CN114984069A - Application of andrographis paniculata in preparation of medicines for preventing neurodegenerative diseases - Google Patents
Application of andrographis paniculata in preparation of medicines for preventing neurodegenerative diseases Download PDFInfo
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- CN114984069A CN114984069A CN202210631039.8A CN202210631039A CN114984069A CN 114984069 A CN114984069 A CN 114984069A CN 202210631039 A CN202210631039 A CN 202210631039A CN 114984069 A CN114984069 A CN 114984069A
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- andrographis paniculata
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Abstract
The invention belongs to the technical field of biomedicine, and discloses an application of andrographis paniculata in preparing a medicament for preventing neurodegenerative diseases, which comprises the following steps: the medicament for neurodegenerative diseases contains the active ingredient of andrographis paniculata. The active ingredients of the andrographis paniculata comprise: the medicine comprises hanbain, oroxylin A, baicalein and swertisin. The active ingredient of Andrographis paniculata Nees works by promoting NGF-induced neurite outgrowth in PC12 cells. The active ingredients of Andrographis paniculata Nees act by inhibiting the production of proinflammatory factors in BV-2 cells induced by LPS. According to the invention, main active ingredients, action targets and signal channels of the andrographis paniculata are analyzed and summarized by a network pharmacology method, and the potential prevention and treatment effects of the andrographis paniculata on AD and PD are determined by combining related activity measurement, so that a new strategy and a certain pharmacology basis can be provided for the research and development of neurodegenerative disease drugs.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of andrographis paniculata in preparation of a medicament for preventing neurodegenerative diseases.
Background
At present, the incidence of neurodegenerative diseases is rising year by year with the increasing aging of the population. According to the predictions of the world health organization, neurodegenerative diseases will become second most common cause of death after cardiovascular diseases in the next 20 years. Alzheimer's Disease (AD) is the most common neurodegenerative disease in the clinic, the leading cause of Alzheimer's disease, and is becoming one of the most expensive, deadliest, and heaviest diseases of this century at an extremely rapid pace. AD is mainly manifested as neuropsychiatric symptoms such as cognitive dysfunction, progressive memory impairment, personality changes and language disorders. Beta-amyloid (a β) plaques and intraneuronal hyperphosphorylated tau aggregates (neurofibrillary tangles) are typical neuropathological features of AD. It has been found that plaques of a β have synaptic toxicity and are capable of inducing axonal varicose veins and neurite rupture, and hyperphosphorylated tau protein leads to an increase in short spines and filopodia and a decrease in the total dendritic length of hippocampal pyramidal neurons.
Parkinson's Disease (PD), also known as "paralysis agitans", occurs second to AD. Massive loss of dopaminergic neurons in the subthalamic nucleus and the compact areas of the substantia nigra is the most prominent and uniform morphological feature of PD, and thus PD is also considered to be a neurodegenerative disease associated with dopamine depletion in the basal ganglia. PD causes progressive motor and non-motor disabilities, including mood, cognition, sleep, autonomic nerves, and gastrointestinal symptoms. These diseases not only pose a great potential threat to the health and daily life of the elderly, but also further exacerbate the burden on society. However, there is no effective method for completely preventing and treating such diseases at present. Therefore, the search for new and highly effective drugs for preventing and treating neurodegenerative diseases has become a hot point of research.
The Chinese herbal medicine has rich sources and complex structure, most of the Chinese herbal medicine has the effects of multiple components and multiple targets, and particularly has better curative effect on complex diseases such as diabetes, neurodegenerative diseases, inflammation, cancer and the like. Therefore, the utilization of Chinese herbal medicines or the search of active ingredients with the function of preventing and treating neurodegenerative diseases from Chinese herbal medicines has become one of the main starting points of the research and development of neurodegenerative disease medicines. Network pharmacology is a new field, and can combine oral bioavailability prediction, multiple drug target prediction and network analysis to obtain active compounds and prevention targets of target traditional Chinese medicines and comprehensively analyze complex network regulation and control mechanisms of traditional Chinese medicine formulas or single medicines. In recent years, more and more scholars study the potential of Chinese herbal medicines in preventing and treating neurodegenerative diseases by using a network pharmacological method, for example, the action mechanism of dogwood-cistanche for preventing and treating parkinson disease is analyzed by using the network pharmacological method in the prior art 1. Prior art 2 uses a cyber pharmacological approach to determine the potential mechanism of action and molecular targets of Acorus tatarinowii Schott in AD.
Andrographis paniculata (Andrographis paniculata), also known as Chunlian willow, Yijianxi, Nelumbo nucifera, herba Swertiae Dilutae, etc., is the whole herb or leaf of Andrographis paniculata (Burm. f.) Nees of Acanthaceae, and has been widely used as a medicinal plant. The common andrographis herb is cold in nature and bitter in taste, and enters heart, lung, large intestine and bladder channels, so that the common andrographis herb tea not only has the effects of clearing heat and removing toxicity, cooling blood and reducing swelling, but also has various effects of resisting cancer, viruses, tumors, diabetes and the like.
Through the above analysis, the problems and defects of the prior art are as follows: the prior art has no method for applying andrographis paniculata to medicines for preventing neurodegenerative diseases. The invention determines key active ingredients, action targets and signal channels of the common andrographis herb in preventing neurodegenerative diseases by using a network pharmacological method for reference, reveals possible action mechanisms of the common andrographis herb, and provides basic theoretical basis for clinical application of the common andrographis herb. Meanwhile, a lead compound with neuritis resistance and neurotrophic effect is obtained through activity research, and a pharmaceutical basis is provided for the research of medicines for preventing neurodegenerative diseases.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides an application of andrographis paniculata in preparing a medicament for preventing neurodegenerative diseases.
The invention is realized by the application of andrographis paniculata, which contains not less than 1.5 percent of total amount of andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide in the preparation of drugs for preventing neurodegenerative diseases according to dry product.
Further, the medicament for neurodegenerative diseases contains an active ingredient of andrographis paniculata.
Further, the active ingredients of the andrographis paniculata include: radix Stellariae extract, oroxylin A, Scutellariae radix flavone and herba Capsellae flavone.
Further, the active ingredient of Andrographis paniculata Nees acts by promoting NGF-induced neurite outgrowth in PC12 cells.
Further, the active ingredient of Andrographis paniculata Nees acts by inhibiting the production of proinflammatory factors in BV-2 cells induced by LPS.
Further, the neurodegenerative disease includes: alzheimer's disease and Parkinson's disease.
Another object of the present invention is to provide a netpharmacology-based method for measuring andrographis paniculata activity, which verifies the use of andrographis paniculata in preparing a drug for preventing neurodegenerative diseases, the netpharmacology-based method for measuring andrographis paniculata activity comprising:
step one, TCMSP is used for obtaining and screening active ingredients of common andrographis herb; and obtaining potential targets related to the active ingredients of the andrographis paniculata through SEA, Swiss, STITCH and BATMAN-TCM databases;
step two, screening and obtaining targets related to Alzheimer's disease and Parkinson's disease in the potential targets by using CTD, TTD, GeneCards, PharmGKB and MAS 3.0;
step three, performing gene body analysis and Kyoto gene and KEGG analysis on the target spots obtained in the step two through DAVID;
step four, constructing an active ingredient-target spot and a target spot-passage network diagram of the andrographis paniculata by adopting Cytoscape;
and step five, analyzing the obtained active ingredient-target and target-pathway network diagram of the andrographis paniculata to determine the active ingredients in the active ingredients of the andrographis paniculata, which can be used for preparing the medicines for preventing the neurodegenerative diseases.
Further, in the first step, the obtaining and screening of the active ingredients of andrographis paniculata by TCMSP comprises: screening the active ingredients of the andrographis paniculata with OB value more than or equal to 30% and DL value more than or equal to 0.18 by TCMSP and constructing an andrographis paniculata active ingredient database.
Further, in the fourth step, the method for constructing the active component-target and target-pathway network diagram of the andrographis paniculata by using Cytoscape comprises the following steps:
leading main active ingredients, action targets and signal channels related to Alzheimer's disease and Parkinson's disease in the common andrographis herb into Cytoscape, carrying out network topology analysis, and constructing a visual active ingredient-target and target-channel network diagram of the common andrographis herb.
Further, the network pharmacology-based andrographis paniculata activity determination method further comprises the following steps:
the neurotrophic and anti-neuritic activities of the active ingredients of the andrographis paniculata part were examined using Nerve Growth Factor (NGF) -induced PC12 cells and Lipopolysaccharide (LPS) -induced BV-2 cells as models.
In combination with the technical solutions and the technical problems to be solved, please analyze the advantages and positive effects of the technical solutions to be protected in the present invention from the following aspects:
first, aiming at the technical problems existing in the prior art and the difficulty in solving the problems, the technical problems to be solved by the technical scheme of the present invention are closely combined with results, data and the like in the research and development process, and some creative technical effects are brought after the problems are solved. The specific description is as follows:
the invention aims at part of the 29 compounds obtained by screening to carry out the tests of neurotrophic and anti-neuritis activity. The results show that the andrographis paniculata active ingredient 24 can remarkably promote the growth of nerve axons of the NGF-induced PC12 cells, and the compound 16 can remarkably inhibit the production of proinflammatory factors in the LPS-induced BV-2 cells.
The invention systematically analyzes potential targets of andrographis paniculata for preventing and treating AD and PD and key signal channels based on a network pharmacological method, provides a theoretical basis for andrographis paniculata for preventing and treating neurodegenerative diseases, and provides a method and an idea for the research of subsequent related medicines.
The invention screens the active ingredients of the andrographis paniculata by using a network pharmacology method, effectively analyzes potential targets related to the neurodegenerative diseases AD and PD, obtains 116 targets related to the AD and 90 targets related to the PD, finds that the hancein, the oroxylin A, the baicalein and the capsaicine flavone in the active ingredients of the andrographis paniculata have more targets for the AD and the PD, and supposes that the compounds are important compounds for the effect of the andrographis paniculata on preventing and treating the neurodegenerative diseases. Meanwhile, a 'target-signal path' network is constructed in a visualized manner, and analysis shows that the action pathways of the andrographis paniculata for preventing and treating AD and PD are mainly related to the promotion of cell survival, the inhibition of apoptosis, the participation in cell proliferation and cell cycle processes, the influence on the interaction of a nerve active ligand-receptor and the like.
Secondly, considering the technical scheme as a whole or from the perspective of products, the technical effect and advantages of the technical scheme to be protected by the invention are specifically described as follows:
according to the invention, main active ingredients, action targets and signal channels of the andrographis paniculata are analyzed and summarized by a network pharmacology method, and the potential prevention and treatment effects of the andrographis paniculata on AD and PD are determined by combining related activity measurement, so that a new strategy and a certain pharmacology basis can be provided for the research and development of neurodegenerative disease drugs.
Third, as an inventive supplementary proof of the claims of the present invention, there are also presented several important aspects:
(1) the expected income and commercial value after the technical scheme of the invention is converted are as follows:
the invention realizes networking and systematization of research on drug action diseases, so that the research on the andrographis paniculata has purposiveness and targeting property, the research cost of the drug is greatly saved, and the research period is shortened. Meanwhile, a template is provided for obtaining a high-activity compound by combining a specific experiment, and the efficiency of drug research is improved.
(2) The technical scheme of the invention solves the technical problems which are always desired to be solved but are not successfully achieved:
the invention provides a technical basis for the research and development of medicines for treating neurodegenerative diseases which are difficult to solve in the century, and is expected to prevent the occurrence and development of the neurodegenerative diseases by using common andrographis herb which is a medicinal and edible food.
Drawings
FIG. 1 is a flowchart of a method for determining Andrographis paniculata Nees activity based on cyber pharmacology according to an embodiment of the present invention;
FIG. 2 is a graph showing the number of disease targets corresponding to the active ingredients of Andrographis paniculata Nees provided in the examples of the present invention (A and B are the number of target points corresponding to AD and PD, respectively);
FIG. 3 is a network diagram of "active ingredient-target-disease" provided by an embodiment of the present invention (A and B are associated with AD and PD, respectively);
FIG. 4 is a GO enrichment analysis graph provided by an embodiment of the invention (A and B are related to AD and PD, respectively);
FIG. 5 is a diagram of the "target-signal path" of Andrographis paniculata Nees for the prevention and treatment of AD (A) and PD (B) according to the present invention;
FIG. 6 is a schematic representation of the effect of Andrographis paniculata Nees active ingredient on NGF-induced neurite outgrowth in PC12 cells provided by examples of the present invention;
FIG. 6(A) is a graph showing the effect of compounds 1, 2, 3,4, 16 and 28 at 10. mu.M on NGF-induced differentiation rates of PC12 cells;
FIG. 6(B) is a graph showing the effect of Compound 24 on NGF-induced differentiation rates of PC12 cells at various concentrations provided by the examples of the present invention;
FIG. 6(C) is a schematic diagram showing the effect of 1, 2, 3,4, 16 and 28 on the morphology of PC12 cells according to the present invention;
FIG. 6(D) is a schematic diagram showing the effect of 24 on the morphology of PC12 cells according to the present invention;
FIG. 7 is a schematic illustration showing the effect of the active ingredient of Andrographis paniculata Nees on the production of pro-inflammatory mediators in BV-2 cells induced by LPS according to the present invention;
FIG. 7(A) is a graph showing the effect of compounds 3,4, 16 and 28 provided in the examples of the present invention on the concentration of NO in the supernatant of LPS-induced BV-2 cells at 1 and 10. mu.M, respectively;
FIG. 7(B) is a graph showing the effect of Compound 16 on the concentration of NO in the supernatant of LPS-induced BV-2 cells at various concentrations provided in the examples of the present invention;
FIG. 7(C) is a graph showing the effect of 16 on the concentration of IL-6 in the supernatant of LPS-induced BV-2 cells at various concentrations, as provided in the examples of the present invention;
FIG. 7(D) is a graph showing the effect of different concentrations of TNF- α on LPS-induced BV-2 cell supernatant, as provided by the examples of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
First, an embodiment is explained. This section is an illustrative example developed to explain the claims in order to enable those skilled in the art to fully understand how to implement the present invention.
As shown in fig. 1, the method for measuring andrographis paniculata activity based on network pharmacology provided in the embodiments of the present invention includes:
s101, obtaining and screening active ingredients of andrographis paniculata by TCMSP; and obtaining potential targets related to the active ingredients of the andrographis paniculata through SEA, Swiss, STITCH and BATMAN-TCM databases;
s102, screening CTD, TTD, GeneCards, PharmGKB and MAS 3.0 to obtain targets related to Alzheimer 'S disease and Parkinson' S disease in the potential targets;
s103, performing gene ontology analysis and Kyoto gene and KEGG analysis on the target point obtained in the step S102 through DAVID;
s104, constructing an active component-target point and a target point-channel network diagram of the andrographis paniculata by adopting Cytoscape;
and S105, analyzing the obtained active ingredient-target and target-pathway network diagram of the andrographis paniculata, and determining the active ingredients in the active ingredients of the andrographis paniculata, which can be used for preparing the medicines for preventing the neurodegenerative diseases.
In step S101, the obtaining and screening of active ingredients of andrographis paniculata by TCMSP according to the embodiments of the present invention includes: screening the active ingredients of the andrographis paniculata with OB value more than or equal to 30% and DL value more than or equal to 0.18 by TCMSP and constructing an andrographis paniculata active ingredient database.
In step S104, the method for constructing an active ingredient-target and target-pathway network diagram of andrographis paniculata by using Cytoscape according to the embodiments of the present invention includes:
leading main active ingredients and effects related to Alzheimer's disease and Parkinson's disease in the common andrographis herb into Cytoscape, carrying out network topology analysis, and constructing a visual active ingredient-target and target-pathway network diagram of the common andrographis herb.
The method for measuring the activity of the andrographis paniculata based on network pharmacology provided by the embodiment of the invention further comprises the following steps:
the neurotrophic and anti-neuritic activities of the active ingredients of the andrographis paniculata part were examined using Nerve Growth Factor (NGF) -induced PC12 cells and Lipopolysaccharide (LPS) -induced BV-2 cells as models.
The total content of andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide should not be less than 1.5% calculated on dried product.
And II, application embodiment. In order to prove the creativity and the technical value of the technical scheme of the invention, the part is the application example of the technical scheme of the claims on specific products or related technologies.
The andrographis paniculata or the active ingredients of the andrographis paniculata provided by the embodiment of the invention are applied to prepare the medicine for treating, relieving and preventing neurodegenerative diseases.
EXAMPLE 1 Collection method of active ingredients of Andrographis paniculata Nees
The active ingredients of the andrographis paniculata are searched by means of a traditional Chinese medicine system pharmacology database and an analysis platform (TCMSP) (http:// tcmspw. com/TCMSP. php), and the screening standard is as follows: OB value (oral bioavailability) is more than or equal to 30% and DL value (drug-likeness) is more than or equal to 0.18. Screening to obtain 29 active ingredients of herba Andrographitis including hancein, oroxylin A, SUJIENNING flavone, and Scutellariae radix flavone.
Example 2 method for collecting related target spots of Andrographis paniculata Nees and AD and PD
The method comprises the steps of setting a search species type to be 'Homo sapiens' by means of a library of Simiarity Ensemble Approach (SEA, http:// SEA. bkslab. org /), Swiss Target Prediction (http:// www.swisstargetprediction.ch /), STITCH (http:// stick. embl. de /) and BATMAN (http:// biont. ncpsb. org/bat-TCM /) and searching Target point information of main active ingredients of the common andrographis herb, and merging the library to obtain the common andrographis herb action Target point. The Target obtained above was introduced into Comparative Toxicogenics Database (CTD, http:// ctdbase. org /), Therapeutic Target Database (TTD, http:// bid. num. edu. sg/group/cjttd /), GeneCards: The human gene Database (https:// www.genecards.org /), Pharmacogenomics Knowledgebase (https:// www.pharmgkb.org /) and Mobile analysis System 3.0(MAS 3.0, http:// bio. capetalbio. coli/MAS 3/), and The search species were classified as "Home samples" and "PD's' syndrome" respectively, and relevant targets were collected by using "PD 7. fig.7https://cytoscape.org/) And using the Merge function to summarize the Target point information of each database to draw an Active ingredient-Target point Network diagram (Active ingredient-Target-Network). The obtained baicalein, oroxylin A, baicalein, caffeic acid and tsukushinin flavone in the andrographis paniculata are probably main active ingredients related to AD and mainly aim at gene targets such as PTGS2, PTGS1, MAPT, CYP1B1, ABCB1 and the like; oroxylin A, hancein, baicalein, sapogenin flavone, andrographis paniculata flavone and glyceryl monooleate are possible main active ingredients related to PD, and mainly aim at gene targets such as PRKCD, ADORA1, MAPT, ABCB1 and the like.
Example 3 Collection method of Andrographis paniculata Nees and AD and PD related Signal pathways
And converting the screened action target into a gene name, uploading the gene name to a DAVID database, and carrying out KEGG signal path enrichment analysis. The enrichment of the KEGG channel of AD prompts that 31 targets are enriched on 23 channels, and mainly relates to signal channels such as Alzheimer's disease, PI3K-Akt signaling pathway, pathway in cancer, Toxoplasma and the like; the enrichment of the KEGG channel of PD prompts that 27 targets are enriched on 13 channels, and mainly relates to signal channels such as Alzheimer's disease, pathway in cancer, Neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and the like.
Example 4 neurotrophic Activity of partial ingredients of Andrographis paniculata
1. Cell: PC12 cells were provided from the cell bank of Chinese academy of sciences.
2. Reagent: fetal bovine serum was supplied by Hyclone, horse serum and DMEM medium by Gibco, polylysine by Sigma, and NGF by Wuhanhai Biopharmaceutical GmbH.
3. Medicine preparation: compounds 1, 2, 3,4, 16 and 28 are provided by Shanghai-derived Phyllobiotech, Inc.
4. The experimental method comprises the following steps: PC12 cells were cultured in DMEM medium containing 10% horse serum, 5% fetal bovine serum and 1% penicillin/streptomycin at 37 deg.C with 5% CO 2 Culturing in a constant humidity incubator to logarithmic phase. PC12 cells were cultured at 2X 10 4 The density of each well was inoculated in Polylysine (PLL) -coated 24-well plates and co-treated with different concentrations of test compound and 20ng/mL NGF for 72h after adherence. In the experiment, 0.1% DMSO is used as a blank control, and 20ng/mL NGF is used as a positive control. After the compound is acted for 72h, the morphological change of the PC12 cells is observed. When counting, the cells which contain one or more neurites and at least one of which has the length larger than or equal to the diameter of the soma are regarded as positive cells. The cell differentiation rate is defined as the number of positive cells/total cells × 100%.
5. And (3) test results: compounds 1, 2, 3,4 and 28 have significant neurite outgrowth-inhibiting effects. Meanwhile, the neurite outgrowth-promoting effect of compound 24 was gradually enhanced with the increase in concentration. Compared with NGF (cell differentiation rate of 11.49%), the cell differentiation rates of 24 at 0.4 and 0.5. mu.M were 17.93% and 18.71%, respectively.
EXAMPLE 5 anti-neuritic Activity of Andrographis paniculata partial fraction
1. Cell: BV-2 cells were provided by the cell bank of the Chinese academy of sciences.
2. Reagent: fetal bovine serum was supplied by Hyclone, DMEM medium by Gibco, LPS by Sigma, NO detection kit by Biyunnan Bioreagent, Inc., TNF-. alpha.and IL-6 detection kit by doctor's Biotech, Inc.
3. Medicine preparation: compounds 3,4, 16 and 28 are provided by Shanghai-derived leaf Biotech, Inc.
4. The experimental method comprises the following steps: (1) and (3) determination of NO concentration: BV-2 cells were cultured in DMEM medium containing 10% FBS and 1% penicillin/streptomycin at 37 ℃ with 5% CO 2 Culturing in an incubator to logarithmic phase. Cells were plated at 2X 10 4 The density of each well was seeded in 96-well plates and cultured for 24h to allow the cells to adhere. The samples were co-treated with different concentrations of test compound and 1. mu.g/mL LPS for 24 h. The concentration of NO in the culture supernatant was measured using Griess reagent. (2) TNF-alpha and IL-6 concentration assay: after cells were treated with different concentrations of compound and 1. mu.g/mL LPS for 6h (TNF- α) or 24h (IL-6), the effect of the compound on the concentration of proinflammatory mediators tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6) in the culture supernatant of BV-2 cells induced by LPS was examined using a kit, respectively.
5. And (3) test results: 16 of compounds 3,4, 16 and 28 was able to significantly inhibit NO production. The NO inhibition by compound 16 was significantly enhanced with increasing concentration, especially at 20. mu.M, with almost 100% NO inhibition. In addition, the concentration of IL-6 and TNF- α decreased significantly with increasing concentration of compound 16.
And thirdly, evidence of relevant effects of the embodiment. The embodiment of the invention achieves some positive effects in the process of research and development or use, and has great advantages compared with the prior art, and the following contents are described by combining data, diagrams and the like in the test process.
The technical effects of the present invention will be further explained below with reference to specific experiments.
1. Data and method
1.1 Collection and screening of active ingredients of Andrographis paniculata Nees
Active ingredients of andrographis paniculata are searched by means of a traditional Chinese medicine system pharmacology database and an analysis platform (TCMSP) (http:// tcmspw.com/tcmsp.php), and the screening standards are as follows: OB value (oral bioavailability) is more than or equal to 30% and DL value (drug-likeness) is more than or equal to 0.18.
1.2 action target for collecting active ingredients of Andrographis paniculata Nees
The method comprises the steps of setting a search species class as 'Homo sapiens' by means of a library of simple Engine Approach (SEA, http:// SEA. bkslab. org /), Swiss Target Prediction (http:// www.swisstargetprediction.ch /), STITCH (http:// batch. erase. de /) and BAT-TCM (http:// bionet. ncpsb. org/batch-TCM /)1 databases, searching information of main active ingredient targets of the common andrographis herb, merging the databases to obtain the common andrographis herb action targets and carrying out subsequent analysis.
1.3 acquisition of AD and PD disease targets
The obtained Target points are imported into a comprehensive Toxicogenics Database (CTD, http:// ctdbase. org /), a theoretical Target Database (TTD, http:// bid. num. edu. sg/group/cjtd /), GeneCards: The human gene Database (https:// www.genecards.org /), Pharmacogenerics Knowledge Database (https:// www.pharmgkb.org /) and a Mobile analysis System 3.0(MAS 3.0, http:// bio. capetalbio. 3/), and retrieval species are set as "Home samples", retrieval words are respectively "Alzheimer's" and "Parkinson's ' 3/), and The relevant Target points are collected as a Network Database, and The activity of The Target points are analyzed by a subsequent analysis.
1.4 construction of an "active ingredient-target-disease" network
The main Active ingredients of the andrographis paniculata, and Target point information of AD and PD are led into Cytoscope ver.3.7.0(https:// Cytoscope.org /), action targets of the main Active ingredients of the andrographis paniculata on AD and PD are respectively screened out by using the Merge function, an Active ingredient-Target point-Disease Network diagram is drawn, and the control Network diagram is further analyzed to obtain the main Active ingredients of the andrographis paniculata for preventing and treating AD and PD.
1.5KEGG pathway and GO functional enrichment analysis
And converting the screened effect targets into gene names, uploading the gene names to a DAVID database, performing KEGG signal path enrichment analysis and GO function enrichment analysis, and investigating the function distribution of AD and PD related effect targets and possibly related signal regulation and control paths.
1.6 evaluation of NGF-induced neurite outgrowth Activity of PC12 cells
PC12 cells were cultured in DMEM medium containing 10% Horse Serum (HS), 5% Fetal Bovine Serum (FBS) and 1% penicillin/streptomycin at 37 deg.C with 5% CO 2 Culturing in a constant humidity incubator to logarithmic phase.
PC12 cells were cultured at 2X 10 4 The density of each well was inoculated in Polylysine (PLL) -coated 24-well plates and co-treated with different concentrations of test compound and 20ng/mL NGF for 72h after adherence. In the experiment, 0.1% DMSO is used as a blank control, and 20ng/mL NGF is used as a positive control. After the compound is acted for 72h, the morphological change of the PC12 cells is observed. When counting, the cells containing one or more neurites, at least one of which has a length greater than or equal to the diameter of the cell body, are considered positive. The cell differentiation rate was defined as the number of positive cells/total cells × 100%.
1.7 anti-neuritic Activity
BV-2 cells were cultured in DMEM medium containing 10% FBS and 1% penicillin/streptomycin at 37 ℃ with 5% CO 2 Culturing in an incubator to logarithmic phase.
1.7.1 determination of NO content in LPS-induced BV-2 cells
Cells were plated at 2X 10 4 The density of each well was seeded in 96-well plates and cultured for 24h to allow the cells to adhere. The samples were co-treated with different concentrations of test compound and 1. mu.g/mL LPS for 24 h. The concentration of NO in the culture supernatant was measured using Griess reagent.
1.7.2 determination of TNF-. alpha.and IL-6 concentrations in LPS-induced BV-2 cells
After cells were co-treated with different concentrations of compound 16 and 1. mu.g/mL LPS for 6h (TNF- α) or 24h (IL-6), the effect of 16 on the concentration of proinflammatory mediators tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6) in LPS-induced BV-2 cell culture supernatant was examined using the kit, respectively.
2. As a result, the
2.1 screening results of active ingredients of Andrographis paniculata Nees
Screening to obtain 29 active ingredients of herba Andrographitis, and using in constructing herba Andrographitis active ingredient database, including hancein, oroxylin A, storagenin flavone, Scutellariae radix flavone, etc., wherein the specific active ingredients are shown in Table 1.
TABLE 1 Andrographis paniculata Nees active principle
2.2 results of obtaining the action target of Andrographis paniculata Nees active ingredient
Searching SEA, Swiss Target Prediction, STITCH and BATMAN-TCM databases according to a set search strategy, deriving action Target point information of all searched active ingredients of the common andrographis herb, and removing repeated data to obtain 553 action Target points in total.
2.3 obtaining results of AD, PD target spots
Respectively taking 'Alzheimer's disease 'and' Parkinson's disease' as disease keywords, searching CTD, TTD, GeneCards, PharmGKB and MAS 3.0 databases according to a set search strategy, deriving all searched andrographis paniculata active ingredient action target point information, and after removing repeated data, obtaining 116 AD target points (A in figure 2) and 90 PD target points (B in figure 2) in total.
2.4 network construction and analysis of active ingredients and targets
The main active ingredients and action targets related to the andrographis paniculata, AD and PD are led into Cytoscape ver.3.7.0 software for network topology analysis and construction of a visual analysis network diagram. The degree (degree) in the network refers to the number of edges associated with the node, the magnitude of the degree is related to the magnitude of the function of the component in the disease, and the larger the value is, the higher the possibility of preventing and treating the disease of the component is. The average value in the network diagram of "active ingredient-target-AD" is 4.83, and the average value in the network diagram of "active ingredient-target-PD" is 3.75. As a result, it was found that hancein (value 19), oroxylin a (value 14), baicalein (value 9), caffeic acid (value 8), and tsukunin flavone (value 8) in andrographis paniculata are likely to be major active ingredients related to AD (fig. 3 a), and mainly target gene targets such as PTGS2, PTGS1, MAPT, CYP1B1, ABCB1, and the like; oroxylin a (scale value 13), hancein (scale value 11), baicalein (scale value 7), tsukushinin flavone (scale value 6), andrographolide (scale value 6), and glyceryl monooleate (scale value 6) may be main active ingredients (B in fig. 3) related to PD, mainly aiming at gene targets such as PRKCD, ADORA1, MAPT, ABCB1, and the like. The baicalein, oroxylin A, baicalein and thujanin flavone are main active ingredients commonly related to AD and PD.
2.5GO function enrichment analysis and KEGG pathway enrichment analysis
The GO function enrichment analysis shows that the biological process is mainly used when the andrographis paniculata is used for preventing and treating AD, and is mainly related to endogenous drug reaction, lipopolysaccharide reaction, adenylate cyclase inhibition G protein, phospholipase C activation G protein and the like. Cellular processes are mainly associated with axonal terminals, neurodendrites, and molecular functions play a role by affecting G-protein-coupled acetylcholine, drug binding (a in fig. 4). Andrographis paniculata Nees also dominates biological processes in the prevention and treatment of PD, and is mainly related to endogenous drug reaction, lipopolysaccharide reaction, negative regulation of apoptosis, synaptic transmission, cholinergic conductance, and the like. Cellular processes are mainly associated with asymmetric synapses, synaptic transmission, and molecular functions act by affecting the same protein binding, enzyme binding (B in fig. 4).
The enrichment of the KEGG channel of AD indicates that 31 targets are enriched on 23 channels, and mainly relate to signal channels such as Alzheimer's disease, PI3K-Akt signaling path, pathway in cancer, Toxoplasma and the like (A in figure 5); the KEGG channel enrichment of PD suggests that 27 targets are enriched on 13 channels, and mainly relates to signal channels such as Alzheimer's disease, pathway in cancer, Neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and the like (B in FIG. 5). The size of the graph is positively correlated with the degree (degree), the magnitude of the degree is correlated with the magnitude of the function of the pathway in diseases, the larger the value is, the higher the possibility of preventing and treating the diseases through the target is shown, for example, AD and PD are jointly related to signal pathways such as Alzheimer's disease, pathway in cancer, PI3K-Akt signaling pathway and the like.
2.6 Effect of Andrographis paniculata active ingredients on NGF-induced neurite outgrowth of PC12 cells the effect of compounds 1, 2, 3,4, 16 and 28 on NGF-induced neurite outgrowth of PC12 cells at 10. mu.M was tested in a model of NGF-induced PC-12 cells (A in FIG. 6). The results show that compounds 1, 2, 3,4 and 28 have significant neurite outgrowth inhibiting effects. Meanwhile, the test results showed that the neurite outgrowth-promoting effect of compound 24 was gradually enhanced with the increase of the concentration. Compared with NGF (cell differentiation rate of 11.49%), cell differentiation rates of 24 at 0.4 and 0.5. mu.M were 17.93% and 18.71%, respectively (FIG. 6, B).
The experimental group was set up with three independent replicates and data were expressed as mean ± standard deviation with significant differences compared to control as indicated by P <0.05,. P <0.01 and & P <0.001 (one-way analysis of variance ANOVA, Dunnett test).
2.7 Effect of Andrographis paniculata active ingredients on LPS-induced proinflammatory factor concentration in BV-2 cells
The effect of active compounds 3,4, 16 and 28 on LPS-induced NO concentration in the supernatant of BV-2 cells at 1. mu.M and 10. mu.M, respectively, was tested (A in FIG. 7). The results show that compound 16 can significantly inhibit the production of NO. Further studies showed that the NO inhibition of compound 16 was significantly enhanced with increasing concentration, especially at 20. mu.M, with almost 100% NO inhibition (FIG. 7, panel B).
In addition, the effect of Andrographis paniculata Nees active Compound 16 on the levels of proinflammatory factors IL-6 and TNF- α in LPS-induced BV-2 cell culture supernatant was examined using the kit (C in FIG. 7 and D in FIG. 7). The results show that the concentrations of IL-6 and TNF- α decrease significantly with increasing concentrations of compound 16.
The experimental group was set up with five independent replicates and data are presented as mean ± standard deviation with significant differences compared to control as indicated by P <0.05,. P <0.01 and & & P <0.001 (one-way analysis of variance ANOVA, Dunnett test).
3. Conclusion
Under normal physiological conditions, microglia are in a resting state. Under pathological conditions, microglia are continuously over-activated, which in turn promotes the release of proinflammatory factors such as NO, TNF-alpha, IL-6, ROS, etc., thereby damaging healthy neurons, resulting in synaptic dysfunction, loss of synapse, and even neuronal death. A large amount of A beta is commonly accumulated in the brain of an AD patient, and the generated plaques can further induce the activation of microglia, and finally cause damage to neurons. Additional studies have shown that a β deposits can bind to membrane receptors, further leading to neuronal synaptic dysfunction and neuronal apoptosis. Meanwhile, the Abeta oligomer induces Tau phosphorylation at specific pathological positions, thereby damaging the plasticity of hippocampal synapses and causing the phenomenon of memory reduction. A great deal of research also proves that the neuron is extremely vulnerable to oxidative stress due to the characteristics of the neuron, and finally the physiological functions of macromolecules such as protein in the neuron are damaged. In conclusion, the occurrence and development of neurodegenerative diseases are closely related to neuroinflammation, a β aggregation, oxidative stress, and the like. According to research of the literature, the baicalein has the capability of inhibiting a beta secretase pathway related to the treatment of Amyloid Precursor Protein (APP), phosphorylation of Tau protein and A beta accumulation in human neuroblastoma cells. Oroxylin A can inhibit inflammatory response stimulated by LPS by activating the Nrf2-ARE signal pathway resisting oxidative stress and inhibiting the up-regulation of Inducible Nitric Oxide Synthase (iNOS) and COX-2 expression. Meanwhile, in vitro experiments show that oroxylin A can inhibit the survival and growth promotion effects of proinflammatory factors (such as IL-6 and IL-1 beta) by inhibiting the IL-6/Stat3 pathway. Caffeic acid can not only remarkably relieve the learning disorder of an AD model and enhance the cognitive function of the AD model, but also inhibit oxidative stress, inflammation, nuclear factor kB-p 65 protein expression and caspase-3 activity, and can regulate the expression of p53 and phosphorylated p38 MAPK protein. Andrographolide not only prevents the formation of free radicals by protecting mitochondria or inhibiting ROS-producing enzymes, but also promotes the expression of enzymatic or non-enzymatic antioxidants by activating the Nrf2 signaling pathway. In addition, previous research work by the present inventors also showed that andrographolide, the main component of andrographis paniculata, can reduce microglia-mediated neuronal inflammatory injury and oxidative stress-induced neuronal oxidative injury, and that 14-deoxy-11, 12-didehydro-andrographolide and neoandrographolide in andrographis paniculata have certain neurotrophic activity.
In conclusion, the traditional Chinese medicine andrographis paniculata has great potential in preventing and treating neurodegenerative diseases. Therefore, the invention screens the active ingredients of the andrographis paniculata by using a network pharmacology method, effectively analyzes potential targets related to the neurodegenerative diseases AD and PD, obtains 116 targets related to the AD and 90 targets related to the PD, finds that the active ingredients of the andrographis paniculata comprise more targets of the fraxinin, the oroxylin A, the baicalein and the capsaicine flavone for the AD and the PD, and speculates that the compounds are important compounds for the effect of the andrographis paniculata on preventing and treating the neurodegenerative diseases. Meanwhile, a 'target-signal path' network is constructed in a visualized manner, and analysis shows that the action pathways of the andrographis paniculata for preventing and treating AD and PD are mainly related to the promotion of cell survival, the inhibition of apoptosis, the participation in cell proliferation and cell cycle processes, the influence on the interaction of a nerve active ligand-receptor and the like. The invention carries out the test of neurotrophic and anti-neuritis activity aiming at part of the 29 compounds obtained by screening. The results show that the andrographis paniculata active ingredient 24 can remarkably promote the growth of nerve axons of the NGF-induced PC12 cells, and the compound 16 can remarkably inhibit the production of proinflammatory factors in the LPS-induced BV-2 cells.
The invention systematically analyzes potential targets of andrographis paniculata for preventing and treating AD and PD and key signal channels based on a network pharmacological method, provides a theoretical basis for andrographis paniculata for preventing and treating neurodegenerative diseases, and provides a method and an idea for the research of subsequent related medicines.
The invention analyzes and obtains 29 main active ingredients of the andrographis paniculata, 553 action targets of the active ingredients of the andrographis paniculata, 116 targets related to AD and 90 targets related to PD. GO and KEGG analysis shows that andrographis paniculata has potential prevention and treatment effects on AD by mainly passing through chemical components such as hanbain baicalein, oroxylin A, baicalein, perilla nankinetin flavone and caffeic acid, aiming at targets such as PTGS2, PTGS1, MAPT, CYP1B1 and ABCB1, and relating to signal pathways such as Alzheimer's disease, PI3K-Akt signaling pathway, pathways in cancer and Toxoplasma; mainly uses chemical components such as hancein, oroxylin A, baicalein, perilla nankinetin, andrographolide, glycerol monooleate and the like, aims at target points such as PRKCD, ADORA1, MAPT, ABCB1 and the like, and relates to a potential prevention and treatment effect of signal channels such as Alzheimer's disease, pathway in cancer, Neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and the like on PD. Neurotrophic activity results showed that compounds 1, 2, 3,4 and 28 were able to inhibit neurite outgrowth at 10 μ M; compound 24 has significant neurite outgrowth-promoting activity, with a cell differentiation rate of 18.71% (NGF at 10.34%) at 0.5. mu.M. The anti-neuritic activity results show that compound 16 can significantly inhibit LPS-induced production of inflammatory factors NO, TNF- α and IL-6 in BV-2 cells. And (4) conclusion: the potential main active components, target points and signal paths of the andrographis paniculata in preventing and treating neurodegenerative diseases are preliminarily predicted through network pharmacology, so that a new idea is provided for research and development of neurodegenerative disease drugs.
The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. An application of herba Andrographitis in preparing medicine for preventing neurodegenerative diseases is provided.
2. The use according to claim 1, wherein the medicament for neurodegenerative diseases comprises an active ingredient of Andrographis paniculata Nees.
3. The use of claim 1, wherein the active ingredients of Andrographis paniculata Nees comprise: radix Stellariae extract, oroxylin A, Scutellariae radix flavone and herba Capsellae flavone.
4. The use of claim 1, wherein the active ingredient of Andrographis paniculata Nees acts by promoting NGF-induced neurite outgrowth in PC12 cells.
5. The use of claim 1, wherein the active ingredient of Andrographis paniculata Nees acts by inhibiting LPS-induced pro-inflammatory factor production in BV-2 cells.
6. The use of claim 1, wherein the neurodegenerative disease comprises: alzheimer's disease and Parkinson's disease.
7. The Networknifedia activity assay method for verifying the use of claim 1, wherein the Networknifedia activity assay method comprises:
step one, TCMSP is used for obtaining and screening active ingredients of common andrographis herb; and obtaining potential targets related to the active ingredients of the andrographis paniculata through SEA, Swiss, STITCH and BATMAN-TCM databases;
step two, screening and obtaining targets related to Alzheimer's disease and Parkinson's disease in the potential targets by using CTD, TTD, GeneCards, PharmGKB and MAS 3.0;
step three, performing gene ontology analysis and Kyoto gene and KEGG analysis on the target spots obtained in the step two through DAVID;
step four, constructing an active ingredient-target spot and a target spot-passage network diagram of the andrographis paniculata by adopting Cytoscape;
and step five, analyzing the obtained active ingredient-target and target-pathway network diagram of the andrographis paniculata to determine the active ingredients in the active ingredients of the andrographis paniculata, which can be used for preparing the medicines for preventing the neurodegenerative diseases.
8. The cyber-pharmacological-based andrographis paniculata activity assay method of claim 7, wherein the first step of obtaining and screening andrographis paniculata active ingredients using TCMSP comprises: screening the active ingredients of the andrographis paniculata with OB value more than or equal to 30% and DL value more than or equal to 0.18 by TCMSP and constructing an andrographis paniculata active ingredient database.
9. The method for measuring andrographis paniculata activity based on cybepharmacology of claim 7, wherein in the fourth step, the construction of the active ingredient-target and target-pathway network map of andrographis paniculata by using Cytoscape comprises:
leading main active ingredients and effects related to Alzheimer's disease and Parkinson's disease in the common andrographis herb into Cytoscape, carrying out network topology analysis, and constructing a visual active ingredient-target and target-pathway network diagram of the common andrographis herb.
10. The Nephrpharmacology-based Andrographis paniculata Nees activity assay of claim 7, wherein the Nephrpharmacology-based Andrographis paniculata Nees activity assay further comprises:
the neurotrophic and anti-neuritic activity of the active components of the andrographis paniculata part is detected by taking PC12 cells induced by nerve growth factor NGF and BV-2 cells induced by lipopolysaccharide LPS as models.
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| CN113178226A (en) * | 2021-03-24 | 2021-07-27 | 沈阳化工大学 | Method for resisting Alzheimer disease by using cherokee rose fruit triterpenoid |
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| CN113178226A (en) * | 2021-03-24 | 2021-07-27 | 沈阳化工大学 | Method for resisting Alzheimer disease by using cherokee rose fruit triterpenoid |
Non-Patent Citations (1)
| Title |
|---|
| LILI GU ET AL: "A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer\'s disease and experimental validation", 《JOURNAL OF ETHNOPHARMACOLOGY》, vol. 251, pages 9 * |
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