阅读说明：本技术 雷公藤红素在治疗非酒精性脂肪肝炎的药物中的应用 (Application of tripterine in medicine for treating non-alcoholic steatohepatitis ) 是由 李飞 赵琦 于 2019-10-30 设计创作，主要内容包括：本发明公开了一种雷公藤红素在制备预防和/或治疗非酒精性脂肪肝炎的药物中的应用。本发明所述的雷公藤红素或其药学上可接收的盐对小鼠蛋氨酸胆碱缺乏膳食(MCD)诱导的非酒精性脂肪肝炎显示出明显的保护作用,能显著降低这个模型血浆中丙氨酸氨基转移酶(ALT)水平,降低肝脏中的炎症因子以及脂质蓄积,降低肝纤维化因子,恢复胆汁酸动态平衡,可应用于制备非酒精性脂肪肝炎的药物中。(The invention discloses an application of tripterine in preparing a medicament for preventing and/or treating non-alcoholic steatohepatitis. The tripterine or the pharmaceutically acceptable salt thereof has obvious protective effect on non-alcoholic steatohepatitis induced by methionine choline deficiency diet (MCD) of mice, can obviously reduce the alanine Aminotransferase (ALT) level in the plasma of a model, reduce inflammatory factors and lipid accumulation in livers, reduce hepatic fibrosis factors and restore the dynamic balance of bile acid, and can be applied to the preparation of drugs for the non-alcoholic steatohepatitis.)

1. Application of tripterine or pharmaceutically acceptable salt thereof in preparing medicine for preventing and/or treating non-alcoholic steatohepatitis is provided.

2. The application of a pharmaceutical composition containing tripterine or pharmaceutically acceptable salts thereof and pharmaceutically acceptable adjuvants or excipients in the preparation of drugs for preventing and/or treating non-alcoholic steatohepatitis.

3. The use of claim 1 or 2, wherein the tripterine or a pharmaceutically acceptable salt thereof is used for the prevention and/or treatment of non-alcoholic steatohepatitis by reducing lipid levels in the liver, or reducing liver inflammation caused by non-alcoholic steatohepatitis, or reducing liver fibrosis caused by non-alcoholic steatohepatitis.

The technical field is as follows:

the invention relates to a new application of tripterine, in particular to an application of tripterine in the field of pharmacy, and specifically relates to an application of tripterine in preparing a medicine for treating non-alcoholic steatohepatitis (NASH).

Background art:

NASH was first proposed in 1980 and refers to a clinical pathological syndrome characterized by lipopexia degeneration of liver parenchymal cells and liver inflammation without history of excessive drinking. Hepatic cellular necrosis and inflammatory responses of NASH lead to activation of stellate cells, which play a key role in liver fibrosis. NASH, if not effectively treated, will progress to cirrhosis and hepatocellular carcinoma, eventually leading to liver failure and even death. Early NASH can alleviate or even reverse the process of steatosis through lifestyle interventions such as weight loss. Patients with advanced NASH currently have no effective drug treatment.

Tripterine is a pentacyclic triterpenoid compound separated from root bark of Tripterygium Wilfordi (Tripterygium Wilfordi) which is a traditional Chinese medicine. Tripterine can be used for treating edema, hypertension, amyotrophic lateral sclerosis, Parkinson's disease, arthritis, asthma, etc. In addition, tripterine can inhibit the proliferation, development and migration of various tumor cells. However, whether celastrol has the effect of preventing and treating NASH or not is not reported in documents at present.

The invention content is as follows:

the invention aims to overcome the limitation of the prior art, research the protection effect of the tripterine on the NASH and determine the protection effect of the tripterine on the NASH. Meanwhile, the method expands the new application field of the tripterine extracted from tripterygium wilfordii of celastraceae, and the tripterine is applied to the treatment of NASH, so that the method has obvious effect.

In order to achieve the above purpose of the present invention, the present invention provides the following technical solutions:

application of tripterine or pharmaceutically acceptable salt thereof in preparing medicine for preventing and/or treating non-alcoholic steatohepatitis is provided.

The application of a pharmaceutical composition containing tripterine or pharmaceutically acceptable salts thereof and pharmaceutically acceptable adjuvants or excipients in the preparation of drugs for preventing and/or treating non-alcoholic steatohepatitis.

The use as described, wherein the tripterine or a pharmaceutically acceptable salt thereof is used for preventing and/or treating non-alcoholic steatohepatitis by reducing lipid levels in the liver, or reducing liver inflammation caused by non-alcoholic steatohepatitis, or reducing liver fibrosis caused by non-alcoholic steatohepatitis.

The tripterine is extracted from Tripterygium wilfordii hook of Tripterygium of Celastraceae, and is produced by Chengdu ruifengsi biotechnology limited, and the tripterine has molecular formula of C₂₉H₃₈O₄The structural formula is as follows:

the mechanism of action for treating NASH is as follows: tripterine has the effect of promoting bile acid excretion, and its action mechanism probably influences Farnesoid X Receptor (FXR) signaling pathway in liver or intestinal tract. In addition, tripterine may regulate body bile acid homeostasis via intestinal flora. Finally, tripterine improves bile acid synthesis genes (cholesterol 7 alpha hydroxylase (CYP7a1)) and reduces the formation of bile acids in vivo, inhibiting the further synthesis of bile acids from the source. Tripterine improves bile acid absorption transporters (such as sodium taurocholate cotransporter polypeptide (Ntcp), organic anion transport polypeptide 4(Oatp 4)); increase the expression of bile acid outflow transporters (such as cholate output pump (Bsep) and multidrug resistance protein 2(Mrp2)), promote bile acid excretion, and thus achieve the effect of treating NASH.

The use requirements are as follows: the administration mode is oral administration, and the dosage is 0.01-1000mg/kg body weight/day corresponding to the body weight of corresponding patients.

Using the object: patients with NASH.

The invention has the beneficial effects that: the invention researches and proves that tripterine can be used for treating NASH through a mouse NASH model induced by MCD, can obviously improve physiological and biochemical indexes of plasma, obviously inhibit liver inflammation, improve bile acid and lipid dynamic balance, and has obvious curative effect on NASH.

Description of the drawings:

FIG. 1: MCS blank group, MCD model group, tripterine treatment group mouse liver histopathology section picture.

FIG. 2: tripterine can improve physiological and biochemical indexes of blood plasma.

FIG. 3: the A tripterine improves the expression level of inflammatory factor tumor necrosis factor alpha (Tnfa); the B tripterine improves liver fibrosis related factors.

FIG. 4: tripterine restores Triglyceride (TG) levels in the liver; b tripterine restores Total Cholesterol (TC) levels in the liver; celastrol restores TG levels in plasma; d tripterine restores TC levels in plasma.

FIG. 5: tripterine improves bile acid level in plasma; b tripterine improves the synthesis and transport related genes of bile acid in liver.

The specific implementation mode is as follows:

the invention will be further explained by the following specific embodiments with reference to the attached drawings. It should be understood that the following examples are only illustrative of the present invention, and are not intended to limit the scope of the present invention.