阅读说明：本技术 葡萄籽原花青素在制备预防或治疗氟化物肾脏毒性方面药物或保健食品中的应用 (Application of grape seed procyanidin in preparation of medicine or health food for preventing or treating fluoride nephrotoxicity ) 是由 王二辉 刘永峰 翟德胜 卜勇军 席金彦 于 2019-10-30 设计创作，主要内容包括：本发明公开了葡萄籽原花青素在制备预防或治疗氟化物肾脏毒性方面药物或保健食品中的应用,更进一步地说是在制备抑制因氟化物暴露所致肾组织MDA含量增多、GSH水平下降、CAT活性和SOD活性下降的药物中的应用。以氟化钠为代表,研究了葡萄籽原花青素对因氟化钠暴露所致肾毒性的的预防和治疗作用,证明原花青素能抑制有氟化钠所致的肾毒性,作用强于维生素C有较好的效果,从而提出原花青素作为活性物质在制备因有氟化物暴露所致的肾毒性药物中的应用。本发明为原花青素发掘了新的医疗用途,开拓了一个新的应用领域,对于解决氟化物暴露引起的肾毒性提供了有意义的参考。(The invention discloses application of grape seed procyanidin in preparation of a medicine or health food for preventing or treating fluoride nephrotoxicity, and further relates to application in preparation of a medicine for inhibiting increase of MDA content of kidney tissues, reduction of GSH level, and reduction of CAT activity and SOD activity caused by fluoride exposure. The prevention and treatment effects of grape seed procyanidin on nephrotoxicity caused by sodium fluoride exposure are researched by taking sodium fluoride as a representative, and the procyanidin can inhibit the nephrotoxicity caused by the sodium fluoride and has a better effect than vitamin C, so that the application of procyanidin as an active substance in the preparation of nephrotoxicity medicaments caused by the fluoride exposure is provided. The invention explores new medical application for procyanidine, develops a new application field, and provides meaningful reference for solving nephrotoxicity caused by fluoride exposure.)

1. The grape seed procyanidin has an obvious effect of reducing the nephrotoxicity caused by fluoride, improving the oxidative stress injury of the kidney, reducing the excessive apoptosis of kidney cells and protecting the structure and the function of the kidney.

2. Application of grape seed procyanidin in preparing medicine for inhibiting increase of kidney tissue MDA content, reduction of GSH level, and reduction of CAT activity and SOD activity caused by fluoride exposure is provided.

3. Use according to claim 1 or 2, characterized in that: the fluoride is sodium fluoride.

4. Use according to claim 1, characterized in that: the medicine for preventing or treating fluoride nephrotoxicity is a conventional preparation formulation, wherein the dosage of grape seed procyanidin is more than effective dose, and the effective dose is 50-500 mg/kg/day.

5. Use according to claim 1, characterized in that: the effective amount is preferably 100-300 mg/kg/day.

Technical Field

The invention belongs to the technical field of new medical application of grape seed procyanidin, and particularly relates to application of grape seed procyanidin in preparation of medicines or health-care foods for preventing or treating fluoride nephrotoxicity.

Background

Endemic fluorosis is a disease that seriously harms human health, causing extensive damage to non-osseous systems and organs in addition to fluorosis and fluorosis teeth. In most provinces of China, severe fluorosis regions exist, and drinking water type and coal-fired type chronic fluorosis mainly exist. According to statistics, except Shanghai and Hainan, other 29 provinces, autonomous regions and direct prefectures all have endemic fluorosis regions in China. The total disease area (county, city and flag) is up to 1308, wherein the coal-fired fluorosis is 200, the threatened population is 3430 ten thousand, the dental fluorosis patient is 1801 ten thousand, and the fluorosis patient is up to 151 ten thousand; drinking water type fluorosis 1108, threatened population 8000 more than ten thousand, fluorine plaque patients 2149 ten thousand, fluorine osteonosus patients 136 ten thousand. The pathogenesis of fluorosis has not been fully elucidated so far, and thus the prevention and treatment of this disease is considerably difficult. Currently, endemic fluorosis is listed as a key disease in the existing endemic diseases in China, and further deep research on pathogenesis of fluorosis and search of early diagnosis indexes are provided to certain strategic heights. Numerous animal studies have demonstrated that chronic fluorosis, in addition to causing osteofluorosis and dental fluorosis, causes metabolic disorders of the bone, and has serious effects on other non-osseous organs (such as brain, liver, kidney, heart, etc.), especially pathological changes of subcellular structure and various metabolic changes. Therefore, intensive studies on non-bone organs or tissues are conducted, which is favorable for comprehensively discussing the occurrence mechanism of fluorotoxic systemic effects. The research has important guiding significance for determining the effect of the sodium fluoride on the kidney injury, searching for sensitive diagnosis indexes and further preventing and treating the endemic fluorosis.

Procyanidins (Procyanidins, molecular formula C)₃₀H₂₆O₁₂) Is a polymer with a special molecular structureA bioflavonoid. Generally a reddish brown powder, slightly smelling, astringent, soluble in water and most organic solvents. Procyanidine is widely distributed, exists in skins, shells, seeds, kernels, flowers and leaves of many plants, and has the highest content and abundant types of procyanidine in grape seeds. Typically grape seed extract or French maritime pine bark extract. Procyanidine (grape seed extract) is a novel high-efficiency antioxidant, the compounds have various biological activities, are known for high efficiency, low toxicity, high bioavailability and strong antioxidant capacity, and are the most effective antioxidant for eliminating free radicals of a human body internationally recognized at present. Experiments prove that the anti-free radical oxidation capacity of the procyanidin is 50 times of that of the vitamin E and 20 times of that of the vitamin C, the procyanidin can be quickly and completely absorbed, the highest blood concentration can be reached after the procyanidin is orally taken for 20 minutes, and the metabolic half-life period is up to 7 hours. Research shows that the procyanidine has various effects of improving blood circulation, protecting vision, eliminating edema, losing weight, reducing cholesterol, resisting virus and the like.

For example, patent publication No. CN102600127A discloses the use of procyanidins or plant extracts containing procyanidins in the preparation of drugs or health foods for preventing or treating lipid metabolism disorder diseases. The patent document with the publication number of CN102940624A discloses the application of procyanidine in a traditional Chinese medicine cinnamon aqueous extract in preparing a medicament for treating diabetes, and researches show that the cinnamon procyanidine can take anti-islet amyloid polypeptide aggregation as a target spot, and has great application value in preparing the medicament for treating type 2 diabetes. Patent document No. CN1745747B discloses the use of procyanidins in preparing a medicament for treating colitis, and particularly discloses the use of procyanidins in preparing a medicament for treating ulcerative colitis. Patent document CN107213147A discloses the use of procyanidins in the prevention and treatment of flavivirus infection, and in particular its effect against zika virus.

In recent years, it has been found that intervention with antioxidants such as procyanidins can protect against oxidative damage to chemicals and drugs. Researches show that the procyanidine has a certain protective effect on oxidative damage of testis caused by heavy metals such as fluorine, nickel and cadmium, and semicarbazide, zearalenone, arsenic trioxide, cisplatin, trans-fatty acid and the like. In addition, researches report that procyanidine has a strong protective effect on oxidative damage of the liver caused by sodium fluoride, and whether procyanidine has a protective effect on renal damage caused by sodium fluoride is not reported.

This study has demonstrated that oxidative stress and the resulting induction of renal cell apoptosis are important mechanisms of sodium fluoride kidney injury. At present, the research on the application of the procyanidine is carried out deeply, but the effect of protecting the renal toxicity of the fluoride by the procyanidine is not reported in a patent document. The invention develops a new application field of procyanidine, and provides reference for relieving the renal toxicity of fluoride-exposed persons in high-fluorine areas. The invention provides a certain scientific basis for developing functional foods and medicines for treating or preventing fluoride nephrotoxicity.

Disclosure of Invention

The invention aims to provide the application of grape seed procyanidin in preparing medicines or health-care foods for preventing or treating fluoride nephrotoxicity, and further expands the application field of procyanidin.

The invention adopts the following technical scheme for realizing the aim, and the grape seed procyanidin is applied to the preparation of medicines or health-care foods for preventing or treating fluoride nephrotoxicity.

Further, the grape seed procyanidin is applied to the preparation of medicines for inhibiting the increase of MDA content of kidney tissues, the reduction of GSH level, and the reduction of CAT activity and SOD activity caused by fluoride exposure, wherein the fluoride is sodium fluoride.

The medicine for preventing or treating fluoride nephrotoxicity can be any applicable conventional preparation formulation, wherein the dosage of the grape seed procyanidin is more than effective amount, can be selected according to specific conditions, and is generally 50-500 mg/kg/day, preferably 100-300 mg/kg/day.

The invention is proved by rat experiments that: the grape seed procyanidine has an obvious effect of reducing the renal toxicity of rats fed with sodium fluoride, improving renal oxidative stress injury, protecting the kidney structure, reducing excessive apoptosis of kidney cells, and protecting the kidney structure and function.

The invention has the following beneficial effects: 1. the invention explores a new medical application of the grape seed procyanidin and develops a new application field of the anthocyanin; animal experiments show that the grape seed procyanidin has low concentration required for treating fluoride nephrotoxicity and no toxic or side effect.

The invention takes sodium fluoride as a representative, researches the prevention and treatment effects of grape seed procyanidin on nephrotoxicity caused by sodium fluoride exposure, proves that procyanidin can inhibit nephrotoxicity caused by sodium fluoride, has better effect than vitamin C, and provides the application of procyanidin as an active substance in the preparation of nephrotoxicity medicaments caused by fluoride exposure.

The invention explores new medical application for procyanidine, develops a new application field, and provides meaningful reference for solving nephrotoxicity caused by fluoride exposure.

Drawings

FIG. 1 shows the histopathological changes of the kidney of rats in each test group in example 1;

FIG. 2 shows the apoptosis of the kidney cells of rats in each experimental group;

figure 3 is the rat kidney Bax and Bcl-2 protein expression levels (. p <0.05,. p <0.01 compared to HFD) for each experimental group.

Detailed Description

The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.