阅读说明：本技术 灵仙新苷在治疗雷公藤甲素所致肝损伤的药物中的应用 (Application of clematis chinensis glycoside in medicine for treating liver injury caused by triptolide ) 是由 刘丽芳 夏文瑞 辛贵忠 于 2019-10-24 设计创作，主要内容包括：本发明公开了灵仙新苷在制备治疗雷公藤甲素所致肝损伤的药物中的应用,从传统中药威灵仙中获得的灵仙新苷对雷公藤甲素在治疗类风湿性关节炎(RA)时所致肝损伤具有保护作用。药理学试验证明,灵仙新苷可以有效降低给予雷公藤甲素的CIA模型大鼠的肝毒性相关血清生化指标,并且在细胞水平有同样的效果,这一结果进一步通过代谢组学的方法得到了验证。(The invention discloses application of clematis chinensis glycoside in preparing a medicine for treating liver injury caused by triptolide, wherein the clematis chinensis glycoside obtained from a traditional Chinese medicine clematis root has a protective effect on the liver injury caused by the triptolide when treating Rheumatoid Arthritis (RA). pharmacological tests prove that the clematis chinensis glycoside can effectively reduce the serum biochemical indexes related to hepatotoxicity of a CIA model rat given the triptolide, and has the same effect at the cellular level, and the result is verified by a method of metabonomics in step .)

1. Application of new glycoside of radix Clematidis in preparing medicine for treating liver injury caused by triptolide or medicine containing triptolide is provided.

2. The use of claim 1, wherein the triptolide-containing medicament is a single or compound Chinese medicinal preparation prepared from triptolide-containing medicinal materials and extracts thereof.

3. Use according to claim 1, characterized in that said clematis glycoside is clematis glycoside or a composition comprising same.

4. The use as claimed in claim 3, wherein the composition is prepared from the clematis glycoside and pharmaceutically acceptable auxiliary materials into a pharmaceutical dosage form.

5. Use according to claim 4, characterized in that the pharmaceutical dosage form is a tablet, capsule, granule, powder, syrup, pill.

6. Use according to claim 4, characterized in that the pharmaceutically acceptable adjuvant is a diluent, a wetting agent or a lubricant.

7. Use according to claim 6, characterized in that the diluent is lactose, starch, dextrin, powdered sugar, microcrystalline cellulose or aerosil; the wetting agent is water or 30-80% ethanol; the lubricant is magnesium stearate or pulvis Talci.

Technical Field

The invention relates to application of a compound, in particular to application of clematis chinensis glycoside in a medicine for treating liver injury caused by triptolide.

Background

It is systemic autoimmune diseases mainly manifested by chronic, progressive and aggressive Arthritis, and its clinical characteristics are that peripheral joint synovitis then causes cartilage destruction and bone assault, resulting in joint deformity and stiffness, finally resulting in functional loss, with very high disability rate.

Triptolide (TP), also known as Triptolide, is a epoxy diterpene lactone compound extracted from roots, leaves, flowers and fruits of tripterygium wilfordii belonging to the family celastraceae, is which is a main active component of tripterygium wilfordii, has anti-inflammatory and immunosuppressive effects, has good treatment effects on RA, and has clinical application, however, a large number of researches show that Triptolide is also which is a main toxic component of tripterygium wilfordii, has serious toxicity on digestive system, circulatory system, urinary system, reproductive system, immune system and the like of an organism, wherein hepatotoxicity is particularly obvious, and a mechanism of the Triptolide causing hepatotoxicity is mainly characterized by abnormal metabolism of cytochrome P450 enzymes, induction of oxidative stress and apoptosis, immune-mediated injury, autophagy excess induction of nos caused by peroxidation and the like.

The clematis root is pungent and salty in taste and warm in nature, has the effects of dispelling wind, removing dampness, dredging collaterals and relieving pain, and is mainly used for treating symptoms such as rheumatic arthralgia, numbness of limbs, spasm and spasm of tendons and vessels, difficulty in flexion and extension and the like clinically. 2015 edition "Chinese pharmacopoeia" contains dried root and rhizome derived from Clematis chinensis Osbeck, Clematis hexapetala pall. or Clematis manshuria Rupr. of Ranunculaceae. In recent years, the chemical components and the drug effects of clematis chinensis have been studied more and more intensively, and especially, the anti-inflammatory effect of the saponin components in the clematis chinensis is well proved. The clematis chinensis glycoside (C-AR) is monomer saponin with high content in northeast clematis chinensis, and has molecular formula of C₈₂H₁₃₄O₄₃The molecular weight is 1807.93, and the oleanane type pentacyclic triterpene saponin has good anti-inflammatory and analgesic effects, and the structural formula is shown as follows.

According to the reports of the literature, in various compounds, the purpose of reducing the toxicity of the tripterygium wilfordii is achieved by matching the medicinal materials such as liquorice, pseudo-ginseng and the like, and the researches show that the triterpenoid saponins such as glycyrrhizic acid, notoginsenoside R1 and the like play an important role in attenuation, and a research idea is provided for the attenuation research of the traditional Chinese medicine tripterygium wilfordii.

Metabonomics aims at biological body fluid (such as blood, urine and the like), cell tissue extracts, cell culture fluid and the like, evaluates the influence of exogenous stimuli (such as drugs and toxicants) on an organism by qualitatively and quantitatively analyzing the change of endogenous metabolites in a biological system, namely, measures the change condition of the metabonomic group caused by external stimulation, simultaneously carries out bioinformatics analysis on the metabonomic group data, and integrally researches the regulation and response mechanism of the organism to the external stimulation from the perspective of a system biochemical spectrum. Metabonomics is a starting point for researching the whole metabolic change of an organism and can comprehensively reflect the metabolic change of each tissue in the organism caused by the action of a medicament, so that the metabonomics has the characteristic of objectively reflecting the whole change. The metabolic omics technology can comprehensively reflect the change of the in-vivo metabolism of the triptolide induced hepatotoxicity, find out the toxicity-inducing/attenuation biomarkers and corresponding metabolic pathways, provide thinking for deeply understanding the liver toxicity-inducing mechanism of the triptolide, and provide a new idea for the research of reducing the triptolide hepatotoxicity.

Disclosure of Invention

The purpose of the invention is as follows: the invention aims to provide the protective effect of the clematis chinensis glycoside on the hepatotoxicity caused by the administration of triptolide in the treatment of rheumatoid arthritis, and indicates that the clematis chinensis glycoside has good application prospect in the preparation of medicaments for treating liver injury caused by triptolide.

The technical scheme is as follows: the application of the clematis chinensis glycoside in preparing the medicine for treating liver injury caused by triptolide or a medicine containing triptolide is disclosed.

The medicine containing triptolide is a single or compound traditional Chinese medicine preparation prepared from triptolide-containing medicinal materials and triptolide extracts.

The clematis chinensis glycoside is clematis chinensis glycoside or a composition containing the same.

The composition is prepared into a medicament form by adding pharmaceutically acceptable auxiliary materials into the clematis chinensis glycoside.

The dosage forms of the medicine are tablets, capsules, granules, powder, syrup and pills.

The pharmaceutically acceptable auxiliary material is a diluent, a wetting agent or a lubricant.

The diluent is lactose, starch, dextrin, sugar powder, microcrystalline cellulose or micropowder silica gel; the wetting agent is water or 30-80% ethanol; the lubricant is magnesium stearate or pulvis Talci.

The invention utilizes a Collagen-induced arthritis (CIA) rat model to evaluate the potential anti-inflammatory activity of the clematis chinensis glycoside and the protection effect on liver damage caused by triptolide. Therapeutic administration is adopted during experimental design, and Wistar rats and II type collagen solution are used for inducing and constructing a model. The results show that the combination of the clematis chinensis glycoside and the triptolide still has obvious anti-inflammatory effect, can improve the relevant symptoms in the attack process of RA, and obviously relieves the liver injury caused by the triptolide after the combination.

Because products in tryptophan metabolism participate in processes such as oxidative stress, tricarboxylic acid cycle and the like, and the processes are closely related to liver injury, the invention preliminarily inspects the change of metabolic tracks and the change of tryptophan metabolism level after single triptolide and combined new impatiens, and further discloses the action mechanism of the new impatiens for improving the liver injury by steps.

The experiment of the invention shows that the clematis chinensis glycoside can still have obvious anti-inflammatory effect when triptolide is combined, can improve relevant symptoms in the disease process of rheumatoid arthritis, and obviously reduces liver injury caused by triptolide after combined medication, thereby explaining that new drugs with good curative effect and high safety can be developed from the clematis chinensis glycoside for reducing the liver injury caused by the triptolide-containing drugs as main components.

Drawings

FIG. 1 is an HPLC chart for quantitative analysis of clematis chinensis glycoside;

FIG. 2 shows the modeling and administration process of CIA rats;

FIG. 3 is a graph of the effect of C-AR, TP and combination on body weight, toe swelling and arthritis scores in CIA rats;

FIG. 4 is a graph of the effect of C-AR, TP and combination on the inflammatory factors IL-1 β and TNF- α in the synovium of CIA rats;

FIG. 5 is a graph of the effect of C-AR, TP and combination on CIA rat liver tissue;

FIG. 6 shows the effect of C-AR, TP and combination on the biochemical indicators of CIA rat serum;

FIG. 7 is a graph of the effect of C-AR, TP and combination on biochemical indicators associated with liver injury in HepG2 cells;

FIG. 8 is the change in metabolic trajectories of rat liver and serum;

FIG. 9 shows the change in the content of tryptophan metabolism-related products in rat liver.

Detailed Description

In earlier researches, the purity of the clematis chinensis glycoside prepared from clematis chinensis medicinal materials reaches 90.16% by using a peak area classification method, the clematis chinensis glycoside is shown in the attached figure 1, the clematis chinensis glycoside used in experiments is extracted from the traditional Chinese medicine clematis chinensis, the specific extraction method is shown in CN200510040825.7, and triptolide is purchased from Nanjing Zelang medicine science and technology Limited.