Study on the reduction of cholesterol by berberine through a unique mechanism

Is cholesterol high, is it useful to eat berberine?

Reminder: This article is a scientific research paper. If you have high cholesterol, please follow the doctor's advice. Don't go to the pharmacy to buy berberine. If you have a diarrhea, you can buy the medicine yourself.

The article shared today is to study berberine to lower cholesterol. In Nature Medicine, another study of top Chinese medicines.

Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. 2004. Nature Medicine.

Let me talk about something that has nothing to do with scientific research, but is related to publishing high-scoring articles. Everyone pays attention to the writing of this article, the author is a master. In the abstract, the description begins with clinical experiments, highlights the clinical significance, and then introduces the mechanism. But the text, starting with cell molecular experiments, finally mentions clinical trials. Two narrative methods are combined. It is not easy to do scientific research. Not only must we design the project well, but we also need to rack our brains to write the article.

Figure 1 Upregulation of LDLR expression by BBR in human hepatoma cell lines.

One is the cell experiment. Everyone looks at the sputum cells. HepG2 and 7402 are both liver cancer cells. For reference, if the normal cell strain is not or difficult to operate in our own research, then the corresponding tumor cell line can be considered.

In the description of the article, liver cancer cells were used as a cell model, and the detection index was the expression level of LDLR (screening by molecular indicators). The compounds extracted from more than 700 traditional Chinese medicines were screened to obtain berberine. Mr. Tu has used more than 500 single herbs for the screening of artemisinin.

The conclusion is that berberine can upregulate LDLR. ( drug and drug target molecular correlation data )

The bcd map is an mRNA level assay. e is a protein level test, and there is no WB result for å•¥. This protein is 640 amino acids, less than 100kd, but the key is membrane protein, which may be the reason for not providing WB results. The f-picture can be considered as a functional experiment, and berberine promotes the uptake of cholesterol by cells ( drug evaluation: cell experiment ).

Figure 2 BBR increases LDLR expression by stabilizing LDLR mRNA through the 5' proximal section of the LDLR mRNA 3'UTR.

Looking for a mechanism, it was found that berberine upregulates LDLR mRNA, not through transcriptional levels, but by increasing mRNA stability. ( drug target mechanism )

1. A positive control (statin) was used here to demonstrate that berberine does not regulate the LDLR promoter. A negative control is required when proven to be functional. A positive control is necessary when it proves to be non-functional.

2, d map is the addition of actinomycin D in the cells to inhibit RNA synthesis, and then look at the amount of mRNA. It has been found that berberine can inhibit the degradation (stability) of LDLR mRNA. The stability of mRNA regulation is generally in the 3'UTR, and the ef map explores where the regulatory site is.

Figure 3 Blocking ERK activation abolished the regulatory effect of BBR on LDLR.

Berberine regulates LDLR through the ERK signaling pathway ( drug target mechanism ). Because of the above mechanism of mRNA stability, the mechanism of the signal pathway is routinely done. In fact, if you want to be deep, it should be along the above mRNA stability, looking for the stability site on the LDLR 3'UTR ARE is a combination of what is related to mRNA stability.

Figure 4 BBR reduces plasma LDL-c and increases liver LDLR expression in hamsters.

Animal experiments, first modeling HFHC, and then see the effect of dosing treatment, found that berberine can provide expression of LDLR in the liver, reduce serum cholesterol and LDL-c. ( Evaluation of efficacy: animal experiment )

Table 1 Effects of BBR on serum lipids in the subgroup of hypercholesterolemic patients who were not taking other medication before or during BBR treatment.

Clinical trials, human sample testing. Berberine can lower cholesterol, triglycerides and LDL-c.

Table 2 Effect of BBR on liver and kidney functions of the subgroup of hypercholesterolemic patients who were not taking other medication before or during BBR treatment.

In clinical trials, human sample testing shows how berberine is toxic to the liver and kidneys. It has no effect on the kidney and improves liver function.

Finally, we summarize the research content of the Chinese medicine subject:

First, the efficacy evaluation

Cell experiments: Detection of berberine by liver cancer cells can increase the uptake of cholesterol by cells.

Animal experiments: HFHC model, berberine can reduce cholesterol in serum.

Human experiment: Patients treated with berberine can lower serum cholesterol.

Second, the drug mechanism - drug target identification

1. Clinical relevance: In animal models, berberine can reduce LDLR in the liver.

2, drug target function: This is not done alone, because it is known.

3. Correlation between drugs and drug targets

Molecular correlation: berberine upregulates LDLR.

Functional relevance: Did not do, in fact, you can add berberine to the cells, then interfere with LDLR to see if the intake of cholesterol is reduced.

4, drug target mechanism: berberine regulates the stability of LDLR mRNA, this place is done relatively fine, and in the past it is believed that through LDLR transcription to play a different role, the color of the place.

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 “Jibo”.

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