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Application of xenicane type diterpenoid compound to preparation of antioxidative neuroprotective drugs

A compound and anti-oxidation technology, which can be used in drug combinations, nervous system diseases, anti-toxins, etc., and can solve the problem of epoxyhydroxyacetyldictyolal having no medicinal function reports, etc.

Active Publication Date: 2019-10-29
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, epoxyhydroxyacetyldictyolal has no medicinal function reported

Method used

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  • Application of xenicane type diterpenoid compound to preparation of antioxidative neuroprotective drugs
  • Application of xenicane type diterpenoid compound to preparation of antioxidative neuroprotective drugs
  • Application of xenicane type diterpenoid compound to preparation of antioxidative neuroprotective drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 compound to H 2 o 2 Inhibition assay of induced oxidative damage in neuron-like PC12 cells

[0027] The PC12 cells in the logarithmic growth phase were inoculated in a 96-well culture plate at 3000 cells / well, with 100 μL of medium per well, at 37°C with 5% CO 2 overnight in the incubator. Compound (2, 10 μM) or TBHQ (positive control, 10 μM) was added to each well for pre-incubation for 18 h, and then given a certain concentration of H 2 o 2 (450μM) stimulation for 24h, and finally add 20μL of MTT solution (5mg / mL) into the incubator to continue culturing. After 4 hours, the liquid in each well was sucked away, DMSO (120 μL / well) was added, oscillated and mixed for 10 minutes, and the absorbance (A value) was measured at a wavelength of 490 nm with an enzyme-linked immunosorbent assay instrument, and the DMSO group was blank control B. The cell survival rate was calculated (experimental group A value / control group B value×100%), and the experiment was re...

Embodiment 2

[0029] Example 2 compound to H 2 o 2 Effect of neuron-like PC12 cell colony formation after injury

[0030] PC12 cells in the logarithmic growth phase were seeded in a 12-well culture plate at 1000 cells / well, with 1 mL of medium per well, and incubated overnight in an incubator. Add compounds (1, 2 μM) or TBHQ (positive control, 2 μM) to each well for pre-incubation for 24 hours, and then give a certain concentration of H 2 o 2 (100 μM) stimulation. After 24 hours, replace with fresh medium, place in an incubator containing 5% CO2 at 37°C and continue culturing for 6 days until the cells grow to visible colonies. After fixing with 4% paraformaldehyde, colonies were stained with crystal violet for 15-20 min.

[0031] Experimental results such as figure 2 As shown, colony formation experiments further confirmed the effect of xenicane-type diterpenoid epoxyhydroxyacetyldictyolal on H 2 o 2 Induced protective effect on oxidative damage of PC12 cells, and when the compoun...

Embodiment 3

[0032] Example 3 compound to H 2 o 2 Determination of LDH leak rate in induced neuron-like PC12 cells

[0033]Lactate dehydrogenase (LDH) is ubiquitous in every cell and is a common intracellular enzyme. When the cell membrane is damaged, LDH will leak into the culture medium. Therefore, the LDH leakage rate can represent the integrity of the cell membrane and cell viability. The PC12 cells in the logarithmic growth phase were inoculated in a 96-well culture plate at 5000 cells / well, with 100 μL of medium per well, at 37°C containing 5% CO 2 overnight in the incubator. Compounds (0.5, 1, 2 μM) were added to each well for pre-incubation for 18 h, and then given a certain concentration of H 2 o 2 (450μM) stimulation for 24h. After drug stimulation, the leakage rate of LDH was detected according to the instructions of the LDH detection kit.

[0034] Experimental results such as image 3 shown, with H 2 o 2 Compared with the injury group, epoxyhydroxyacetyldictyolal, a xe...

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PUM

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Abstract

The invention provides application of an xenicane type diterpenoid compound epoxyhydroxyacetyldictyolal to preparation of antioxidative neuroprotective drugs. The diterpenoid compound epoxyhydroxyacetyldictyolal can significantly inhibit the neuronal PC12 cell oxidative damage induced by H2O2, promote PC12 cell colony formation, and inhibit release of lactate dehydrogenase (LDH). Diterpene is an excellent antioxidant, has the protective effect on the oxidative damage of nerve cells, and can be used for preventing or treating the cerebral ischemia-reperfusion injury.

Description

technical field [0001] The invention belongs to the field of medicaments, and specifically refers to the application of xenicane-type diterpene compound epoxyhydroxyacetyldictyolal in the preparation of antioxidant and neuroprotective drugs. Background technique [0002] Cerebral stroke is an important disease that endangers human health, and ischemic stroke accounts for 80%-85% of stroke. Thrombolysis is the main treatment for ischemic stroke, but it is easy to cause ischemia-reperfusion injury due to oxidative stress when blood supply is restored. Therefore, the use of antioxidants to scavenge reactive oxygen species can play a neuroprotective role, and is an important strategy to prevent and treat cerebral ischemia-reperfusion injury. [0003] Xenicane-type diterpenes are a class of terpenoids containing a cyclononane skeleton, mainly derived from marine brown algae, soft corals and gorgonians. These compounds have novel structures and diverse biological activities, and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/336A61P39/06A61P25/00A61P9/10
CPCA61K31/336A61P9/10A61P25/00A61P39/06
Inventor 严鹏程吴建章赵敏李歌毛琦琦方城燕奚一源
Owner WENZHOU MEDICAL UNIV
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