Application of rabdosia sasakii in treatment of chronic atrophic gastritis and precancerous lesions of gastric cancer

Abstract

The present application provides the application of Rabdosia serra extract in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer, wherein the Rabdosia serra extract includes Rabdosia serra aerial part extract, Rabdosia serra underground part extract, Rabdosia serra total part extract and eluate thereof, etc. The present application also provides the application of compounds in Rabdosia serra in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer, wherein the compounds in Rabdosia serra are selected from oridonin, rabdosin C, norcantharidin, raxofelone and rabdosiin A. The present application proves that Rabdosia serra extract and the compounds in Rabdosia serra have good activity of reversing precancerous lesions of gastric cancer by constructing a cell model (MC cell model) of atrophic gastritis and precancerous lesions of gastric cancer by stimulating GES-1 cells with MNNG.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the application of a fragrant tea vegetable in the treatment of chronic atrophic gastritis and precancerous lesions of gastric cancer. Background Technology

[0002] Atrophic gastritis, a precancerous lesion, is a disease highly correlated with gastric cancer, and there is a lack of universally accepted and highly effective drugs to reverse atrophy, intestinal metaplasia, and dysplasia. Gastric cancer is one of the major malignant tumors. The transitional stage from "gastritis" to "gastric cancer" is called gastric precancerous lesion (PLGC). Chronic atrophic gastritis (CAG) is a representative early manifestation of gastric cancer and is highly correlated with its occurrence. CAG refers to a chronic gastric disease caused by repeated damage to the gastric mucosal epithelium, resulting in a reduction of intrinsic glands, with or without fibrous replacement, intestinal metaplasia, and / or pseudopyloric gland metaplasia. Moderate to severe intestinal metaplasia (especially colonic type intestinal metaplasia) or dysplasia are representative early manifestations of gastric cancer. The incidence of CAG in my country is on the rise. Currently, Western medicine has no effective treatment to reverse this inflammation-cancer transformation. Due to the advantages of traditional Chinese medicine in treating disease before it occurs, it can better improve patients' symptoms and effectively block the cancerous transformation of chronic atrophic gastritis.

[0003] With the development of metabolomics and evidence-based medicine, the development of new resources and efficacy of traditional Chinese medicine has become a hot topic. There are approximately 150 species of plants in the genus *Isodon* (Schrad. ex Benth.) Spach. of the Lamiaceae family, with nearly 100 species distributed in my country, the southwest region being its diversity center. *Isodon* is widely used within this genus and has significant economic and academic value. The entire plant of *Isodon* can be used medicinally. It is included in the 2020 edition of the *Pharmacopoeia of the People's Republic of China* and possesses effects such as clearing heat and dampness, promoting blood circulation and removing blood stasis, detoxifying and reducing swelling. It can be used to treat damp-heat jaundice, urinary tract infections, edema, traumatic injuries, rheumatic pain, amenorrhea, sore throat, mastitis, hemorrhoids, carbuncles, and snake bites. However, there are few reports on its pharmacological efficacy, and its medicinal effects require further research. Summary of the Invention

[0004] This invention provides the application of fragrant tea herbs in the preparation of medicines for the prevention and / or treatment of diseases; the diseases are selected from: atrophic gastritis, precancerous lesions of gastric cancer.

[0005] According to an embodiment of the present invention, the atrophic gastritis is chronic atrophic gastritis.

[0006] According to an embodiment of the present invention, the herb *Corydalis yanhusuo* is an extract of *Corydalis yanhusuo*. According to an embodiment of the present invention, the medicine contains only *Corydalis yanhusuo*, a traditional Chinese medicine.

[0007] According to an embodiment of the present invention, the preparation method of the herb extract is as follows: using herb as raw material, solvent extraction is performed, and the extract is obtained after concentration. Preferably, the sampling part of herb is the aerial part; preferably, the solvent is any one, two or more (i.e., mixed solvent) of water and ethanol (e.g., 95% ethanol); preferably, the extraction method is selected from ultrasonic extraction, reflux extraction, maceration extraction, etc.; preferably, after solvent extraction, the solvent extract can be further separated and purified by column chromatography.

[0008] According to an embodiment of the present invention, the herb extract comprises: herb aerial part extract, herb underground part extract, herb aqueous extract (heading position), herb aqueous extract water eluent after separation by macroporous adsorption resin, herb aqueous extract 50% ethanol eluent after separation by macroporous adsorption resin, and herb aqueous extract 95% ethanol eluent after separation by macroporous adsorption resin; preferably, the herb extract is selected from: herb aerial part extract, herb underground part extract, and herb aqueous extract 95% ethanol eluent after separation by macroporous adsorption resin.

[0009] According to an embodiment of the present invention, the preparation method of the above-ground part extract of *Hedychium coronarium* is as follows: take the above-ground part of *Hedychium coronarium*, crush and sieve it, extract it with solvent to obtain filtrate, concentrate it under reduced pressure to obtain the above-ground part extract of *Hedychium coronarium*.

[0010] Preferably, the extraction solvent is water; preferably, the volume (mL) of the extraction solvent is 10 times the mass (g) of the aerial parts of the herb *Tea japonica*; preferably, the extraction is performed 3 times; preferably, the extraction time is 60 min; preferably, after vacuum concentration, the herb is optionally further freeze-dried.

[0011] For example, the preparation method of the above-ground part extract of *Gnaphalium affine* is as follows: the above-ground part of *Gnaphalium affine* is pulverized by a ball mill and passed through a No. 4 sieve. An appropriate amount of the above-ground part powder is placed in an Erlenmeyer flask, and 10 times, 10 times, and 10 times the amount of water are added in sequence for ultrasonic extraction for 60 min each. After filtration, the filtrates are combined, concentrated under reduced pressure, and freeze-dried to obtain the above-ground part extract of *Gnaphalium affine*.

[0012] According to an embodiment of the present invention, the preparation method of the extract of the underground part of the herbaceous tea plant is as follows: take the underground part of the herbaceous tea plant, crush and sieve it, extract it with solvent to obtain the filtrate, concentrate it under reduced pressure to obtain the extract of the underground part of the herbaceous tea plant.

[0013] Preferably, the extraction solvent is water; preferably, the volume (mL) of the extraction solvent is 10 times the mass (g) of the underground part of the tea plant; preferably, the extraction is performed 3 times; preferably, the extraction time is 60 min; preferably, after vacuum concentration, the product is optionally further freeze-dried.

[0014] For example, the preparation method of the extract of the underground part of the herb is as follows: the underground part of the herb is pulverized by a ball mill and passed through a No. 4 sieve. An appropriate amount of the underground part powder is placed in an Erlenmeyer flask, and 10 times the amount of water is added in sequence for ultrasonic extraction for 60 minutes. After filtration, the filtrates are combined, concentrated under reduced pressure, and freeze-dried to obtain the extract of the above-ground part of the herb.

[0015] According to an embodiment of the present invention, the preparation method of the aqueous extract of fragrant tea plant is as follows: take fragrant tea plant, crush and sieve it, extract it with solvent to obtain filtrate, concentrate it under reduced pressure to obtain the aqueous extract of fragrant tea plant;

[0016] Preferably, the extraction solvent is water; preferably, the volume (mL) of the extraction solvent is 10 times the mass (g) of the tea buds; preferably, the extraction is performed 3 times; preferably, the extraction time is 60 min; preferably, after vacuum concentration, the tea buds are optionally further freeze-dried.

[0017] For example, the preparation method of the aqueous extract of fragrant tea leaves is as follows: fragrant tea leaves are pulverized by ball mill and passed through a No. 4 sieve. An appropriate amount of powder is placed in an Erlenmeyer flask, and 10 times the amount of water is added in sequence for ultrasonic extraction for 60 minutes. After filtration, the filtrates are combined, concentrated under reduced pressure, and freeze-dried to obtain the aqueous extract of fragrant tea leaves.

[0018] According to an embodiment of the present invention, after obtaining the aqueous extract of *Tea japonica*, the aqueous extract of *Tea japonica* is further separated and purified by column chromatography to obtain the eluent of the aqueous extract of *Tea japonica*.

[0019] According to an embodiment of the present invention, the method for preparing the eluent of the aqueous extract of fragrant tea vegetable is as follows:

[0020] The above-mentioned herbaceous tea extract is dissolved in water, then eluted and purified by column chromatography to obtain the corresponding eluent. According to an embodiment of the present invention, the column chromatography is selected from: macroporous adsorption resins (e.g., D101, SP825, etc.), MCI-filled column chromatography (gel column chromatography), and C18-filled column chromatography (reversed-phase C18 column chromatography); preferably, macroporous adsorption resins. According to an embodiment of the present invention, when macroporous adsorption resins are used, the elution solvent is water, 20% ethanol, 20%-50% ethanol, or 50%-95% ethanol; preferably, water, 50% ethanol, or 95% ethanol.

[0021] According to an embodiment of the present invention, the preparation method of the eluent of the aqueous extract of the herbaceous tea plant is as follows: the aqueous extract of the herbaceous tea plant is dissolved in water and then separated by macroporous adsorption resin. The eluent solvents are water, 50% ethanol and 95% ethanol solvent in sequence, to obtain water eluent, 50% ethanol eluent and 95% ethanol eluent respectively.

[0022] According to an embodiment of the present invention, the method for preparing the water eluent after separation of the aqueous extract of *Tea japonica* by macroporous adsorption resin is as follows: the aqueous extract of *Tea japonica* is dissolved in water and then separated by macroporous adsorption resin, with the eluent solvents being water, 50% ethanol, and 95% ethanol solvent in sequence, to obtain the water eluent.

[0023] According to an embodiment of the present invention, the method for preparing the 50% ethanol eluent after separation of the aqueous extract of *Tea japonica* by macroporous adsorption resin is as follows: the aqueous extract of *Tea japonica* is dissolved in water and then separated by macroporous adsorption resin, with the eluent solvents being water, 50% ethanol, and 95% ethanol solvent in sequence, to obtain the 50% ethanol eluent.

[0024] According to an embodiment of the present invention, the method for preparing the 95% ethanol eluent after separation of the aqueous extract of *Tea japonica* by macroporous adsorption resin is as follows: the aqueous extract of *Tea japonica* is dissolved in water and then separated by macroporous adsorption resin, with the eluents being water, 50% ethanol, and 95% ethanol in sequence, to obtain the 95% ethanol eluent. Preferably, the drug may further contain pharmaceutically acceptable excipients.

[0025] Preferably, the drug may further contain other active ingredients; preferably, the active ingredients are used to prevent and / or treat atrophic gastritis and precancerous lesions of gastric cancer.

[0026] This invention also provides the use of compounds in coriander tea in the preparation of remedies for the prevention and / or treatment of diseases;

[0027] The diseases mentioned are selected from: atrophic gastritis and precancerous lesions of gastric cancer;

[0028] The compounds in the coriander tea are selected from one, two or more of the following compounds: oridonin, salsacin, epidotin, lacidonin, and blue calyxin.

[0029] According to an embodiment of the present invention, the atrophic gastritis is chronic atrophic gastritis.

[0030] According to an embodiment of the present invention, the compounds in the coriander tea are selected from: oridonin, salsaponin, epidotin, lacidonin, and blue calyxin.

[0031] Preferably, the drug may further contain pharmaceutically acceptable excipients.

[0032] Preferably, the drug may further contain other active ingredients; preferably, the active ingredients are used to prevent and / or treat atrophic gastritis and precancerous lesions of gastric cancer.

[0033] Beneficial effects

[0034] This invention provides the application of *Hedychium coronarium* extract in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer. The *Hedychium coronarium* extract includes extracts from the aerial parts, underground parts, and main parts of *Hedychium coronarium*, as well as their eluates. This invention demonstrates, through the construction of a cell model (MC cell model) of atrophic gastritis and precancerous lesions of gastric cancer using GES-1 cells stimulated with MNNG, that the *Hedychium coronarium* extract has good activity in reversing precancerous lesions of gastric cancer.

[0035] This invention also provides the application of compounds from coriander tea in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer. The compounds in the coriander tea are selected from: oridonin, citronellol, epidotin, lacidonin, and scabra-acid. This invention demonstrates, through the construction of a cell model (MC cell model) of atrophic gastritis and precancerous lesions of gastric cancer using MNNG stimulation of GES-1 cells, that the compounds in coriander tea have good activity in reversing precancerous lesions of gastric cancer. Attached Figure Description

[0036] Figure 1 Effects of different parts of *Tea japonica*, different elution methods (1A), and different monomeric compounds (1B) on MC cell viability **p≤0.01, ****p≤0.0001, compared with the control group.

[0037] Figure 2 UPLC-Q-TOF / MS BPI chromatograms of extracts from different parts of the plant and under different elution methods.

[0038] All experimental data were determined and provided as x ± s. Multiple comparisons were performed using one-way ANOVA to determine statistical significance. In the survey, changes with a p-value less than 0.05 were considered statistically significant. Detailed Implementation

[0039] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0040] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0041] Example 1: Growth inhibitory effect of *Tea japonica* extract on MC cells

[0042] 1. Construction of the MC cell model

[0043] Cell thawing: GES-1 cells (immortalized human gastric mucosal epithelial cell line, catalog number iCel1-h062) were purchased from Cybio (Shanghai) Biotechnology Co., Ltd. The frozen cells were removed from the liquid nitrogen container and gently thawed in a 37°C water bath. Cells were transferred to centrifuge tubes, a suitable amount of preheated culture medium was added, and the cells were collected after centrifugation at 1100 rpm for 5 min, discarding the supernatant. Cells were seeded into culture dishes, 5 mL of complete culture medium was added, and the cells were mixed by pipetting and shaking. The dishes were then incubated in a CO2 incubator at 37°C, 5% CO2, and saturated humidity.

[0044] Cell passage: When GES-1 cells adhere and grow to more than 90% of the bottom area of ​​the culture flask, passage is performed. Add 3 mL of trypsin to the cell culture medium and incubate at 37°C for 2-3 minutes. Transfer the floating cells that have detached from the bottom of the dish to a centrifuge tube, centrifuge, discard the supernatant, add an appropriate amount of complete culture medium, mix well by pipetting, transfer to a culture flask, and incubate in a sterile incubator at 37°C and 5% CO2.

[0045] Cell modeling: When the GES-1 cell growth density reaches 80-90%, add 5 mL of serum-free RPMI 1640 medium and 15 μL of 0.01 mol / L MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) mixed solution to achieve a final concentration of 3 × 10⁻⁶. -5 The medium was 1 mol / L and cultured in a sterile incubator at 37°C and 5% CO2 for 24 hours. After 24 hours, the medium was replaced with complete medium without MNNG. A large number of cells died within 5-7 days, and the remaining cells grew to 70-80% within 3-4 days. The cells were then digested and passaged according to the GES-1 cell culture method. At this point, the cells were MC cells (a cell model of gastric cancer precancerous lesions induced by MNNG stimulation of GES-1 cells).

[0046] 2. Preparation of experimental samples

[0047] 2.1 Preparation of vitamins positive control samples

[0048] Vitacoenzyme was used as a positive control and purchased from Guangxi Dahai Sunshine Pharmaceutical Co., Ltd. The vitacoenzyme tablets were decocted and ground into a uniform powder. 2.5g of the vitacoenzyme powder was weighed and added to 10mL of purified water. The mixture was incubated at 37℃ for 30min, sonicated for 1h, and then at 9000 rpm for 10min to prepare a 0.25g / mL stock solution. An appropriate amount of the stock solution was diluted with blank culture medium to a concentration of 28.8mg / mL for cell intervention.

[0049] 2.2 Preparation of samples from the herb *Tea japonica* administration group

[0050] Preparation of the aerial part extract of *Hedysarum heterotropoides* (XCC-DS): The aerial part of *Hedysarum heterotropoides* was pulverized by ball mill and passed through a No. 4 sieve. An appropriate amount of the aerial part powder was placed in an Erlenmeyer flask, and 10 times the amount of water was added in sequence for ultrasonic extraction for 60 min each. After filtration, the filtrates were combined, concentrated under reduced pressure, and freeze-dried to obtain the aerial part extract of *Hedysarum heterotropoides*.

[0051] Preparation of the underground part extract of *Hedysarum heterotropoides* (XCC-DX): The underground part of *Hedysarum heterotropoides* was pulverized by ball mill and passed through a No. 4 sieve. An appropriate amount of the underground part powder was placed in an Erlenmeyer flask, and 10 times the amount of water was added in sequence for ultrasonic extraction for 60 min each. After filtration, the filtrates were combined, concentrated under reduced pressure, and freeze-dried to obtain the aboveground part extract of *Hedysarum heterotropoides*.

[0052] Preparation of total aqueous extract of *Tetracentron sinense* (DQ-XCC): *Tetracentron sinense* (including the above-ground and underground parts) was pulverized by ball mill and passed through a No. 4 sieve. An appropriate amount of powder was placed in an Erlenmeyer flask, and 10 times the amount of water was added sequentially for ultrasonic extraction for 60 min each. After filtration, the filtrates were combined, concentrated under reduced pressure, and freeze-dried to obtain the aqueous extract of *Tetracentron sinense*.

[0053] Preparation of eluents from the total aromatic herb aqueous extract: The total aromatic herb aqueous extract (DQ-XCC) (800.0 g) was dissolved in water and separated by a D101 macroporous adsorption resin column (eluting solvents were water → 50% ethanol → 95% ethanol in sequence). The corresponding eluents were combined, concentrated under reduced pressure, and lyophilized to obtain the eluents from the total aromatic herb aqueous extract. 365.4 g of water eluent (XCC-H2O), 194.7 g of 50% ethanol eluent (XCC-50% EtOH), and 18.9 g of 95% ethanol eluent (XCC-95% EtOH) were obtained.

[0054] Take 5 mg of the lyophilized powder of the above-mentioned *Corydalis yanhusuo* drug treatment group samples (*Corydalis yanhusuo* aerial part extract (XCC-DS), *Corydalis yanhusuo* underground part extract (XCC-DX), preparation of total *Corydalis yanhusuo* aqueous extract (DQ-XCC), water eluent of total *Corydalis yanhusuo* aqueous extract (XCC-H2O), 50% ethanol eluent of total *Corydalis yanhusuo* aqueous extract (XCC-50% EtOH), and 95% ethanol eluent of total *Corydalis yanhusuo* aqueous extract (XCC-95% EtOH)), add 5 mL of water to dissolve and prepare a 1 mg / mL stock solution, and add an appropriate amount to blank culture medium to dilute to a concentration of 200 μg / mL for intervention of MC cells.

[0055] Intervention in MC cells: Logarithmic growth phase MC cells were collected, and the cell suspension concentration was adjusted. 100 μL was added to each well, with 6 replicates. The cells were incubated at 37°C with 5% CO2 for 16-48 hours and observed under an inverted microscope. A blank control group was established, while the remaining cells were treated with the following drugs: vitamins solution group (28.8 mg / mL), and various *Hedychium coronarium* treatment groups (200 μg / mL), for 24 hours each.

[0056] 3. Experimental Results: Effects of vitamins positive control solution and *Hedychium coronarium* extract solution on MC cell viability

[0057] Experimental results show that ( Figure 1 A): Compared with the Control group (MC cells), the activity of MC cells decreased significantly after intervention with vitamin solution (mean cell viability was 18.10%), which was statistically significant (P<0.05), indicating that vitamin solution can inhibit MC cell activity. In different *Corydalis yanhusuo* treatment groups, the aerial part extract of *Corydalis yanhusuo* (XCC-DS, mean cell viability 62.84%), the underground part extract of *Corydalis yanhusuo* (XCC-DX, mean cell viability 90.86%), and the 95% ethanol eluent of the total aqueous extract of *Corydalis yanhusuo* (XCC-95% EtOH, mean cell viability 10.95%) showed the same inhibitory effect as vitamin solution. Among them, the inhibitory effect of the aerial part extract of *Corydalis yanhusuo* and the 95% ethanol eluent of the total aqueous extract of *Corydalis yanhusuo* on MC cells was statistically significant compared with the control group (P<0.05), indicating that both have the activity of reversing precancerous lesions of gastric cancer, and the inhibitory effect of the 95% ethanol eluent of the total aqueous extract of *Corydalis yanhusuo* was better than that of the aerial part extract of *Corydalis yanhusuo*.

[0058] Example 2: Metabolomics analysis of herb extract

[0059] LC-MS Metabolomics Analysis: The samples from the *Hedysarum heterotropoides* drug group in Example 1 were analyzed for metabolomics using LC-MS. LC-MS analysis parameters and conditions: Chromatographic conditions: ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.7 μm); column temperature 40℃; flow rate 0.5 mL / min; injection volume 1 μL. The mobile phase was A: 0.1% FA-water; B: 0.1% FA-acetonitrile. The gradient elution program was as follows: 0–0.5 min, 5% B; 0.5–1 min, 5% A–12% B; 1–6 min, 12% B–16% B; 6–13 min, 16% B–20% B; 13–13.5 min, 20% B–23% B; 13.5–22 min, 23% B–38% B; 22–24 min, 38% B–50% B; 24–27 min, 50% A–70% B; 27–28 min, 70% B–98% B; 28–30 min, 98% B. Mass spectrometry conditions: Waters G2-XS high-resolution mass spectrometer, MS. E Acquisition mode: ESI ion source, positive and negative ion scanning; capillary voltage: 2.5KV(-); 0.5KV(+); ion source temperature: 100℃; cone voltage: 40V; desolvation gas flow rate: 900L / h; desolvation temperature: 450℃; cone gas flow rate: 50L / h; acquisition range: 50-1500Da; collision energy: low energy scan: 6eV; high energy: 35-50eV(+), 45-60eV(-). Accurate mass numbers were calibrated using leucine enkephalin.

[0060] The chemical characteristics of the samples in the herb-treated group in Example 1 are as follows: Figure 2As shown in the results, the number and types of compounds contained in the extracts of *Hedychium coronarium* from different parts and with different elution solvents differed significantly in LC-MS chromatograms. The 95% ethanol eluent of both the aerial part extract and the total aqueous extract of *Hedychium coronarium* exhibited inhibitory effects on MC cells, with the 95% ethanol eluent of the total aqueous extract showing stronger inhibitory effects than the aerial part extract. This is reflected in the LC-MS chromatograms, where compounds with retention times of 16.43 min or 16.46 min were clearly common components of both extracts (*Hedychium coronarium* underground part extract (XCC-DX), preparation of the total aqueous extract of *Hedychium coronarium* (DQ-XCC), water eluent of the total aqueous extract of *Hedychium coronarium* (XCC-H2O), and 50% ethanol eluent of the total aqueous extract of *Hedychium coronarium* (XCC-50%)). The compound was not included in the LC-MS spectrum of EtOH. Further identification revealed that the compound was cyanidin, and its content in the 95% ethanol eluent of the total *Corydalis yanhusuo* aqueous extract was higher than that in the aerial extract of *Corydalis yanhusuo*, indirectly proving that cyanidin may be an active compound that reverses precancerous lesions of the stomach. Furthermore, the spectra of different parts of *Corydalis yanhusuo* showed that each extract or eluent contained terpenoids and flavonoids, such as oridonin, cyanidin caudacin, epidotin, and lacidonin.

[0061] Example 3: Inhibitory effect of monomeric components in fragrant tea on MC cell growth

[0062] The following substances were purchased from Beijing Beterrenkang Co., Ltd.: Rhododendron acetonide, Rhododendron acetonide, Rhododendron acetonide, and Rhododendron acetonide.

[0063] The MC cell modeling method is as described in Example 1.

[0064] Experimental samples: Take appropriate amounts of oridonin, euryale feroxin, epidotin, lacidonin, and blue calyxin and add them to 50 μL of DMSO to dissolve. Take an appropriate amount of the dissolved sample and add it to blank culture medium to dilute to a concentration of 50 μg / mL for intervention in MC cells.

[0065] Experimental Results: Effects of positive control drugs vitamins solution and herbal compounds solution on MC cell viability

[0066] Experimental results show that ( Figure 1B): Compared with the Control group (MC cells), the activity of MC cells was significantly decreased after intervention with different monomeric compound solutions and vitamins solution from *Gnaphalium affine*, which was statistically significant (P<0.05). Among them, the average cell viability of MC cells after intervention with oridonin, kamebakaurine, epinodosin, lasiodonin, and glaucocalyxin A were 20.74%, 22.63%, 22.15%, 26.26%, and 32.33%, respectively; indicating that each monomeric compound and vitamins solution could inhibit the activity of MC cells. Therefore, the above-mentioned monomeric compounds in *Gnaphalium affine* have the activity of reversing precancerous lesions of gastric cancer.

[0067] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The use of *Gynostemma pentaphyllum* in the preparation of medicines for the prevention and / or treatment of diseases; the diseases are selected from: atrophic gastritis, precancerous lesions of gastric cancer.

2. The application according to claim 1, characterized in that, The herb described is a herb extract; Preferably, the preparation method of the herb extract is as follows: herb extract is obtained by solvent extraction and concentration; preferably, after solvent extraction, the solvent extract can be further separated and purified by column chromatography.

3. The application according to claim 2, characterized in that, The herb extract includes: herb aerial part extract, herb underground part extract, herb water extract, herb water eluent after separation by macroporous adsorption resin, herb water extract 50% ethanol eluent after separation by macroporous adsorption resin, and herb water extract 95% ethanol eluent after separation by macroporous adsorption resin. Preferably, the herb extract is selected from: herb aerial part extract, herb underground part extract, and 95% ethanol eluent after separation of herb aqueous extract by macroporous adsorption resin.

4. The application according to claim 3, characterized in that, The preparation method of the above-ground part extract of *Hedychium coronarium* is as follows: take the above-ground part of *Hedychium coronarium*, crush and sieve it, extract it with solvent to obtain the filtrate, concentrate it under reduced pressure to obtain the above-ground part extract of *Hedychium coronarium*. And / or, the preparation method of the extract of the underground part of the herb is as follows: take the underground part of the herb, crush and sieve it, extract it with solvent to obtain the filtrate, concentrate it under reduced pressure to obtain the extract of the underground part of the herb. And / or, the preparation method of the aqueous extract of fragrant tea leaves is as follows: take fragrant tea leaves, crush and sieve them, extract with solvent to obtain filtrate, concentrate under reduced pressure to obtain the aqueous extract of fragrant tea leaves.

5. The application according to claim 3 or 4, characterized in that, After obtaining the aqueous extract of the herbaceous tea plant, the aqueous extract of the herbaceous tea plant was further separated and purified by column chromatography to obtain the eluent of the aqueous extract of the herbaceous tea plant. Preferably, the preparation method of the eluent of the aqueous extract of the herbaceous tea plant is as follows: after dissolving the aqueous extract of the herbaceous tea plant in water, it is eluted and purified by column chromatography to obtain the corresponding eluent; Preferably, the column chromatography is selected from: macroporous adsorption resin, MCI-filled column chromatography, and C18-filled column chromatography; preferably, when macroporous adsorption resin is used, the elution solvent is water, 50% ethanol, and 95% ethanol in sequence.

6. The application according to claim 5, characterized in that, The specific method for preparing the eluent from the aqueous extract of *Tea japonica* is as follows: the aqueous extract of *Tea japonica* is dissolved in water and then separated by macroporous adsorption resin. The eluent solvents are water, 50% ethanol, and 95% ethanol, respectively, to obtain the water eluent, the 50% ethanol eluent, and the 95% ethanol eluent.

7. The application according to any one of claims 1-6, characterized in that, The drug may further contain pharmaceutically acceptable excipients; Preferably, the drug may further contain other active ingredients; preferably, the active ingredients are used to prevent and / or treat atrophic gastritis and precancerous lesions of gastric cancer.

8. The application of compounds in coriander tea in the preparation of drugs for the prevention and / or treatment of diseases; The diseases mentioned are selected from: atrophic gastritis and precancerous lesions of gastric cancer; The compounds in the coriander tea are selected from one, two or more of the following compounds: oridonin, salsacin, epidotin, lacidonin, and blue calyxin.

9. The application according to claim 8, characterized in that, The drug may further contain pharmaceutically acceptable excipients; Preferably, the drug may further contain other active ingredients; preferably, the active ingredients are used to prevent and / or treat atrophic gastritis and precancerous lesions of gastric cancer.

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