Last time, we shared the article about blood, from Huanglian Jiedu Tang to the root of Huangqi, and then to find an effective ingredient baicalein in the root of Astragalus. Classical compound drug research ideas. Not doing it well. The article of 2005 can be understood.
Today's article shared with you, Rosmarinic acid and baicalin epigenetically de-repress Pparγ in hepatic stellate cells for their anti-fibrotic effect. 2012. Hepatology.
The compound to be made is Yang-Gan-Wan (YGW), and the disease is liver fibrosis. Let's take a look at this article.
Fig.1 YGW prevents and reverses hepatic stellate cell (HSC) activation in culture.
When YGW aqueous extract was added to rat HSC cells, it was found to prevent the activation of HSC. Efficacy evaluation: cell experiment - cell phenotype . Several molecular markers α1collagen, alpha-SMA, and TGF-β1 were detected, which are classical indicators of fibrosis. (Evaluation of efficacy: cell experiment - molecular indicators) . PPARγ, everyone notices, not the molecular indicator, but the mechanism of the drug, we say the A gene. It can be seen that PPARγ rises after dosing. ( Drug target identification: drug and drug target molecular correlation)
Fig.2 PPARγ epigenetic repression is lifted with YGW extract.
This picture is very important and deep. What is done is the mechanism of the drug target. In the case of culture, HSC will have a fibrotic phenotype and PPARγ will decrease. However, after the addition of the drug YGW, PPARγ increased (concave gene) . Why did PPARγ show this change? It turned out that there was a change in methylation and acetylation on the promoter (drug target mechanism) . Everyone looks at this picture by themselves, there are concave font changes, and there are also mountain type changes.
Fig.3 Suppression of IKK and NF-κB with YGW.
Figure 2 shows the mechanism upstream of the drug target. This picture is the mechanism downstream of the drug target.
Fig.4 Identification of active components.
Start looking for active ingredients. Using the cell phenotype for functional screening, RA and BC were found to be two active components. In fact, we can also use molecular indicators to filter the functions here. (Evaluation of efficacy: cell experiment)
Fig.5 Rosmarinic acid (RA) and baicalin (BC) are the YGW's active components to render epigenetic de-repression of Pparγ.
The YGW mechanism that has been discovered before is done again on RA and BC. Added animal experiments. Figure I, ( Evaluation of efficacy: animal experiment)
Before the final summary, let me talk about a few backgrounds.
1. PPARγ inhibition of HSC activation has been reported.
2. The regulation of PPARγ by epigenetics has also been reported.
3, YGW can inhibit liver fibrosis has also been reported.
The innovation of this article lies in the new relationship, as well as effective monomers and new drugs. Another highlight of this article is that it is very beautiful in epigenetic regulation, although this is not very innovative.
To sum up, start with the compound and go to the final monomeric active ingredient. The mechanism of the drug, PPARγ, was explored.
First, the efficacy evaluation
Cell experiments: compound YGW, monomer RA and BC.
Animal experiment: BDL animal model.
Second, the drug mechanism - drug target identification
1. Clinical relevance (none)
2, drug target function (none) (previously reported)
3. Correlation between drugs and drug targets
Molecular correlation: drug up-regulation of PPARγ
Functional relevance (none) (previously reported)
4. Drug target mechanism: epigenetic changes of upstream-promoter; downstream-signal molecule detection.
PS: I hope that friends who have more exchanges with Jibo in learning and experimentation can pay attention to Jikai Gene WeChat and reply to the words “Jiboâ€.
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