US20140030364A1 - Antiviral compositions comprising ethanol extract of tetracera scandens and use thereof - Google Patents

Antiviral compositions comprising ethanol extract of tetracera scandens and use thereof Download PDF

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Publication number
US20140030364A1
US20140030364A1 US13/852,321 US201313852321A US2014030364A1 US 20140030364 A1 US20140030364 A1 US 20140030364A1 US 201313852321 A US201313852321 A US 201313852321A US 2014030364 A1 US2014030364 A1 US 2014030364A1
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Prior art keywords
ethanol extract
scandens
present
reverse transcriptase
composition
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Abandoned
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US13/852,321
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English (en)
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Ji Chang You
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Industry Academic Cooperation Foundation of Catholic University of Korea
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Industry Academic Cooperation Foundation of Catholic University of Korea
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Assigned to THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION reassignment THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: YOU, JI CHANG
Publication of US20140030364A1 publication Critical patent/US20140030364A1/en
Priority to US14/467,610 priority Critical patent/US9084758B2/en
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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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the present invention relates to an antiviral composition including an ethanol extract of Tetracera scandens as an effective component, and use thereof.
  • RNA viruses are viruses having RNA as their genomes.
  • the RNA viruses have (+)-stranded RNA (positive sense RNA), complimentary ( ⁇ )-stranded RNA (negative sense RNA), or double-stranded RNA, which is transcribed into mRNA, as their genomes.
  • the (+)-stranded RNA may be translated to produce proteins when host cells are infected with the (+)-stranded RNA, and the ( ⁇ )-stranded RNA is converted into (+)-stranded RNA by RNA polymerase, and then translated to produce proteins. Therefore, an infection rate is high in the case of viruses having (+)-stranded RNA.
  • RNA viruses have RNA as their genomes, there is no proof-reading done by DNA polymerase, which leads to a significant increase in mutagenesis compared with DNA viruses.
  • new RNA viruses such as SARS, hepatitis C, and polio, which cause diseases in humans, continue to appear, and there is a limit in producing vaccines against the new RNA viruses.
  • commercially available antiviral agents include nucleoside derivatives such as iododeoxyuridine (IDU), acyclovir (ACV) or azidothymidine (AZT), or proteins such as interferon (IFN).
  • IDU iododeoxyuridine
  • ACV acyclovir
  • AZT azidothymidine
  • IFN interferon
  • various side effects of the antiviral agents for example, cytotoxicity, hepatotoxicity and drug resistance, have been reported. Therefore, there is a demand for development of a therapeutic agent for preventing or treating viral infections which has superior effects and few side
  • Tetracera scandens is a flowering plant which belongs to the Dilleniaceae family and grows mainly in Vietnam, and much research on its medical effects is being conducted.
  • T. scandens has a pharmacological effect on an inflammatory response (Biol. Pharm. Bull. (2004) 27: 1414), and it was disclosed that a 4H-chromen-4-one derivative included in an extract of T. scandens serves to enhance glucose intake (Korean Patent No. 10-0979459).
  • T. scandens shows an antiviral effect by inhibiting reverse transcriptase activities of RNA viruses.
  • the present invention is designed to solve the problems of the prior art, and it is an object of the present invention to provide a composition for preventing or treating a viral infection, which includes an ethanol extract of Tetracera scandens as an effective component.
  • One aspect of the present invention provides a composition for preventing or treating a viral infection, which includes an ethanol extract of T. scandens as an effective component.
  • the ethanol may be 10% to 100% ethanol.
  • the composition may inhibit reverse transcriptase activities of an RNA virus.
  • the virus is an RNA virus.
  • the RNA virus may be selected from the group consisting of an influenza virus, a human immunodeficiency virus, a coronavirus, and tobacco mosaic virus.
  • FIG. 1 is a diagram showing the results of confirming the cytotoxicity of an ethanol extract of Tetracera scandens using a GLO assay
  • FIG. 2 is a diagram showing the results obtained by measuring the antiviral activities of the ethanol extract of T. scandens
  • FIG. 3 is a diagram showing the results obtained by determining an effect of the ethanol extract of T. scandens on inhibition of reverse transcriptase activities.
  • FIG. 4 is a diagram showing the results obtained by determining an effect of the ethanol extract of T. scandens on inhibition of intracellular reverse transcriptase activities.
  • the present inventors have conducted much research on a pharmaceutical composition for preventing and/or treating a viral infection, which has superior effects and few side effects. Therefore, the present invention was completed based on these facts.
  • the ethanol extract inhibits reverse transcriptase activities of viruses (see Example 4), and also that the ethanol extract exhibits no toxicity in a host cell and effectively inhibits reverse transcriptase activities of viruses to suppress growth of the viruses (see Examples 3 and 5).
  • the ethanol extract of T. scandens according to the present invention is expected to be applied to prevention and/or treatment of various kinds of infections of RNA viruses. Therefore, one aspect of the present invention provides a composition preventing and/or treating a viral infection, which includes the ethanol extract of T. scandens as an effective component.
  • a concentration of the ethanol is not limited, but may be preferably in a range of 10% to 100%, more preferably 60% to 80%.
  • the composition is applicable to all kinds of RNA viruses using reverse transcriptase since the composition inhibits reverse transcriptase activities of viruses to suppress growth of the viruses.
  • the RNA virus may be an influenza virus, a human immunodeficiency virus, a coronavirus, or tobacco mosaic virus.
  • composition according to the present invention may include a pharmaceutically available carrier.
  • the pharmaceutically available carrier may include physiological saline, polyethylene glycol, ethanol, a vegetable oil, and isopropyl myristate, but the present invention is not limited thereto.
  • Another aspect of the present invention provides a method of treating a viral infectious disease.
  • the method includes administering a pharmaceutically effective amount of a composition including an ethanol extract of T. scandens as an effective component to a subject.
  • the term “subject” refers to a patient in need of treatment of a disease, and, more particularly, a mammal such as a human, a non-human primate, a mouse, a rat, a dog, a cat, a horse, and cattle.
  • the pharmaceutically effective amount of the composition may be properly adjusted according to body weight, age, sex, and health condition of a patient, diet, an administration time, a method of administration, an excretion rate, and severity of a disease.
  • a desirable dose of the composition according to the present invention may vary according to conditions and body weight of a patient, severity of a disease, a type of a drug, a route of administration, and duration, and may be properly selected by those skilled in the art.
  • the composition may preferably be administered daily at a dose of 0.001 to 100 mg/kg, and more preferably a dose of 0.01 to 30 mg/kg.
  • the composition may be administered once a day, or administered in divided doses.
  • the ethanol extract of T. scandens according to the present invention may be present at a content of 0.0001 to 10% by weight, preferably 0.001 to 1% by weight, based on the total weight of the composition.
  • composition according to the present invention may be administered to a mammal such as a rat, a mouse, a domestic animal and a human through various routes of administration.
  • a method of administration is not limited.
  • the composition may be administered orally, rectally, or by intravenous, intramuscular, subcutaneous, endocervical, or intracerebroventricular injection.
  • T. scandens To prepare an ethanol extract of T. scandens, 30 to 40 g of T. scandens was immersed in 100 mL of 70% ethanol, and then cultured for 3 days. Thereafter, the cultured solution was put into a speed bag, and dried at 40° C. for 24 hours to prepare 200 g of an ethanol extract of T. scandens . Then, 500 ⁇ L of dimethyl sulfoxide (DMSO) was added per 40 mg of the prepared ethanol extract, which was then stored as a 20 ⁇ M concentrated solution.
  • DMSO dimethyl sulfoxide
  • the ethanol extract of T. scandens prepared in the same manner as in Example 1 was diluted with 0.5% DMSO to an increasing concentration of 0.4, 4, 40, and 400 ⁇ g/mL, and then treated with MT-4 cell line (1 ⁇ 10 4 cells) as T-lymphocyte cells. Then, the resulting reaction mixture was cultured at 37° C. for 3 days under a 5% CO 2 condition, and cell viability was measured using a Cell Titer-Glo assay kit. A group of MT-4 cells treated only with 0.5% DMSO was used as the control. The results are shown in FIG. 1 .
  • the cytotoxicity was increasingly expressed according to a concentration of the ethanol extract of T. scandens .
  • the ethanol extract of T. scandens exhibited no toxicity to cells when a concentration of the ethanol extract was equal to or less than 4 ⁇ g/mL, but approximately 90% of the cells died when the ethanol extract was present at a concentration of 400 ⁇ g/mL.
  • the ethanol extract of T. scandens had a mean CC 50 (50% cytotoxic concentration) value of 40 ⁇ g/mL.
  • an MT-4 cell line (2 ⁇ 10 5 cells) was treated with the ethanol extract of T. scandens prepared in the same manner as in Example 1 at concentrations of 0, 0.4, and 4 ⁇ g/mL, infected with 20,000 pg of a human immunodeficiency virus (HIV) in which an Nef protein was substituted with an EGFP protein, and then cultured at 37° C. for 3 days under a 5% CO 2 condition. Thereafter, the cultured cells were centrifuged at 6,000 rpm for 3 minutes to obtain a cell pallet.
  • HAV human immunodeficiency virus
  • FIGS. 2A and 2B it was revealed that the positive control which was treated with 1 nM AZT having no effect on cell viability exhibited an antiviral activity of 49.8%, and samples treated with 0.4 ⁇ g/mL and 4 ⁇ g/mL of the ethanol extract had antiviral activities of 34.7% and 86.8%, respectively.
  • FIG. 2C it was also revealed that the cytotoxicity was increasingly expressed according to a concentration of the ethanol extract of T. scandens , and the ethanol extract of T. scandens had an IC 50 (50% maximal inhibition concentration) value of 2.0 to 2.5 ⁇ g/mL. Also, it was revealed that the ethanol extract of T. scandens had an antiviral activity of substantially 100% when the ethanol extract was present at a concentration of 6 ⁇ g/mL.
  • HIV reverse transcriptase (3 units) were treated with the ethanol extract of T. scandens at an increasing concentration of 0, 0.125, 0.25, 0.5, 1, 2, 4, 8, and 16 ⁇ g/mL and activities of HIV reverse transcriptase were measured using an Enzchek Reverse Transcriptase assay kit (Invitrogen). 0.5% DMSO was used as the negative control, and AZT, AZTTP, Efavirenz, and Etravirine were used as the positive controls. The results are shown in FIG. 3 .
  • an MT-4 cell line (5 ⁇ 10 5 cells) was treated with the ethanol extract of T. scandens prepared in the same manner as in Example 1 at concentrations of 0, 0.31, 0.63, 1.25, 2.5, 5, and 10 ⁇ g/mL, infected with 100,000 pg of HIV in which an Nef protein was substituted with an EGFP protein, and then cultured at 37° C. for 24 hours under a 5% CO 2 condition.
  • DNA was extracted from the cultured cells using a DNeasy mini kit (Qiagen), and then subjected to quantitative DNA-polymerase chain reaction (PCR) using Light Cycler 480 (Roche), SYBR Green I Master mix (Roche) and HIV-1-specific LTR primers (Forward: 5′-GATCTGAGCCTGGGAGCTCTC-3′, and Reverse: 5′-CCTTTCGCTTTCAAGTCCCTGTTC-3′) to quantify viral cDNA.
  • PCR DNA-polymerase chain reaction
  • cDNA synthesis in an RNA virus was decreased according to a concentration of the ethanol extract of T. scandens. Also, it could be seen that the cDNA synthesis was decreased by approximately 50% when the ethanol extract was present at a concentration of 2.5 ⁇ g/mL.
  • the ethanol extract of T. scandens according to the present invention inhibited the synthesis of cDNA by effectively inhibiting the reverse transcriptase activities of the RNA virus in the cells, thereby inhibiting growth of the RNA virus.
  • the ethanol extract of T. scandens according to the present invention was able to be used to prevent or treat a viral infection.
  • the present invention provides a composition for preventing or treating a viral infection, which includes the ethanol extract of T. scandens as an effective component. More particularly, the present invention provides a pharmaceutical composition including an ethanol extract of T. scandens , which is able to be used to prevent or treat diseases caused by a viral infection since the ethanol extract of T. scandens functions to inhibit the reverse transcriptase activities of viruses.
  • the ethanol extract of T. scandens according to the present invention has low toxicity and few side effects since the ethanol extract is a plant extract, and is expected to be widely used to prevent and/or treat diseases caused by various kinds of RNA viruses since the ethanol extract effectively inhibits reverse transcriptase activities to suppress synthesis of DNA.

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US13/852,321 2012-07-24 2013-03-28 Antiviral compositions comprising ethanol extract of tetracera scandens and use thereof Abandoned US20140030364A1 (en)

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KR20120080407A KR101426996B1 (ko) 2012-07-24 2012-07-24 테트라케라 스캔덴스 에탄올 추출물을 유효성분으로 포함하는 항바이러스 조성물 및 이의 용도
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CN103860697B (zh) * 2014-03-20 2017-02-08 中国中医科学院广安门医院 一种用于治疗外感热病的中药组合物及其用途
KR101982657B1 (ko) * 2018-04-30 2019-05-27 대한민국(환경부 국립생물자원관장) 테트라세라 로우레이리 추출물을 이용한 항염증용 조성물

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KR20090091615A (ko) * 2008-02-25 2009-08-28 한국생명공학연구원 근육세포에서 포도당 흡수를 증가시키는 데이츄 추출물과이로부터 분리한 4ｈ-크로멘-4-온 유도체

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EP0973533A4 (en) 1997-03-14 2001-03-14 Univ California METHOD FOR INHIBITING BACTERIAL CYTOTOXICITY
ES2298618T3 (es) 2002-10-24 2008-05-16 Immupharm A/S Composiciones farmaceuticas que comprenden flavonoides y mentol.

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KR20090091615A (ko) * 2008-02-25 2009-08-28 한국생명공학연구원 근육세포에서 포도당 흡수를 증가시키는 데이츄 추출물과이로부터 분리한 4ｈ-크로멘-4-온 유도체

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