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Use of Methyl Ophiopogon Flavonoid A in the preparation of medicine for preventing and/or treating non-alcoholic fatty liver disease and liver injury

A kind of methyl Ophiopogon flavonoid, non-alcoholic technology, applied in the direction of drug combination, pharmaceutical formula, organic active ingredients and so on

Active Publication Date: 2021-07-30
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although many Nrf2 agonists (such as curcumin and resveratrol, etc.) of traditional Chinese medicine and natural medicine monomers are currently undergoing clinical trials, they still face many difficulties and challenges in the process of development.

Method used

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  • Use of Methyl Ophiopogon Flavonoid A in the preparation of medicine for preventing and/or treating non-alcoholic fatty liver disease and liver injury
  • Use of Methyl Ophiopogon Flavonoid A in the preparation of medicine for preventing and/or treating non-alcoholic fatty liver disease and liver injury
  • Use of Methyl Ophiopogon Flavonoid A in the preparation of medicine for preventing and/or treating non-alcoholic fatty liver disease and liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1. Preliminary research on the therapeutic effect and mechanism of EA and MoA on NAFLD mouse model

[0067] 1. Establishment and verification of NAFLD mouse model

[0068] 1.1 Experimental animal grouping, feeding and sample collection

[0069] 12 wild-type and Nrf2 knockout homozygous (Nrf2- / -) C57BL / 6 mice (bred by our laboratory) were selected, and the mice were randomly divided into 2 groups (same genotype), 6 in each group, male and female Half and half. After 1 week of adaptive feeding with 12h light and 12h darkness alternately, they were fed with high-fat feed for 2 months. See Table 2-1 for grouping and feeding scheme.

[0070] Table 2-1 Grouping and feeding scheme of mice (n=6).

[0071]

[0072] After feeding for 2 months, mice were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.5g / kg). The liver tissue was soaked in 4% paraformaldehyde fixative, and the remaining liver tissue was stored at -70°C until use. Whole blood was...

Embodiment 2

[0232] Example 2. In vitro cell model verification of the therapeutic effect of EA and MoA on NAFLD via the Nrf2 pathway

[0233] In this embodiment, except the following medicines, all the other medicine sources are the same as above:

[0234] Reactive oxygen species (ROS) test box (E004, built in Nanjing); fatty acid-free-BSA (B2064, SIGMA, USA); oleic acid (O1383, SIGMA, USA); palmitic acid (P0500, SIGMA, USA).

[0235] 1. Establishment and verification of NAFLD cell model

[0236] 1.1 Solution preparation

[0237] 1) 1640 complete medium: same as Example 1.

[0238] 2) DMEM complete medium: same as Example 1.

[0239] 3) 0.25% trypsin: same as Example 1.

[0240] 4) PBS solution: Take a bag of PBS powder, add 1L UP water according to the instructions, mix well, and set aside.

[0241] 5) 20% fatty acid-free-BSA solution: Weigh 0.6g of fatty acid-free-BSA, put it in a 50mL centrifuge tube, add 3mL of PBS solution preheated to 55°C, and centrifuge directly at room tempe...

Embodiment 3

[0460] Example 3. Study on the preventive effect and mechanism of EA and MoA on APAP liver injury in NAFLD mouse model

[0461] In this experimental example, except for the following drugs, the sources of other drugs are the same as above: acetaminophen suspension drops (Tylenol, Shanghai Johnson Pharmaceutical Co., Ltd.).

[0462] 1.1 Determination of APAP administration time

[0463] 1.1.1 Experimental animal grouping, drug administration and sample collection

[0464] 18 wild-type C57BL / 6 mice bred in our laboratory were selected and randomly divided into 3 groups, 6 mice in each group, half male and half male. After 1 week of adaptive feeding with 12h light and 12h darkness alternately, the treatment group was given the maximum safe dose of APAP (150mg / kg) by intragastric administration at 9:00 in the morning (APAP-AM) and 5:00 in the afternoon (APAP-PM). Administration for 3 days, once a day. See Table 4-1 for grouping and dosing regimen.

[0465] Table 4-1 Grouping a...

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Abstract

The present invention provides the use of methyl Ophiopogon flavonoid A in preparing a medicine for preventing and / or treating non-alcoholic fatty liver disease and liver damage. The experimental results show that methyl Ophiopogon flavonoid A is an agonist of Nrf2, which can increase the level of GSH in the liver and reduce the level of ROS in hepatocytes by up-regulating the expression of Nrf2 and its downstream antioxidant factors and transporters. Reduce oxidative stress and inflammation, maintain liver cell function, and thus play a role in the treatment of NAFLD. In addition, Methyl Ophiopogon Flavonoid A could prevent the hepatotoxicity of normal dose APAP due to increased NAFLD by upregulating the expression of Nrf2 and its downstream antioxidant factors and transporters, increasing the level of GSH in the liver. Therefore, Methyl Ophiopogon Flavonoid A has a good application prospect in the preparation of NAFLD treatment drugs and APAP hepatotoxicity prevention drugs.

Description

technical field [0001] The invention belongs to the field of medicines, and in particular relates to the use of methyl radix flavone A in the preparation of medicines for preventing and / or treating non-alcoholic fatty liver disease and liver damage. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver injury associated with genetic predisposition and insulin resistance. The pathological feature of this clinical disease was hepatic steatosis and the patient had no history of excessive alcohol consumption. The disease spectrum of NAFLD includes: non-alcoholic simple fatty liver, non-alcoholic steatohepatitis (Nonalcoholic steatohepatitis, NASH) and its related liver cirrhosis and hepatocellular carcinoma (Hepatocellularcarcinoma, HCC). NAFLD can not only lead to disability and death related to liver disease, but also closely related to the high incidence of metabolic syndrome, type II diabetes and atherosclerotic cardiovas...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/357A61P1/16
CPCA61K31/357A61P1/16
Inventor 余璐王凌蒋学华
Owner SICHUAN UNIV