14.96 µg/rat), bergapten (25.44 µg/rat), and psoralidin (2.78 µg/rat) were measureable in rat plasma up to 10 h or 24 h after a single oral dosage. These compounds showed quite different plasma concentration–time curves (Figure 3). The AUC0–24 h for psoralen and isopsoralen (9977±5955 ng•h/mL and 20350±11537 ng•h/mL) were much higher than those of xanthotoxin and bergapten (162±64.7 and 143±73.2 ng•h/mL). Psoralidin was measurable in plasma, but the concentration was maintained at a relatively low level up to 24 h post-dose. The PK parameters are shown in Table 3. Psoralen, isopsoralen, xanthotoxin, and bergapten have comparable elimination half-lives (T1/2), about 3 h to 4 h, whereas psoralidin has a much longer T1/2 of about 24 h.


Material basis of Chinese herbal formulas explored by combining pharmacokinetics with network pharmacology.

Pei L, Bao Y, Liu S, Zheng J, Chen X - PLoS ONE (2013)

Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585395&req=5

pone-0057414-g003: Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.
Mentions: Although 12 compounds were detected in D7, 4 (aconitine, hypaconitine, mesaconitine, and benzoylaconitine) were not detected in rat plasma after D7 administration. Of the other 8 compounds detected, only psoralen (157.80 µg/rat), isopsoralen (242.80 µg/rat), xanthotoxin (14.96 µg/rat), bergapten (25.44 µg/rat), and psoralidin (2.78 µg/rat) were measureable in rat plasma up to 10 h or 24 h after a single oral dosage. These compounds showed quite different plasma concentration–time curves (Figure 3). The AUC0–24 h for psoralen and isopsoralen (9977±5955 ng•h/mL and 20350±11537 ng•h/mL) were much higher than those of xanthotoxin and bergapten (162±64.7 and 143±73.2 ng•h/mL). Psoralidin was measurable in plasma, but the concentration was maintained at a relatively low level up to 24 h post-dose. The PK parameters are shown in Table 3. Psoralen, isopsoralen, xanthotoxin, and bergapten have comparable elimination half-lives (T1/2), about 3 h to 4 h, whereas psoralidin has a much longer T1/2 of about 24 h.

Bottom Line: However, the bioactive compounds that account for their therapeutic effects remain unclear.Up to 12 compounds were detected in the BZ decoction, but only 5 could be analyzed using PK parameters.Combined PK results, network pharmacology analysis revealed that 4 compounds might serve as the material basis for BZ.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

ABSTRACT
The clinical application of Traditional Chinese medicine (TCM), using several herbs in combination (called formulas), has a history of more than one thousand years. However, the bioactive compounds that account for their therapeutic effects remain unclear. We hypothesized that the material basis of a formula are those compounds with a high content in the decoction that are maintained at a certain level in the system circulation. Network pharmacology provides new methodological insights for complicated system studies. In this study, we propose combining pharmacokinetic (PK) analysis with network pharmacology to explore the material basis of TCM formulas as exemplified by the Bushen Zhuanggu formula (BZ) composed of Psoralea corylifolia L., Aconitum carmichaeli Debx., and Cnidium monnieri (L.) Cuss. A sensitive and credible liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the simultaneous determination of 15 compounds present in the three herbs. The concentrations of these compounds in the BZ decoction and in rat plasma after oral BZ administration were determined. Up to 12 compounds were detected in the BZ decoction, but only 5 could be analyzed using PK parameters. Combined PK results, network pharmacology analysis revealed that 4 compounds might serve as the material basis for BZ. We concluded that a sensitive, reliable, and suitable LC-MS/MS method for both the composition and pharmacokinetic study of BZ has been established. The combination of PK with network pharmacology might be a potent method for exploring the material basis of TCM formulas.

Show MeSH