CN114099599A - Application of composition of ciliate desert-grass and beta-caryophyllene in preventing and treating virus infection - Google Patents
Application of composition of ciliate desert-grass and beta-caryophyllene in preventing and treating virus infection Download PDFInfo
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- CN114099599A CN114099599A CN202111391574.2A CN202111391574A CN114099599A CN 114099599 A CN114099599 A CN 114099599A CN 202111391574 A CN202111391574 A CN 202111391574A CN 114099599 A CN114099599 A CN 114099599A
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- NPNUFJAVOOONJE-ZIAGYGMSSA-N β-(E)-Caryophyllene Chemical compound C1CC(C)=CCCC(=C)[C@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-ZIAGYGMSSA-N 0.000 title claims abstract description 68
- 239000000203 mixture Substances 0.000 title claims abstract description 42
- NPNUFJAVOOONJE-UHFFFAOYSA-N beta-cariophyllene Natural products C1CC(C)=CCCC(=C)C2CC(C)(C)C21 NPNUFJAVOOONJE-UHFFFAOYSA-N 0.000 title claims abstract description 34
- NPNUFJAVOOONJE-UONOGXRCSA-N caryophyllene Natural products C1CC(C)=CCCC(=C)[C@@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-UONOGXRCSA-N 0.000 title claims abstract description 34
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/89—Cyperaceae (Sedge family)
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention provides a composition for preventing and/or treating virus infection, which comprises shortleaf kyllinga herb or extract thereof and beta-caryophyllene; wherein the virus comprises RNA virus and DNA virus, the RNA virus is RNA virus causing fever infectious disease, and is selected from one or more of HIV virus, Ebola virus, Marburg virus, Lassa fever virus, rabies virus, hepatitis A virus and hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are not included; the DNA virus is selected from one or more of hepatitis B virus and HPV virus. Particularly, the invention discovers that the composition of the shortleaf meadowsweet herb and the beta-caryophyllene can effectively inhibit cell infection caused by HIV pseudovirus, and compared with the single application of the shortleaf meadowsweet herb and the beta-caryophyllene, the composition has a synergistic effect. Therefore, the compound can effectively prevent and/or treat virus infection or diseases caused by virus infection, and can be used as an antiviral drug.
Description
Technical Field
The invention belongs to the technical field of pharmacy and antivirus, and particularly relates to an application of a composition of shortleaf kyllinga herb and beta-caryophyllene in preventing and/or treating virus infection.
Background
A virus is a noncellular organism that is small, simple in structure, must be parasitic in living cells and proliferated in a replicative manner. The chemical components of the viral nucleic acid are DNA or RNA, and the viruses are divided into two main categories, namely DNA viruses and RNA viruses. Nucleic acids can be linear or circular and can be divided into single or double strands.
DNA viruses are widely present in humans, vertebrates, insects, and in a variety of continuous cell lines, each virus infects only one animal (with individual exceptions) and causes only a few diseases.
RNA viruses have two replication modes, namely self-replication and reverse transcription, and in the replication process of viral RNA, the activity of enzyme of an error repair mechanism is very low and almost none, so that the mutation is very quick. RNA viruses are more susceptible to disease, are more lethal to the host, are more mutable, and are more diverse than DNA viruses, are more difficult to develop effective vaccines, and are difficult to prevent.
HIV, a Human Immunodeficiency Virus, is a Virus that causes a defect in the Human immune system. The virus destroys the immunity of the human body, resulting in the loss of resistance of the immune system, thereby causing various diseases and cancers to be preserved in the human body, and finally resulting in Acquired Immune Deficiency Syndrome (AIDS).
The HIV virus is a Lentivirus (Lentivirus) that infects cells of the human immune system, and belongs to a kind of retrovirus. AIDS virus mainly invades the immune system of human body, including CD4+ T lymphocyte, monocyte macrophage and DC, etc., and is mainly characterized in that the quantity of CD4+ T lymphocyte is continuously reduced, finally the cell immune function of human body is deficient, and various opportunistic infections and tumors are caused. Aids virus infection increases the risk of cold, influenza and pneumonia, as well as the risk of pulmonary hypertension. In addition, HIV also makes it easier for infected individuals to infect tuberculosis.
At present, the modern medicine for treating AIDS mainly comprises four methods: antiviral therapy, immunodeficiency therapy, treatment of symptomatology infection and tumor therapy, but medicines commonly used in western medicine may have large side effects, such as liver and kidney injury, rash, granulocytopenia and the like.
The traditional medicine treatment has obvious advantages in preventing diseases, improving clinical symptoms, preventing mild to severe and severe to critical.
The shortleaf kyllinga herb is a cyperaceae plant shortleaf kyllinga herb, the rhizome of which grows and creeps, and has a plurality of internodes, the length of the internodes is about 1.5 cm, and each node is provided with a stalk. The chemical components of the shortleaf kyllinga herb contain volatile oil, and the shortleaf kyllinga herb can be used for treating cold and wind-cold, fever and coldness headache, arthralgia and myalgia, cough, malaria, jaundice, dysentery, pyocutaneous disease and pyogenic infections, and traumatic injuries and knife wounds. At present, the application of the shortleaf meadowsweet in the aspect of antivirus is not much concerned.
Beta-caryophyllene is a bicyclic sesquiterpene compound, which is present in many plant essential oils, such as clove essential oil, ginger essential oil, pepper essential oil or cinnamon essential oil, and the like, and is defined as a gras (general recognited as safe) food compound by the FDA in the united states because of low toxicity, and is approved for use in cosmetics and food additives; at present, there is not much concern about the medical application of beta-caryophyllene.
Disclosure of Invention
The invention aims to provide a composition for preventing and/or treating virus infection and application thereof in resisting virus.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides the application of a composition of shortleaf kyllinga herb or an extract thereof and beta-caryophyllene in preparing a medicament and/or food for preventing and/or treating viral infection or diseases caused by viral infection.
The shortleaf kyllinga herb is a centipede belonging to the family Cyperaceae.
In the composition, the shortleaf kyllinga herb can be in the form of hay, powder or extract, the shortleaf kyllinga herb extract refers to an aqueous extract or an organic solvent extract of shortleaf kyllinga herb, the organic solvent is selected from one or more of methanol, ethanol, propanol, acetone, petroleum ether, diethyl ether and ethyl acetate, and the preferred solvent is selected from one or more of water, ethanol, diethyl ether and ethyl acetate.
The virus comprises RNA virus and DNA virus, the RNA virus is RNA virus causing fever infectious disease, and is selected from one or more of HIV virus, Ebola virus, Marburg virus, Lassa fever virus, rabies virus, hepatitis A virus and hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are not included; the DNA virus is selected from one or more of hepatitis B virus and HPV virus.
Preferably, the virus is selected from one or more of HIV virus, ebola virus, rabies virus, HPV virus and hepatitis b virus.
The diseases include AIDS, hemorrhagic fever, rabies, hepatitis A, hand, foot and mouth, respiratory tract infection, pharyngolaryngitis, rash, lymphadenectasis, hepatitis B and/or cervical infection. Preferably, the disease is acquired immunodeficiency syndrome and its complications caused by HIV infection.
In a second aspect, the invention provides the use of a composition of shortleaf kyllinga herb or an extract thereof and beta-caryophyllene for the prophylactic and/or therapeutic treatment of a viral infection or a disease caused by a viral infection.
The shortleaf kyllinga herb is a centipede belonging to the family Cyperaceae.
In the composition, the shortleaf kyllinga herb can be in the form of hay, powder or extract, the shortleaf kyllinga herb extract refers to an aqueous extract or an organic solvent extract of shortleaf kyllinga herb, the organic solvent is selected from one or more of methanol, ethanol, propanol, acetone, petroleum ether, diethyl ether and ethyl acetate, and the preferred solvent is selected from one or more of water, ethanol, diethyl ether and ethyl acetate.
The virus comprises RNA virus and DNA virus, the RNA virus is RNA virus causing fever infectious disease, and is selected from one or more of HIV virus, Ebola virus, Marburg virus, Lassa fever virus, rabies virus, hepatitis A virus and hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are not included; the DNA virus is selected from one or more of hepatitis B virus and HPV virus.
Preferably, the virus is selected from one or more of HIV virus, ebola virus, rabies virus, HPV virus and hepatitis b virus.
The diseases include AIDS, hemorrhagic fever, rabies, hepatitis A, hand, foot and mouth, respiratory tract infection, pharyngolaryngitis, rash, lymphadenectasis, hepatitis B and/or cervical infection. Preferably, the disease is acquired immunodeficiency syndrome and its complications caused by HIV infection.
In a third aspect, the present invention provides a composition for preventing and/or treating viral infection, comprising Grateloupia filicina or an extract thereof and beta-caryophyllene.
The shortleaf kyllinga herb is a centipede belonging to the family Cyperaceae.
In the composition, the shortleaf kyllinga herb can be in the form of hay, powder or extract, the shortleaf kyllinga herb extract refers to an aqueous extract or an organic solvent extract of shortleaf kyllinga herb, the organic solvent is selected from one or more of methanol, ethanol, propanol, acetone, petroleum ether, diethyl ether and ethyl acetate, and the preferred solvent is selected from one or more of water, ethanol, diethyl ether and ethyl acetate.
The virus comprises RNA virus and DNA virus, the RNA virus is RNA virus causing fever infectious disease, and is selected from one or more of HIV virus, Ebola virus, Marburg virus, Lassa fever virus, rabies virus, hepatitis A virus and hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are not included; the DNA virus is selected from one or more of hepatitis B virus and HPV virus.
In some embodiments, the virus is an HIV virus.
In some embodiments, the virus is an ebola virus.
In some embodiments, the virus is a rabies virus.
In some embodiments, the virus is an HBV virus.
In some embodiments, the virus is an HPV virus.
Preferably, the composition is a pharmaceutical composition, which further comprises a pharmaceutically acceptable adjuvant and/or carrier.
Preferably, the pharmaceutical composition is in a form of gastrointestinal administration, injection administration or respiratory administration.
Preferably, the pharmaceutical composition is in a dosage form selected from the group consisting of powder, tablet, granule, capsule, solution, emulsion, suspension, injection, spray, aerosol, and powder spray.
Preferably, the composition is a food composition, which further comprises a dietetically acceptable adjuvant and/or carrier.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention discovers that the composition of the shortleaf kyllinga herb or the extract thereof and the beta-caryophyllene can effectively inhibit cell infection caused by HIV pseudovirus, and the inhibition effect is higher than that of the application of the shortleaf kyllinga herb and the beta-caryophyllene alone. In the composition of the shortleaf kyllinga herb and the beta-caryophyllene, the concentrations of the shortleaf kyllinga herb and the beta-caryophyllene are relatively reduced compared with the single application, and although the dosage is reduced, the inhibition effect on viruses is obviously improved, thereby showing that the combined application of the shortleaf kyllinga herb and the beta-caryophyllene has the synergistic effect. Therefore, it can be used for preventing and/or treating diseases caused by HIV virus infection. When the composition of the shortleaf kyllinga herb and the beta-caryophyllene is applied to medicines and/or foods, the dosage can be greatly reduced, and the dosage is small, the effect is good, so that the possible side effect or adverse reaction of a human body can be reduced.
(2) The composition of the shortleaf kyllinga herb or the extract thereof and the beta-caryophyllene provided by the invention can effectively prevent and/or treat diseases (including AIDS, hemorrhagic fever, rabies, hepatitis A, hand, foot and mouth, respiratory tract infection, sphagitis, rash, lymphadenectasis, hepatitis B and/or cervical infection and the like) caused by virus infection, and can be applied as an antiviral medicament.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
This example provides a composition of an aqueous extract of Grateloupia filicina and beta-caryophyllene.
8.9 g of dry centipede herb, after being cleaned, 500 ml of water is added, the mixture is heated for 20 minutes, and supernatant is taken out and filtered, and the mixture is diluted to 2187 times. Adding beta-caryophyllene to make the final concentration of the beta-caryophyllene in the solution be 5 mg/mL.
Comparative example 1
This comparative example provides an aqueous solution of beta-caryophyllene at a concentration of 5 mg/mL.
Comparative example 2
The present comparative example provides an aqueous extract of Pteris vittata.
8.9 g of dry centipede herb, after being cleaned, 500 ml of water is added, the mixture is heated for 20 minutes, and supernatant is taken out and filtered, and the mixture is diluted to 2187 times.
Experimental example 1 Performance test
The substances provided in example 1 and comparative examples 1-2 were subjected to a performance test, and whether the sample had an inhibitory effect on HIV pseudovirus was judged by the following test method:
experiment of
The HIV neutralization test comprises two parts, namely pseudovirus preparation and detection after pseudovirus infection, wherein the pseudovirus preparation is realized by cotransfecting eukaryotic expression cells (293FT) by two plasmids: one of the plasmids is pSG3 Δ Env, which expresses all genes of HIV except Env (i.e. backbone plasmid); another plasmid is pcDNA3.1-Env, which expresses the full-length Env gene. In pseudovirus production, only the backbone plasmid is transcribed into viral genomic RNA and packaged into pseudovirus, and thus the pseudovirus produced does not have the replication ability to produce progeny virus, but only has a single round of infection. TZM-bl cells are HeLa cells with modified CXCR4+, the modified cells stably express surface molecules CD4 and CCR5, and further modification enables the genome of the cells to integrate firefly luciferase reporter genes, and the expression of the firefly luciferase reporter genes is controlled by HIV long terminal repeat sequences. In the pseudovirus infection process, the HIV pseudovirus strain infects TZM-bl cells through a cell surface receptor and an auxiliary receptor, the intracellular Tat gene is expressed, the expressed Tat protein activates the expression of a reporter gene in cis, and after a corresponding luciferase substrate is added, a generated luminescence signal (relative luminescence unit, RLU) is in direct proportion to the number of viruses infecting the cells.
Incubation and sample application
Plate paving: TZM-bl cells were seeded in 96-well plates and cultured for 24 h.
Sample group: the diluted samples were mixed with HIV pseudovirus (200TCID50) in 50. mu.L aliquots, incubated for 1h at 37 ℃ in an incubator, and added to pre-plated TZM-bl cells.
Positive control group: HIV pseudovirus (200TCID50) and complete medium were mixed in equal volumes of 50. mu.L each, incubated for 1h at 37 ℃ in an incubator, and added to pre-plated TZM-bl cells.
Negative control group: mu.L of complete medium was taken, incubated for 1h at 37 ℃ in an incubator and added to the pre-plated TZM-bl cells.
In the sample group, the positive control group and the negative control group, after 1 hour of addition to the TZM-bl cells plated in advance, DEAE accelerating agent was added to a final concentration of 15. mu.g/ml at 37 ℃ with 5% CO2The cultivation was continued in the incubator for 48 h. The chemiluminescence apparatus performs luminescence value detection on samples in a 96-well plate.
Inhibition (%) < 1- (mean sample RLU-mean negative control RLU)/(mean positive control RLU-mean negative control RLU).
When the inhibition rate is less than 50%, it indicates that the sample has substantially no neutralization inhibition.
Table 1 shows the results of testing the materials provided in example 1 and comparative examples 1-2:
TABLE 1
| Sample (I) | RLU | Inhibition rate/%) |
| Example 1 | 1.18E+05 | 93.56 |
| Comparative example 1 | 1.56E+06 | 14.29 |
| Comparative example 2 | 1.50E+06 | 17.50 |
| Positive control | 1.83E+06 | - |
Note: the RLU value for the negative control was 270.
As can be seen from the comparison between example 1 and comparative examples 1-2, the inhibition rates were less than 20% when Pteris vittata alone and when beta-caryophyllene alone were used, indicating that there was substantially no neutralization inhibition of HIV infection. Surprisingly, when the beta-caryophyllene and the shortleaf kyllinga herb are combined and applied in the same amount as in the comparative examples 1-2, the inhibition rate of HIV infection reaches over 90 percent, and unexpected technical effect is obtained.
Experimental example 2.
To further verify the effect of the composition of Grateloupia filicina extract and β -caryophyllene, the composition of example 1 was diluted to 1/0.75 times, 1/0.5 times, 1/0.4 times, and 1/0.25 times. The degree of inhibition of HIV pseudovirus by the sample was determined in the same manner as in Experimental example 1.
Table 2 shows the results of the test of the composition of example 1 after dilution:
TABLE 2
As can be seen from the experimental results in Table 2, the composition of Geranium strictipes and beta-caryophyllene still has an inhibitory effect of 80% or more when diluted to 2.5 times. This indicates that in the composition of the shortleaf kyllinga herb and the beta-caryophyllene, although the concentrations of the shortleaf kyllinga herb and the beta-caryophyllene are further reduced compared with the concentrations of the shortleaf kyllinga herb and the beta-caryophyllene which are used independently, the virus inhibition effect is still remarkable. When the composition of the shortleaf kyllinga herb and the beta-caryophyllene is applied to medicines and/or foods, the dosage of each component can be greatly reduced, and because the dosage is small and the effect is good, the possible side effect or adverse reaction of a human body can be reduced, the possible intolerance or sensitization of the medicines or the foods is further reduced, the safety is greatly improved, and the composition has very important significance for practical application.
As can be seen from the above examples and performance tests, the composition of the shortleaf kyllinga herb or the extract thereof and the beta-caryophyllene provided by the invention has a good inhibitory effect on HIV pseudoviruses, and can be used for preventing and/or treating diseases or symptoms caused by HIV virus infection.
The applicant states that the present invention is illustrated by the above examples of compositions for the prevention and/or treatment of viral infections according to the present invention, but the present invention is not limited to the above detailed methods, i.e. it is not meant to imply that the present invention must rely on the above detailed methods for its implementation. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
Claims (10)
1. Use of a combination of Grateloupia filicina or an extract thereof and beta-caryophyllene for the manufacture of a medicament and/or food for the prevention and/or treatment of viral infections or diseases caused by viral infections, wherein the viruses include RNA viruses and DNA viruses, the RNA viruses are RNA viruses causing febrile infectious diseases and are selected from one or more of HIV viruses, Ebola viruses, Marburg viruses, Lassa viruses, rabies viruses, hepatitis A viruses, hand-foot-and-mouth viruses, with the proviso that influenza viruses and herpes viruses are excluded; the DNA virus is selected from one or more of hepatitis B virus and HPV virus.
2. The use according to claim 1, wherein the virus is selected from one or more of the group consisting of HIV virus, ebola virus, rabies virus, HPV virus and hepatitis b virus.
3. The use of claim 1, wherein the disease comprises aids, hemorrhagic fever, rabies, hepatitis a, hand, foot and mouth, respiratory tract infections, pharyngolaryngitis, rash, lymphadenectasis, hepatitis b and/or cervical infections.
4. Use of a composition of shortleaf kyllinga herb or extract thereof and beta-caryophyllene for the prevention and/or treatment of viral infection or disease caused by viral infection, wherein the virus comprises RNA virus and DNA virus, the RNA virus is an RNA virus causing febrile infectious disease and is selected from one or more of HIV virus, ebola virus, marburg virus, lassa fever virus, rabies virus, hepatitis a virus, hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are excluded; the DNA virus is selected from one or more of hepatitis B virus and HPV virus.
5. The use according to claim 4, wherein the virus is selected from one or more of the group consisting of HIV virus, Ebola virus, rabies virus, HPV virus and hepatitis B virus.
6. The use of claim 4, wherein the disease is selected from the group consisting of AIDS, hemorrhagic fever, rabies, hepatitis A, hand, foot and mouth, respiratory tract infections, pharyngolaryngitis, rash, lymphadenectasis, hepatitis B and/or cervical infections.
7. A composition for preventing and/or treating viral infection, comprising Grateloupia filicina or its extract and beta-caryophyllene;
wherein the virus comprises RNA virus and DNA virus, the RNA virus is RNA virus causing fever infectious disease, and is selected from one or more of HIV virus, Ebola virus, Marburg virus, Lassa fever virus, rabies virus, hepatitis A virus and hand-foot-and-mouth virus, with the proviso that influenza virus and herpes virus are not included; the DNA virus is selected from one or more of hepatitis B virus and HPV virus;
preferably, the virus is selected from one or more of HIV virus, ebola virus, rabies virus, HPV virus and hepatitis b virus.
8. The composition of claim 7, wherein the composition is a pharmaceutical composition, further comprising a pharmaceutically acceptable excipient and/or carrier.
9. The composition of claim 8, wherein the pharmaceutical composition is in a form for gastrointestinal administration, injection administration or respiratory administration;
preferably, the pharmaceutical composition is in a dosage form selected from the group consisting of powder, tablet, granule, capsule, solution, emulsion, suspension, injection, spray, aerosol, and powder spray.
10. The composition according to claim 7, wherein the composition is a food composition, further comprising a dietetically acceptable adjuvant and/or carrier.
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Non-Patent Citations (2)
| Title |
|---|
| ESTARI MAMIDALA等: "Potent HIV-1 Reverse Transcriptase Activity β-caryophyllene: A Novel Terpenoid Component Isolated from Terminalia chebula Ritz", 《MADRIDGE J FOOD TECHNOL》 * |
| REMYA MOHANRAJ等: "Anti HIV-1 and Anti-Bacterial activity of the leaf extracts of Aristolochia elegans", 《J.TROP.MED.PLANTS》 * |
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