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Application of triacetyl andrographolide as medicine for regulating degradation of autophagosome

A technology of andrographolide, triacetyl, applied in the field of medicine, can solve the problem of not providing the pharmacodynamic data of triacetylandrographolide learning ability improvement effect, unable to know the learning and memory impairment of triacetylandrographolide, unable to reasonably Infer the validity and other issues to achieve the effect of inhibiting signal activation, improving learning and memory ability, and reducing cell damage

Pending Publication Date: 2022-02-11
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese patent document CN101129354 discloses the structure, preparation method and anti-inflammatory, immunosuppressive and anti-tumor effects of the compound; Chinese patent document CN101371832 discloses the application of the compound in the preparation of inflammatory cytokine inhibitors. Inhibitory effect of acetylandrographolide on LPS-induced TNF-α, IL-6 and NO production in RAW264.7 cells, and body temperature, blood pressure and serum TNF-α, IL-1β in LPS-induced endotoxic shock rabbits There is no pharmacodynamic data on the effect of triacetylandrographolide on the improvement of learning ability, and the mechanism of triacetylandrographolide in vivo and the relationship with the degradation of autophagosomes have not been clear. , more importantly, a large number of literature reports suggest that inflammation and inflammatory factors are involved in the occurrence and development of most diseases, and it is not reasonable to infer that the patent ( CN101371832) the effectiveness of the 56 kinds of diseases described, there is no way to know whether triacetylandrographolide can improve learning and memory impairment

Method used

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  • Application of triacetyl andrographolide as medicine for regulating degradation of autophagosome
  • Application of triacetyl andrographolide as medicine for regulating degradation of autophagosome
  • Application of triacetyl andrographolide as medicine for regulating degradation of autophagosome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: The improvement effect of triacetylandrographolide on learning and memory impairment in ApoE4 transgenic mice

[0024] 1. Experimental materials

[0025] Experimental animals: 8-month-old C57BL / 6J mice, SPF grade, half male and half male, purchased from Speiford (Beijing) Experimental Animal Technology Co., Ltd., animal quality certificate number: SCXK (Beijing) 2019-0010. ApoE4 transgenic mice were purchased from Jackson Laboratory and bred in the SPF animal room. In this study, 8-month-old ApoE4 mice (body weight 25-30 g) were used for experiments. The temperature of the mouse breeding environment was 23-25 ​​°C, the relative humidity was 50-65%, the light control was 12 / 12 h alternating light and dark, and the mice were given ordinary feed, and the mice could obtain food and water freely.

[0026] Drugs and reagents: Triacetylandrographolide: prepared by our laboratory, its purity was determined by normalization method to be ≥98.5%; the drug was dissolved...

Embodiment 2

[0057] Example 2: Effect of triacetylandrographolide on autophagy in 3×Tg-AD mice

[0058] 1. Experimental materials

[0059] Experimental animals: 8-month-old C57BL / 6J mice, SPF grade, half male and half male, purchased from Speiford (Beijing) Experimental Animal Technology Co., Ltd., animal quality certificate number: SCXK (Beijing) 2019-0010. APP / PS1 / Tau triple transgenic (3×Tg-AD) mice were donated by the Experimental Animal Center of the Academy of Military Medical Sciences and bred in the SPF animal room. Eight-month-old 3×Tg-AD mice were used in the experiment, half male and half male (body weight 25-30 g). The temperature of the feeding environment was 23 ± 2 °C, the relative humidity was 50-65%, the light was controlled to alternate between light and dark for 12 / 12 h, and the mice were given ordinary feed, and the mice had free access to food and water.

[0060] Drugs and reagents: Triacetylandrographolide: prepared in our laboratory, its purity measured by normaliz...

Embodiment 3

[0089] Example 3: Triacetylandrographolide on Aβ 25-35 Effects of oligomer-induced injury in HT22 cells

[0090] 1. Experimental materials

[0091] Aβ 25-35 Freeze-dried powder, HT22 cells, cell culture medium.

[0092] 2. Experimental method

[0093] Preparation of Aβ oligomers: Take 10 mg Aβ freeze-dried powder and hexafluoroisopropanol (HFIP) (pre-cooled on ice) frozen at -20 °C, add to Aβ 25-35 Add 2220 µL HFIP to the lyophilized powder bottle, vortex and mix well, and let stand at room temperature for 60 min until the liquid is clear to obtain Aβ-HFIP solution (1 mM). Take 40 sterile EP tubes and fill each with 55 µL of Aβ-HFIP solution. The HFIP was evaporated to dryness using a vacuum freeze dryer to obtain a colorless and transparent Aβ peptide film, which was stored at -20 °C. Just before use, 11 µL of DMSO was added to the EP tube equipped with the peptide film, and ultrasonicated in a water bath for 10 min to obtain a DMSO solution of Aβ (5 mM). Add pre-coole...

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Abstract

The invention belongs to the field of medicines, and relates to application of andrographolide, in particular to application of triacetyl andrographolide as a medicine for regulating autophagosome degradation. The invention relates to an application of triacetyl andrographolide in preparation of a medicine for promoting autophagosome clearance. The invention also discloses application of triacetyl andrographolide as a medicine for simultaneously reducing the expression levels of LC3-II and P62 in the brain. Triacetyl andrographolide also can be used as a medicine for reducing phosphorylation levels of Akt and mTOR, improving learning and improving memory. An APP / PS1 / Tau triple transgenic model mouse and an ApoE4 transgenic mouse are utilized to prove that the triacetyl andrographolide can effectively improve the learning and memory ability of a model animal and reduce the levels of A[beta]1-40 and A[beta]1-42 in the brain of a model animal. Triacetyl andrographolide can inhibit the activation of Akt-mTOR signals in both in-vivo and in-vitro models, relieve the excessive accumulation of LC3-II and P62, and reduce the aggregation of autophagosome.

Description

technical field [0001] The invention belongs to the field of medicine and relates to the application of andrographolide, in particular to the application of triacetylandrographolide as a medicine for regulating autophagosome degradation. Background technique [0002] With the acceleration of population aging, changes in people's lifestyles, and increased pressure from social competition, the incidence of Alzheimer's disease (AD), Parkinson's disease, vascular dementia, stroke, and depression These neurological diseases, as well as diseases such as traumatic brain injury, hypertension, diabetes and menopausal syndrome, will be accompanied by impairment of learning and memory functions. Among them, AD is the most common disease that causes learning and memory impairment. The main clinical manifestations are cognitive impairment, aphasia, agnosia, and personality and behavior changes. The disease brings great psychological and economic burdens to the patient's family and societ...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61P25/28
CPCA61K31/365A61P25/28
Inventor 韩光周云丰庞晓斌谢欣梅张海瑜赵倩赵军利
Owner HENAN UNIVERSITY
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