Use of Liriodendron Chinense (Hemsl.) Sarg. or Extract thereof in the Preparation of Medicament for Reducing Serum Uric Acid Level and Preventing and Treating Uric Acid Nephropathy

Abstract

The present disclosure relates to the field of medicaments, and particularly to use of Liriodendron chinense (Hemsl.) Sarg. or an extract thereof in the preparation of a medicament for reducing a serum uric acid level and preventing and treating uric acid nephropathy, and belongs to the field of medicaments. In one aspect, the present disclosure provides use of Liriodendron chinense (Hemsl.) Sarg. or an extract thereof in the preparation of a medicament for reducing a serum uric acid level. In another aspect, the present disclosure further provides use of Liriodendron chinense (Hemsl.) Sarg. or an extract thereof in the preparation of a medicament for treating and/or preventing uric acid nephropathy. Animal experiments have confirmed that the Liriodendron chinense (Hemsl.) Sarg. can significantly reduce the serum uric acid level, and relieve degrees of renal tubular dilation, glomerulosclerosis, and renal interstitial fibrosis of hyperuricemic mice. Further research shows that the Liriodendron chinense (Hemsl.) Sarg. plays a role in reducing the serum uric acid level by promoting renal uric acid excretion. The use of the present disclosure can provide a new medicament choice for clinical treatment of hyperuricemia and hyperuricemic nephropathy caused by the hyperuricemia.

Claims

1. A method for reducing a serum uric acid level, comprising administering a subject in need thereof Liriodendron chinense (Hemsl.) Sarg. or an extract thereof.

2. A method for treating or preventing gout, comprising administering a subject in need thereof Liriodendron chinense (Hemsl.) Sarg. or an extract thereof.

3. A method for treating or preventing uric acid nephropathy, comprising administering a subject in need thereof Liriodendron chinense (Hemsl.) Sarg. or an extract thereof.

4. The method according to claim 3, wherein the Liriodendron chinense (Hemsl.) Sarg. or an extract thereof satisfies at least one of the following: reduces a level of at least one of serum creatinine, serum uric acid, blood urea nitrogen, or urine microalbumin; relieves renal tubular dilation and/or glomerulosclerosis; relieves renal fibrosis; or reduces an expression quantity of at least one of collagen fiber 1, fibronectin, or ?-smooth muscle actin in a kidney.

5. The method according to claim 3, wherein the Liriodendron chinense (Hemsl.) Sarg. or an extract thereof promotes renal uric acid excretion.

6. The method according to claim 5, wherein the Liriodendron chinense (Hemsl.) Sarg. or an extract thereof is in a formulation prepared by using the Liriodendron chinense (Hemsl.) Sarg. or the extract thereof as an active ingredient and adding pharmaceutically acceptable adjuvants or auxiliary ingredients.

7. The method according to claim 6, wherein the formulation is an oral formulation or an injectable formulation.

8. The method according to claim 7, wherein a medicinal part of the Liriodendron chinense (Hemsl.) Sarg. is at least one of roots, bark, branches, or leaves.

9. The method according to claim 8, wherein the extract is an alcohol extract and/or water extract; preferably, the alcohol is C.sub.1 to C.sub.6 fatty alcohol; further preferably, the alcohol is ethanol.

10. The method according to claim 9, wherein a preparation method of the extract comprises the following steps: adding the Liriodendron chinense (Hemsl.) Sarg. into an aqueous ethanol solution for extraction, and concentrating a extracting solution, thus obtaining the extract.

11. The method according to claim 10, wherein the extraction satisfies at least one of the following: adding into 75% v/v aqueous ethanol solution for extraction; allowing the solid-liquid ratio to be 500 g/5 L; or performing extracting for 3 hours under a boiling condition.

12. The method according to claim 2, wherein the Liriodendron chinense (Hemsl.) Sarg. or an extract thereof promotes renal uric acid excretion.

13. The method according to claim 12, wherein the Liriodendron chinense (Hemsl.) Sarg. or an extract thereof is in a formulation prepared by using the Liriodendron chinense (Hemsl.) Sarg. or the extract thereof as an active ingredient and adding pharmaceutically acceptable adjuvants or auxiliary ingredients.

14. The method according to claim 13, wherein the formulation is an oral formulation or an injectable formulation.

15. The method according to claim 14, wherein a medicinal part of the Liriodendron chinense (Hemsl.) Sarg. is at least one of roots, bark, branches, or leaves.

16. The method according to claim 15, wherein the extract is an alcohol extract and/or water extract; preferably, the alcohol is C.sub.1 to C.sub.6 fatty alcohol; further preferably, the alcohol is ethanol.

17. The method according to claim 16, wherein a preparation method of the extract comprises the following steps: adding the Liriodendron chinense (Hemsl.) Sarg. into an aqueous ethanol solution for extraction, and concentrating a extracting solution, thus obtaining the extract.

18. The method according to claim 17, wherein the extraction satisfies at least one of the following: adding into 75% v/v aqueous ethanol solution for extraction; allowing the solid-liquid ratio to be 500 g/5 L; or performing extracting for 3 hours under a boiling condition.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0032] FIG. 1 is a diagram of detection results of serum creatinine, serum uric acid, blood urea nitrogen and urine microalbumin of mice in Embodiment 1;

[0033] FIG. 2 is a diagram of PAS staining of kidney tissues of the mice in Embodiment 1;

[0034] FIG. 3 is a diagram of MASSON staining and ?-smooth muscle actin immunohistochemical staining of kidneys of the mice in Embodiment 2;

[0035] FIG. 4 is a diagram of detection results of expression quantities of collagen fiber 1, fibronectin, and ?-smooth muscle actin of the kidneys of the mice in Embodiment 2; and

[0036] FIG. 5 is a diagram of detection results of uric acid excretion quantities in the 24-hour urine of the mice in Embodiment 3.

DETAILED DESCRIPTION OF EMBODIMENTS

[0037] The solution of the present disclosure will be explained below in combination with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present disclosure and should not be construed as limiting the scope of the present disclosure. The contents in the embodiments in which the specific technology or condition are not indicated shall be carried out according to the technology or condition described in the literatures in the art or according to the product specification. The reagents or instruments used without the manufacturer's indication are all conventional products that are commercially available.

[0038] Preparation of an extract of Liriodendron chinense (Hemsl.) Sarg.: adding 500 g of the Liriodendron chinense (Hemsl.) Sarg. (including bark, branch, and leaf parts) into 5 L of 75% v/v aqueous ethanol solution, boiling for 3 hours, filtering, and evaporating the solvent to dryness, thus obtaining a brown solid extract.

[0039] Experimental methods: male C57BL/6 mice are randomly divided into a normal group, a model group, a positive control group (allopurinol 10 mg/kg/d), a low-dose treatment group (250 mg/kg/d) with the extract of the Liriodendron chinense (Hemsl.) Sarg., and a high-dose treatment group (500 mg/kg/d) with the extract of the Liriodendron chinense (Hemsl.) Sarg., with 6 mice in each group. The mice in the model group and each treatment group are given a gavage of adenine (160 mg/kg/d) and oteracil potassium (2400 mg/kg/d) for model establishing, while the normal group is given a gavage of an equal volume of double distilled water. The model establishing lasts for 3 weeks. During the model establishing, each treatment group is given a gavage of the extract of the Liriodendron chinense (Hemsl.) Sarg. and the allopurinol, and the normal group and the model group are given a gavage of an equal volume of double distilled water. The treatment lasts for 3 weeks. On the 21st day, 24-hour urine of the mice is collected by metabolic cages, and then the mice are sacrificed

[0040] Embodiment 1. Effects of Liriodendron chinense (Hemsl.) Sarg. on reducing serum uric acid and preventing and treating uric acid nephropathy

[0041] Blood samples of mice are centrifuged for 15 min at 3000 r/min at a room temperature, and then serums are taken for measuring biochemical indicators. Urine samples of the mice are centrifuged for 10 min at 800 g/min at the room temperature, and then upper-layer urine is taken for measuring a level of urine microalbumin. Serum creatinine and Blood Urea Nitrogen (BUN) are detected by using an automatic biochemical analyzer (TC6010L, Jiangxi Tecom Technology Co., Ltd.); and serum uric acid and urine microalbumin are detected by using an automatic biochemical analyzer (BS-240, Shenzhen Mindray Bio-Medical Electronics Co., Ltd.). Experimental results are shown in FIG. 1. PAS staining is conducted on kidney tissues of the mice, and results are shown in FIG. 2.

[0042] As can be seen from FIG. 1, the Liriodendron chinense (Hemsl.) Sarg. can significantly reduce a serum uric acid level and improve renal functions (reducing levels of the serum creatinine, the BUN and the urine microalbumin). Moreover, the relieving effect on the serum creatinine, the BUN and the urine microalbumin in the high-dose treatment group with the Liriodendron chinense (Hemsl.) Sarg. is significantly better than that in the low-dose treatment group (**P<0.01, and ****P<0.0001 compared with the normal group; .sup.?P<0.05, .sup.??P<0.01, .sup.???P<0.001, and .sup.????P<0.0001 compared with the model group).

[0043] As can be seen from FIG. 2, after treatment with the Liriodendron chinense (Hemsl.) Sarg., renal tubular dilation and glomerulosclerosis of kidneys of the hyperuricemic mice are significantly relieved.

[0044] Embodiment 2. Relieving effect of Liriodendron chinense (Hemsl.) Sarg. on chronic uric acid renal fibrosis

[0045] The expression of collagen fibers of kidneys is evaluated by MASSON staining. Meanwhile, ?-smooth muscle actin (?-SMA) immunohistochemical staining is conducted on the kidneys. Experimental results are shown in FIG. 3. Results of Western blot of the kidneys are shown in FIG. 4.

[0046] As can be seen from FIG. 3, after treatment with the Liriodendron chinense (Hemsl.) Sarg., a degree of renal interstitial fibrosis of hyperuricemic mice is significantly relieved. ?-SMA immunohistochemical staining shows that the Liriodendron chinense (Hemsl.) Sarg. can effectively inhibit expression of interstitial ?-SMA.

[0047] As can be seen from FIG. 4, expressions of collagen fiber 1, fibronectin, and ?-smooth muscle actin of the kidneys of the hyperuricemic mice are significantly increased, and after treatment with the Liriodendron chinense (Hemsl.) Sarg., their expressions in the kidneys can be significantly reduced.

[0048] Embodiment 3. Liriodendron chinense (Hemsl.) Sarg. reduces a serum uric acid level by promoting renal uric acid excretion

[0049] On the 21st day of the experiment, 24-hour urine of mice is collected by metabolic cages, and urine volumes are recorded. Urine samples of the mice are centrifuged for 10 min at 800 g/min at a room temperature, and then upper-layer urine is taken for measuring a uric acid level in the urine with an automatic biochemical analyzer (BS-240, Shenzhen Mindray Bio-Medical Electronics Co., Ltd.). Uric acid excretion quantity in the 24-hour urine=24-hour urine volume?uric acid concentration in the 24-hour urine. Experimental results are shown in FIG. 5.

[0050] As can be seen from FIG. 5, the uric acid excretion quantity in the 24-hour urine of the mice in the model group is significantly decreased (P<0.0001 compared with a normal group). After treatment with the Liriodendron chinense (Hemsl.) Sarg., the uric acid excretion quantity in the urine is significantly increased, and the high-dose group (P<0.000) compared with the model group) is better than the low-dose group (P<0.01 compared with the model group).

[0051] The above results show that the Liriodendron chinense (Hemsl.) Sarg. reduces the serum uric acid level by promoting renal uric acid excretion.