阅读说明：本技术 胡椒碱在制备sEH抑制剂中的应用 (Application of piperine in preparation of sEH inhibitor ) 是由 刘中博 毕开顺 于 2019-03-01 设计创作，主要内容包括：本发明涉及中药化学和分子生物学技术领域,公开了胡椒碱在制备sEH抑制剂中的应用,所述胡椒碱用式(I)所示,酶动力学活性测试及药效团结果显示：胡椒碱具有较好的抑制sEH活性作用。此化合物毒副作用小,水溶性好。基于可溶性环氧化物水解酶的作用原理,本化合物有预防和治疗消化性溃疡等消化道疾病的功效,可用于制备sEH抑制剂。<Image he="373" wi="700" file="DDA0001982872800000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention relates to the technical field of traditional Chinese medicine chemistry and molecular biology, and discloses an application of piperine in preparation of an sEH inhibitor, wherein the piperine is shown in a formula (I), and an enzyme kinetic activity test and a pharmacodynamic group result show that: piperine has good effect of inhibiting sEH activity. The compound has small toxic and side effects and good water solubility. Based on the action principle of soluble epoxide hydrolase, the compound has the effects of preventing and treating digestive tract diseases such as peptic ulcer and the like, and can be used for preparing sEH inhibitors.)

1. Use of piperine in the preparation of a sEH inhibitor, the piperine being represented by formula (I):

2. the use of claim 1, wherein the sEH inhibitor is useful in the preparation of a medicament for the treatment of hypertension, pain, and inflammatory diseases.

3. Application of piperine as an sEH inhibitor in preparing a medicament for treating digestive tract ulcer.

Technical Field

The invention relates to the technical field of traditional Chinese medicine chemistry and molecular biology, in particular to application of piperine separated from pepper in preparation of an sEH inhibitor.

Background

At present, Peptic Ulcer (PUD) which is a digestive tract disease becomes a common public health problem in China. Peptic ulcer is a common multiple disease, with a global incidence of about 4% (NajmW I.Peptic ulcer [ J ]. Primary Care Clinics in Office Practice,2011,38(3): 383) and 394.) and can occur at different ages, with duodenal ulcer mostly occurring in teenagers and gastric ulcer mostly occurring in the middle-aged and elderly people (Chenzhu, Linguo et al, Utility science [ M ]. Shanghai: Redding university Press 2010: 1981.). Statistics show that about 8740 million people worldwide were diagnosed with the Disease 2015 and resulted in 267500 deaths (colloids G2 MM. Global, regional, and national levels of basic mortalities, 1990): analytical analysis for the Global bureau of Disease Study 2015

2015[ J ]. Lancet,2016,388(10053): 1775-1812.). Although the death rate of PUDs is not high compared to other diseases, it causes great inconvenience to the life and labor of patients, and 100% eradication is impossible with any treatment regimen (survey cooperative group. chinese peptic ulcer treatment status survey report [ J ]. chinese digestive journal, 2007,27 (2)). The research shows that if the chronic ulcer is not treated in time, the mucosa epithelium at the edge of the ulcer is stimulated for a long time and gradually develops atypical hyperplasia so as to become cancerized. Although there has been considerable research on the diagnosis and treatment of digestive tract diseases, the discovery of new therapeutic approaches and drugs for these diseases is still a hot spot in current research.

Soluble epoxide hydrolase (sEH) is an enzyme that plays an irreplaceable role in the body of mammals in the nature and is characterized by high selectivity on lipid epoxy fatty acid. Studies have shown that sEH is present in mammals primarily in the liver, kidney, gut, brain and vasculature. Epoxyeicosatrienoic acids (EETs) are biologically active metabolites of arachidonic acid, and sEH can be used as a high-efficiency catalyst in mammalian bodies to catalyze EETs to inactivate their metabolism and convert them into dihydroxyeicosatrienoic acids (DHETs) corresponding to the reactants. EETs with strong biological activity can participate in the process of various physiological functions, and can play roles of vasodilating, blood pressure lowering and the like in the body of a mammal, and play an anti-inflammatory role in a plurality of diseases such as inflammatory bowel disease, chronic peptic ulcer, septicemia and the like.

On the principle, by inhibiting the activity of sEH enzyme, the level and the activity of EETs in organisms can be improved, so that various digestive tract diseases such as peptic ulcer, chronic gastritis and the like can be relieved and treated. Because of this, finding potentially potent sEH inhibitors as pharmaceutical products for the treatment of hypertension, pain, inflammatory diseases, etc. has become a major focus of research. The professor of Shanghai pharmaceutical research institute of Chinese academy of sciences in the south and the middle of China is turning the center of gravity of research to the research and development of sEH inhibitors. While foreign companies such as Merck have developed four classes of sEH inhibitors in turn, pfeiri and japanese sumitomo pharmaceuticals have also advanced in this area. Today, the search for new potent sEH inhibitors is undoubtedly an important direction in the development of new drugs for digestive tract diseases and anti-inflammatory analgesics.

Pepper is a traditional Chinese medicine in China, and the medicinal history is long. It is originally recorded in the book Xin Xi Cao (newly revised materia Medica) Piper nigrum Xijon, shaped like cascara Sagrada, and is very spicy in taste. The pepper is pungent in flavor and hot in nature, enters stomach and large intestine channels, and has the effects of warming middle-jiao and descending qi, eliminating phlegm and removing toxicity. Modern medical research shows that pepper can be used for treating symptoms such as dyspepsia, cough, bronchitis, abdominal pain and diarrhea. Piperine is a compound extracted from pepper and is also a main active ingredient thereof. The piperine has antioxidant, tranquilizing, anticonvulsive, blood lipid reducing, antidepressant, antitumor, and anti-inflammatory effects on gastrointestinal diseases. In recent years, the biological activity and pharmacological action of piperine have been widely studied, but most of them have been studied immunologically for digestive tract diseases and various inflammations, and there has been no study and report on piperine as a soluble epoxide hydrolase inhibitor.

Disclosure of Invention

The invention aims to provide application of piperine in preparation of a sEH inhibitor.

The technical scheme of the invention is summarized as follows:

the application of piperine in the preparation of sEH inhibitors is shown in a formula (I),

the sEH inhibitor piperine can treat peptic ulcers.

The invention has the advantages that: enzyme kinetic activity test and pharmacophore results show that piperine has a good effect of inhibiting sEH activity. The compound has small toxic and side effects and good water solubility, has the effects of preventing and treating digestive tract diseases such as peptic ulcer and the like based on the action principle of soluble epoxide hydrolase, and can be used for preparing sEH inhibitors.

Piperine can be formulated with pharmaceutically acceptable carriers into pharmaceutical compositions to act as sEH inhibitors.

Detailed Description

The present invention will be further illustrated by the following specific examples.