CN114042146B - Bovine bone peptide composition and application thereof in preparation of medicines for regulating intestinal flora and preventing and treating osteoporosis - Google Patents
Bovine bone peptide composition and application thereof in preparation of medicines for regulating intestinal flora and preventing and treating osteoporosis Download PDFInfo
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Abstract
The invention relates to the technical field of bioactive peptides, in particular to a bovine bone peptide composition and application thereof in preparing medicines for regulating intestinal flora and preventing and treating osteoporosis. The bovine bone peptide composition provided by the invention can be used for preventing and treating osteoporosis, promoting the growth and development of femur, regulating calcium and phosphorus metabolism, promoting bone formation and reducing bone resorption. Through in vivo biological evaluation of animals, the bovine bone peptide composition provided by the invention can change the diversity of intestinal flora and the composition of species community of mice, so that the deregulated intestinal flora is normal, bone metabolism is regulated, and osteoporosis is improved.
Description
Technical Field
The invention relates to the technical field of bioactive peptides, in particular to a bovine bone peptide composition and application thereof in preparing medicines for regulating intestinal flora and preventing and treating osteoporosis.
Background
In addition to self cells, millions of microorganisms are present in the human body, of which about 90% are present in the human intestinal tract, known as the intestinal flora. With the continuous development of technology, researchers find that intestinal flora is not only related to physiological states of human body such as personality and aging, but also is closely related to the occurrence and development of various diseases of human body, such as autoimmune diseases such as inflammatory bowel disease, asthma, osteoporosis, brain diseases such as parkinsonism, and the like. It has also been proposed by researchers that modulation of the intestinal flora might be an effective way to treat diseases, e.g. using the intestinal flora to combat diabetes, parkinson's disease, alcoholic fatty liver disease, etc.
Osteoporosis is a common disorder of bone metabolism, and the main clinical manifestations are reduced bone density, impaired bone microstructure, bone pain, susceptibility to fracture, etc. Osteoporosis is a complex causative agent, mainly involving inflammation, aging, nutritional disorders, oxidative stress, hormonal metabolic disorders, and the like. Currently, the most commonly used osteoporosis treatment drugs are chemical drugs, such as estrogen modulators, bisphosphonates, selective cathepsin K inhibitors, and the like. The use of these drugs improves bone health to some extent, increases patient survival rate, but also increases the risk of developing breast cancer, venous vascular embolism to varying degrees. In recent years, more and more studies have shown that osteoporosis is closely related to the intestinal flora. Intestinal flora can influence bone metabolism through the "intestinal-bone axis", and is an important cause of osteoporosis. Further researches show that the intestinal flora can directly or indirectly influence the absorption and metabolism of medicaments and nutrient substances by organisms, thereby influencing the treatment effect of medicaments and the like on osteoporosis. Therefore, the osteoporosis prevention and treatment with intestinal flora as a target point is a treatment strategy with great application prospect.
Bone collagen peptide, which is called bone peptide for short, is a kind of bioactive polypeptide prepared by enzymolysis of animal bones, and is widely used for food and medicine for improving bone health. Bovine bone peptide is the most common type of bone peptide, and mainly includes cattle bone peptide, yak bone peptide, and the like. Studies show that bovine bone peptide can promote bone formation, enhance osteoblast activity, inhibit apoptosis and weaken bone loss in vivo by activating Wnt/beta-catenin, EGFR and other signal channels, and has obvious anti-osteoporosis activity at both in vitro cell level and in vivo animal level. Although bovine bone peptide is an important source of drugs for preventing and treating osteoporosis, the clinical therapeutic effect of bovine bone peptide alone is not remarkable.
The traditional Chinese medicine has the characteristics of remarkable curative effect, multiple action targets, small toxic and side effects, suitability for long-term administration and the like, and has an important effect in preventing and treating osteoporosis. Eucommia ulmoides and achyranthes are common medicinal and edible Chinese medicinal materials in China, are listed as superior products in Shennong Ben Cao Jing, and have the effects of tonifying liver and kidney, strengthening tendons and bones and the like. Based on the research of modern pharmacology, eucommia ulmoides and achyranthes bidentata can inhibit skeletal inflammation, promote osteoblast proliferation and inhibit osteoclast differentiation by regulating the signaling pathways such as RANKL/RANK/OPG, wnt/beta-catenin and the like. At present, no public report about the application of eucommia ulmoides and achyranthes bidentata combined bovine bone peptide in remodeling intestinal flora to prevent and treat osteoporosis is yet seen.
Disclosure of Invention
The invention aims to provide a bovine bone peptide composition which can be used for preparing medicines for regulating intestinal flora and preventing and treating osteoporosis. The bovine bone peptide composition provided by the invention can be used for preventing and treating osteoporosis by remodelling intestinal flora.
In a first aspect, the invention provides a bovine bone peptide composition which is prepared from the following raw materials in parts by weight: 8-50 parts of bovine bone peptide, 10-30 parts of eucommia ulmoides and 5-20 parts of radix achyranthis bidentatae; the bovine bone peptide is obtained by digestion treatment of fresh yellow bovine bone or yak bone with neutral protease and compound protease.
Preferably, the bovine bone peptide composition provided by the invention is prepared from the following raw materials in parts by weight: 30-50 parts of bovine bone peptide, 10-20 parts of eucommia ulmoides and 5-10 parts of achyranthes bidentata.
The eucommia bark is dried bark derived from eucommia bark of eucommia family; the radix Achyranthis bidentatae is dry root derived from radix Achyranthis bidentatae of Amaranthaceae.
Preferably, the bovine bone peptide composition provided by the invention is prepared from the following raw materials in parts by weight: 8-10 parts of bovine bone peptide, 20-30 parts of eucommia ulmoides and 10-15 parts of achyranthes bidentata.
In a second aspect, the invention provides a preparation method of the bovine bone peptide composition, which comprises the steps of mixing eucommia ulmoides and achyranthes bidentata with water, heating and boiling for 0.5-1h, adding bovine bone peptide, continuously boiling for 15-30min, filtering, and removing residues to obtain the bovine bone peptide composition.
In order to facilitate obtaining the bovine bone peptide composition in an oral liquid state, the method for preparing the bovine bone peptide composition comprises the following steps:
Soaking Eucommiae cortex and Achyranthis radix in water for 0.5-2 hr, boiling, heating, decocting until the water content of the soaking solution is 20-35%, removing residue, standing at room temperature, and adding bovine bone peptide to dissolve completely.
In the third aspect, in the preparation method provided by the invention, in order to prepare solid preparations such as powder, tablets and the like by better tabletting in combination with functional foods or pharmaceutically acceptable auxiliary materials, when eucommia ulmoides extracts and achyranthes bidentata extracts are used for preparing the bovine bone peptide composition, the eucommia ulmoides extracts and achyranthes bidentata extracts can be obtained by the following methods:
firstly, the eucommia bark and the achyranthes root are respectively added with water and decocted to prepare the eucommia bark or achyranthes root extract. Then the eucommia bark extract, the achyranthes root extract and the bovine bone peptide are mixed according to the weight ratio of (2-1.5): (1-2): (6-8) mixing to obtain the bovine bone peptide composition.
Preferably, decocting Eucommiae cortex or Achyranthis radix with water to 45-55% of the volume of the mixed solution, removing residue, heating to the mixed solution to be viscous, cooling to solidify, and grinding into powder to obtain Eucommiae cortex extract or Achyranthis radix extract;
the invention also claims the application of the bovine bone peptide composition or the bovine bone peptide composition prepared by the preparation method in preparing powder, oral liquid, granules, tablets and/or capsules by combining with auxiliary materials acceptable in pharmacy or functional food.
And the application of the bovine bone peptide composition or the preparation method in preparing the medicament for preventing and treating osteoporosis.
The invention has the advantages that:
(1) The bovine bone peptide composition provided by the invention can obviously improve basic growth and development indexes such as weight, body length and the like of an osteoporosis rat, and promote the growth of the size and weight of femur; effectively improves negative calcium balance and bone metabolic disorder caused by calcium deficiency, and regulates the balance between bone resorption and bone formation.
(2) The bovine bone peptide composition provided by the invention can obviously change the intestinal flora structure of an osteoporosis rat, obviously increase the abundance of beneficial bacteria of the chaetoviridae family, reduce the abundance of harmful bacteria of the erysipelas family, and improve the intestinal metabolism function and the intestinal health and maintain the intestinal immune homeostasis by influencing the distribution of the intestinal flora.
(3) The bovine bone peptide composition provided by the invention has simple components, can be used for preparing medicines for regulating intestinal flora and preventing and treating osteoporosis, can be added into functional foods for preventing and treating osteoporosis and regulating intestinal flora, opens up a new medicinal way of the bovine bone peptide composition, and has practical application and popularization values.
Drawings
FIG. 1 is a graph showing the effect of different substances on the intestinal flora diversity of an osteoporosis rat in the present invention; wherein, M, osteoporosis model group; CBP, bovine bone peptide group; YBP, yak bone peptide group; TCM, eucommia ulmoides/achyranthes group; cbp_tcm, bovine bone peptide combination group; bp_tcm, yak bone peptide combination group.
Detailed Description
The present invention will be described in detail with reference to examples. In the embodiment of the invention, the bovine bone peptide is a bovine bone small molecule bioactive peptide obtained by treating fresh cattle bone or fresh yak bone with a two-step enzymolysis method of neutral protease and compound protease. The eucommia ulmoides is derived from dry bark of eucommia ulmoides belonging to family eucommia. The radix Achyranthis bidentatae is derived from dry root of radix Achyranthis bidentatae of Amaranthaceae.
EXAMPLE 1 bovine bone peptide composition prepared from bovine bone peptide, eucommia ulmoides and achyranthes bidentata
The present example provides a bovine bone peptide composition prepared from bovine bone peptide, eucommia ulmoides and achyranthes bidentata. The method comprises the following specific steps:
mixing 30g of eucommia ulmoides and 15g of achyranthes bidentata with 500mL of water, heating and decocting for 1h, adding 10g of yak bone peptide or cattle bone peptide, continuously decocting for 15min, filtering, and removing residues.
EXAMPLE 2 oral liquid prepared from bovine bone peptide, eucommia ulmoides and achyranthes bidentata
The present example provides an oral liquid prepared from bovine bone peptide, eucommia ulmoides and achyranthes bidentata. The method comprises the following specific steps:
Soaking 50g of eucommia ulmoides and 50g of achyranthes bidentata decoction pieces in 600mL of water for 1h, boiling, heating for 1h, decocting to 120mL, removing residues, standing the decoction at room temperature, adding 20g of bovine bone peptide, dissolving completely, adding proper pharmaceutically acceptable auxiliary materials, and making into oral liquid.
EXAMPLE 3 preparation of bovine bone peptide composition from eucommia ulmoides extract, achyranthes bidentata extract and bovine bone peptide
The present example provides a bovine bone peptide composition prepared from eucommia ulmoides extract, achyranthes bidentata extract and bovine bone peptide. The method comprises the following specific steps:
Mixing 48g of eucommia ulmoides, 24g of achyranthes bidentata and 800mL of water, heating and boiling to 300mL, removing dregs, respectively freeze-drying to obtain eucommia ulmoides extract powder and achyranthes bidentata extract powder, and mixing eucommia ulmoides extract, achyranthes bidentata extract and yak bone peptide according to the weight ratio of 10:5:30, uniformly mixing to obtain the product.
Example 4 other preparations prepared from eucommia ulmoides extract, achyranthes bidentata extract and bovine bone peptide
This example provides other formulations of the bovine bone peptide composition. The method comprises the following steps:
Decocting Eucommiae cortex and Achyranthis radix with water respectively until the volume is reduced by half, removing residues, heating to obtain solution, cooling to solidify, grinding into powder, mixing Eucommiae cortex extract, achyranthis radix extract and bovine bone peptide at a weight ratio of 15:8:40, adding appropriate functional food or pharmaceutically acceptable adjuvants, and tabletting to obtain solid preparations such as powder and tablet.
The bovine bone peptide composition prepared by the invention has good technical effect through repeated experiments, and the related experimental data are as follows:
Experiment one: impact of bovine bone peptide composition on rat body weight and femur
Establishment of an osteoporosis rat model: SPF grade SD rats (70+ -10 g) of 4 weeks old are selected, and after normal adaptive feeding for one week, an osteoporosis rat model is constructed by feeding low-calcium feed. The experiments were divided into six groups, namely an osteoporosis model group, a cattle bone peptide group, a yak bone peptide group, an eucommia/achyranthes root group, a cattle bone peptide group and a yak bone peptide group. The administration was performed 1 time per day by gastric lavage for 6 weeks. Body weight of each group of rats was measured and recorded during feeding. After the experiment is finished, the rats of each group are sacrificed, the femur of the two sides of each group is stripped, the surface muscle and connective tissue of the bones are removed, and the femur wet weight and the femur midpoint diameter of each group of rats are measured. The experimental results showed (table 1) that there was a different degree of increase in the weight, wet weight of femur, and femur diameter of rats, regardless of the cattle bone peptide combination group or the yak bone peptide combination group, compared to not only the osteoporosis model group, but also the cattle bone peptide group and the eucommia ulmoides/achyranthes bidentata group fed alone.
TABLE 1 Effect of bovine bone peptide compositions on rat body weight and femur
| Grouping | Average body weight/g | Wet weight of femur/g | Femur diameter/cm |
| Osteoporosis model set | 291.83±25.06 | 0.60±0.09 | 4.05±0.19 |
| Cattle bone peptide group | 311.06±38.46 | 0.65±0.08 | 4.09±0.30 |
| Yak bone peptide group | 297.22±18.45 | 0.67±0.02 | 4.12±0.11 |
| Eucommia ulmoides/achyranthes bidentata group | 298.30±18.74 | 0.67±0.04 | 4.17±0.15 |
| Cattle bone peptide combination group | 324.72±16.21 | 0.68±0.08 | 4.25±0.35 |
| Yak bone peptide combination group | 302.86±24.80 | 0.72±0.09 | 4.24±0.24 |
Experiment II: influence of bovine bone peptide composition on serum biochemical index of osteoporosis rat
After the abdominal aorta blood is taken, each group of rats is sacrificed, the taken blood is stood at 37 ℃ for 2 hours, the temperature is 4 ℃ overnight, and the upper serum is frozen at-80 ℃ for standby. The serum blood calcium content of each group of rats was examined strictly according to the instructions of the corresponding kit, and the bone morphogenetic protein-2 (BMP-2) and the inflammatory factor interleukin-1 beta (IL-1 beta) were examined. Experimental results show (Table 2), compared with the control group, the bovine bone peptide composition can remarkably improve the blood calcium content, promote the expression of bone formation marker BMP-2, and inhibit the secretion of bone resorption marker IL-1 beta. Experimental results show that the bovine bone peptide composition corrects negative calcium balance to a certain extent, promotes bone formation and inhibits bone resorption.
TABLE 2 Effect of bovine bone peptide compositions on serum Biochemical indicators of osteoporotic rats
Experiment III: effect of bovine bone peptide composition on intestinal flora diversity in osteoporotic rats
Collecting the feces of each group of rats under aseptic environment, and preserving at-80 ℃ for standby. Microorganisms in feces were isolated and genomic DNA was extracted, and microbial diversity analysis was performed against bacterial 16SrDNA using Illumina Miseq platform. NMDS analysis at OTU level was performed based on unweighted-unifrac distance algorithm. The experimental results show (fig. 1) that the distribution of each set of samples is relatively discrete. The results showed that the structure of the intestinal flora of the rats was changed after treatment with the bovine bone peptide composition group, and there was a significant difference between groups (stress=0.159).
Experiment IV: influence of bovine bone peptide composition on composition of intestinal bacterial community of osteoporosis rat
Based on statistics of species abundance of intestinal flora of each group of rats at the family level, the results show (table 3) that the bovine bone peptide composition can increase abundance of intestinal beneficial bacteria lactobacillus (lactobacillus) of osteoporosis rats while reducing abundance of harmful bacteria bacteroides (Bacteroidaceae). The lactobacillus can be used as beneficial bacteria for maintaining intestinal flora steady state, and has effects in improving calcium bioavailability, increasing bone mass, and protecting bone health. Bacteroides are deadly bacteria of intestinal conditions, and the increase of the abundance of bacteroides is closely related to the immune dysfunction of the organism and the dysbacteriosis of intestinal tracts. The results show that the bovine bone peptide composition can regulate intestinal flora of an osteoporosis rat, and the effect of regulating osteoporosis is achieved by regulating the steady state of the intestinal flora.
TABLE 3 relative abundance of intestinal microbiota at the scientific level for each group of rats
| Grouping | Lactobacilli family | Bacteroides (Paeniaceae) |
| Osteoporosis model set | 4.39±1.96 | 11.97±9.88 |
| Cattle bone peptide group | 6.87±2.08 | 7.31±0.42 |
| Yak bone peptide group | 5.20±1.01 | 2.10±1.43 |
| Eucommia ulmoides/achyranthes bidentata group | 6.58±2.16 | 7.93±5.34 |
| Cattle bone peptide combination group | 9.76±8.52 | 1.75±0.71 |
| Yak bone peptide combination group | 6.15±1.37 | 3.43±0.51 |
The above experiments are carried out on the bovine bone peptide compositions prepared in different embodiments of the present invention, and the same or similar effects can be obtained, so that only a summary description is provided and no detailed description is given.
In conclusion, the bovine bone peptide composition provided by the invention can obviously improve basic growth and development indexes such as weight, body length and the like of an osteoporosis rat, and promote the growth of the size and weight of femur; effectively improves negative calcium balance and bone metabolic disorder caused by calcium deficiency, and regulates the balance between bone resorption and bone formation. Meanwhile, the composition can obviously change the intestinal flora structure of an osteoporosis rat, obviously increase the abundance of beneficial bacteria, namely the chaetomiaceae, reduce the abundance of harmful bacteria, namely the erysipelas, improve the intestinal metabolism function and the intestinal health by influencing the distribution of the intestinal flora, maintain the intestinal immune homeostasis, can be effectively used for preparing medicines for regulating the intestinal flora and preventing and treating the osteoporosis, can also be used for preventing and treating the osteoporosis in functional foods, regulates the intestinal flora, exploits a novel medicinal way of the bovine bone peptide composition, and has practical application and popularization value.
While the invention has been described in detail in the foregoing general description and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.
Claims (6)
1. The bovine bone peptide composition is characterized by being prepared from the following raw materials in parts by weight: 8-10 parts of bovine bone peptide, 20-30 parts of eucommia ulmoides and 10-15 parts of achyranthes bidentata; the bovine bone peptide is a bovine bone small molecule bioactive peptide obtained by treating fresh cattle bones through a two-step enzymolysis method of neutral protease and composite protease;
The eucommia ulmoides is derived from dry bark of eucommia ulmoides belonging to the family eucommia; the radix Achyranthis bidentatae is derived from dry root of radix Achyranthis bidentatae of Amaranthaceae;
Mixing Eucommiae cortex and Achyranthis radix with water, heating and decocting for 0.5-1 hr, adding bovine bone peptide, decocting for 15-30min, filtering, and removing residues to obtain bovine bone peptide composition.
2. The bovine bone peptide composition according to claim 1, wherein eucommia ulmoides and achyranthes bidentata are taken and immersed in water, the medicinal materials are soaked for 0.5-2 hours, the heating and boiling are continued until the soaking liquid is 20-35% of the initial water content, the dregs are removed by filtration, and the decoction is placed at room temperature, and then the bovine bone peptide is added to be fully dissolved, so that the bovine bone peptide composition is obtained.
3. A method for preparing the bovine bone peptide composition according to claim 1, which is characterized in that eucommia bark and achyranthes root are respectively boiled with water to prepare traditional Chinese medicine extracts; then the eucommia bark extract, the achyranthes root extract and the bovine bone peptide are mixed according to the weight ratio of (2-1.5): (1-2): (6-8) mixing.
4. The preparation method of claim 3, wherein the traditional Chinese medicine extract is prepared by decocting eucommia ulmoides or achyranthes bidentata with water until the volume of the mixed solution is 45-55% of the initial water content, removing residues, continuously heating until the mixed solution is viscous, cooling and solidifying, and grinding into powder to obtain eucommia ulmoides extract or achyranthes bidentata extract.
5. Use of a bovine bone peptide composition according to any one of claims 1-2 or a bovine bone peptide composition prepared by a method according to any one of claims 3-4 in combination with pharmaceutically or functionally food acceptable excipients for the preparation of a powder, an oral liquid, a granule, a tablet and/or a capsule.
6. Use of a bovine bone peptide composition according to any one of claims 1-2 or a bovine bone peptide composition obtained by the method of any one of claims 3-4 in the manufacture of a medicament for the prevention and treatment of osteoporosis.
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