Application of saponin compound in preparation of medicine for treating rheumatoid arthritis

Abstract

The invention provides an application of a saponin compound in preparation of a medicine for treating rheumatoid arthritis. The saponin has a structure as shown in a formula (I). Wherein X and R1-R7 are as defined in the specification of the invention. A series of animal experiments prove that the saponin compound provided by the invention shows the capability of remarkably relieving rheumatoid arthritis symptoms and reducing related serum inflammation indexes, and can be used as a potential rheumatoid arthritis treatment medicine.

Description

Technical Field

[0001] This invention belongs to the field of medicine, specifically relating to the use of a saponin compound and its pharmaceutically acceptable salt in the preparation of a drug for treating rheumatoid arthritis, and a pharmaceutical composition for treating rheumatoid arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic disease of unknown etiology, primarily characterized by inflammatory synovitis. It is characterized by polyarticular, symmetrical, and invasive joint inflammation. RA mainly affects small joints such as the hands and feet, typically with a symmetrical distribution. The inflammation is invasive, gradually destroying joint structure. Besides joint inflammation, RA can also affect other organs and systems, such as the heart, lungs, and kidneys. Most RA patients have elevated levels of rheumatoid factor in their blood, a crucial diagnostic indicator. The synovial tissue of RA patients undergoes proliferative changes, leading to synovial thickening. Extensive infiltration of inflammatory cells into the interstitium: Numerous inflammatory cells (such as lymphocytes and macrophages) infiltrate the synovial interstitium, triggering an inflammatory response. Microvascular angiogenesis and pannus formation: The formation of new blood vessels and pannus is a significant pathological feature of RA, further damaging joint structure. Cartilage and bone destruction: Long-term inflammation leads to the destruction of cartilage and bone tissue, ultimately resulting in joint deformities and functional impairment.

[0003] Drug treatment primarily includes: Nonsteroidal anti-inflammatory drugs (NSAIDs): used to relieve pain and reduce inflammation. Glucocorticoids: have potent anti-inflammatory and immunosuppressive effects, rapidly relieving pain and inflammation. DMARDs: including traditional DMARDs and biologics, which can halt the progression of inflammation and prevent joint tissue damage. Biologics: treat rheumatoid arthritis by inhibiting specific inflammatory mediators or pathways. Physical therapy: including heat therapy, cold therapy, massage, physical therapy, and exercise therapy, which can relieve joint pain and swelling and improve joint function. Surgical treatment: for patients with severe conditions or those unresponsive to drug treatment, surgical treatment may be considered, such as arthroscopic surgery or joint replacement. Rheumatoid arthritis is a progressive disease, therefore early diagnosis and early treatment are crucial.

[0004] Modern research has found that saponins in bitter melon have various biological activities. Bitter melon saponins significantly lower blood glucose levels, and their hypoglycemic effect in animal models is slow and persistent. Bitter melon saponins do not affect fasting plasma insulin levels in rats, but significantly reduce postprandial blood glucose and cholesterol levels; while significantly increasing muscle glycogen and liver glycogen content, it is speculated that bitter melon saponins may lower blood glucose levels by regulating glucocorticoid levels and stimulating glycogen synthesis. Other studies have found that bitter melon saponins can improve the immunity of model animals and significantly increase CD8+ in the thymus of aging mice.+ The number of CD4+CD8+ double-positive T cells was significantly reduced, as were the number of CD4+CD8+ double-positive T cells in the thymus and spleen. Momordica saponins also exhibited certain cholesterol-lowering activity. Studies have shown that momordica saponins significantly reduced plasma cholesterol levels in rats after feeding, demonstrating an anti-fatty liver effect. No reports were found regarding momordica saponins' anti-rheumatoid arthritis effects. Summary of the Invention

[0005] This invention provides the application of a plant-derived saponin in the preparation of a drug for treating rheumatoid arthritis. The saponin has the structure shown in formula (Ⅰ). == indicates that it is selected from double bonds or single bonds. This indicates that the expression is selected from a single bond or no bond. Two adjacent == symbols cannot both be double bonds. When it is a single bond, the carbon atom connected to it also has a single bond. When there is no bond, the carbon atom connected to it has either a double bond or a single bond, and R1 and R3 are selected from H, OH, CH3, and... , , The sugar residues formed by the condensation of any one, two or three of them, R2, R4-R7 are independently selected from H, OH, CH3, CHO, OCH3.

[0006]

[0007] Preferably, when the == next to the left ring indicates a double bond, the saponin compound has the structure shown in formula (II): wherein R11 and R12 are selected from H, OH, CH3, and , , R13 is selected from H, CH3 or CHO, and R14-17 are selected from H, OH, CH3 or OCH3.

[0008]

[0009] Preferably, when the == next to the left ring indicates a single bond, the saponin compound has the structure shown in formula (III): wherein R21 is selected from H, OH, CH3, and , , R22 is formed by the condensation of any one, two or three of the sugar residues in H, OCH3.

[0010]

[0011] More preferably, the saponin compound is selected from the structures shown below:

[0012]

[0013]

[0014] More preferably, in the above-mentioned uses, the saponin compounds and their pharmaceutically acceptable derivatives are prepared into clinically acceptable tablets, capsules, powders, mixtures, pills, granules, syrups, plasters, suppositories, aerosols, ointments, or injections by adding conventional excipients according to conventional processes.

[0015] The present invention also provides a pharmaceutical composition for treating rheumatoid arthritis, characterized in that the pharmaceutical composition contains the saponin compounds described in the present invention and their pharmaceutically acceptable salts.

[0016] The advantages of this invention are: through research, this invention has found that the saponin compounds of this invention have a significant therapeutic effect on relieving inflammatory swelling of the rat paw, and can be used as a potential drug for the treatment of rheumatoid arthritis, providing more options for rheumatoid arthritis patients. Example

[0017] Fresh bitter melon was selected as raw material and pulverized. Then, 95% ethanol aqueous solution was used as solvent for extraction by heating and reflux extraction of the pulverized bitter melon, with a material-to-liquid ratio (mass-to-volume ratio of bitter melon powder to ethanol aqueous solution) of 1:3. Each extraction lasted 30 minutes, and this step was repeated three times. After three extractions, all the collected extracts were combined and concentrated under reduced pressure using a rotary evaporator at 50℃ to obtain concentrated bitter melon extract A. Subsequently, extract A was further purified by column chromatography. HP-20 macroporous resin was selected as the packing material to construct the column chromatography system. A gradient elution was performed sequentially using purified water, 25% ethanol aqueous solution, 60% ethanol aqueous solution, and then 95% ethanol aqueous solution as eluents. The 60% ethanol eluent was collected and concentrated under reduced pressure to obtain extract B. Extract B was further purified using an Agilent SD-1 preparative liquid chromatography (UPLC) column with a reversed-phase C18 column and a 48% methanol-water solution as the mobile phase. Eluent was collected once a peak was detected, at 1.5 BV fractions per fraction, eluting for 15 BV. Each fraction was analyzed by UPLC, and the results were combined, concentrated, and dried to obtain compounds 1-7. Compounds 1-7 were then subjected to further purification. 1 H-NMR, 13The structure was determined by C-NMR and HPLC-MS, and the characterization results are as follows: Compound 1 molecular formula: C 42 H 72 O 15 [M+H]+: 817.09 1 H-NMR(CD3OD,400MHz) δ 5.72 (1H), 5.38 (11H), 4.99 (1H), 4.97 (1H), 4.63 (2H), 4.32 (1H), 4.25 (1H), 4.02 (2H), 3.99 (1H), 3.95 (2H), 3.84 (2H),3.79 (1H), 3.80 (1H), 3.69 (1H), 3.67 (2H), 3.22 (1H), 2.11 (2H), 2.05 (1H),1.84 (4H), 1.71 (4H), 1.66 (2H), 1.64 (1H), 1.58 (1H), 1.52 (3H), 1.37 (2H),1.33 (3H), 1.27 (3H), 1.09 (3H), 1.03 (6H), 0.95 (3H), 0.93 (3H).

[0018] 1313C-NMR(CD3OD, 400 MHz) δ 141.15 (1C), 118.62 (1C), 104.33 (1C), 103.21(1C), 84.08 (1C), 78.26 (1C), 76.99 (2C), 77.23 (1C), 76.35 (1C), 75.34 (1C),75.10 (1C), 75.08 (1C), 74.37 (1C), 72.09 (1C), 71.52 (1C), 71.42 (1C), 69.29(1C), 62.17 (1C), 50.66 (1C), 49.39 (1C), 47.28 (1C), 46.08 (1C), 45.22 (1C),41.97 (1C), 40.37 (1C), 37.54 (1C), 36.27 (2C), 34.55 (1C), 28.58 (1C), 28.41(1C), 27.39 (1C), 27.18 (2C), 25.44(1C), 24.33 (1C), 22.34 (1C), 19.91 (1C),18.26 (1C), 14.39 (1C), 13.28 (1C).

[0019] Molecular formula of Compound 2: C 47 H 80 O 19 , [M+H]+: 949.13 11H NMR (CD3OD, 400MHz) δ 5.88 (1H), 5.72 (1H), 5.44 (13H), 5.06 (1H), 4.93 (1H), 4.92 (1H), 4.66 (2H), 4.57 (1H), 4.33 (1H), 4.28 (1H), 4.15 (1H), 4.12 (1H), 4.09 (2H), 4.02 (1H), 3.99 (1H), 3.95 (2H), 3.93 (1H), 3.88 (2H), 3.82 (1H), 3.81 (1H), 3.77 (1H), 3.67 (1H), 3.15 (1H), 2.09 (2H), 2.03 (1H), 1.85 (4H), 1.70 (4H), 1.65 (2H), 1.62 (1H), 1.57 (1H), 1.52 (3H), 1.35 (2H), 1.30 (3H), 1.27 (3H), 1.11 (3H), 1.04 (6H), 0.98 (3H), 0.95 (3H).

[0020] 1313C-NMR(CD3OD, 400 MHz) δ 141.20 (1C), 118.50 (1C), 106.65 (1C), 104.90(1C), 103.20 (1C), 84.10 (1C), 78.70 (1C), 78.00 (1C), 77.78 (1C), 77.30(1C), 76.10 (2C), 75.30 (1C), 75.10 (1C), 74.95 (1C), 74.70 (1C), 74.65 (1C),74.50 (1C), 72.10 (1C), 71.15 (1C), 70.90 (1C), 68.50 (1C), 66.90 (1C), 62.50(1C), 50.00 (1C), 49.00 (1C), 47.70 (1C), 46.00 (1C), 45.30 (1C), 41.90 (1C),40.70 (1C), 37.20 (1C), 36.10 (2C), 34.50 (1C), 28.40 (1C), 28.30 (1C), 27.90(1C), 27.80 (2C), 25.80 (1C), 24.10 (1C), 22.10 (1C), 19.00 (1C), 18.00 (1C),14.70 (1C), 13.60 (1C).

[0021] Compound 3 Molecular formula: C 42 H 72 O 15 , [M+H]+: 817.03 11H NMR (CD3OD, 400 MHz): δ 5.70 (1H), 5.34 (11H), 4.95 (1H), 4.94 (1H), 4.64 (2H), 4.29 (1H), 4.15 (1H), 4.02 (2H), 3.99 (1H), 3.92 (2H), 3.86 (2H), 3.79 (1H), 3.83 (1H), 3.68 (1H), 3.64 (2H), 3.12 (1H), 2.07 (2H), 2.02 (1H), 1.81 (4H), 1.66 (4H), 1.63 (2H), 1.62 (1H), 1.54 (1H), 1.53 (3H), 1.32 (2H), 1.30 (3H), 1.28 (3H), 1.13 (3H), 1.01 (6H), 0.99 (3H), 0.97 (3H).

[0022] 13 13C-NMR (CD3OD, 400 MHz) δ 141.20 (1C), 118.48 (1C), 104.82 (1C), 103.17 (1C), 84.21 (1C), 78.05 (1C), 77.75 (2C), 77.12 (1C), 76.13 (1C), 75.31 (1C), 75.11 (1C), 75.08 (1C), 74.62 (1C), 72.13 (1C), 71.19 (1C), 71.16 (1C), 69.67 (1C), 62.52 (1C), 50.08 (1C), 49.13 (1C), 47.52 (1C), 46.10 (1C), 45.33 (1C), 41.87 (1C), 40.71 (1C), 37.23 (1C), 36.14 (2C), 34.41 (1C), 28.43 (1C), 28.32 (1C), 27.87 (1C), 27.81 (2C), 25.82 (1C), 24.14 (1C), 22.12 (1C), 19.04 (1C), 18.03 (1C), 14.66 (1C), 13.61 (1C).

[0023] Molecular formula of Compound 4: C 37 H 60 O9 [M+H]+: 648.84 11H NMR (CD3OD, 400 MHz): δ 10.03 (1H), 5.75 (1H), 5.74 (1H), 5.56 (1H), 5.50 (1H), 5.37 (5H), 4.93 (1H), 4.21 (1H), 4.00 (1H), 3.94 (2H), 3.85 (1H), 3.81 (1H), 3.69 (1H), 3.48 (3H), 3.14 (1H), 2.26 (2H), 2.13 (2H), 1.94 (1H), 1.83 (2H), 1.68 (4H), 1.64 (2H), 1.61 (1H), 1.55 (1H), 1.54 (3H), 1.52 (6H), 1.33 (2H), 1.14 (3H), 1.04 (3H), 0.98 (3H), 0.91 (3H).

[0024] 13 13C-NMR (CD3OD, 400 MHz) δ 208.30 (1C), 146.30 (1C), 137.55 (1C), 129.05 (1C), 126.60 (1C), 103.20 (1C), 78.00 (1C), 77.78 (1C), 76.50 (1C), 75.00 (1C), 74.90 (1C), 73.80 (1C), 71.15 (1C), 62.50 (1C), 53.85 (1C), 52.20 (1C), 51.80 (1C), 50.20 (1C), 48.50 (1C), 47.70 (1C), 45.30 (1C), 40.20 (1C), 39.60 (1C), 36.10 (3C), 34.50 (1C), 28.30 (1C), 28.20 (1C), 27.10 (1C), 26.60 (1C), 25.80 (2C), 22.10 (1C), 19.30 (1C), 18.55 (1C), 18.02 (1C).

[0025] Molecular formula of Compound 5: C 36 H 58 O9 [M + H]+: 634.8510 11H NMR (CD3OD, 400 MHz): δ 10.05 (1H), 5.91 (1H), 5.73 (1H), 5.72 (1H), 5.46 (1H), 5.35 (6H), 4.92 (1H), 4.20 (1H), 3.97 (1H), 3.93 (2H), 3.86 (1H), 3.80 (1H), 3.70 (1H), 3.12 (1H), 2.25 (2H), 2.15 (2H), 1.92 (1H), 1.80 (2H), 1.67 (4H), 1.63 (2H), 1.60 (1H), 1.54 (1H), 1.52 (3H), 1.35 (6H), 1.32 (2H), 1.12 (3H), 1.03 (3H), 0.96 (3H), 0.89 (3H).

[0026] 13 13C-NMR (CD3OD, 400 MHz) δ 208.29 (1C), 146.23 (1C), 139.70 (1C), 126.58 (1C), 125.40 (1C), 103.21 (1C), 78.02 (1C), 77.76 (1C), 76.49 (1C), 75.01 (1C), 73.79 (1C), 71.13 (1C), 70.70 (1C), 62.48 (1C), 53.83 (1C), 52.18 (1C), 51.77 (1C), 48.47 (1C), 47.59 (1C), 45.26 (1C), 40.18 (1C), 39.55 (1C), 36.09 (3C), 34.46 (1C), 29.80 (2C), 28.29 (1C), 28.17 (1C), 27.09 (1C), 26.56 (1C), 22.09 (1C), 19.29 (1C), 18.53 (1C), 18.00 (1C). Molecular formula of Compound 6: C 37 H 60 O8 [M + H]+: 632.91 11H NMR (MeOH-d4, 400 MHz) δ 5.90 (1H), 5.73 (1H), 5.61 (1H), 5.55 (1H), 5.38 (4H), 4.91 (1H), 4.87 (1H), 4.07 (2H), 4.00 (1H), 3.89 (2H), 3.79 (1H), 3.75 (1H), 3.62 (1H), 3.46 (3H), 2.78 (2H), 2.28 (2H), 1.85 (2H), 1.70 (4H), 1.65 (2H), 1.59 (1H), 1.54 (1H), 1.51 (6H), 1.48 (2H), 1.32 (2H), 1.13 (6H), 1.02 (3H), 0.96 (3H), 0.90 (3H).

[0027] 13 13C-NMR (MeOH-d4, 400 MHz) δ 137.50 (1C), 132.80 (1C), 130.90 (1C), 129.05 (1C), 103.19 (1C), 79.50 (1C), 78.00 (1C), 77.78 (1C), 76.80 (1C), 75.45 (1C), 75.00 (1C), 74.90 (1C), 71.15 (1C), 62.50 (1C), 56.90 (1C), 53.00 (1C), 52.18 (1C), 50.17 (1C), 48.49 (1C), 45.31 (1C), 40.80 (2C), 39.59 (1C), 36.12 (3C), 34.52 (1C), 28.60 (1C), 28.40 (1C), 28.17 (1C), 26.70 (2C), 25.77 (2C), 19.32 (1C), 18.59 (1C), 17.97 (1C). Molecular formula of Compound 7: C 37 H 60 O8, [M + H]+: 632.87 1H NMR(MeOH-d4,400MHz) δ 5.88 (1H), 5.75 (1H), 5.61 (1H), 5.56 (1H), 5.37 (4H), 4.87 (1H), 4.38 (1H), 4.07 (2H), 3.94 (2H), 3.48 (3H), 3.45 (1H),3.39 (1H), 3.36 (1H), 3.35 (1H), 2.78 (2H), 2.26 (2H), 1.83 (2H), 1.68 (4H),1.64 (2H), 1.61 (1H), 1.55 (1H), 1.52 (6H), 1.51 (2H), 1.33 (2H), 1.13 (6H),1.04 (3H), 0.98 (3H), 0.91 (3H). 13 C-NMR(MeOH-d4,400MHz) δ 137.55 (1C), 132.81 (1C), 130.89 (1C), 129.04 (1C), 103.50 (1C), 79.51 (1C), 78.10 (1C), 76.82 (1C), 76.10 (1C),75.46 (1C), 74.91 (1C), 72.00 (1C), 70.35 (1C), 62.55 (1C), 56.90 (1C), 53.02(1C), 52.20 (1C), 50.20 (1C), 48.50 (1C), 45.30 (1C), 40.81 (2C), 39.60 (1C),36.10 (3C), 34.50 (1C), 28.63 (1C), 28.40 (1C), 28.20 (1C), 26.71 (2C), 25.80(2C), 19.30 (1C), 18.55 (1C), 18.00 (1C). Example 2: Experimental study on the joint therapeutic effects of saponins on rats with rheumatoid arthritis Experimental animals: SPF-grade female six-week-old SD rats, weighing 180g±20g, were acclimatized in the animal room for one week before the experiment.

[0028] Experimental reagents: Saponin compounds were prepared in Example 1.

[0029] Experimental Methods: Rats were randomly divided into a control group (n=8) and a model group (n=64). On days 1 and 7, the model group underwent subcutaneous injections at multiple points near the tail root of the rats with a 1:1 emulsion of bovine type II collagen and complete Freund adjuvant to induce metatarsophalangeal joint swelling, simulating rhabdomyolysis (RA). The degree of swelling of the rat paw joints was visually observed after inflammation, and the following scoring system was used for model selection: 0 points: no redness or swelling in the hind paws; 1 point: mild swelling in the hind paws; 2 points: moderate swelling in the hind paws; 3 points: severe swelling in the hind paws; 4 points: swelling of both the hind paws and ankle joints or accompanied by deformity. Rats scoring 1 or higher were randomly assigned to a treatment group. Rats with successful model establishment were randomly divided into 8 groups of 8 each: the model group and groups containing saponin compounds 1-7. The control group and model group were administered 0.5% sodium carboxymethyl cellulose via gavage. The drug groups were given the corresponding drugs at a concentration of 100 mg / kg diluted with 0.5% sodium carboxymethyl cellulose. This administration was repeated for five weeks. The volume of the right paw of each rat was measured weekly using a volumetric gauging instrument, and the data were recorded and statistically analyzed. On day 35, rats were anesthetized with 4% chloral hydrate, and 5 mL of blood was collected from the inferior vena cava using a disposable syringe. After centrifugation at 4000 rpm for 10 minutes, the supernatant was collected and stored for later use. Serum concentrations of TNF-α, IL-1β, and IL-18 were detected using an ELISA kit.

[0030] Data statistical methods: SPSS 20.0 statistical software was used for data significance analysis.

[0031] result The data in Table 1 show that saponin compounds have a positive alleviating effect on inflammatory swelling of the rat paw. In the model group, the right paw of the rats showed significant swelling after inflammation was induced. After intervention with compounds 1-7, compared with the model group, the swelling of the right paw of the rats in the seven compound groups was significantly improved starting from the second week. In particular, saponin compounds 6 and 7 showed better efficacy.

[0032] Furthermore, Table 2 shows the effects of saponin compounds on the expression levels of key inflammatory cytokines TNF-α, IL-1β, and IL-18 in the serum of rat models. Compared with the blank control group, the expression of these three inflammatory cytokines in the model group rats was significantly upregulated, indicating that the inflammation model was successfully established. Compared with the model group, all saponin compound groups showed inhibitory effects on inflammatory cytokines, with saponin compounds 6 and 7 showing better effects in inhibiting the expression of these inflammatory cytokines, significantly superior to compounds 1-5. This indicates that saponin compounds 6-7 have a more significant effect in alleviating the inflammatory response and have potential clinical application prospects.

[0033] Table 1. Effect of extracts on inflammatory swelling of rat paw soles (mL) Group Week 1 Week 2 Week 3 Week 4 Week 5 Blank group 0.79 0.86 0.99 1.08 1.17 Model group <![CDATA[2.05 ## ]]> <![CDATA[2.13 ## ]]> <![CDATA[2.22 ## ]]> <![CDATA[2.27 ## ]]> <![CDATA[2.29 ## ]]> Compound 1 1.80 1.87 1.75 1.72 1.68* Compound 2 1.78 1.82 1.84 1.75 1.72* Compound 3 1.70 1.82 1.70 1.68 1.65* Compound 4 1.91 1.95 1.78 1.69* 1.62* Compound 5 1.67 1.74 1.77 1.75 1.73* Compound 6 1.79 1.67* 1.51** 1.44** 1.39** Compound 7 1.82 1.63* 1.48** 1.39** 1.33** Note: Compared with the control group in the same period ## P < 0.01 Compared with the same period model group, * P < 0.05, ** P < 0.01 Table 2. Effects of the extract on serum TNF-α, IL-1β, and IL-18 in rats (pg / mL) Group TNF-α IL-1β IL-18 Blank group 96.77 54.23 67.19 Model group <![CDATA[189.71 ## ]]> <![CDATA[132.61 ## ]]> <![CDATA[125.22 ## ]]> Compound 1 137.25* 90.27 92.46 Compound 2 178.33 82.15* 88.06* Compound 3 154.46 79.31* 101.25 Compound 4 125.42** 70.86** 91.10 Compound 5 138.24* 92.36 79.55* Compound 6 121.33** 80.11* 76.16** Compound 7 119.23** 71.28** 74.37** Note: Compared with the control group in the same period # P < 0.05 ## P < 0.01 Compared with the same period model group, * P < 0.05, ** P < 0.01.

Claims

1. The use of saponin compounds represented by formula (Ⅰ) and their pharmaceutically acceptable salts, esters, prodrugs, or solvates in the preparation of medicaments for treating rheumatoid arthritis, wherein, == indicates that it is selected from a double bond or a single bond. This indicates that the expression is selected from a single bond or no bond. Two adjacent == symbols cannot both be double bonds. When it is a single bond, the carbon atom connected to it also has a single bond. When there is no bond, the carbon atom connected to it has either a double bond or a single bond, and R1 and R3 are selected from H, OH, CH3, and... , , The sugar residues formed by the condensation of any one, two, or three of them, R2, R4-R7 are independently selected from H, OH, CH3, CHO, OCH3. 。 2. The application according to claim 1, characterized in that: The saponin compounds described herein have the structure shown in formula (II): wherein R11 and R12 are selected from H, OH, CH3, and , , The glycosyl residues formed by the condensation of any one, two, or three of the components, wherein R13 is selected from H, CH3, or CHO, and R14-17 are selected from H, OH, CH3, or OCH3. 。 3. The application according to claim 1, characterized in that: The saponin compounds described herein have the structure shown in formula (III): wherein R21 is selected from H, OH, CH3, and , , R22 is selected from H, OCH3, and is formed by the condensation of one, two, or three of the sugar residues. 。 4. The application according to claim 1 or 2, characterized in that: The saponin compounds described above have the following structures:

5. The application according to claim 1 or 3, characterized in that: The saponin compounds described above have the following structures:

6. The use according to any one of claims 1-5, characterized in that, The drug also includes pharmaceutically acceptable carriers.

7. The use according to any one of claims 1-6, characterized in that, The drug is formulated with conventional excipients into clinically acceptable tablets, capsules, oral liquids, powders, pills, granules, or injections.

8. A pharmaceutical composition for treating rheumatoid arthritis, characterized in that, The pharmaceutical composition contains a saponin compound as described in any one of claims 1-5 and its pharmaceutically acceptable salt.

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