Lactobacillus paracasei NB23 strain and its use for increasing muscle mass and preventing metabolic syndrome
The Lactobacillus paracasei NB23 strain addresses muscle loss by promoting muscle growth and reducing inflammation, effectively treating sarcopenia and metabolic syndrome.
Patent Information
- Application Number
- JP2024169647
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2023-11-09
- Filing Date
- 2024-09-27
- Publication Date
- 2025-12-02
- Estimated Expiration
- 2044-09-27
AI Technical Summary
Current treatments for sarcopenia, a condition characterized by muscle mass loss, are inadequate, as patients struggle to maintain exercise and dietary habits, necessitating a more effective approach to increase muscle mass and prevent metabolic syndrome.
The use of the Lactobacillus paracasei NB23 strain, which promotes muscle protein synthesis, muscle cell proliferation, and has anti-inflammatory and antioxidant properties, is administered to improve muscle mass and prevent metabolic syndrome.
The Lactobacillus paracasei NB23 strain effectively increases muscle mass, reduces inflammation, and improves metabolic indicators, thereby treating or preventing sarcopenia and related diseases.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a novel probiotic strain and its uses, in particular, Lactobacillus paracasei NB23 and its use in increasing muscle mass and preventing metabolic syndrome. [Background technology]
[0002] Muscles account for approximately 40-50% of the human body's weight, and muscle mass and strength are closely related to the body's metabolism and ability to maintain activity. Research has shown that muscle mass decreases annually after the age of 30, and the rate of decline increases with age, with muscle mass decreasing by approximately 10-20% between the ages of 40 and 50 compared to the muscle mass at age 30. Age-related muscle loss is also related to exercise and eating habits. A decrease in muscle mass not only affects one's appearance, but also impacts an individual's behavior and activity, resulting in increased susceptibility to lower back and back pain, difficulty lifting heavy objects, slower movement, and impaired memory.
[0003] Currently, there are no treatments for sarcopenia, which is caused by muscle mass loss, and patients can only be advised to improve their diet and exercise habits. This means that to improve the symptoms of sarcopenia, patients need to consume high protein and increase the duration of resistance exercise. However, most patients find it difficult to continue improving their exercise and dietary habits, making sarcopenia one of the conditions that is difficult to treat. Therefore, it is understandable that the development of compositions that can help treat or improve muscle mass loss and related diseases is an important challenge. Summary of the Invention [Problem to be solved by the invention]
[0004] The main objective of the present invention is to provide the Lactobacillus paracasei NB23 strain and its use for increasing muscle mass and preventing metabolic syndrome. The Lactobacillus paracasei NB23 strain disclosed in the present invention is a probiotic that is safe for the human body and has various physiological activities, including promoting muscle protein synthesis and muscle mass, promoting muscle cell proliferation and hypertrophy, anti-inflammatory and antioxidant properties, and can therefore be developed into lactic acid bacteria-related products. [Means for solving the problem]
[0005] To achieve the above-mentioned objectives, the present invention discloses Lactobacillus paracasei NB23 and its use for increasing muscle mass and preventing metabolic syndrome. The Lactobacillus paracasei NB23 strain was deposited at the Food Industry Development Research Institute, Hsinchu, Taiwan on October 4, 2023, under the accession number BCRC911201.
[0006] In one embodiment of the present invention, the composition disclosed comprises an effective amount of the Lactobacillus paracasei NB23 strain or a metabolite thereof, and the composition can be a food, a dietary supplement, a pharmaceutical composition, etc.
[0007] For example, when the composition is a food product, the composition contains an effective amount of the Lactobacillus paracasei NB23 strain and a food-acceptable ingredient, or when the composition is a pharmaceutical composition, the composition contains an effective amount of the Lactobacillus paracasei NB23 strain and a pharmaceutically acceptable ingredient.
[0008] In the following example of the present invention, the Lactobacillus paracasei NB23 strain has the activity of inhibiting NF-κB and Fox-O, and therefore can prevent muscle protein degradation or muscle cell apoptosis. Therefore, a composition containing the Lactobacillus paracasei NB23 strain or its metabolites can be used to treat or prevent sarcopenia or its related symptoms, such as muscle atrophy, muscle weakness, difficulty in movement, and poor grip strength.
[0009] In another embodiment of the present invention, the Lactobacillus paracasei NB23 strain can activate IGF-1 (insulin-like growth factor) and insulin, thereby activating the PI-3K / Akt / mTOR pathway and promoting protein synthesis in muscle cells. Therefore, by administering the Lactobacillus paracasei NB23 strain or a composition containing its metabolites to an individual, the muscle synthesis rate can be improved, thereby increasing the individual's muscle mass and achieving the effects of increasing muscle mass and improving related diseases caused by muscle deficiency.
[0010] In yet another embodiment of the present invention, there is provided a use of the Lactobacillus paracasei NB23 strain in the preparation of a composition for treating or ameliorating metabolic syndrome. Specifically, the Lactobacillus paracasei NB23 strain can reduce blood pressure, triglycerides, and fasting blood glucose levels, and increase HDL cholesterol. Therefore, administration of a composition containing the Lactobacillus paracasei NB23 strain or its metabolites to an individual can prevent or treat metabolic syndrome and its associated diseases.
[0011] In one embodiment of the present invention, the Lactobacillus paracasei NB23 strain is used to prepare a composition for treating or ameliorating cardiovascular disease. The Lactobacillus paracasei NB23 strain has anti-inflammatory and cytotoxicity-reducing activity, as well as the activity of controlling cardiovascular sclerosis indicators. Therefore, administering a composition containing the Lactobacillus paracasei NB23 strain or its metabolites to an individual can achieve the effect of preventing or treating cardiovascular disease.
[0012] Among these, cardiovascular diseases are caused by hardening of blood vessels.
[0013] Among these, cardiovascular sclerosis indicators include LDL cholesterol, HDL cholesterol, total cholesterol / LDL cholesterol (ratio), LDL cholesterol / HDL cholesterol (ratio), vitamin D, etc.
[0014] Among these, cytotoxicity indicators include CRP (C-reactive protein), LDH (lactate dehydrogenase), TNFα, IL-6, and the like. [Brief explanation of the drawings]
[0015] [Figure 1] This shows the results of an analysis of the amount of PIK protein expression in muscle cells after culturing muscle cells with different strains of lactic acid bacteria. [Figure 2] This shows the results of an analysis of mTOR protein expression levels in muscle cells after culturing muscle cells with different strains of lactic acid bacteria. [Figure 3] This shows the results of an analysis of the amount of AKT protein expression in muscle cells after culturing muscle cells together with different strains of lactic acid bacteria. DETAILED DESCRIPTION OF THE INVENTION
[0016] The present invention discloses Lactobacillus paracasei NB23 and its use for increasing muscle mass and anti-metabolic syndrome. Specifically, the Lactobacillus paracasei NB23 strain disclosed in the present invention has the ability to activate the IGF-1 signaling pathway, PI3K / Akt / mTOR, reduce inflammation and cytotoxicity indicators CRP (C-reactive protein), LDH (lactate dehydrogenase), TNFα, and IL-6, reduce cardiovascular sclerosis indicators LDL-C (LDL cholesterol), TC / HDL-C (total cholesterol / HDL cholesterol), and LDL-C / HDL-C ratio, and improve cardiovascular disease indicators HDL-C (HDL cholesterol) and vitamin D. At the same time, it has the activity to control metabolic syndrome indicators, such as lowering systolic blood pressure, lowering triglycerides, lowering fasting blood glucose, and increasing HDL-C. Therefore, by administering an effective amount of the Lactobacillus paracasei NB23 strain or its metabolites to an individual, it can effectively achieve the effects of treating or preventing metabolic syndrome and related diseases caused by muscle loss or insufficient muscle mass, as well as metabolic syndrome and related diseases.
[0017] The Lactobacillus paracasei NB23 strain disclosed in the present invention was deposited at the Food Industry Development Research Institute, Hsinchu Foundation, Taiwan on October 4, 2023, with the deposit number BCRC911201.
[0018] Among these, the Lactobacillus paracasei NB23 strain disclosed in the present invention is a Gram-positive bacterium isolated from pickled vegetables, and its culture conditions are Lactobacillus MRS Broth, a growth temperature of 37°C, and an anaerobic environment.
[0019] The term "effective amount" refers to the amount of probiotics or their metabolites administered that can achieve relief or amelioration of one or more symptoms of the disease being treated, reduction in the discomfort of one or more symptoms, or slowing the progression of the disease.
[0020] The term "composition" refers to a composition containing the Lactobacillus paracasei NB23 strain or its metabolites disclosed in the present invention as a major active ingredient, which can be prepared in various dosage forms based on factors such as the intended target and mode of use, and can contain excipients, vehicles, and other ingredients acceptable in the pharmaceutical or food industry. For example, the composition can be a pharmaceutical, dietary supplement, food, or therapeutic preparation.
[0021] The term "metabolites" refers to by-products produced during the cultivation of the Lactobacillus paracasei NB23 strain disclosed in the present invention, which may be present in the culture medium.
[0022] The term "administration" refers to the act or method of administering the Lactobacillus paracasei NB23 strain disclosed in the present invention, its metabolites, or compositions containing the above-mentioned strains or their metabolites to an individual, for example, orally, by implantation, etc.
[0023] In the following, several embodiments of the present invention will be described in detail with reference to the accompanying drawings in order to explain the technical features of the present invention and the effects that can be achieved thereby.
[0024] Cells such as C2C12 myoblasts used in the following examples are biological materials that can be easily obtained by those skilled in the art, and do not need to be deposited.
[0025] All human testing content and procedures disclosed in the following examples comply with ethical standards.
[0026] Example 1: Muscle cell culture
[0027] C2C12 myocytes were cultured in 5% CO2 at 37°C, and growth medium was provided as needed during the culture process. The medium used was DMEM containing 5% fetal bovine serum, 1% 4mM L-glutamine, 1.5g / L sodium bicarbonate, 4.5g / L glucose, 100μg / mL streptomycin, and 10 units / mL penicillin, with a pH of 7.1-7.4.
[0028] Example 2: Antioxidant testing
[0029] The lactic acid bacteria listed in Table 1 were prepared and cultured. The culture supernatants containing each strain were disrupted and diluted 16, 50, and 200 times to obtain samples of each lactic acid bacteria at different dilutions. C2C12 muscle cells were then treated with each sample. The absorbance of each group of cells was analyzed, and the DPPH radical scavenging ability of each strain was calculated. The results are shown in Table 2.
[0030] Table 1: Lactic acid bacteria samples and their origins JPEG0007778416000001.jpg233153JPEG0007778416000002.jpg11153
[0031] Table 2: DPPH radical scavenging ability of each lactic acid bacteria strain JPEG0007778416000003.jpg202126
[0032] As can be seen from the results in Table 2, overall, the higher the sample dilution ratio of the lactic acid bacteria samples, the lower their DPPH radical scavenging ability. Among these, the 8-fold diluted concentration had the best antioxidant effect, followed by the 16-fold diluted concentration.
[0033] Furthermore, strain NB42 was the only strain that did not reach 50% or more at the 8-fold dilution concentration, and the DPPH radical scavenging rate at the 50-fold and 200-fold dilutions did not reach 40%. At the 16-fold dilution concentration, strain NB17 had a DPPH radical scavenging rate of 71.82%, and the strains with the best DPPH radical scavenging effect at the 50-fold and 200-fold dilutions were strains NB34, NB17, and NB23, respectively.
[0034] Example 3: Cell viability test
[0035] The lactic acid bacteria listed in Table 1 were prepared and cultured. Each strain of lactic acid bacteria containing the culture supernatant was disrupted and diluted 16, 50, and 200 times to obtain samples of each lactic acid bacteria at different dilutions. C2C12 muscle cells were then treated with each sample. The viability of the C2C12 muscle cells treated with the lactic acid bacteria samples at different dilutions was then tested using the MTT assay. The results are shown in Table 3 below.
[0036] Table 3: Viability of muscle cells after treatment with different dilutions of Lactobacillus strains. JPEG0007778416000004.jpg208170
[0037] As can be seen from the results in Table 3, the lactic acid bacteria samples exhibited dose- and time-dependent effects on C2C12 muscle cells at a 16-fold dilution. The higher the concentration of the lactic acid bacteria sample, the lower the muscle cell viability, and the longer the incubation time, the lower the viability. After 72 hours of incubation with muscle cells at a 16-fold dilution, the viability of strains NB04, 10, 18, 20, 30, 36, 42, and 43 exceeded 100%. However, these eight strains tended to remain at the bottom of the 96-well plate and could not be removed by filtration. This was primarily due to the cell membrane properties of these strains, which facilitated their binding to muscle cells. Therefore, although the measured viability was high, it was not useful as a reference, and these eight strains were excluded from subsequent testing.
[0038] Example 3: Analysis of protein expression levels in muscle cells
[0039] Based on the results in Tables 2 and 3, and taking into consideration the feasibility of quantifying each strain, we selected the following lactic acid bacteria: NB07, NB17, NB23, and NB34. Each of these bacteria was cultured with C2C12 muscle cells for 12 and 24 hours. After 24 hours of co-culture, the protein content of the C2C12 muscle cells treated with each of the bacteria was examined by Western blotting, as well as the expression levels of PI3K, Akt, and mTOR proteins, which are involved in muscle growth in the cells. The results are shown in Table 4 and Figures 1 to 3. The gene protein concentrations shown in Figures 1 to 3 were quantified using ImageJ software from the results (band color intensity) obtained by Western blotting.
[0040] Table 4: Protein content after co-cultivation of each lactic acid bacteria strain with muscle cells JPEG0007778416000005.jpg105146
[0041] As can be seen from the results of Table 4 and Figures 1 to 3, the lactic acid bacteria strains with the most excellent effect on improving muscle cell mass were NB23, NB07, NB34, and NB17, in that order.
[0042] As can be seen from the results of Examples 2 to 4, the Lactobacillus paracasei NB23 strain disclosed in the present invention can not only scavenge radicals in muscle cells, but also maintain muscle cell proliferation and viability, and simultaneously achieve muscle growth and hypertrophy by increasing the expression levels of PI3K and AKT proteins, and promote muscle synthesis and mass by increasing the expression level of mTOR protein. In other words, the Lactobacillus paracasei NB23 strain disclosed in the present invention has the activity of treating or ameliorating muscle mass deficiency and related disorders. This means that administering an effective amount of the Lactobacillus paracasei NB23 strain, its metabolites, or a composition containing any of the above-mentioned substances to an individual can effectively increase the individual's muscle mass and strength, thereby achieving the effect of treating or preventing sarcopenia and its related symptoms.
[0043] Example 5: Human testing
[0044] The subjects were randomly divided into two groups and the study period was 12 weeks.
[0045] The placebo group received 3g of placebo (maltodextrin starch) every day after breakfast and dinner.
[0046] The NB23 group took one bag (3g / bag) of a sample containing the Lactobacillus paracasei NB23 strain with a viable bacterial count of 50 billion CFU every day after breakfast and dinner.
[0047] Example 6: Analysis of blood pressure, body fat percentage and skeletal muscle percentage
[0048] The subjects in each group in Example 5 were examined for the following items.
[0049] At weeks 0 and 12, the skeletal muscle and body fat percentages of the subjects in each group were examined using a commercially available body fat scale.
[0050] Muscle strength and function were assessed at weeks 0 and 12. Upper limb muscle strength was assessed by grip strength assessment using a hand dynamometer (TTM, Dynamometer, Tokyo, Japan). Lower limb muscle strength was assessed by measuring the number of repetitions in a 1-minute chair sit-to-stand test.
[0051] Analysis was carried out based on the above test results, and the results are shown in Tables 5 to 10 below.
[0052] As can be seen from the results in Tables 5 and 6, there were no differences in the body fat percentage and skeletal muscle percentage of subjects in each group at week 0 of the study. At week 12 of the study, subjects in the NB23 group had significantly greater improvements in skeletal muscle percentage (trunk) and chair sit-to-stand times per minute than the placebo group. Furthermore, as can be seen from the results in Table 7, subjects in the NB23 group had significantly greater improvements than the placebo group in diastolic blood pressure, body fat percentage, skeletal muscle percentage (legs), skeletal muscle percentage (arms), skeletal muscle percentage (trunk), skeletal muscle percentage (average), and chair sit-to-stand times per minute. Of these, skeletal muscle percentage (legs), skeletal muscle percentage (arms), skeletal muscle percentage (trunk), skeletal muscle percentage (average), and chair sit-to-stand times per minute were significantly improved compared to the placebo group, while other items were lower than the placebo group.
[0053] As can be seen from the results in Table 8, the female subjects in the NB23 group had higher total body skeletal muscle ratio, arm skeletal muscle ratio, trunk skeletal muscle ratio, average skeletal muscle ratio, and chair sit-to-stand times per minute than the female subjects in the placebo group. In addition, the female subjects in the NB23 group had a significantly greater decrease in body fat percentage than the female subjects in the placebo group, and the male subjects in the NB23 group had a greater decrease in systolic blood pressure than the female subjects.
[0054] As can be seen from the results in Table 9, the increase in trunk skeletal muscle ratio in subjects aged 40-60 in the NB23 group was significantly higher than that in subjects aged 20-40. As can be seen from the results in Table 10, in the NB23 group, subjects with a BMI of <24 kg / m 2The subjects in the NB23 group had significantly higher increases in trunk skeletal muscle ratio, average skeletal muscle ratio, and chair sit-to-stand times per minute, as well as decreases in diastolic blood pressure, body fat percentage, and average grip strength than the subjects in the placebo group. 2 The mean increase in grip strength in subjects with a BMI < 24 kg / m 2 was larger than that of the subjects.
[0055] Table 5: Analysis of blood pressure, body fat and skeletal muscle percentage for subjects in each group at week 0 of the study JPEG0007778416000006.jpg174148
[0056] Table 6: Analysis of blood pressure, body fat and skeletal muscle percentage for subjects in each group at week 12 of the study JPEG0007778416000007.jpg169148
[0057] Table 7: Difference analysis of blood pressure, body fat, and skeletal muscle percentage between week 0 and week 12 of the study for subjects in each group JPEG0007778416000008.jpg164149
[0058] Table 8: Difference analysis of blood pressure, body fat and skeletal muscle percentage between week 0 and week 12 of the study for subjects of different genders JPEG0007778416000009.jpg174148
[0059] Table 9: Difference analysis of blood pressure, body fat and skeletal muscle percentage between week 0 and week 12 of the study for subjects of different age groups JPEG0007778416000010.jpg175148
[0060] Table 10: Difference analysis of blood pressure, body fat and skeletal muscle percentage between week 0 and week 12 of the study for subjects with different BMIs JPEG0007778416000011.jpg179147
[0061] Example 7: Blood biochemical value testing and analysis
[0062] At week 0 and week 12 of the study, blood biochemical values were examined for the subjects in each group of Example 5. The results are shown in Tables 11 to 15 below. TG stands for triglyceride, TC stands for total cholesterol, LDL-C stands for LDL cholesterol, HDL-C stands for HDL cholesterol, BUN stands for blood urea nitrogen, GOT stands for aspartate aminotransferase, GPT stands for alanine aminotransferase, TP stands for total protein, CRP stands for C-reactive protein, and LDH stands for lactate dehydrogenase.
[0063] As can be seen from the results in Table 11, the cardiovascular sclerosis index factors (TC, LDL-C, LDL-C / HDL-C), renal function index factors (BUN, uric acid), and myocardial infarction / liver function / muscle damage factor-GOT values of the subjects in the NB23 group were significantly lower at week 12 than at week 0. As can be seen from the results in Table 12, the blood vitamin D levels of the subjects in the NB23 group were significantly higher than those of the female subjects in the placebo group, and the values of the index items TG, TC, LDL-C, TC / HDL-C, LDL-C / HDL-C, BUN, creatinine, uric acid, GOT, fasting blood glucose, HbA1C, insulin, and fibrinogen were also significantly lower than those of the placebo group.
[0064] The results in Table 11 showed that 12 weeks after administration of Lactobacillus paracasei NB23, the TG, LDL-C, and BUN levels of the subjects in the NB23 group were significantly lower than those in the placebo group. As can be seen from the results in Table 12, the subjects in the NB23 group had significantly lower cardiovascular sclerosis indicators (plasma TC, LDL-C, LDL-C / HDL-C), renal function indicators (BUN, uric acid), and myocardial infarction / liver function / muscle damage (GOT) after 12 weeks of administration of Lactobacillus paracasei NB23 compared to before the study (week 0), while the placebo group showed no significant differences in any of the indicators in blood biochemistry tests before and after the study.
[0065] As can be seen from the results in Table 13, 12 weeks after administration of Lactobacillus paracasei NB23 strain, the male subjects in the NB23 group showed significantly greater reductions in plasma TG, TC, LDL-C, LDL-C / HDL-C, and LDH levels, as well as serum creatinine, uric acid, GOT, albumin, and insulin than the placebo group, and the female subjects in the NB23 group showed significantly greater reductions in indicators such as TC, LDL-C, LDL-C / HDL-C, uric acid, TG, and HbA1c than the placebo group.
[0066] As can be seen from the results in Table 14, subjects aged 20-40 in the NB23 group showed significantly greater reductions in indicators such as plasma TC, LDL-C, LDL-C / HDL-C, and serum creatinine than the placebo group. After 12 weeks of administration of Lactobacillus paracasei NB23, subjects aged 20-40 in the NB23 group showed significantly greater reductions in indicators such as plasma TG, TC / HDL-C, serum uric acid, fasting blood glucose, and insulin than the placebo group, and the increase in serum fibrinogen was also greater than the placebo group. Subjects aged 40-60 in the NB23 group showed significantly greater reductions in indicators such as plasma LDL-C, uric acid, TG, TC, and LDL-C / HDL-C than the placebo group. Furthermore, subjects aged 20 to 40 in the NB23 group had significantly greater decreases in plasma TC / HDL-C and LDL-C / HDL-C, which are cardiovascular sclerosis factors, than subjects aged 40 to 60 in the NB23 group, but the opposite was true for plasma TP levels.
[0067] The results in Table 15 show that 12 weeks after administration of the Lactobacillus paracasei NB23 strain, the BMI of the NB23 group was <24 kg / m 2 The subjects in the NB23 group showed significantly greater reductions in plasma TC, LDL-C, TC / HDL-C, LDL-C / HDL-C, serum creatinine, HbA1c, and other indicators than the placebo group, and the increase in serum vitamin D was also significantly greater than the placebo group. 2The subjects in the 24-hour group also showed a more significant decrease in indicators such as plasma TG, TC, LDLC, LDL-C / HDL-C, BUN, uric acid, and albumin than the placebo group, and the increase in serum fibrinogen was also greater than in the placebo group.
[0068] As can be seen from the above results, administration of the Lactobacillus paracasei NB23 strain disclosed in the present invention for 12 consecutive weeks reduced the expression of inflammation and cytotoxicity indicators (LDH) in subjects, and simultaneously reduced cardiovascular sclerosis indicators (LDL-C, TC / HDL-C, LDL-C / HDL-C ratio), and improved cardiovascular disease indicators (HDL-C, vitamin D) and metabolic syndrome indicators (decreased systolic blood pressure, triglycerides, and fasting blood glucose, and increased HDL-C).In other words, the Lactobacillus paracasei NB23 strain disclosed in the present invention or its metabolites can be used to treat or prevent metabolic syndrome and cardiovascular-related diseases.
[0069] Table 11: Analysis of blood biochemistry values for subjects in each group at week 0 and week 12 of the study JPEG0007778416000012.jpg153154
[0070] Table 12: Blood biochemical analysis comparing before and after lactobacillus supplementation JPEG0007778416000013.jpg112144
[0071] Table 13: Differential analysis of blood biochemical values in subjects of different genders JPEG0007778416000014.jpg188148
[0072] Table 14: Differential analysis of blood biochemical values of subjects of different age groups JPEG0007778416000015.jpg190148
[0073] Table 15: Differential analysis of blood biochemical values of subjects with different BMI JPEG0007778416000016.jpg188148
[0074] Example 8: Analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation
[0075] At weeks 0 and 12, the inflammation indicators TNF-α, IL-6, and PARP, the cellular protein degradation indicators NF-κB, Fox-O, and MyoD (cell differentiation and maturation factor), and the cellular protein synthesis indicators PI3K, Akt, mTOR (myogenic regulatory factor), insulin, and IGF-1 (insulin-like growth factor) were examined for each subject in Example 5. The results are shown in Tables 16 to 20.
[0076] As can be seen from the results in Table 16, 12 weeks after administration of Lactobacillus paracasei NB23, the MyoD and expression levels of subjects in the NB23 group were significantly higher than those in the placebo group, and the expression levels of muscle protein degradation regulators TNFα, NF-κB, and FoxO were also significantly lower than those in the placebo group. Furthermore, after 12 weeks of the study, subjects in the NB23 group showed a significant increase in the expression level of the myogenic regulator mTOR, but there was no significant difference in the placebo group.
[0077] As can be seen from the results in Table 17, 12 weeks after administration of Lactobacillus paracasei NB23 strain, subjects in the NB23 group had significantly lower serum insulin levels than those in the placebo group, and the levels of TNFα and IL-6 were significantly reduced, and the expression levels of mTOR and MyoD were significantly increased compared to those in the placebo group.
[0078] The results in Table 18 showed that 12 weeks after administration of Lactobacillus paracasei NB23, the reduction in serum TNFα and serum mTOR content were higher in both male and female subjects than in the placebo group, and the serum MyoD levels in female subjects were significantly higher than in the placebo group. Furthermore, the reduction in serum TNFα in female subjects in the NB23 group was significantly greater than in male subjects.
[0079] As can be seen from the results in Table 19, after 12 weeks of administration of the Lactobacillus paracasei NB23 strain, subjects aged 20-40 in the NB23 group showed significantly greater decreases in serum TNFα and insulin than the placebo group, and greater increases in serum MyoD, IGF-1, and mTOR than the placebo group. In the NB23 group, subjects aged 20-40 showed significantly greater decreases in serum TNFα than the placebo group, and greater increases in serum PI3K and mTOR than the placebo group. Furthermore, comparing subjects of different age groups in the NB23 group, after 12 weeks of administration of the Lactobacillus paracasei NB23 strain, subjects aged 20-40 showed significantly greater decreases in serum TNFα than subjects aged 40-60. These results demonstrate that, regardless of the age group of the subjects, 12 weeks after administration of the Lactobacillus paracasei NB23 strain disclosed in the present invention, the content of inflammatory factors such as TNFα in the serum can be reduced and the content of mTOR, a muscle protein synthesis regulator, can be increased.
[0080] As can be seen from the results in Table 20, in the NB23 group, BMI < 24 kg / m 2 The subjects in the 2016 group showed significantly greater increases in serum MyoD, IGF-1, mTOR, and other indicators than the placebo group, and significantly greater decreases in serum TNFα than the placebo group. 2 In subjects in the NB23 group, the reductions in indicators such as serum TNFα and insulin were significantly greater than in the placebo group, and the increases in indicators such as serum mTOR were significantly greater than in the placebo group. Furthermore, among subjects in the NB23 group 12 weeks after administration of the Lactobacillus paracasei NB23 strain, those with a BMI of ≥ 24 kg / m 2 The subjects with a BMI < 24 kg / m2 showed a significant reduction in serum FoxO indices. 2 was significantly larger than that of the other subjects.
[0081] The above results show that the Lactobacillus paracasei NB23 strain disclosed in the present invention can reduce the content of inflammatory factors such as TNFα in the serum of subjects and improve the activity of muscle protein synthesis factors such as mTOR in the serum. This means that by administering an effective amount of the Lactobacillus paracasei NB23 strain disclosed in the present invention or its metabolites to an individual, it is possible to effectively improve the individual's inflammatory response and related diseases, and at the same time, increase the individual's muscle synthesis activity, thereby achieving the effect of treating or improving symptoms caused by muscle deficiency.
[0082] Table 16: Analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation in subjects of each group at week 0 and week 12 of the study JPEG0007778416000017.jpg119160
[0083] Table 17: Differential analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation before and after the test in subjects of each group JPEG0007778416000018.jpg67145
[0084] Table 18: Differential analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation before and after the test in subjects of different genders JPEG0007778416000019.jpg119150
[0085] Table 19: Differential analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation before and after the test in subjects of different age groups JPEG0007778416000020.jpg120150
[0086] Table 20: Differential analysis of factors regulating muscle protein synthesis, degradation, and cell differentiation and maturation before and after the test in subjects with different BMI values JPEG0007778416000021.jpg119150
Claims
1. Lactobacillus paracasei NB23 strain, deposited at the Food Industry Development Research Institute, Hsinchu Foundation, Taiwan on October 4, 2023, with deposit number BCRC911201.
2. A composition for treating or preventing sarcopenia and its associated symptoms, comprising the Lactobacillus paracasei NB23 strain of claim 1.
3. The composition according to claim 2, wherein the Lactobacillus paracasei NB23 strain is used to inhibit NF-κB and Fox-O.
4. A composition for increasing muscle mass, comprising the Lactobacillus paracasei NB23 strain of claim 1.
5. The composition according to claim 4, wherein the Lactobacillus paracasei NB23 strain is used to activate the IGF-1 (insulin-like growth factor-1) signaling pathway.
6. A composition for treating or ameliorating metabolic syndrome, comprising the Lactobacillus paracasei NB23 strain of claim 1.
7. The composition of claim 6, wherein the metabolic syndrome is associated with an imbalance in at least one of the risk factors of blood pressure, blood glucose, LDL cholesterol, and triglycerides.
8. A composition for treating or ameliorating cardiovascular disease, comprising the Lactobacillus paracasei NB23 strain of claim 1.
9. The composition according to claim 8, wherein the cardiovascular disease is caused by hardening of blood vessels.