CN113493749B - Lactobacillus plantarum BFA-LA04 strain with uric acid reducing capacity and application thereof - Google Patents
Lactobacillus plantarum BFA-LA04 strain with uric acid reducing capacity and application thereof Download PDFInfo
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
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- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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Abstract
The invention provides a lactobacillus plantarum BFA-LA04 strain, which has the capacity of reducing uric acid, and the lactobacillus plantarum BFA-LA04 strain has the amino acid sequence shown in SEQ ID NO:1 and the sequence of the 16S rDNA gene shown in SEQ ID NO:2 is shown inclpPThe gene sequence, and the lactobacillus plantarum BFA-LA04 strain is registered in Japanese independent administrative statue product evaluation technology basal disc organization privileged microorganism registration center with the registration number of NITE BP-03110. The invention further relates to the application of the lactobacillus plantarum BFA-LA04 strain.
Description
Technical Field
The invention relates to a lactobacillus plantarum strain, in particular to a lactobacillus plantarum BFA-LA04 strain with a uric acid reducing capacity, and further relates to application of the lactobacillus plantarum BFA-LA04 strain.
Background
Uric acid is a heterocyclic compound (heterocyclic compound) containing carbon, nitrogen, oxygen and hydrogen, and is a product of metabolic decomposition of purine nucleotide (purine nucleotide), and can be excreted via urine.
If uric acid cannot be excreted normally, it will flow to connective tissue through blood and deposit in the form of needle-like crystals (needle-like crystals) in joints, capillaries, skin and other tissues, and at this time, white blood cells will take these as foreign substances and phagocytose them to cause local inflammatory reaction, namely gout (gout). Generally, too high uric acid concentration in blood (i.e. hyperuricemia) is a main cause of gout, and too high uric acid concentration is more likely to cause complications such as diabetes (diabetes), kidney disease (kidney disease), arteriosclerosis (arteriosclerosis), and cardiovascular disease (cardiovascular disease).
Clinically, a doctor can control the uric acid concentration in blood using an existing uricosuric agent (uricosuric agent) which can promote the excretion of uric acid by inhibiting the reabsorption (reabsorption) of uric acid by the proximal renal tubule (proximal tubule) or an existing uric acid production inhibitor (allopurinol), for example; the latter prevents the formation of uric acid by inhibiting xanthine oxidase (xanthine oxidase), the major enzyme that metabolizes xanthine (xanthine) to uric acid, such as probenecid. However, the occurrence rate of side effects of allopurinol is low, but some patients have fatal serious adverse drug reactions to allopurinol, and when the Creatinine Clearance Rate (CCR) of the patients is too low, probenecid loses effectiveness and risks urinary calculus and uric acid nephropathy.
In view of this, if an active ingredient with a significant effect of reducing the uric acid content can be further found, and the active ingredient is expected to be applied to the development of a drug for hyperuricemia, so as to effectively improve the health problems of the people in China.
Disclosure of Invention
In order to solve the problems, the invention aims to provide a lactobacillus plantarum BFA-LA04 strain which has good uric acid reducing capacity.
The invention further aims to provide the application of the Lactobacillus plantarum BFA-LA04 strain in preparing the medicine for treating hyperuricemia.
The lactobacillus plantarum BFA-LA04 strain with the uric acid reducing capacity has the amino acid sequence shown in SEQ ID NO:1 and the sequence of the 16S rDNA gene shown in SEQ ID NO:2, and the Lactobacillus plantarum BFA-LA04 strain deposited at the Japanese independent administration technology agency privileged microorganism deposit center for evaluation of articles, under the accession number NITE BP-03110.
Therefore, the lactobacillus plantarum BFA-LA04 strain can not only decompose xanthine, but also inhibit the activity of xanthine oxidase, so that the lactobacillus plantarum BFA-LA04 strain can be used as an active ingredient for reducing uric acid, can be applied to preparing a hyperuricemia drug, provides a choice for reducing uric acid for patients who are administrated with side effects induced by the existing drugs for promoting uric acid excretion or the existing drugs for inhibiting uric acid production, and has the efficacy of the invention.
Based on the same technical concept, the lactobacillus plantarum BFA-LA04 strain disclosed by the invention is used for preparing a hyperuricemia drug, wherein the lactobacillus plantarum BFA-LA04 strain is deposited in Japanese independent administrative Law evaluation technology basal disc organization privileged microorganism deposition center with the deposition number of NITE BP-03110.
Therefore, the lactobacillus plantarum BFA-LA04 strain can be applied to preparation of a hyperuricemia drug, so that the lactobacillus plantarum BFA-LA04 strain can be administered to the needed individual, the effect of the lactobacillus plantarum BFA-LA04 strain in the needed individual is achieved, the uric acid content in the blood of the needed individual is reduced, and further, complications such as gout, diabetes, kidney diseases, arteriosclerosis, cardiovascular and cerebrovascular diseases and the like caused by hyperuricemia are prevented, and the effect of the invention is achieved.
The invention discloses application of a lactobacillus plantarum BFA-LA04 strain, wherein the lactobacillus plantarum BFA-LA04 strain is administered to a desired individual to reduce the uric acid content in the blood of the desired individual.
The lactobacillus plantarum BFA-LA04 strain is used for the purpose, wherein the lactobacillus plantarum BFA-LA04 strain is orally administered to the needed individual. Therefore, the lactobacillus plantarum BFA-LA04 strain can be taken by a user in a simple and convenient way, and further the lactobacillus plantarum BFA-LA04 strain can play a role in the needed individual body, and the effect of the invention is achieved.
The application of the lactobacillus plantarum BFA-LA04 strain is disclosed, wherein the lactobacillus plantarum BFA-LA04 strain accounts for 1.25 multiplied by 10 5 ～2.5×10 5 CFU/kg/day for 7-30 days. Thus, the lactobacillus plantarum BFA-LA04 strain can effectively exert its biological activity by adjusting the administration dose.
Drawings
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
FIG. 1a: the invention relates to an evolutionary genetic relationship diagram of 16S rDNA genes of lactobacillus plantarum BFA-LA04 strains and other lactobacillus plantarum strains;
FIG. 1b: the evolutionary genetic relationship diagram of clpP genes of the lactobacillus plantarum BFA-LA04 strain and other lactobacillus plantarum strains is shown;
FIG. 2: a bar graph of the survival rate of Lactobacillus plantarum BFA-LA04 strain in different environments in test (A);
FIG. 3: histograms of the changes in xanthine decomposition rate of the Lactobacillus plantarum strains of each group in test (B);
FIG. 4: in test (C), the histogram shows the change in the xanthine oxidase inhibition ratio of each group of Lactobacillus plantarum strain.
Detailed Description
In order to make the aforementioned and other objects, features and advantages of the present invention comprehensible, preferred embodiments accompanied with figures are described in detail below:
the Lactobacillus plantarum BFA-LA04 strain can decompose xanthine, can also inhibit the activity of xanthine oxidase, and further can inhibit the generation of uric acid, so that the Lactobacillus plantarum BFA-LA04 strain can be used as a hyperuricemia drug.
The Lactobacillus plantarum BFA-LA04 strain is obtained by cloning from muskmelon fruits, in detail, after juicing the muskmelon fruits, the raw juice of the muskmelon fruits is coated on MRS solid medium (formula shown in Table 1) containing calcium carbonate, after selecting a single colony, the Lactobacillus plantarum BFA-LA04 strain is further screened from the single colony. The Lactobacillus plantarum BFA-LA04 strain has been deposited in Nite Patent Microorganisms Depositary (NPMD) with deposit number of NITE BP-03110 at 20/01 of 2020 and 20 days of Japan independent administration and human product evaluation technology.
TABLE 1 formulation of MRS solid medium for culturing Lactobacillus plantarum BFA-LA04 strain
In addition, the lactobacillus plantarum BFA-LA04 strain is subjected to molecular identification of 16S rDNA and clpP genes, and has the amino acid sequence shown in SEQ ID NO:1, and a 16S rDNA gene sequence having the sequence shown in SEQ ID NO:2, the 16S rDNA gene sequence and the clpP gene sequence are respectively aligned with the sequence alignment database (BLAST) of the National Center for Biotechnology (NCBI), and the results are shown in tables 2 and 3.
TABLE 2 alignment of 16S rDNA gene sequences of Lactobacillus plantarum BFA-LA04 strains
TABLE 3 comparison of the clpP Gene sequences of Lactobacillus plantarum BFA-LA04 Strain
Furthermore, the 16S rDNA gene sequence and the clpP gene sequence can be used to draw the genetic relationship tree diagrams shown in FIG. 1a and FIG. 1b, respectively, which shows that the Lactobacillus plantarum BFA-LA04 strain is a novel strain belonging to Lactobacillus plantarum.
The lactobacillus plantarum BFA-LA04 strain and a pharmaceutically acceptable carrier or excipient are combined to form a pharmaceutical composition or a food composition, and other active ingredients (e.g., green tea polyphenol, hawthorn, etc.) contributing to uric acid metabolism and/or other active ingredients (e.g., anthocyanin, curcumin, etc.) contributing to xanthine oxidase inhibition can be additionally added to the pharmaceutical composition or the food composition, and can be prepared into any convenient edible form, such as troches, capsules, powder, granules or liquid, and the like, which are orally taken by organisms in a form suitable for eating.
In addition, the Lactobacillus plantarum BFA-LA04 strain can be administered to a desired individual, for example, at 1.25X 10 5 ～2.5×10 5 The CFU/kg/day dosage is continuously administered to the needed individual for 7 to 30 days, so that the active ingredients contained in the lactobacillus plantarum BFA-LA04 strain can act in the needed individual.
To confirm that the Lactobacillus plantarum BFA-LA04 strain is indeed capable of decomposing xanthine and inhibiting xanthine oxidase, the following tests were performed:
(A) Acid resistance and cholate resistance tests of lactobacillus plantarum BFA-LA04 strain
In order to confirm that the lactobacillus plantarum BFA-LA04 strain can survive in a strong acid environment, the lactobacillus plantarum BFA-LA04 strain cultured to a stationary phase is statically cultured for 3 hours in MRS liquid culture medium with pH 6.5 and pH 3.0 respectively, and is coated into the MRS solid culture medium after obtaining a proper dilution factor by a continuous dilution method, and the number of bacteria is counted after culturing for 24 hours at 37 ℃.
Referring to FIG. 2, in the environment of pH 3.0, after 3 hours, about 10 still remains 5 Survival of CFU/mL of lactobacillus plantarum BFA-LA04 strain shows that the lactobacillus plantarum BFA-LA04 strain can survive in a strongly acidic environment and thus can pass through gastric juices, entering the intestine to exert its effect.
Then, to confirm that the Lactobacillus plantarum BFA-LA04 strain of the present invention can survive in an environment with bile salts, the experiment further included the step of subjecting the Lactobacillus plantarum BFA-LA04 strain cultured to the stationary phase to static culture in MRS medium containing 0.2%, 0.3% and 0.4% bile salts for 3 hours, followed by serial dilution, after obtaining appropriate dilution factor, spreading the strain onto MRS solid medium, and counting the number of cells after culturing at 37 ℃ for 24 hours.
Referring to FIG. 2, in an environment containing 0.2%, 0.3%, 0.4% bile salt, the number of viable bacteria still reaches 10 after 3 hours 5 Above CFU/mL, the lactobacillus plantarum BFA-LA04 strain can survive in an environment containing bile salts, and therefore can survive for a long timeIn the intestine to exert its effect.
(B) Xanthine decomposition ability of Lactobacillus plantarum BFA-LA04 Strain
This experiment compared the xanthine-decomposing ability of a novel Lactobacillus plantarum strain (i.e., the Lactobacillus plantarum BFA-LA04 strain) cloned from melon fruit with other Lactobacillus plantarum strains of the same genus and species. In particular, the other lactobacillus plantarum strain of the same genus and species includes lactobacillus plantarum strains, numbered BCRC 10069 and BCRC 910787, respectively, which were obtained from the center for biological resource conservation and research at the institute of food industry development, taiwan, china.
Culturing the lactobacillus plantarum strain to a stagnation period, adding the strain into an MRS liquid culture medium diluted by 10 times, adding xanthine and glucose, culturing for 2 to 4 hours, obtaining a supernatant, analyzing the xanthine content by HPLC, and converting the xanthine decomposition rate of each lactobacillus plantarum strain.
As shown in FIG. 3, after 2 hours of cultivation, the xanthine decomposition rate of Lactobacillus plantarum BFA-LA04 strain was already higher than that of Lactobacillus plantarum of other same genus (BCRC 910787, BCRC 10069, p < 0.05), and after 4 hours of cultivation, the xanthine decomposition rate of Lactobacillus plantarum BFA-LA04 strain was already higher than that of Lactobacillus plantarum of other same genus (BCRC 910787, BCRC 10069, p < 0.02), indicating that the Lactobacillus plantarum BFA-LA04 strain indeed has better xanthine decomposition ability than that of Lactobacillus plantarum of other same genus.
(C) Xanthine oxidase inhibition capability of Lactobacillus plantarum BFA-LA04 strain
In this test, the lactobacillus plantarum strain was cultured until the lag phase, a new MRS liquid medium was added, and after 2, 4, and 6 hours of culture, a supernatant was obtained, xanthine oxidase was added to the supernatant, the reaction was carried out at 37 ℃ for 10 minutes, xanthine was added, the reaction was carried out at 37 ℃ for 30 minutes, the reaction was terminated with hydrochloric acid, and the uric acid content was analyzed by HPLC, thereby converting the xanthine oxidase inhibition ratio of each lactobacillus plantarum strain.
Referring to FIG. 4, after 2, 4, and 6 hours of culture, the xanthine oxidase inhibition rate of Lactobacillus plantarum BFA-LA04 was significantly higher than that of other Lactobacillus plantarum strains of the same genus (BCRC 910787, BCRC 10069, p ≦ 0.001), indicating that the Lactobacillus plantarum BFA-LA04 strain indeed has better xanthine oxidase inhibition ability than other Lactobacillus plantarum strains of the same genus.
In conclusion, the lactobacillus plantarum BFA-LA04 strain of the present invention not only can decompose xanthine, but also can inhibit the activity of xanthine oxidase, and thus can be used as an active ingredient for reducing uric acid, and can be applied to the preparation of hyperuricemia drugs, and provides a choice for reducing uric acid for patients who are administered with the existing uricosuric drugs or the existing uricosuric drugs which induce side effects, which is the efficacy of the present invention.
Furthermore, the lactobacillus plantarum BFA-LA04 strain of the present invention can be applied to the preparation of a drug for hyperuricemia, and therefore, can be administered to the desired individual, so that the lactobacillus plantarum BFA-LA04 strain can act in the desired individual to reduce the uric acid content in the blood of the desired individual, thereby preventing the occurrence of complications such as gout, diabetes, kidney disease, arteriosclerosis, cerebrovascular and cardiovascular and cerebrovascular diseases caused by hyperuricemia, and thus, the efficacy of the present invention is provided.
Sequence listing
<110> Kangpin science and technology Limited
<120> lactobacillus plantarum BFA-LA04 with uric acid reducing capacity and application thereof
<150> TW109109204
<151> 2020-03-18
<160> 2
<170> PatentIn version 3.5
<210> 1
<211> 1555
<212> DNA
<213> Lactobacillus plantarum (Lactobacillus plantarum)
<400> 1
agagtttgat cctggctcag gacgaacgct ggcggcgtgc ctaatacatg caagtcgaac 60
gaactctggt attgattggt gcttgcatca tgatttacat ttgagtgagt ggcgaactgg 120
tgagtaacac gtgggaaacc tgcccagaag cgggggataa cacctggaaa cagatgctaa 180
taccgcataa caacttggac cgcatggtcc gagcttgaaa gatggcttcg gctatcactt 240
ttggatggtc ccgcggcgta ttagctagat ggtggggtaa cggctcacca tggcaatgat 300
acgtagccga cctgagaggg taatcggcca cattgggact gagacacggc ccaaactcct 360
acgggaggca gcagtaggga atcttccaca atggacgaaa gtctgatgga gcaacgccgc 420
gtgagtgaag aagggtttcg gctcgtaaaa ctctgttgtt aaagaagaac atatctgaga 480
gtaactgttc aggtattgac ggtatttaac cagaaagcca cggctaacta cgtgccagca 540
gccgcggtaa tacgtaggtg gcaagcgttg tccggattta ttgggcgtaa agcgagcgca 600
ggcggttttt taagtctgat gtgaaagcct tcggctcaac cgaagaagtg catcggaaac 660
tgggaaactt gagtgcagaa gaggacagtg gaactccatg tgtagcggtg aaatgcgtag 720
atatatggaa gaacaccagt ggcgaaggcg gctgtctggt ctgtaactga cgctgaggct 780
cgaaagtatg ggtagcaaac aggattagat accctggtag tccataccgt aaacgatgaa 840
tgctaagtgt tggagggttt ccgcccttca gtgctgcagc taacgcatta agcattccgc 900
ctggggagta cggccgcaag gctgaaactc aaaggaattg acgggggccc gcacaagcgg 960
tggagcatgt ggtttaattc gaagctacgc gaagaacctt accaggtctt gacatactat 1020
gcaaatctaa gagattagac gttcccttcg gggacatgga tacaggtggt gcatggttgt 1080
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ggggatgacg tcaaatcatc atgcccctta tgacctgggc tacacacgtg ctacaatgga 1260
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tgccgcggtg aatacgttcc cgggccttgt acacaccgcc cgtcacacca tgagagtttg 1440
taacacccaa agtcggtggg gtaacctttt aggaaccagc cgcctaaggt gggacagatg 1500
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gatgacgaca gtgatgatga agcacttgaa gttgacattg cttccaatgg tggcgatgtt 180
tttgcggcta gtgagattta cactatgcta aagaattatg ctggcaatgt aacagttaat 240
attcaaggct tagcagctag tgcggcaagc gtggttgcta tggctggcga tcacatcaac 300
atttcaccaa ctgctcagat tatgatccat aaggcttggt cacaaccggc tggtaatgct 360
gacgatctgg agcatgaagc cagtatttta aatggcattg atcaatcaat tgccagtgct 420
tatgaagcaa aaactggcat ggagcaagct gacttgctac agctaatggc aaatgaaaca 480
tggttaaccg ctagtgatgc cgttgataaa ggttttgctg acgaaattat gtttgctaat 540
gatcaacaat tacaaccggt gaacgctatt tcacacattc cacctaaatc tgcagttaat 600
aagctgctga atctcattta caaggcggat aaggataaaa ctaagccgtc taaagaagaa 660
aatactacta atagtcaatc tgctgaatta cgaaacagca aattggctat tttatttgga 720
aaaaatcaaa aggaggccaa ctaa 744
Claims (5)
1. A lactobacillus plantarum BFA-LA04 strain with uric acid reducing capacity is characterized by having a sequence shown in SEQ ID NO:1 and the sequence of the 16S rDNA gene shown in SEQ ID NO:2 is shown inclpPThe gene sequence, and the lactobacillus plantarum BFA-LA04 strain is registered in Japanese independent administrative statue product evaluation technology basal disc organization privileged microorganism registration center with the registration number of NITE BP-03110.
2. The application of the Lactobacillus plantarum BFA-LA04 strain is used for preparing a hyperuricemia drug, and is characterized in that the Lactobacillus plantarum BFA-LA04 strain is registered in a registered microorganism registration center of a product evaluation technology base plate institution of independent administrative Law of Japan, and the registration number of the registered microorganism is NITE BP-03110.
3. The use of the Lactobacillus plantarum BFA-LA04 strain according to claim 2, wherein the Lactobacillus plantarum BFA-LA04 strain is administered to a desired individual to reduce uric acid levels in the blood of the desired individual.
4. The use of the Lactobacillus plantarum BFA-LA04 strain of claim 3, wherein the Lactobacillus plantarum BFA-LA04 strain was administered orally to the desired subject.
5. The use of the Lactobacillus plantarum BFA-LA04 strain according to claim 3, wherein the Lactobacillus plantarum BFA-LA04 strain is 1.25 x 10 5 ～2.5×10 5 CFU/kg/day for 7-30 days.
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| TWI634207B (en) * | 2017-10-20 | 2018-09-01 | 葡萄王生技股份有限公司 | A lactobacillus plantarum, composition, culturing method and use of decrease uric acid, improvement of allergy and/or decrease blood sugar |
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| Title |
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| 节杆菌M3黄嘌呤氧化酶的诱导效应研究;王静等;《生物技术》;20081215(第06期);69-71 * |
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