CN111671740A - Application of 6-shogaol in preparation of medicine for inhibiting liver injury caused by endotoxin and medicine for inhibiting liver injury caused by endotoxin - Google Patents
Application of 6-shogaol in preparation of medicine for inhibiting liver injury caused by endotoxin and medicine for inhibiting liver injury caused by endotoxin Download PDFInfo
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Abstract
The invention discloses application of 6-shogaol in preparation of a medicine for inhibiting liver injury caused by endotoxin and a medicine for inhibiting liver injury caused by endotoxin, belonging to the field of natural medicines. The invention discovers for the first time that the 6-shogaol has good effect of protecting liver injury caused by endotoxin, does not show adverse reactions such as side effects and the like in the experimental process, and is expected to be developed into a new generation of safe and effective medicine for preventing and treating liver injury.
Description
Technical Field
The invention relates to the technical field of natural medicines, and particularly relates to application of 6-shogaol in preparation of a medicine for inhibiting liver injury caused by endotoxin and a medicine for inhibiting liver injury caused by endotoxin.
Background
Gram-negative bacterial infections often result in the development of a systemic inflammatory response, endotoxin (LPS) being the major glycolipid component of the cell wall of gram-negative bacteria, LPS causes increased production of inflammatory factors and Reactive Oxygen Species (ROS) in the body and causes damage to multiple organs of the body, including the liver, kidneys and brain. The liver is an important organ for maintaining immune homeostasis and metabolism, and under the action of LPS, the liver has dysfunction, inflammatory reaction and apoptosis, and is extremely harmful.
Ginger (Zingiberinficinale) is a plant used as both medicine and food, and the anti-inflammatory activity of the ginger is widely reported and applied. 6-shogaol is the main active ingredient in dried ginger and is concerned by more and more scholars at home and abroad.
At present, the research on 6-shogaol mostly focuses on the research on anti-inflammatory and anti-cancer mechanisms, and the research shows that the 6-shogaol can inhibit the secretion of HMC-1 cell inflammatory factors by regulating NF kappa B channels and JNK phosphorylation; LPS-induced secretion of RAW264.7 macrophage NO and PGE2 can be inhibited by NF kappa B; can improve neuroinflammation and cognitive disorder of senile dementia animal model.
However, there is no report on the activity of protecting liver damage caused by LPS and the mechanism thereof.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide application of 6-shogaol in preparing a medicine for inhibiting liver injury caused by endotoxin and a medicine for inhibiting liver injury caused by endotoxin, so that the 6-shogaol is developed into a new generation of safe and effective medicine for preventing and treating liver injury.
The invention is realized by the following steps:
in a first aspect, the application provides the use of 6-shogaol in the manufacture of a medicament for inhibiting liver damage caused by endotoxin.
In an alternative embodiment, 6-shogaol is used to prepare a formulation that enhances the enzymatic activity of liver antioxidant enzymes.
In an alternative embodiment, 6-shogaol is used to prepare a formulation that enhances SOD enzyme activity.
In an alternative embodiment, 6-shogaol is used to prepare an agent that enhances CAT enzyme activity.
In an alternative embodiment, 6-shogaol is used in the preparation of a formulation for ameliorating the inflammatory response of the liver.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of liver inflammation gene mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of IL-6mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of iNOS mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of COX-2mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of liver inflammatory protein expression.
In an alternative embodiment, 6-shogaol is used in the preparation of NF κ B pathway inhibitors.
In an alternative embodiment, 6-shogaol is used to prepare inhibitors of the degradation of the nfkb inhibitory protein I κ B α.
In an alternative embodiment, 6-shogaol is used to prepare inhibitors of NF κ B subunit p65 protein expression.
In an alternative embodiment, 6-shogaol is used to prepare a formulation for reducing hepatic malondialdehyde levels.
In an alternative embodiment, 6-shogaol is used in the preparation of a formulation for improving hepatocyte apoptosis.
In an alternative embodiment, 6-shogaol is used in the preparation of a formulation for ameliorating mitochondrial pathway induced hepatocyte apoptosis.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of apoptosis-related gene mRNA expression and/or apoptosis-related protein expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of Apaf-1mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of Bax mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of caspase-3 activity.
In a second aspect, the present application provides a medicament for inhibiting liver damage caused by endotoxin, the medicament comprising 6-shogaol.
In an alternative embodiment, the medicament further comprises pharmaceutically acceptable excipients.
In an alternative embodiment, the drug is prepared primarily from 6-shogaol and a pharmaceutical carrier, preferably the pharmaceutical carrier comprises lactose or corn starch.
In alternative embodiments, the medicament is a tablet, capsule, granule, oral liquid, or injection.
The invention has the following beneficial effects:
the invention discovers for the first time that the 6-shogaol has good effect of protecting liver injury caused by endotoxin, does not show adverse reactions such as side effects and the like in the experimental process, and is expected to be developed into a new generation of safe and effective medicine for preventing and treating liver injury.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a graph showing the results of 6-shogaol in improving oxidative stress of mouse liver;
FIG. 2 is a graph showing the results of 6-shogaol in improving the liver inflammatory response of mice;
FIG. 3 is a graph showing the results of 6-shogaol in improving mouse hepatocyte apoptosis.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The application of the 6-shogaol provided by the application in preparing the medicine for inhibiting the liver injury caused by the endotoxin and the medicine for inhibiting the liver injury caused by the endotoxin are specifically explained below.
The application provides application of 6-shogaol in preparation of a medicine for inhibiting liver injury caused by endotoxin.
The inventor proposes that the 6-shogaol can play a role in inhibiting liver damage caused by endotoxin in the following ways so as to have the potential of preparing a medicament for treating or assisting in treating liver damage caused by LPS: for example, the antioxidant enzyme system is enhanced to play a role in improving oxidative stress of liver, the inflammatory response of liver is improved by inhibiting the expression of inflammation-related genes and proteins, and the apoptosis of liver cells is improved by inhibiting the expression of apoptosis-related genes and proteins.
In an alternative embodiment, 6-shogaol is used to prepare a formulation that enhances the enzymatic activity of liver antioxidant enzymes.
In an alternative embodiment, 6-shogaol is used to prepare a formulation that enhances the enzymatic activity of SOD (superoxide dismutase).
In an alternative embodiment, 6-shogaol is used to prepare a formulation that enhances the enzymatic activity of CAT (catalase).
The 6-shogaol enhances the enzyme activity of at least one of SOD and CAT, thereby playing a role in enhancing an antioxidant enzyme system and improving the oxidative stress of the liver, and further playing a role in inhibiting the liver injury caused by endotoxin.
In alternative embodiments, 6-shogaol may also be used to prepare a formulation for reducing hepatic malondialdehyde levels, which may have the effect of ameliorating oxidative stress in the liver caused by endotoxin.
In an alternative embodiment, 6-shogaol is used in the preparation of an agent for ameliorating the inflammatory response of the liver, for example in the preparation of an NF κ B pathway inhibitor.
In an alternative embodiment, 6-shogaol is used to prepare inhibitors of degradation of I κ B α protein as NF κ B inhibitory proteins.
In an alternative embodiment, 6-shogaol is used to prepare inhibitors of p65 protein expression as the NF κ B subunit.
The 6-shogaol is used for inhibiting I kappa B alpha degradation and/or inhibiting p65 expression so as to play a role in inhibiting a liver NF kappa B pathway.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of liver inflammation gene mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of IL-6 (interleukin-6) mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of iNOS (nitric oxide synthase) mRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of COX-2 (cyclooxygenase) mRNA expression.
The 6-shogaol is used for inhibiting the expression of at least one of IL-6, iNOS and COX-2, thereby playing a role in inhibiting the inflammatory reaction of the liver.
On the basis, the activation of the NF kappa B pathway can be inhibited through 6-shogaol, so that the expression of liver inflammation gene mRNA and/or protein is inhibited, the liver inflammation reaction is improved, and the effect of inhibiting liver injury caused by endotoxin is achieved.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of mitochondrial pathway apoptosis-related gene mRNA expression and/or protein expression.
In an alternative embodiment, 6-shogaol is used to make an inhibitor of Apaf-1mRNA expression and/or an inhibitor of BaxmRNA expression.
In an alternative embodiment, 6-shogaol is used to prepare an inhibitor of caspase-3 (cysteine protease) activity.
The 6-shogaol is used for inhibiting the expression of at least one of mRNA and/or protein of apoptosis related genes, so that the activation of a mitochondrial apoptosis pathway is inhibited, and the effect of improving liver damage caused by endotoxin is achieved.
In the light of the above, the 6-shogaol can inhibit the activation of liver NF kB pathway and the mRNA expression of inflammation related genes (IL-6, iNOS and COX-2), enhance the antioxidant activity (SOD and CAT) of liver, reduce the level of liver Malondialdehyde (MDA), and inhibit the apoptosis of liver cells by reducing the mRNA expression of mitochondrial pathway apoptosis related genes and the caspase-3 activity and the like, thereby improving the mouse liver injury caused by LPS.
In addition, the application also provides a medicine for inhibiting liver damage caused by endotoxin, which comprises 6-shogaol.
In an alternative embodiment, the above-mentioned medicament further comprises pharmaceutically acceptable excipients.
It should be noted that the above 6-shogaol can be extracted from the dried ginger according to the conventional method, and the specific extraction steps and processes are not described herein in any detail.
In alternative embodiments, the 6-shogaol and pharmaceutically acceptable excipients can be processed according to conventional methods to prepare different forms of drugs, such as tablets, capsules, granules, oral liquids, injections, etc.
In an alternative embodiment, the medicament may be prepared primarily from 6-shogaol and a pharmaceutical carrier. By reference, the above-mentioned pharmaceutical carrier may comprise, for example, lactose or corn starch.
During preparation, 6-shogaol can be uniformly mixed with drug carrier lactose or corn starch, and the like, and then the granules are granulated and prepared into capsules; or tabletting to obtain tablet; or drying and making into granule; or processing 6-shogaol into injection by conventional method.
The medicine containing 6-shogaol provided by the above is expected to become a new generation of safe and effective medicine for preventing and treating liver injury.
The features and properties of the present invention are described in further detail below with reference to examples.
Examples
Experiment on prevention effect of 6-shogaol on LPS (lipopolysaccharide) induced mouse liver damage:
1. animals: 24 ICR mice at 8 weeks of age;
2. grouping: after a week of pre-feeding all mice were randomized into 3 groups of 8: normal group (Control), LPS-treated group (Model), 6-Shogaol group (6-Shogaol).
3. Sample preparation: 6-shogaol is firstly dissolved in a small amount of DMSO and diluted by normal saline before gastric lavage to ensure that the content of the DMSO is lower than 1 percent.
4. The administration scheme is as follows: 6-shogaol mice were dosed with 6-shogaol solution (20mg/kg body weight) for 7 days, control and LPS mice were gavaged with the corresponding solvents, LPS mice and 6-shogaol mice were intraperitoneally injected with 10mg/kg LPS solution on day 8, and dissected 24h later.
5. Detection indexes are as follows: liver SOD, CAT, MDA levels; liver inflammation gene IL-6, iNOS, COX-2mRNA expression; liver I κ B α, p65 protein expression, liver Bax and Apaf-1mRNA expression, and caspase-3 activity.
As a result: as shown in FIG. 1, LPS caused a decrease in the activity of the antioxidant enzyme systems (SOD and CAT) in the liver of mice, and an increase in MDA levels, indicating that the mice developed oxidative stress.
After the stomach is perfused with the 6-shogaol, the antioxidant system of the mouse is enhanced, the SOD activity of the mouse is obviously improved (p is less than 0.05), in addition, the MDA level is also obviously reduced (p is less than 0.05), and the level reaches the level of a control group, which shows that the 6-shogaol can improve the liver oxidative stress caused by LPS.
As shown in FIG. 2, LPS caused the inflammation of mouse liver, and the expression of IL-6, iNOS, and COX-2mRNA reached 8 times, 40 times, and 85 times of the control group (p <0.01), respectively, indicating that the mouse liver had severe inflammation.
6-shogaol significantly reversed this, with 35.0%, 84.5% and 52.4% reduction in IL-6, COX-2 and iNOS expression, respectively (p < 0.01).
As the NF kappa B pathway is involved in the expression of the genes, the expression of NF kappa B inhibitor protein I kappa B alpha and NF kappa B subunit p65 protein is further detected. LPS causes I kappa B alpha degradation and p65 expression increase (p <0.01), which indicates that NF kappa B pathway is activated, and 6-shogaol can effectively prevent activation of NF kappa B pathway to further inhibit inflammatory reaction (p < 0.01).
Apaf-1 and Bax are involved in apoptosis caused by mitochondrial pathway, as shown in FIG. 3, the expression of Apaf-1 and Bax mRNA of mouse liver treated by LPS is increased by about 1.5 times, which indicates that the mouse liver cell is apoptotic, and the expression of the two is obviously reduced after 6-shogaol treatment.
Increased expression of Apaf-1 and Bax may trigger activation of a caspase cascade, where caspase-3 is a key regulator of apoptosis, and model mouse caspase-3 activity is significantly increased (p <0.01), which is significantly inhibited by 6-shogaol (p < 0.05).
The results show that the 6-shogaol has the function of protecting LPS (lipopolysaccharide) from inducing mouse liver cell apoptosis.
In conclusion, the invention discovers for the first time that 6-shogaol has good effect of protecting liver injury caused by endotoxin, does not show adverse reactions such as side effects and the like in the experimental process, and is expected to be developed into a new generation of safe and effective medicine for preventing and treating liver injury.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
- Application of 6-shogaol in preparing medicine for inhibiting liver injury caused by endotoxin is disclosed.
- 2. The use according to claim 1, wherein the 6-shogaol is used for preparing a preparation for enhancing the enzymatic activity of liver antioxidant enzymes;preferably, the 6-shogaol is used for preparing a preparation for enhancing SOD enzyme activity;preferably, the 6-shogaol is used for preparing a preparation for enhancing CAT enzyme activity.
- 3. The use according to claim 1, wherein the 6-shogaol is used in the preparation of a formulation for ameliorating the inflammatory response of the liver.
- 4. The use according to claim 1, wherein the 6-shogaol is used for preparing an inhibitor of liver inflammation gene mRNA expression;preferably, the 6-shogaol is used for preparing an inhibitor of IL-6mRNA expression;preferably, the 6-shogaol is used for preparing an inhibitor of iNOS mRNA expression;preferably, the 6-shogaol is used to prepare an inhibitor of COX-2mRNA expression.
- 5. The use according to claim 1, wherein the 6-shogaol is used for preparing an inhibitor of liver inflammatory protein expression.
- 6. The use according to claim 1, wherein the 6-shogaol is used for preparing NF κ B pathway inhibitors;preferably, the 6-shogaol is used for preparing an inhibitor for degradation of NF kappa B inhibitory protein Ikappa B alpha;preferably, the 6-shogaol is used for preparing the inhibitor for the expression of the NF kappa B subunit p65 protein
- 7. The use according to claim 1, wherein the 6-shogaol is used in the preparation of a formulation for reducing the level of hepatic malondialdehyde.
- 8. The use according to claim 1, wherein the 6-shogaol is used for preparing a preparation for improving hepatocyte apoptosis;preferably, the 6-shogaol is used for preparing a preparation for improving the liver cell apoptosis caused by a mitochondrial pathway.
- 9. The use according to claim 8, wherein the 6-shogaol is used for preparing an inhibitor of apoptosis-related gene mRNA expression and/or apoptosis-related protein expression;preferably, the 6-shogaol is used to prepare an inhibitor of Apaf-1mRNA expression;preferably, the 6-shogaol is used for preparing an inhibitor of Bax mRNA expression;preferably, the 6-shogaol is used for preparing an inhibitor of caspase-3 activity.
- 10. A medicament for inhibiting liver damage caused by endotoxin, wherein the medicament comprises 6-shogaol;preferably, the medicament also comprises pharmaceutically acceptable auxiliary materials;preferably, the medicament is prepared from 6-shogaol and a medicament carrier, and more preferably, the medicament carrier comprises lactose or corn starch;preferably, the medicament is a tablet, a capsule, a granule, an oral liquid or an injection.
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| CN111012893A (en) * | 2020-01-08 | 2020-04-17 | 中国农业科学院农业质量标准与检测技术研究所 | Ginger extract with anti-inflammatory activity and preparation method thereof |
| US20200206297A1 (en) * | 2016-11-22 | 2020-07-02 | University Of Louisville Research Foundation, Inc. | Compositions and methods for treatment of alcohol induced liver injury |
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2020
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| CN101721397A (en) * | 2009-12-08 | 2010-06-09 | 中国药科大学 | Medical application of 6-shogaol for treating cervical cancer, leukemia and breast cancer |
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| US20200206297A1 (en) * | 2016-11-22 | 2020-07-02 | University Of Louisville Research Foundation, Inc. | Compositions and methods for treatment of alcohol induced liver injury |
| CN111012893A (en) * | 2020-01-08 | 2020-04-17 | 中国农业科学院农业质量标准与检测技术研究所 | Ginger extract with anti-inflammatory activity and preparation method thereof |
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Application publication date: 20200918 |