阅读说明：本技术 杨梅素在制备治疗血吸虫病药物中的应用 (Application of myricetin in preparation of medicine for treating schistosomiasis ) 是由 吕志跃 黄萍 成韶芸 胡玥 周旻昱 周洪利 马玉斌 于 2020-02-28 设计创作，主要内容包括：本发明公开了杨梅素在制备治疗血吸虫病药物中的应用。本发明通过体外观察杨梅素的抗日本血吸虫作用,以及建立日本血吸虫感染小鼠模型进行体内实验,发现杨梅素无论在体内外均具有良好的血吸虫杀虫作用,以及对日本血吸虫感染小鼠肝脏纤维化的改善作用。并且,杨梅素的杀虫作用与阳性药物吡喹酮效果相当,可代替其在日本血吸虫病上的应用,为避免临床耐药提供可能,具有较大的应用前景。(The invention discloses an application of myricetin in preparing a medicament for treating schistosomiasis. The invention discovers that the myricetin has good schistosome disinsection effect no matter in vivo or in vitro and improves the hepatic fibrosis of the mouse infected by the schistosoma japonicum through in vitro observation of the schistosoma japonicum anti-schistosoma japonicum effect of the myricetin and establishment of a mouse model infected by the schistosoma japonicum for in vivo experiments. In addition, the insecticidal effect of myricetin is equivalent to the positive drug praziquantel, and the myricetin can replace the application of myricetin in schistosomiasis japonica, provides possibility for avoiding clinical drug resistance, and has a wide application prospect.)

1. Application of myricetin in preparing medicine for treating schistosomiasis is provided.

2. Application of myricetin in preparing medicine for inhibiting schistosomiasis is provided.

3. Application of myricetin in preparing medicine for inhibiting oviposition of schistosome is provided.

4. Application of myricetin in preparing medicine for reducing the load of eggs of schistosome and eggs of liver in host infected by schistosome is provided.

5. Application of myricetin in preparing medicine for improving liver disease injury caused by schistosome is provided.

6. Use according to claim 5, wherein the pathological damage of the liver is liver fibrosis.

7. The use of any one of claims 1 to 6, wherein the schistosoma japonicum is Schistosoma japonicum.

8. A medicine for treating schistosomiasis is characterized by containing myricetin.

Technical Field

The invention relates to the technical field of biology, in particular to the technical field of prevention and treatment of schistosomiasis japonica, and more particularly relates to a new application of myricetin in preparation of drugs for treating schistosomiasis japonica.

Background

Schistosomiasis is prevalent in 78 countries and regions worldwide as a neglected tropical disease, with 7.79 million people threatened, with a conservative estimate of about 2.30 million people infected, with 1.2 million people symptomatic, resulting in nearly 30 million deaths annually in africa in the south of sahara alone from schistosomiasis. Schistosomiasis is a parasitic disease caused by a parasite of the genus schistosoma, and there are mainly six human-related species of schistosomiasis organisms, of which schistosoma mansoni, schistosoma japonicum and schistosoma japonicum are the most prevalent. The average life of the schistosoma japonicum in the host is 3-10 years, and the living time can even be as long as 40 years in some cases. Although schistosoma japonicum cannot proliferate in the final host, it can produce large numbers of eggs deposited in the liver or other organs, the mature female worms will lay hundreds and thousands of eggs every day, long term parasitism and large numbers of eggs cause infection and disease transmission.

In the absence of an effective vaccine, chemotherapy is an important means of preventing and treating schistosomiasis today. The first choice of drug currently used in the clinic is praziquantel, which is effective against all species of schistosomes infecting humans and has low toxic side effects. However, the application of praziquantel has many limitations, and the praziquantel is only effective on early childhood insects (3-6 h) and adults just penetrating into the skin, has weak effect on the childhood insects, has no preventive effect, and is a big problem in blood control work due to repeated infection of a treated person after treatment. Meanwhile, because the long-term large-scale repeated use of the praziquantel in the circulation area easily causes the drug resistance of schistosoma, British scholars adopt sub-dose praziquantel to treat infected mice in a laboratory to induce schistosoma mansoni praziquantel resistant strains, so that the search for an effective drug capable of replacing the praziquantel is very urgent.

Myricetin of formula C₁₅H₁₀O₈Is a natural flavonol compound widely existing in many natural plants, fruits and vegetables, and has the functions ofThe compound has wide pharmacological activities including antioxidant, antitumor, anti-inflammatory, antimicrobial, antiallergic, cardiovascular and neuron protecting, and has little toxic and side effects, and no toxic effect or death is found when 1000mg/kg myricetin is injected into the abdominal cavity of a mouse. In addition, it has been shown that dihydromyricetin can reduce CCl₄Protective action of induced mouse liver fibrosis lesion (Kuang plement, Rogming, Jialei, et al. dihydromyricetin on lipid peroxidation injury of liver fibrosis rat [ J]Chinese medicine, 2009, 6(18): 26-28.); dihydromyricetin has obvious therapeutic action on schistosomiasis hepatic fibrosis (Zhuilong, Wangjunjie, Chenmeizi, et al. Experimental research of dihydromyricetin for treating schistosomiasis hepatic fibrosis [ J]Chinese clinical pharmacology and therapeutics, 2010,15(4): 381-384.). At present, only dihydromyricetin is found to have a treatment effect on organ pathological injury of schistosomiasis-induced hepatic fibrosis after schistosomiasis infection, but no report is found on the effect of myricetin in treating schistosomiasis and the effect of myricetin in schistosomiasis-induced hepatic fibrosis.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a new application of myricetin in preparing a medicament for treating schistosomiasis.

The above object of the present invention is achieved by the following technical solutions:

according to the invention, firstly, the effect of resisting schistosoma japonicum in vitro is observed in vitro, the myricetin is found to have a good effect of resisting schistosoma japonicum in vitro, a schistosoma japonicum infected mouse model is further established for an in vivo experiment, the myricetin is found to have a good schistosoma japonicum disinsection effect no matter inside and outside a body, the myricetin can effectively inhibit the oviposition amount of the schistosoma japonicum, and the inhibition effect is not obviously different from that of a positive drug praziquantel, so that the myricetin and the praziquantel can effectively reduce the liver egg deposition, and the myricetin can reduce the infection of pathogenic polypide from the source, thereby playing a role in treating schistosomiasis. Meanwhile, the myricetin is found to have the improvement effect on the liver fibrosis of mice infected with schistosoma japonicum. The insecticidal effect of myricetin is equivalent to that of a positive drug praziquantel, and the myricetin can replace the application of myricetin in schistosomiasis japonica, provides possibility for avoiding clinical drug resistance and has a great application prospect.

Therefore, the following applications of myricetin are all within the scope of the present invention:

application of myricetin in preparing medicine for treating schistosomiasis is provided.

Application of myricetin in preparing medicine for inhibiting schistosomiasis is provided.

Application of myricetin in preparation of medicine for inhibiting oviposition of schistosome

Application of myricetin in preparing medicine for reducing the load of eggs of schistosome and eggs of liver in host infected by schistosome is provided.

Application of myricetin in preparing medicine for improving liver disease injury caused by schistosome is provided.

Preferably, the pathological injury to the liver is liver fibrosis.

Preferably, the schistosoma japonicum is schistosoma japonicum.

The invention also provides a medicament for treating schistosomiasis, which contains myricetin.

Compared with the prior art, the invention has the following beneficial effects:

the invention provides an application of myricetin in preparing a medicament for treating schistosomiasis. The research of the invention finds that the myricetin can have good anti-schistosoma japonicum effect, and the in-vivo experimental result proves that the myricetin obviously reduces the load of eggs and liver eggs in mice infected with schistosoma japonicum, and obviously improves the liver fibrosis lesion of the mice; the myricetin can be used for treating schistosomiasis japonica in the early stage, and has a treatment and improvement effect on liver pathological injury caused by the attack of schistosomiasis japonica in the later stage. Moreover, the myricetin has the effect equivalent to that of the positive drug praziquantel, can replace the application of praziquantel in the diseases, and provides possibility for avoiding clinical drug resistance.

Drawings

FIG. 1 is the chemical structural formula of myricetin and its influence on Schistosoma japonicum; FIG. 1A is the structure of myricetin compound, and FIG. 1B is the survival curve of Schistosoma japonicum after the myricetin with different concentrations acts.

FIG. 2 is a scanning electron micrograph of Schistosoma japonicum after the action of myricetin (A, male worm; B, female worm; Oral sucker; ventral sucker; tegument; gynecophoral gland).

FIG. 3 is H & E staining pattern of mouse liver infected with Schistosoma japonicum after myricetin action.

FIG. 4 is a Masson staining pattern of the liver of mice infected with Schistosoma japonicum after myricetin action.

FIG. 5 shows the expression of factors related to liver fibrosis of mice infected with Schistosoma japonicum after myricetin action.

Detailed Description

The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. The reagents, methods and apparatus employed in the present invention are conventional in the art, unless otherwise indicated.

Unless otherwise indicated, reagents and materials used in the following examples are commercially available.