Application of fennel extract in the preparation of foods and medicines for improving osteoporosis

Abstract

This invention discloses the application of fennel water extract in the preparation of foods and medicines for improving osteoporosis. It relates to the field of natural medicine technology. This invention uses raw fennel and salt-preserved fennel as raw materials, which are processed through standardized purification and salt-soaking, followed by water extraction to obtain fennel water extract. This invention establishes a dual efficacy evaluation system using a prednisolone-induced zebrafish skull osteoporosis in vivo model and an in vitro model of MC3T3-E1 cell osteogenic differentiation. It systematically examines the in vivo anti-osteoporosis effects, embryonic development safety, and in vitro cytotoxicity and osteogenic differentiation activity of fennel water extracts with different processing methods and concentrations. Salt-preserved fennel shows superior efficacy compared to raw fennel at the same concentration. This invention provides a scientific basis for the application of fennel in the development of anti-osteoporosis drugs.

Description

Technical Field

[0001] This invention relates to the field of natural medicine technology, and more specifically to the application of fennel water extract in the preparation of foods and medicines that improve osteoporosis. Background Technology

[0002] Currently, the prevention and treatment of osteoporosis mainly rely on Western medicines such as calcium supplements, vitamin D, bisphosphonates, estrogen replacement therapy, and parathyroid hormone analogs. However, long-term use has adverse reactions and limitations, including gastrointestinal irritation, mandibular osteonecrosis, increased cardiovascular risk, and high costs. Traditional Chinese medicine and natural products, due to their multi-target, holistic regulatory, and high safety profiles, show unique advantages in the prevention and treatment of osteoporosis. Fennel (Fennel arvense) is a plant belonging to the Apiaceae family. Foeniculum vulgare The dried, ripe fruit of Mill. is a medicinal and edible variety with traditional effects such as warming the kidneys and liver, dispelling cold and relieving pain, regulating qi and stomach. Modern pharmacological studies have shown that it contains a variety of active ingredients such as volatile oils, flavonoids, and phenolic acids, and has anti-inflammatory, antioxidant, antibacterial and estrogen-like effects.

[0003] However, there is almost no research on the anti-osteoporosis activity of fennel in the existing technology, and there are no reports on the application of its water extract in the prevention and treatment of osteoporosis. At the same time, existing research on the anti-osteoporosis effects of traditional Chinese medicine generally suffers from problems such as unclear effective components, unclear mechanisms of action, and imperfect in vitro and in vivo evaluation systems, which restricts the development of new traditional Chinese medicine drugs for osteoporosis. Summary of the Invention

[0004] In view of this, the present invention provides the application of fennel water extract in the preparation of foods and medicines for improving osteoporosis. Using raw fennel and salt-preserved fennel as raw materials, after standardized cleaning and salt-soaking processing, fennel water extract is prepared by water extraction. This invention establishes a dual efficacy evaluation system using a prednisolone-induced zebrafish skull osteoporosis in vivo model and an in vitro model of MC3T3-E1 cell osteogenic differentiation. It systematically examines the in vivo anti-osteoporosis effects, embryonic development safety, and in vitro cytotoxicity and osteogenic differentiation activity of fennel water extracts with different processing methods and concentrations. Salt-preserved fennel shows superior efficacy compared to raw fennel at the same concentration. This invention provides a scientific basis for the application of fennel in the development of anti-osteoporosis drugs.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] Application of fennel extract in the preparation of foods and medicines that improve osteoporosis.

[0007] Preferred: Fennel seeds are the dried, mature fruits of the fennel plant (Apiaceae family), which are then prepared as raw fennel seeds or salt-preserved fennel seeds.

[0008] Preferred method: Cleaning process of raw fennel seeds: Take fennel seeds, remove impurities, and sieve to obtain raw fennel seeds.

[0009] The preferred method for preparing salt-soaked fennel is as follows: Take raw fennel and salt in a mass ratio of 10:1. First, dissolve the salt in water, then mix it with the fennel and let it absorb all the salt water. After soaking at 25±2℃ for 2 hours, bake over a low heat until the surface is yellowish-black and has a slight aroma, thus obtaining salt-soaked fennel.

[0010] Preferred method for preparing fennel water extract: Take fresh fennel or salt-soaked fennel, add distilled water at a material-to-water mass ratio of 1:10, heat and reflux for extraction, and filter; add distilled water to the filter residue at a material-to-water mass ratio of 1:8, reflux for extraction, combine the two filtrates, concentrate under reduced pressure and freeze dry to obtain fennel water extract.

[0011] Preferred concentrations of fennel extract in zebrafish for promoting osteogenic differentiation are 50-300 mg / L. The effective concentration of fennel extract in promoting osteogenic differentiation at the cellular level is 15-25 mg / L.

[0012] Preferred concentrations of fennel water extract in promoting osteogenic differentiation in zebrafish are 200-300 mg / L; and fennel water extract in promoting osteogenic differentiation at the cellular level is 20-25 mg / L.

[0013] Preferred: Fennel water extract prevents and treats osteoporosis by promoting osteoblast differentiation, increasing alkaline phosphatase activity, and increasing the formation of mineralized nodules.

[0014] Preferred dosage forms: tablets, capsules, granules, oral liquids or pills.

[0015] Preferred: The drug is used for the prevention and treatment of glucocorticoid-induced secondary osteoporosis, postmenopausal osteoporosis, senile osteoporosis, and osteoporosis-induced bone loss.

[0016] As can be seen from the above technical solution, compared with the prior art, the present invention discloses the application of fennel extract in the preparation of foods and medicines that improve osteoporosis, and the technical effects achieved are as follows: (1) This invention is the first to discover that the water extract of fennel has significant anti-osteoporosis activity, can significantly promote osteogenic differentiation of zebrafish skull and restore bone loss, opening up new uses for the traditional Chinese medicine fennel.

[0017] (2) This invention confirms that the water extract of fennel can significantly promote the differentiation of MC3T3-E1 osteoblasts and increase ALP (alkaline phosphatase) activity. Its mechanism of action is related to promoting osteoblast differentiation.

[0018] (3) This invention compared the anti-osteoporosis effects of raw fennel and salt-soaked fennel, and found that the efficacy was better after salt-soaking, providing a scientific basis for clinical use.

[0019] (4) The safety evaluation results show that the fennel water extract has no obvious toxicity within the effective concentration range, has little impact on the hatching rate and survival rate of zebrafish embryos, and has good safety.

[0020] (5) Fennel is a food and medicine product with wide availability and low price, and has good development prospects. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0022] Figure 1 The attached figure shows the effect of different concentrations of fresh fennel extract provided by this invention on the survival rate of juvenile zebrafish.

[0023] Figure 2 The attached figure shows the effect of different concentrations of fresh fennel extract provided by this invention on the hatching rate of zebrafish embryos.

[0024] Figure 3 The attached figure shows the effect of different concentrations of salt-soaked fennel extract provided by this invention on the survival rate of juvenile zebrafish.

[0025] Figure 4 The attached figure shows the effect of different concentrations of salt-soaked fennel extract provided by this invention on the hatching rate of zebrafish embryos.

[0026] Figure 5 The attached figure shows the effect of different concentrations of fresh fennel extract provided by the present invention on the area of ​​alizarin red staining in a zebrafish osteoporosis model.

[0027] Figure 6 The attached figure shows the effect of different processing methods of fennel water extract (250 mg / L) provided by the present invention on the area of ​​alizarin red staining in a zebrafish osteoporosis model.

[0028] Figure 7 The attached figure shows the effect of different concentrations of fresh fennel extract provided by this invention on the survival rate of MC3T3-E1 cells.

[0029] Figure 8 The attached figure shows the effect of different concentrations of salt-soaked fennel extract provided by this invention on the survival rate of MC3T3-E1 cells.

[0030] Figure 9 The attached figure shows the effect of different concentrations of fresh fennel extract provided by this invention on ALP staining of MC3T3-E1 cells.

[0031] Figure 10 The attached figure shows the effect of different processing methods of fennel water extract (20 mg / L) provided by the present invention on ALP staining of MC3T3-E1 cells. Detailed Implementation

[0032] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] This invention discloses the application of fennel water extract in the preparation of foods and medicines that improve osteoporosis.

[0034] In the examples, any raw materials and reagents not mentioned are commercially available, and any methods not mentioned are conventional experimental methods, such as: The fennel seeds were purchased from a local Chinese medicinal herb market in Ningxia and identified as fennel (Apiaceae family). Foeniculum vulgare The dried, ripe fruit of Mill. meets the relevant provisions of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0035] Prednisolone was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., while etidronate sodium, MS-222, and alizarin red S were all purchased from Shanghai Yuanye Biotechnology Co., Ltd. α -MEM culture medium, fetal bovine serum, and penicillin-streptomycin solution were purchased from Nanjing Shenghang Biotechnology Co., Ltd.; BCIP / NBT alkaline phosphatase colorimetric kit, 4% paraformaldehyde phosphate buffer, and MTT cell proliferation and cytotoxicity assay kit were purchased from Shanghai Beyotime Biotechnology Co., Ltd.

[0036] Laboratory animals and cells Wild-type AB strain zebrafish ( Danio rerio Zebrafish were provided and bred by our laboratory's zebrafish breeding center. Breeding conditions: water temperature 28.5±0.5℃, light / dark cycle 14 h / 10 h, pH 7.0-7.5, conductivity 500-1000 μs / cm. They were fed artificial pellet feed and live brine shrimp daily. Artemia salina (Each twice.)

[0037] MC3T3-E1 mouse preclavicular osteoblasts were cultured in a solution containing 10% fetal bovine serum and 1% penicillin-streptomycin. α In MEM medium, culture in a 37°C, 5% CO2 incubator, and passage every 2-3 days.

[0038] Example 1 Processing techniques and preparation of water extracts from fennel Cleaning process of raw fennel seeds: Take an appropriate amount of fennel seeds, and according to the general requirements for raw Chinese medicinal materials, remove the fruit stalks and impurities, and sift out the ash to obtain raw fennel seeds.

[0039] Preparation of salt-preserved fennel seeds: Take an appropriate amount of raw fennel seeds, and use 10 g of salt per 100 g of fennel seeds. First, dissolve the salt in an appropriate amount of water, mix it with the fennel seeds, and let it absorb the salt water. Let it soak for 2 hours (at an ambient temperature of 25±2℃). Then, bake it over a low heat until the surface is yellowish-black and has a slight aroma. This will give you salt-soaked fennel seeds.

[0040] Preparation of Fennel Water Extract Take 100 g each of raw fennel seeds or salt-preserved fennel seeds, soak them in 10 times the amount of distilled water for 30 min, heat and reflux for 1.5 h, filter through four layers of gauze; add 8 times the amount of distilled water to the filter residue and reflux for 1 h, combine the two filtrates, concentrate under reduced pressure, freeze dry, and store at 4℃ for later use.

[0041] Dilute to the required concentration with the appropriate solvent before use.

[0042] Example 2 Establishment and pharmacodynamic evaluation of a zebrafish osteoporosis model Experimental methods Establishment of a zebrafish osteoporosis model Healthy zebrafish juveniles 72 hours (3 dpf) post-fertilization were selected and observed under a dissecting microscope. Juveniles with normal development and uniform morphology were selected for the experiment. The juveniles were randomly divided into 24-well cell culture plates, with 30 fish per well.

[0043] The study was divided into a blank group (fish tank water), a model group (25 μmol / L prednisolone), a positive control group (25 μmol / L prednisolone + 30 mg / L etidronate sodium), and different concentrations of fennel water extract administration groups (25 μmol / L prednisolone + 50-300 mg / L raw or salt-preserved fennel water extract). Each group had 3 replicates.

[0044] Administer medication starting at 3 dpf, changing half the volume of the medication solution daily. Do not feed the juvenile fish during the medication period. The culture temperature is 28.5 ℃, the culture period is 5 days, and the experiment ends at 9 dpf.

[0045] Safety evaluation of fennel water extract on zebrafish embryo development Zebrafish fertilized eggs were collected, and normally developing embryos were selected under a dissecting microscope and randomly divided into 6-well culture plates, with 50 embryos per well. 8 mL of exposure solution containing different concentrations of fennel extract was added to each well, with three replicates for each concentration. Seven concentration groups were established: 0 mg / L (blank control), 50 mg / L, 100 mg / L, 150 mg / L, 200 mg / L, 250 mg / L, and 300 mg / L. Embryos were exposed for 120 h (until 6 days post-flop), with dead embryos or juveniles removed every 12 h, and half a volume of fresh exposure solution replaced every 24 h.

[0046] The development of embryos and juveniles in each group was observed and recorded at 24, 48, 60, 72, 84, 96 and 120 hpf. The number of embryos hatched and the number of juveniles that survived at each time point were counted, and the hatching rate and survival rate were calculated.

[0047] Hatching rate (%) = (Number of hatched embryos / Total number of embryos) × 100% Survival rate (%) = (Number of surviving juveniles / Total number of embryos) × 100% Alizarin Red Staining and Bone Mass Analysis After the drug administration experiment, zebrafish juveniles were anesthetized and euthanized by placing them in MS-222 (100 mg / L) solution. After removing the MS-222 solution, the juveniles were fixed in 4% paraformaldehyde phosphate buffer for 2-3 h. After removing the fixative, the following treatments were performed sequentially: dehydration with 50% ethanol for 10 min; staining with alizarin red solution prepared with 0.5% KOH overnight in the dark; rinsing with ultrapure water to remove excess stain; treatment with a mixed bleaching solution of 1.5% H2O2 and 1% KOH for 0.3-2 h; clearing with graded glycerol (0.5% KOH:glycerol = 3:1 treatment for 0.5-8 h, 1:1 treatment for 6-24 h, 1:3 treatment for 6-24 h), and finally stored in pure glycerol.

[0048] The skull was observed and photographed under a stereomicroscope, and the area stained with alizarin red was quantitatively analyzed using ImageJ image analysis software. The stained area was used as an evaluation index of bone mass.

[0049] Experimental results Effects of raw fennel extract on hatching rate and survival rate of zebrafish embryos like Figure 1 and Figure 2As shown, within the concentration range of 50-300 mg / L, the hatching rate and juvenile survival rate of raw fennel water extract in zebrafish reached over 80%, with no significant difference compared to the blank control group, indicating that raw fennel water extract has no obvious toxicity to zebrafish embryonic development within the effective concentration range.

[0050] Effects of salt-infused fennel extract on hatching rate and survival rate of zebrafish embryos like Figure 3 and Figure 4 As shown, within the concentration range of 50-300 mg / L, the salt-soaked fennel water extract resulted in a hatching rate of over 80% for zebrafish embryos and a survival rate of over 80% for juveniles, with no significant difference compared to the blank control group, indicating that the salt-soaked fennel water extract also has good safety.

[0051] Pharmacodynamic evaluation of fennel extract in a zebrafish osteoporosis model Dose-response relationship of raw fennel extract A zebrafish osteoporosis model was established using the method described above (Establishment of Zebrafish Osteoporosis Model). Simultaneously, raw fennel extract was administered at concentrations of 50, 100, 150, 200, 250, and 300 mg / L, respectively. Alizarin red staining and quantitative analysis were performed at 9 dpf.

[0052] like Figure 5 As shown, compared with the blank group, the area of ​​Alizarin Red staining in the skull of the model group (25 μmol / L prednisolone) was significantly reduced, indicating that the osteoporosis model was successfully established. Compared with the model group: (1) The staining area of ​​the 50 mg / L raw fennel extract group was not significantly different from that of the model group, indicating that this concentration was ineffective; (2) The 100 mg / L group showed a significantly enhanced anti-osteoporosis effect, with a significantly higher staining area than the model group and the positive drug group; (3) The anti-osteoporosis effect of the 150 mg / L group was further enhanced, and the staining area was significantly increased compared with the model group and the positive drug group; (4) The 200-300 mg / L group can significantly reverse the bone loss induced by prednisolone, and the staining area is restored to a level close to the normal level of the blank group. The efficacy is better than that of the positive control drug etidronate sodium (30 mg / L).

[0053] The above results indicate that the ameliorative effect of raw fennel extract on the osteoporosis model of zebrafish is dose-dependent, with an effective concentration range of 50-300 mg / L. The efficacy is optimal at 200-300 mg / L, and there is no significant difference between groups.

[0054] Comparison of the medicinal effects of fennel water extract prepared by different methods At a concentration of 250 mg / L, the therapeutic effects of raw fennel and salt-preserved fennel extract on a zebrafish osteoporosis model were compared.

[0055] like Figure 6 As shown, at a dosage concentration of 250 mg / L, the alizarin red staining area in each treatment group of raw fennel and salt-preserved fennel extract was significantly higher than that in the model group and the positive control group, indicating that fennel processed in different ways can effectively reverse prednisolone-induced bone loss. Among them, salt-preserved fennel was more effective than raw fennel, and there was no significant difference compared with the blank group, indicating that it could reverse bone loss.

[0056] Example 3 Establishment and evaluation of the MC3T3-E1 cell osteogenic differentiation model Experimental methods Cell Culture and Osteogenic Induction MC3T3-E1 cells were seeded with a solution containing 10% fetal bovine serum and 1% penicillin-streptomycin. α Incubate the cells in MEM medium at 37°C in a 5% CO2 incubator. When the cells reach 70% confluence, replace with osteogenic induction medium (containing 50 μg / mL ascorbic acid and 10 mM...). β -Sodium glycerophosphate α (MEM complete medium), continue culturing for 7 days, changing the medium every 2 days.

[0057] Establishment of an MC3T3-E1 cell osteoporosis model MC3T3-E1 cells were seeded in culture plates. After the cells adhered, 15 μg / L prednisolone was added to the culture medium for 24 h to establish a glucocorticoid-induced osteoporosis model of MC3T3-E1 cells.

[0058] Evaluation of the toxicity of fennel water extract to MC3T3-E1 cells (MTT assay) MC3T3-E1 cells in logarithmic growth phase were harvested, digested with trypsin, and counted. The cell density was adjusted to 2.5 × 10⁻⁶ cells using complete culture medium. 4Cells / mL. 200 μL of cell suspension was seeded into each well of a 96-well plate and incubated overnight to allow cell adhesion. The original culture medium was discarded, and 200 μL of culture medium containing different concentrations (10, 15, 20, 25 mg / L) of raw or saline-treated fennel extract was added to each well, with 6 replicates per group. A cell-free control group, a normal cell control group, and a positive control group were also included. After culturing for 24 h, the culture medium was discarded, and 90 μL of fresh culture medium and 10 μL of MTT solution (5 mg / mL) were added to each well. Incubation continued for another 4 h. The supernatant was discarded, and 110 μL of Formazan dissolving solution was added to each well. The plates were shaken at low speed for 10 min to fully dissolve the crystals, and the absorbance (OD) of each well was measured at 490 nm using a microplate reader.

[0059] Cell viability (%) = (OD value of experimental group - OD value of blank group) / (OD value of control group - OD value of blank group) × 100% ALP staining MC3T3-E1 cells were seeded in 6-well plates (2 × 10⁻⁶). 4 Cells per well were cultured in α-MEM complete medium for 2 days. Then, the medium was replaced with osteogenic induction medium for further culture, and a cell osteoporosis model was established by adding 15 μg / mL prednisolone. Cells were then administered raw or saline-infused fennel extract at concentrations of 10, 15, 20, and 25 mg / L, respectively. A blank control group, a model group, and a positive control group were also included. After 7 days of culture, the medium was discarded, the cells were washed twice with PBS, and fixed with 4% paraformaldehyde for 30 min. After washing with PBS, BCIP / NBT ALP staining reagent was added, and staining was performed in the dark for 30 min. The colorimetric reaction was terminated by gently rinsing twice with distilled water, and the cells were observed under a stereomicroscope. The staining area in the experimental and control groups was quantitatively analyzed using ImageJ software, and ALP activity was evaluated as a percentage of staining area.

[0060] Experimental results MTT cytotoxicity results like Figure 7 and Figure 8 As shown, within the concentration range of 10-25 mg / L, the survival rate of both raw and salt-processed fennel extracts against MC3T3-E1 cells was above 80%, indicating that neither processing method of fennel extract had a significant growth inhibitory effect on MC3T3-E1 cells within the 10-25 mg / L concentration range, demonstrating good cell safety. This concentration range can be used for subsequent screening of anti-osteoporosis drug efficacy.

[0061] Effects of raw fennel extract on osteogenic differentiation of MC3T3-E1 cells (ALP staining method) like Figure 9 As shown, compared with the control group, the percentage of ALP staining area in the model group (15 μg / L prednisolone) was significantly reduced, indicating that osteogenic differentiation was significantly inhibited and the osteoporosis model was successfully established. Compared with the model group, the ALP staining area in all treatment groups of raw fennel (10-25 mg / L) increased. Among them, the ALP staining area in all treatment groups of raw fennel (20-25 mg / L) was significantly increased, indicating that the aqueous extract of raw fennel at this concentration range can effectively restore the osteogenic differentiation capacity of MC3T3-E1 cells.

[0062] Comparison of the medicinal effects of fennel water extract prepared by different methods At a concentration of 20 mg / L, the effects of raw fennel and salt-preserved fennel extract on osteogenic differentiation of MC3T3-E1 cells were compared. Figure 10 After treatment with 20 mg / L raw fennel, the cell staining area significantly increased compared to the model group, and osteogenic activity was significantly restored, comparable to the positive control group. However, the staining area in the 20 mg / L salt-treated fennel group showed no statistically significant difference from the blank group, and was significantly higher than the model group, positive control group, and raw fennel group at the same concentration. This indicates that salt-treated fennel has a significantly better promoting effect on osteogenic differentiation than raw fennel, effectively reversing model-induced osteogenic inhibition and restoring cell mineralization capacity. Microscopic staining results were consistent with quantitative data; the salt-treated fennel group showed denser positive staining signals and a wider mineralization-related positive area, directly confirming its stronger osteogenic promoting effect.

[0063] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0064] Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Application of fennel water extract in the preparation of foods and medicines that improve osteoporosis.

2. The application according to claim 1, characterized in that, The fennel mentioned is the dried, mature fruit of the fennel plant (Apiaceae family), which is then prepared as either raw fennel or salt-preserved fennel.

3. The application according to claim 2, characterized in that, The purification process for raw fennel seeds is as follows: take fennel seeds, remove impurities, and sieve them to obtain raw fennel seeds.

4. The application according to claim 2, characterized in that, The processing method of salt-soaked fennel is as follows: Take raw fennel and salt in a mass ratio of 10:

1. First, dissolve the salt in water, then mix it with the fennel and let it absorb the salt water. After soaking at 25±2℃ for 2 hours, bake over a low heat until the surface is yellow-black and has a slight aroma, and you will get salt-soaked fennel.

5. The application according to claim 4, characterized in that, The preparation method of the fennel water extract is as follows: Take fresh fennel or salt-preserved fennel, add distilled water at a material-to-water mass ratio of 1:10, heat and reflux for extraction, and filter; add distilled water to the filter residue at a material-to-water mass ratio of 1:8, reflux for extraction, combine the two filtrates, concentrate under reduced pressure and freeze dry to obtain the fennel water extract.

6. The application according to claim 1, characterized in that, The effective concentration of the fennel extract in promoting osteogenic differentiation in zebrafish was 50-300 mg / L. The effective concentration of the fennel extract in promoting osteogenic differentiation at the cellular level is 15-25 mg / L.

7. The application according to claim 6, characterized in that, The effective concentration of the fennel water extract in promoting osteogenic differentiation at the zebrafish level is 200-300 mg / L; the effective concentration of the fennel water extract in promoting osteogenic differentiation at the cellular level is 20-25 mg / L.

8. The application according to claim 1, characterized in that, The fennel extract prevents and treats osteoporosis by promoting osteoblast differentiation, increasing alkaline phosphatase activity, and increasing the formation of mineralized nodules.

9. The application according to claim 1, characterized in that, The dosage form of the drug is tablets, capsules, granules, oral liquid, or pills.

10. The application according to claim 1, characterized in that, The drug is used to prevent and treat glucocorticoid-induced secondary osteoporosis, postmenopausal osteoporosis, senile osteoporosis, and osteoporosis-induced bone loss.

Images