Limits...
Pathway as a pharmacological target for herbal medicines: an investigation from reduning injection.

Liu J, Sun K, Zheng C, Chen X, Zhang W, Wang Z, Shar PA, Xiao W, Wang Y - PLoS ONE (2015)

Bottom Line: The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated.More importantly, our predicted results were also experimentally validated.Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China.

ABSTRACT
As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.

No MeSH data available.


Effects of RDN on LPS-induced MAPKs activation in RAW 264.7 cells.Cells were pretreated with control solution or RDN for 2 h, followed by incubation with or without LPS (1 μg/ml) for a fixed time. Phosphorylated ERK1/2, p38 and JUK as well as non-phosphorylated proteins were detected after being incubated for 30 min (A). And after 18 h, the proteins of ERK1/2 and c-Jun regardless of phosphorylated or not were also examined (B). And (C) depicts the putative modulation pathways that respond to RDN therapeutic molecular mechanisms in LPS-stimulated RAW 264.6 cells, where blue downward arrows and red upward arrows represent decreased and increased tendency of a target respectively.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4382287&req=5

pone.0123109.g007: Effects of RDN on LPS-induced MAPKs activation in RAW 264.7 cells.Cells were pretreated with control solution or RDN for 2 h, followed by incubation with or without LPS (1 μg/ml) for a fixed time. Phosphorylated ERK1/2, p38 and JUK as well as non-phosphorylated proteins were detected after being incubated for 30 min (A). And after 18 h, the proteins of ERK1/2 and c-Jun regardless of phosphorylated or not were also examined (B). And (C) depicts the putative modulation pathways that respond to RDN therapeutic molecular mechanisms in LPS-stimulated RAW 264.6 cells, where blue downward arrows and red upward arrows represent decreased and increased tendency of a target respectively.

Mentions: As shown in Fig 7A, stimulated with LPS for 30 min results in a significant increasing in the amount of phosphorylation of JNK, p38 and ERK1/2 compared with the control group. No changes in the total ERK, JNK and p38 kinase were observed in RAW 264.7 cells when treated with LPS or LPS and RDN for 30 min. The LPS-induced increasing of the activated form of JNK in RAW 264.7 cells was reduced in a dose-dependent manner by addition of gradient concentration of RDN. On the contrary, the activation of p38 MAP kinase was significantly increased in RAW 264.7 cells after being incubated with LPS and RDN, but the production of TNF-α was unchanged (data are not shown) and the mRNA of IL-1β and IL-6 were markedly decreased compared with LPS stimulated cells (Fig 5B and 5C), which is in coincidence with a previous report [27]. For the increased activation of ERK1/2 after being incubated with LPS and RDN for 30 min, it may enhance the cell-mediated immunity to remove foreign substances which give rise to inflammation in the early stages. Interestingly, in a dosage-dependent manner, total protein expression levels of ERK1/2 and c-Jun were decreased in cells after treated with RDN for 18 h (Fig 7B). The regulation action of RDN in LPS-stimulated RAW 264.7 cells may be associated with the earlier and persistent effects.


Pathway as a pharmacological target for herbal medicines: an investigation from reduning injection.

Liu J, Sun K, Zheng C, Chen X, Zhang W, Wang Z, Shar PA, Xiao W, Wang Y - PLoS ONE (2015)

Effects of RDN on LPS-induced MAPKs activation in RAW 264.7 cells.Cells were pretreated with control solution or RDN for 2 h, followed by incubation with or without LPS (1 μg/ml) for a fixed time. Phosphorylated ERK1/2, p38 and JUK as well as non-phosphorylated proteins were detected after being incubated for 30 min (A). And after 18 h, the proteins of ERK1/2 and c-Jun regardless of phosphorylated or not were also examined (B). And (C) depicts the putative modulation pathways that respond to RDN therapeutic molecular mechanisms in LPS-stimulated RAW 264.6 cells, where blue downward arrows and red upward arrows represent decreased and increased tendency of a target respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4382287&req=5

pone.0123109.g007: Effects of RDN on LPS-induced MAPKs activation in RAW 264.7 cells.Cells were pretreated with control solution or RDN for 2 h, followed by incubation with or without LPS (1 μg/ml) for a fixed time. Phosphorylated ERK1/2, p38 and JUK as well as non-phosphorylated proteins were detected after being incubated for 30 min (A). And after 18 h, the proteins of ERK1/2 and c-Jun regardless of phosphorylated or not were also examined (B). And (C) depicts the putative modulation pathways that respond to RDN therapeutic molecular mechanisms in LPS-stimulated RAW 264.6 cells, where blue downward arrows and red upward arrows represent decreased and increased tendency of a target respectively.
Mentions: As shown in Fig 7A, stimulated with LPS for 30 min results in a significant increasing in the amount of phosphorylation of JNK, p38 and ERK1/2 compared with the control group. No changes in the total ERK, JNK and p38 kinase were observed in RAW 264.7 cells when treated with LPS or LPS and RDN for 30 min. The LPS-induced increasing of the activated form of JNK in RAW 264.7 cells was reduced in a dose-dependent manner by addition of gradient concentration of RDN. On the contrary, the activation of p38 MAP kinase was significantly increased in RAW 264.7 cells after being incubated with LPS and RDN, but the production of TNF-α was unchanged (data are not shown) and the mRNA of IL-1β and IL-6 were markedly decreased compared with LPS stimulated cells (Fig 5B and 5C), which is in coincidence with a previous report [27]. For the increased activation of ERK1/2 after being incubated with LPS and RDN for 30 min, it may enhance the cell-mediated immunity to remove foreign substances which give rise to inflammation in the early stages. Interestingly, in a dosage-dependent manner, total protein expression levels of ERK1/2 and c-Jun were decreased in cells after treated with RDN for 18 h (Fig 7B). The regulation action of RDN in LPS-stimulated RAW 264.7 cells may be associated with the earlier and persistent effects.

Bottom Line: The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated.More importantly, our predicted results were also experimentally validated.Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China.

ABSTRACT
As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.

No MeSH data available.