CN111658658B - Application of xylooligosaccharide in preparation of medicine for resisting deep vein thrombosis - Google Patents
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Abstract
The invention provides application of xylo-oligosaccharide in preparing a medicine for resisting deep vein thrombosis, belonging to the technical field of biomedicine. The invention provides application of xylo-oligosaccharide in preparing a medicine for resisting deep vein thrombosis. The raw materials of the xylo-oligosaccharide comprise corncob, bagasse or wheat bran. Experiments prove that by feeding three kinds of xylo-oligosaccharides from different sources to a deep vein thrombosis mouse model, the results show that all three xylo-oligosaccharide groups can inhibit the formation of deep vein thrombosis and have statistical differences (p < 0.05) compared with a blank control group. Therefore, the xylo-oligosaccharide provided by the invention is used as an active ingredient of a potential deep vein thrombosis medicine, and the xylo-oligosaccharide or other oligosaccharides are combined to prepare a potential medicine capable of preventing and treating deep vein thrombosis.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of xylo-oligosaccharide in preparation of a medicine for resisting deep vein thrombosis.
Background
Deep vein thrombosis (Deep venous thrombosis, DVT) refers to a condition in which blood clots in deep vein vessels, resulting in complete or incomplete occlusion of the vessels [1]. Usually due to the lag of blood clotting in the deep venous circulation [2], commonly found in the lower extremities. And thrombus formed by the lower limb falls down and can flow to the lung through blood, thereby causing pulmonary artery to be blocked and further causing pulmonary embolism (Pulmonary embolism, PE). Pulmonary embolism refers to venous blood clots flowing through the right side of the heart to the pulmonary circulation with blood flow and residing in one or more branches of the pulmonary artery [3], with high morbidity and mortality, with thrombus from deep veins in the legs or arms being the most common [4]. The most severe pulmonary artery embolism usually originates from the deep veins of the lower extremities and/or pelvis [5]. In addition, if the deep venous thrombosis is not treated in time or is not treated correctly, sequela can easily appear, limb swelling can occur to cause limb movement inconvenience, early and slight twilight conditions are accompanied by limb acid, sinking, trapping and swelling, and large-area pigmentation of lower limbs can occur after a long time, or superficial secondary vein expansion, skin itching, ulcer and the like can occur. Even after treatment, deep venous thrombosis and pulmonary embolism may cause post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension, respectively [3,4], once that has occurred, the patient may require long-term additional medical care and treatment, severely affecting the quality of life of the patient.
At present, the specific molecular mechanism of deep vein thrombosis is yet to be explored, and all corresponding indexes of clinical detection cannot be included, so that a timely and effective method cannot be adopted to reduce the death risk of a patient. Therefore, in order to realize the accurate control and treatment of deep vein thrombosis in the early days, the regulation mechanism and molecular mechanism of deep vein thrombosis are researched from various aspects, and the method has important clinical significance and social value.
Intestinal microorganisms are considered as symbionts of animal organisms, play an important role in nutrient metabolism, immune regulation and the like, and contribute to maintaining the steady state of intestinal tracts. Thousands of microorganisms inhabit the human intestinal tract and produce a variety of metabolic bioactive signaling molecules that affect body health [6]. For normal healthy subjects, the homeostasis of the intestinal microbiota is maintained in the body, the growth of pathogenic microorganisms is controlled, and this dynamic balance between humans and microorganisms is called the microecological balance. Factors affecting the microecological balance are external environmental factors, as well as host factors. Such as beneficial flora, maintain its stability by producing bacteriocins, antibiotics and their metabolites, and competing for nutrition, space competition to prevent invasion of the passing flora. The ecological balance can maintain the normal physiological functions of the host, such as nutrition, immunity, digestion, etc. Once this microecological balance is deregulated, a substantial bloom of pathogenic microorganisms may be induced, leading to intestinal related diseases such as Inflammatory Bowel Disease (IBD), obesity, allergic diseases, diabetes, autism, colorectal cancer and cardiovascular diseases etc. [7] [8] [9]. In animal models, sterile mice receiving fecal microbiota transplantation have been shown to be susceptible to obesity and atherosclerosis, suggesting that fecal microbiota transplantation has great potential in the treatment of a range of complex diseases [10] [11].
In order to reasonably regulate the ecological balance of intestinal microorganisms, in recent years, eating prebiotics has evolved into an important dietary strategy by which intestinal microorganism formation can be improved, thereby promoting health. Prebiotics (pre-biotics), originally defined in 1995 by Gibson and Roberfroid as "an indigestible food ingredient, beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, improving host health [12]. Among them, oligosaccharides are becoming more and more important as prebiotic functional food ingredients. Oligosaccharide sugars can be extracted from a variety of biomass sources by enzymatic hydrolysis, and can also be synthesized by enzymatic transfer reactions using oligosaccharides [13]. Because it is not absorbed in the small intestine, it can directly enter the large intestine and become the proliferation factor of some beneficial bacteria, thus regulating the ecological balance of intestinal microorganisms, enhancing the immunity and health balance of the organism.
With the recent increasing understanding of intestinal microorganisms, studies have found that intestinal flora and its metabolites are capable of affecting the occurrence of cardiovascular diseases in several ways, such as affecting lipid metabolism via bile acid pathways, promoting the formation of atheromatous plaques, and that intestinal flora translocation can promote the occurrence of heart failure, etc. These studies indicate that intestinal microorganisms are closely related to a variety of diseases, but their relationship between deep vein thrombosis remains to be explored further.
Xylo-oligosaccharides (XOS) are oligosaccharides of 2-7 xylose single molecules, linked by beta-1, 4 [14], which are common dietary fiber hydrolysates in corn stalks, wheat bran and rice bran [15]. XOS as an "intestinal power source" [16] has the least effective amount and the strongest function compared to other oligosaccharides, and after reaching the colon, it is utilized by microorganisms in the host colon, greatly improving gastrointestinal function, promoting digestion and absorption of food and discharge of intestinal waste [17]. In addition, XOS showed potent antioxidant and antibacterial activity in vitro [18]. Although XOS is not digestible by humans, it can be metabolized by intestinal microorganisms [19]. Furthermore, XOS can promote the growth of bifidobacteria and lactobacilli in the gut and increase the Short Chain Fatty Acid (SCFA) content in these gut microorganisms, enhancing gut barrier function [20]. In particular, dietary supplementation with XOS can increase the relative abundance of lactobacillus and bifidobacterium, enhancing the expression of claudin Occludin (OCLN) in cecal tissue in the gut [21]. Both XOS and bifidobacteria can enhance immune function in the host [22]. And there are studies that find the association of XOS in various diseases such as: XOS can enhance insulin sensitivity and reverse changes in microbial composition caused by insulin insensitivity in pre-diabetic patients [23]; XOS can also modulate intestinal flora in obese rats, increase SCFA levels, and reduce High Fat Diet (HFD) -induced colonic inflammation, etc. However, there is no report on the therapeutic effect of xylo-oligosaccharide on deep vein thrombosis.
Reference to the literature
[1]Bevis P M,Smith F C T.Deep vein thrombosis[J].Surgery(United Kingdom),Elsevier Ltd,2016,34(4):159–164.
[2]Derek G.WallerBSc(HONS),DM,MBBS(HONS),FRCPAnthony P.SampsonMA,PhD,FHEA Fbp.Platelets and platelet aggregation Blood coagulation and the coagulation cascade[J].Medical Pharmacology and Therapeutics(Fifth Edition),2018:175–190.
[3]Heinrich F.Pulmonary embolism[J].Deutsches medizinisches Journal,1970,21(7):430–444.
[4]Leroyer C.Pulmonary embolism[J].Revue du Praticien,1999,49(5):561–567.
[5]Gupta.K N B S R D L L N.Catheter Directed Thrombolysis Of Pulmonary Embolism[J].StatPearls Publishing,2020.
[6]Wang Z,Zhao Y.Gut microbiota derived metabolites in cardiovascular health and disease[J].Protein and Cell,Higher Education Press,2018,9(5):416–431.
[7]Battson M L,Lee D M,Jarrell D K,et al.Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction[J].American journal of physiology.Endocrinology and metabolism,2018,314(5):E468–E477.
[8]Degruttola A K,Low D,Mizoguchi A,et al.Current understanding of dysbiosis in disease in human and animal models[J].Inflammatory Bowel Diseases,2016,22(5):1137–1150.
[9]Yang T,Santisteban M M,Rodriguez V,et al.Gut microbiota dysbiosis is linked to hypertension.[J].Hypertension.,2016,65(6):1331–1340.
[10]Turnbaugh P J,Ley R E,Mahowald M A,et al.An obesity-associated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444(7122):1027–1031.
[11]Gregory J C,Buffa J A,Org E,et al.Transmission of atherosclerosis susceptibility with gut microbial transplantation[J].Journal of Biological Chemistry,2015,290(9):5647–5660.
[12]Ouwerkerk J P,Ark K C H Van Der,Davids M,et al.Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer[J].APPLIED AND ENVIRONMENTAL MICROBIOLOGY,2016,82(23):6983–6993.
[13]Bosscher.D,Breynaert.A,Pieters.L,Hermans N.FOOD-BASED STRATEGIES TO MODULATE THE COMPOSITION OF THE INTESTINAL MICROBIOTA AND THEIR ASSOCIATED HEALTH EFFECTS[J].JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY,2009,60(Suppl6):5–11.
[14]Jordan D B,Wagschal K.Properties and applications of microbial β-D-xylosidases featuring the catalytically efficient enzyme from Selenomonas ruminantium[J].Applied Microbiology and Biotechnology,2010,86(6):1647–1658.
[15]Manrique Vergara D,González Sánchez M E.Grasos De Cadena Corta(/>Butírico)Y Patologías Intestinales[J].Nutricion hospitalaria,2017,34:58–61.
[16]Moens F,Verce M,De Vuyst L.Lactate-and acetate-based cross-feeding interactions between selected strains of lactobacilli,bifidobacteria and colon bacteria in the presence of inulin-type fructans[J].International Journal of Food Microbiology,Elsevier B.V.,2017,241:225–236.
[17]M S,Fredslund F,Majumder A,et al.Enzymology and structure of the GH13_31 glucan 1,6-α-glucosidase that confers isomaltooligosaccharide utilization in the probiotic lactobacillus acidophilus NCFM[J].Journal of Bacteriology,2012,194(16):4249–4259.
[18]Yonglin Gao,Shumin Zhang,Chunmei Li,Lin Xiao J S Y.Acute and subchronic toxicity of xylo-oligosaccharide in mice and rats[J].Toxicology Mechanisms and Methods,2012,22(8):605–610.
[19]Gao Y,Wang Y,Li Y,et al.Repeated sub-chronic oral toxicity study of xylooligosaccharides(XOS)in dogs[J].Regulatory Toxicology and Pharmacology,Elsevier Ltd,2017,86:379–385.
[20]Li Z,Summanen P H,Komoriya T,et al.In vitro study of the prebiotic xylooligosaccharide(XOS)on the growth of Bifidobacterium spp and Lactobacillus spp[J].International Journal of Food Sciences and Nutrition,2015,66(8):919–922.
[21]Christensen E G,Licht T R,Leser T D,et al.Dietary Xylo-oligosaccharide stimulates intestinal bifidobacteria and lactobacilli but has limited effect on intestinal integrity in rats[J].BMC Research Notes,2014,7(1):1–14.
[22]Childs C E,H,Alhoniemi E,et al.Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp.lactis induce bifidogenesis and modulate markers of immune function in healthy adults:A double-blind,placebo-controlled,randomised,factorial cross-over study[J].British Journal of Nutrition,2014,111(11):1945–1956.
[23]Yang J,Summanen P H,Henning S M,et al.Xylooligosaccharide supplementation alters gut bacteria in both healthy and prediabetic adults:A pilot study[J].Frontiers in Physiology,2015,6(Aug):1–11.
Disclosure of Invention
Therefore, the invention aims to provide a new application of the xylo-oligosaccharide, namely the application of the xylo-oligosaccharide in preparing the medicine for resisting deep vein thrombosis, and the xylo-oligosaccharide can effectively inhibit the formation of the deep vein thrombosis.
The invention provides application of xylo-oligosaccharide in preparing a medicine for resisting deep vein thrombosis.
Preferably, the raw materials of the xylo-oligosaccharide comprise corncob, bagasse or wheat bran.
Preferably, the raw material of the xylooligosaccharide is bagasse.
Preferably, the anti-deep vein thrombosis comprises reducing the thrombus length and/or thrombus weight of a formed thrombus.
Preferably, the feeding amount of the xylooligosaccharide is 0.33-0.34 mg/mouse/d.
Preferably, the dosage form of the medicament is preferably an oral dosage form.
Preferably, the oral preparation comprises decoction, oral liquid, syrup, granule, pill, tablet or capsule.
Preferably, the xylo-oligosaccharide is combined with other oligosaccharides to prepare the medicine for preventing and/or treating deep vein thrombosis;
the other kinds of oligosaccharides include fructooligosaccharides and/or maltooligosaccharides.
The invention provides a medicine for resisting deep vein thrombosis, which comprises active ingredients and auxiliary materials, wherein the active ingredients comprise the following components in parts by weight: 1 to 10 parts of xylo-oligosaccharide, 1 to 10 parts of fructo-oligosaccharide and 1 to 10 parts of malto-oligosaccharide.
Preferably, the active ingredients comprise the following components in parts by weight: 3 to 7 parts of xylo-oligosaccharide, 3 to 7 parts of fructo-oligosaccharide and 3 to 7 parts of malto-oligosaccharide.
The invention provides application of xylo-oligosaccharide in preparing a medicine for resisting deep vein thrombosis. Experiments prove that by feeding three kinds of xylo-oligosaccharides from different sources to a deep vein thrombosis mouse model, the results show that all three xylo-oligosaccharide groups can inhibit the formation of deep vein thrombosis and have statistical differences (p < 0.05) compared with a blank control group. Therefore, the xylooligosaccharide provided by the invention is a potential drug capable of preventing and treating deep vein thrombosis.
Furthermore, the invention specifically limits the application of the xylo-oligosaccharide combined with other oligosaccharides to preparing antithrombotic medicaments, greatly enriches the variety of the active ingredients of the medicaments and provides novel antithrombotic medicaments.
Drawings
FIG. 1 is a graph showing that three different sources of xylo-oligosaccharides fed mice significantly inhibit deep vein thrombosis, wherein (A) the morphology of thrombi formed by different treatment groups; (B) A length statistical graph of four groups of thrombus tissues, wherein the p value of the corncob group is 0.0225, the p value of the bagasse group is 0.0002, and the p value of the wheat bran group is 0.0235; (C) A weight statistic graph of four groups of thrombus tissues, wherein the p value of the corncob group is 0.0475, the p value of the bagasse group is 0.0037, and the p value of the wheat bran group is 0.0468; in the figure, p <0.01, indicates that the data are very significantly different in statistical analysis; * P <0.05, indicating significant differences in the data in the statistical analysis; if p >0.05, the data showed no significant differences in the statistical analysis.
Detailed Description
The invention provides application of xylo-oligosaccharide in preparing a medicine for resisting deep vein thrombosis.
The raw materials of the xylo-oligosaccharide are not particularly limited, and the raw materials for preparing the xylo-oligosaccharide are well known in the art. In order to illustrate the effect of the xylo-oligosaccharides from different sources on resisting deep vein thrombosis, the invention is specifically described by taking corncob, bagasse or wheat bran as examples, but the invention is not to be construed as being limited by the scope of protection of the invention. The method for preparing the xylo-oligosaccharide is not particularly limited, and the xylo-oligosaccharide well known in the art can be used for preparing the xylo-oligosaccharide. The source of xylo-oligosaccharides is also available from common commercial sources. In the embodiment of the invention, the corncob-derived xylo-oligosaccharide is purchased from Zhuo Xin biosciences, suzhou, bagasse-derived xylo-oligosaccharide is purchased from Shandong Qianzhen bioengineering, inc., and wheat bran-derived xylo-oligosaccharide is purchased from Shanxi pannier biosciences, inc.
In the present invention, the anti-deep vein thrombosis preferably includes reducing the thrombus length and/or thrombus weight of the formed thrombus. The medicine for resisting deep vein thrombosis comprises the prevention and/or treatment of deep vein thrombosis.
In the invention, the xylo-oligosaccharide is not digested and decomposed through the digestive tract, and the dosage form of the medicament is preferably an oral preparation; the oral preparation comprises decoction, oral liquid, syrup, granule, pill, tablet or capsule. The present invention has no special limitation on the auxiliary materials of the medicine, and adopts the auxiliary materials selected according to different oral dosage forms in the field. The invention is not particularly limited as to the content of xylooligosaccharide in the medicament, and the content of active ingredients of the medicament known in the art can be adopted. The method for preparing the medicine is not particularly limited, and the method for preparing the medicine known in the art can be adopted. The feeding amount of the xylooligosaccharide is preferably 0.33-0.34 mg/mouse/d, and the dosage of the xylooligosaccharide is converted into the dosage of human body administration according to the dosage of animal administration.
The invention provides application of xylo-oligosaccharide combined with other kinds of oligosaccharides in preparing a medicine for preventing and/or treating deep vein thrombosis. The other kinds of oligosaccharides include fructooligosaccharides and/or maltooligosaccharides. The mass ratio of the xylo-oligosaccharide to the fructo-oligosaccharide or the malto-oligosaccharide is preferably 1-10:1-10, more preferably 3-7:3-7, and most preferably 5:2. The type and source of the fructo-oligosaccharide and/or the malto-oligosaccharide are not particularly limited in the present invention, and the type and source of the fructo-oligosaccharide and/or the malto-oligosaccharide known in the art may be used.
The invention provides a medicine for resisting deep vein thrombosis, which comprises active ingredients and auxiliary materials, wherein the medicine comprises the following components in parts by weight: 1 to 10 parts of xylo-oligosaccharide, 1 to 10 parts of fructo-oligosaccharide and 1 to 10 parts of malto-oligosaccharide, preferably: 3 to 7 parts of xylo-oligosaccharide, 3 to 7 parts of fructo-oligosaccharide and 3 to 7 parts of malto-oligosaccharide, more preferably 5 parts of xylo-oligosaccharide, 2 parts of fructo-oligosaccharide and 3 parts of malto-oligosaccharide. The dosage forms and the preparation methods of the medicines are the same as those of the medicines in the application, and are not repeated here.
The application of the xylooligosaccharide provided by the invention in preparing the medicine for resisting deep vein thrombosis is described in detail below with reference to examples, but the xylooligosaccharide is not to be construed as limiting the scope of the invention.
Example 1
Male experimental mice with the age of 4-5 weeks are selected, three kinds of source xylo-oligosaccharide are adopted to feed the mice respectively, namely corncob source xylo-oligosaccharide (n=9), bagasse source xylo-oligosaccharide (n=8) and wheat bran source xylo-oligosaccharide (n=8), the feeding amount of each mouse is 0.335 mg/d, a group of control groups (n=10) for feeding water is arranged, and all the mice drink water normally. After four weeks of feeding, the mice were subjected to inferior vena cava thrombosis surgery to induce deep vein thrombosis when the mice grew to about 20g in weight. And taking out vascular tissues after deep vein thrombosis for 24 hours, photographing and counting the thrombus length, weighing the taken vascular tissues, and counting the thrombus weight.
The results are shown in FIG. 1, wherein (A) the morphology of thrombus formed in the different treatment groups; (B) A length statistical graph of four groups of thrombus tissues, wherein the p value of the corncob group is 0.0225, the p value of the bagasse group is 0.0002, and the p value of the wheat bran group is 0.0235; (C) A weight statistic graph of four groups of thrombus tissues, wherein the p value of the corncob group is 0.0475, the p value of the bagasse group is 0.0037, and the p value of the wheat bran group is 0.0468; in the figure, p <0.01, indicates that the data are very significantly different in statistical analysis; * P <0.05, indicating significant differences in the data in the statistical analysis; if p >0.05, the data showed no significant differences in the statistical analysis.
From the results in fig. 1, it is shown that the deep vein thrombosis is significantly reduced in all three different sources of XOS treated mice compared to the control group, including thrombus length and thrombus weight. Thus, XOS proved to have a significant inhibitory effect on the formation of deep vein thrombosis in mice.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (7)
1. Application of xylooligosaccharide in preparing medicine for resisting deep vein thrombosis is provided.
2. The use according to claim 1, wherein the raw material of xylo-oligosaccharides comprises corncob, bagasse or wheat bran.
3. The use according to claim 1 or 2, characterized in that the raw material of the xylo-oligosaccharide is bagasse.
4. The use according to claim 1, wherein said anti-deep vein thrombosis comprises reducing thrombus length and/or thrombus weight.
5. The use according to claim 1, characterized in that the feeding amount of the xylo-oligosaccharide is 0.33-0.34 mg/mouse/d.
6. The use according to claim 1, wherein the medicament is in the form of an oral dosage form.
7. The use according to claim 6, wherein the oral dosage form comprises a decoction, an oral liquid, a syrup, a granule, a pill, a tablet or a capsule.
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| EP3852775A1 (en) * | 2018-09-20 | 2021-07-28 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
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