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Application of piperine to preparation of drugs for preventing and treating septicemia

A technology for sepsis and piperine, which is applied to the application field of piperine in the preparation of drugs for preventing and treating sepsis, can solve problems such as weakening the effect of anti-infection treatment, and achieve the effects of enhancing activity, preventing apoptosis and preventing sepsis.

Active Publication Date: 2015-12-16
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the abuse of antibiotics, many bacteria have developed drug resistance, which weakens the effect of anti-infective treatment

Method used

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  • Application of piperine to preparation of drugs for preventing and treating septicemia
  • Application of piperine to preparation of drugs for preventing and treating septicemia
  • Application of piperine to preparation of drugs for preventing and treating septicemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Piperine upregulates the activity of intracellular mTORC1

[0042] Piperine at different concentrations (40, 80, 160 μmol / L) was added to cell lines cultured in 6-well plates (prostate cancer cell line LNCaP, human cervical cancer cell line HeLa, mouse macrophage cell line RAW264.7) and incubated for 2 After 1 hour, the protein after cell lysis was collected, and the phosphorylation of mTORC1 downstream substrates p70S6K and 4E-BP1 was detected by Western blot method.

[0043] The results showed that piperine pretreated LNCaP( figure 1 ), HeLa( figure 2 ) and RAW264.7 cells ( image 3 ), up-regulated the phosphorylation of p70S6K and 4E-BP1 proteins in a dose-dependent manner (concentrations of 40, 80, and 160 μmol / L, respectively), without affecting the expression of p70S6K and 4E-BP1 proteins in cells. Figure 1-3The histogram respectively counts the ratio of p-p70S6K / p70S6K to p-4E-BP1 / 4E-BP1 in the three types of cells, *P<0.05 (the difference is statistically s...

Embodiment 2

[0045] Piperine acts as an enhancer of mTORC1 during nutrient deprivation (low intracellular mTORC1 activity)

[0046] 40 μmol / L piperine was added to serum-starved HeLa cell culture medium (serum-free EBSS or DMEM medium), and Western blot was used to detect the phosphorylation of p70S6K, a downstream substrate of mTORC1, to evaluate the activity of mTORC1.

[0047] It was found that after HeLa cells were starved by serum-free EBSS, the phosphorylation level of p70S6K (i.e. the activity of mTORC1) was low, and whether the EBSS medium contained glucose (Glc) or piperine did not affect the expression of p70S6K. Phosphorylation level ( Figure 4 ), indicating that the effect of piperine on mTORC1 is independent of glucose. However, serum-free DMEM medium can activate the phosphorylation of p70S6K, and piperine can significantly enhance the phosphorylation of p70S6K induced by DMEM (***P<0.001). The results indicated that the upregulation of mTORC1 by piperine may be related to...

Embodiment 3

[0049] When the activity of mTORC1 in cells is low, piperine combines with glutamine and leucine to activate the mTORC1 signaling pathway

[0050] Add 40 μmol / L piperine, 0.8 mmol / L L-leucine (L-Leucine, Leu) and 2 mmol / L L-glutamine (L-Glutamine, Gln) (the same below) to serum-starved HeLa cells ( Figure 5-6 ) and mouse peritoneal macrophages ( Figure 7 ) medium.

[0051] The results showed that phosphorylation of p70S6K (indicative of mTORC1 activation) is dependent on the presence of intracellular Gln and Leu. Such as Figure 5 As shown, the activity of mTORC1 was inhibited in HeLa cells under serum and amino acid starvation (50 min) conditions (the first lane). Gln itself cannot activate mTORC1. Leu can slightly upregulate mTORC1 due to the presence of a small amount of Gln in cells after a short period of starvation. The addition of piperine significantly up-regulated the Leu-activated mTORC1 activity (*P<0.01).

[0052] Figure 6 It was further shown that piper...

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Abstract

The invention discloses application of piperine to the preparation of drugs for preventing and treating septicemia. Piperine can strongly enhance the leucine-induced activation of mTORC1. Piperine can prevent bacterial abdominal infection and further prevent septicemia, and can also enhance the functions of macrophages, including bacterial phagocytosis and TNF-alpha and IL-6 secretion capability, to prevent bacterial infection induced macrophage apoptosis. Therefore, piperine or the combination of piperine, leucine and glutamine can enhance the mTORC1 activity of bodies and be used for treating bacterial infections and septicemia.

Description

technical field [0001] The invention belongs to the field of medicines, and in particular relates to the application of piperine in the preparation of medicines for preventing and treating sepsis. Background technique [0002] Piperine (Piperine) is a natural compound extracted from plants of the family Piperaceae, and its molecular formula is C 17 h 19 NO 3 ; The chemical name is (E,E)-1-[5-(1,3-benzodioxolan-5-yl)-1-oxo-2,4-pentadienyl]-piperidine. White crystalline powder. The melting point is 130-133°C. Soluble in acetic acid, benzene, ethanol and chloroform, slightly soluble in ether. Its chemical structure is as follows: [0003] [0004] The theory and practice of traditional Chinese medicine show that pepper enters the stomach and large intestine meridian, warms the middle and dispels cold, lowers qi and eliminates phlegm. It can be used for stomach cold and vomiting, abdominal pain and diarrhea, loss of appetite, epilepsy and excessive phlegm. Simply put,...

Claims

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Application Information

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IPC IPC(8): A61K31/4525A61P31/04
Inventor 欧阳东云何贤辉潘浩徐丽慧黄美云查庆兵施资坚
Owner JINAN UNIVERSITY
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