KR102135797B1 - Composition for preventing or treating cancer comprising glycosyl glycerides from Malva verticillata - Google Patents

Abstract

The present invention is a cancer ( Malva verticillata ) extract, a fraction thereof, a compound represented by the formula (1) or a pharmaceutical composition for preventing or treating cancer comprising as an active ingredient a pharmaceutically acceptable salt of the compound; Food composition; And a method for preparing the compound.
The mallow extract of the present invention, a fraction thereof, and a compound represented by Formula 1 isolated therefrom show cytotoxicity against various cancer cells and induce apoptosis, thus preventing, improving or treating cancer pharmaceutical compositions, food compositions Etc.

Description

Composition for preventing or treating cancer comprising glycosyl glycerides from Malva verticillata}

The present invention is a cancer ( Malva verticillata ) extract, a fraction thereof, a compound represented by the formula (1) or a pharmaceutical composition for preventing or treating cancer comprising as an active ingredient a pharmaceutically acceptable salt of the compound; Food composition; And a method for preparing the compound.

Cancer is one of the diseases with a high mortality rate worldwide. Currently, cancer treatments such as chemotherapy, surgery, and radiation therapy have been developed, but a number of side effects and costs are related to their application. Epidemiological evidence has demonstrated that eating certain foods can potentially prevent cancer by up to 35%. In this regard, bioactive ingredients and diets present in nature provide essential links for the maintenance and promotion of health as well as the prevention of chronic diseases, including cancer. The most practical way to reduce the incidence and mortality of cancer is to delay the carcinogenesis process using chemical cancer prevention agents. This requires safer compounds, especially those derived from natural raw materials for the prevention of chemical cancer.

Mallow ( Malva verticillata, Chinese mallow ) is one of the oldest plants cited in the written literature, and is a leaf vegetable that has long been used in Korea and China. The seeds of mallow have been used as a medicine for diuretics, laxatives, and breast milk in oriental medicine. Polysaccharides, the main component of mallow seeds, have been reported to exhibit anti-complementary, immunological and hypoglycemic activity. On the other hand, mallow leaves have also been used as medicines for the treatment of gastrointestinal and respiratory diseases in oriental medicine. However, little research has been done on the chemical composition of mallow leaves and their biological activity.

Against this background, the present inventors tried to find a chemical cancer preventive agent derived from natural raw materials, and as a result, separated and identified a glycosyl glyceride compound from the malignant fraction, and among the compounds (2S)-1-O-(6 -Deoxy-6-sulfo)-α-D-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride; (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2,3-di-O-linolenoyl glyceride; Or (2S)-1-O-6'-0-(aD-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-palmitoyl glyceride is a cell for cancer cells The present invention was completed by confirming toxicity and inducing apoptosis.

One object of the present invention is a pharmaceutical composition for preventing or treating cancer, comprising a mallow extract, a fraction thereof, a compound represented by Formula 1 separated therefrom, or a pharmaceutically acceptable salt of the compound as an active ingredient. ₁ is -H, linolenoyl, palmitoyl or stearoyl; R ₂ is linolenoyl, palmitoyl or stearoyl; R ₃ is -SO ₃ ^- is to provide a pharmaceutical composition, -OH or glycosyl (glycosyl).

[Formula 1]

Another object of the present invention is to provide a food composition comprising the active ingredient.

Another object of the present invention is a novel compound derived from mallow extract or fraction, (2S)-1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride ((2S) To provide -1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride, compound 5).

Another object of the present invention is to provide a method for preparing a compound represented by Chemical Formula 1, comprising separating the compound represented by Chemical Formula 1 from a mallow extract or a fraction.

Specifically, it is as follows. Meanwhile, each description and embodiment disclosed in the present application may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. In addition, the scope of the present application cannot be considered to be limited by the specific descriptions described below.

One aspect of the present invention for achieving the above object is to prevent or treat cancer comprising an extract, a fraction thereof, a compound represented by the following formula 1 or a pharmaceutically acceptable salt of the compound as an active ingredient As a pharmaceutical composition,

[Formula 1]

In the general formula 1 R ₁ is -H, linoleate leno days, palmitoyl or stearoyl one (stearoyl), and; R ₂ is linolenoyl, palmitoyl or stearoyl; R ₃ is -SO ₃ ^- provides, -OH, or-glycoside jitsu pharmaceutical composition.

Specifically, the fraction may be a mallow n-butanol fraction, and the compound is (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2-O- Linolenoyl-3-O-palmitoyl glyceride (Compound 1), (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2,3-di- O-linolenoyl glyceride (Compound 2), (2S)-1-O-β-D-galactopyranosyl-3-O-palmitoyl glyceride (Compound 3), (2S)-1-O- β-D-galactopyranosyl-3-O-stearoyl glyceride (Compound 4), (2S)-1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride (Compound 5), (2S)-1-O-β-D-galactopyranosyl-3-O-linolenoyl glyceride (Compound 6), (2S)-1-O-β-D-galacto Pyranosyl-2,3-di-O-palmitoyl glyceride (Compound 7), (2S)-1-O-β-D-galactopyranosyl-2,3-di-O-linolenoyl glyceride (Compound 8), (2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-O-palmitoyl glyceride (Compound 9) , (2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-O-linolenoyl glyceride (Compound 10), (2S )-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-palmitoyl glyceride (Compound 11), (2S) )-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2-O-stearoyl-3-O-linolenoyl glyceride (Compound 12 ) And (2S)-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-linolenoyl-glyceride (compound 13) may be one or more compounds selected from the group consisting of, more specifically (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2-O-linol Renoyl-3-O-palmitoyl glyceride (Compound 1); (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2,3-di-O-linolenoyl glyceride (Compound 2); Or (2S)-1-O-6'-0-(α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-palmitoyl glyceride (Compound 11) It may be, but is not limited thereto.

Compounds 1 and 2 include 6-deoxy-6-sulfo saccharides ((6-deoxy-6-sulfo)-α-D-glucopyranose), which are rarely found from natural raw materials. The anti-cancer effect of is not known in the past, Compound 11 shows the best anti-cancer effect among the compounds of the present invention, and the anti-cancer effect of the compound derived from the present invention including compounds 1, 2 and 11 was first confirmed in the present invention .

In other words, the present invention shows that the compounds including compounds 1, 2 and 11 isolated and identified as well as mallow extracts and fractions show excellent anticancer activity against various cancer cells such as HepG2, AGS, HCT-15, and A549. It is based on technical thought, which was first identified by the inventors.

In one embodiment of the present invention, a portion of the mallow above-ground portion or a compound isolated therefrom, specifically, a portion of the mallow above-ground portion, a compound of Formula 1, exhibits cytotoxicity against cancer cells and expresses a protein related to apoptosis It was confirmed that inducing apoptosis of cancer cells by adjusting the level. The fraction or compound has a prophylactic or therapeutic effect on cancer.

In the present invention, "Mallow verticillata ( Chinese mallow)" is a dicotyledonous plant belonging to the Mavales family, which is used as a diuretic, laxative, or lactose in oriental medicine, or for the purpose of treating gastrointestinal and respiratory diseases. It is known to be used, but the anti-cancer effect is not known at all. The mauk can be purchased commercially, or can be used in nature or harvested. Specifically, the roots, stems, and leaves of the mallow can be used without limitation, and more specifically, the entire mallow portion can be used, but is not limited thereto.

In the present invention, the "extract" is an extract obtained by extracting the malt, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a crude product or a purified product of the extract, or a mixture thereof, the extract itself and the extract Contains extracts of all formulations that can be formed using.

The type of the extraction solvent used to extract the extract in the present invention is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent is water; C1 to C4 lower alcohols such as methanol, ethanol, propyl alcohol, and butyl alcohol; Polyhydric alcohols such as glycerin, butylene glycol, and propylene glycol; And hydrocarbon-based solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and dichloromethane; Or a mixture of these may be used, and specifically methanol may be used, but is not limited thereto.

The method for extracting the extract in the present invention is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method may include a hot water extraction method, an ultrasonic extraction method, a filtration method, a reflux extraction method, and the like, which may be performed alone or in combination of two or more methods.

In the present invention, "fraction" means a result obtained by a fractionation method of separating a specific component or a specific group from a mixture containing various components. Specifically, the present invention includes the results of fractionating the mallow extract by various methods such as a solvent fractionation method, an ultrafiltration fractionation method, and a chromatographic fractionation method, and more specifically, it may be an n-butanol fraction of the mallow extract. , But is not limited to this.

In one embodiment of the present invention, the upper part of the dried mallow was extracted and filtered at room temperature with 80% methanol, and evaporated under reduced pressure to obtain an extract, from which water, ethyl acetate (EtOAc) and n-butanol (n- BuOH) fractions were obtained. It was confirmed that the n-butanol fraction in the terrestrial region showed remarkably good cytotoxicity against cancer cells compared to the fraction of water and ethyl acetate, and had an effect of inducing apoptosis. In addition, the glycosyl glyceride compounds 1 to 13 were separated and identified from the n-butanol fraction, and the anticancer effect of each compound was confirmed. In particular, it was confirmed that compounds 1, 2, and 11 show remarkably excellent cytotoxicity against cancer cells, and have an effect of inducing apoptosis.

In addition, the compound derived from the mallow extract or fraction of the present invention may be isolated from other natural sources, or may be a chemically synthesized or commercially available material through a method known in the art, including the relationship to the route of ingestion Can be used in the present invention without.

"Pharmaceutically acceptable salt" in the present invention means a salt in a form that can be used pharmacologically among salts in which cations and anions are bound by electrostatic attraction, and is relatively non-toxic and harmless to the patient. As a concentration having a side effect caused by this salt, any organic or inorganic addition salt of any of the compounds that do not degrade the beneficial efficacy of the compound derived from the mallow extract or fraction of the present invention, specifically compounds 1, 2 and 11 it means. Such salts include acid addition salts formed by pharmaceutically acceptable free acids or metal salts formed by bases.

Organic acids and inorganic acids can be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and tartaric acid can be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid can be used as the organic acid. (maleic acid), succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid, etc. can be used. , But is not limited to this.

In addition, bases can be used to make metal salts that are pharmaceutically or food acceptable. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the inexpensive compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to manufacture sodium, potassium, or calcium salts for pharmaceutical or food use, but is not limited thereto. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

The pharmaceutically acceptable salts include salts of acidic or basic groups that may be present in the compounds derived from the mallow extract or fraction of the present invention, unless otherwise specified. For example, pharmacologically or foodly acceptable salts may include sodium, calcium and potassium salts of hydroxy groups, and other pharmaceutically acceptable salts of amino groups are hydrobromide, sulfate, hydrogen sulfate, phosphate , Hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through a known method of salt preparation.

In the present invention, "cancer" refers to a tumor in which normal tissue cells are formed by the action or factors of various physical, chemical, and biological cancerous substances, and the cancer is included without limitation to the type of cancer. Esophageal cancer, stomach cancer, colon cancer, rectal cancer, oral cancer, pharyngeal cancer, laryngeal cancer, lung cancer, colon cancer, breast cancer, cervical cancer, endometrial cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, kidney cancer, liver cancer, pancreatic cancer, bone cancer, connective tissue Cancer, skin cancer, brain cancer, thyroid cancer, leukemia, Hodgkin's disease, lymphoma or multiple myeloma blood cancer, specifically gastric cancer, lung cancer, colorectal cancer or liver cancer, more specifically gastric cancer, but not limited thereto It does not work.

In one embodiment of the present invention, the compound of the present invention, including the n-butanol fraction of the terrestrial part, compounds 1, 2 and 11, exhibits excellent anticancer effects against various cancer cells such as HepG2, AGS, HCT-15, and A549. Confirmed.

"Prevention" in the present invention means any action that delays the onset or progression of cancer by administration of the composition of the present invention.

"Treatment" in the present invention means any action in which symptoms related to the development of cancer are improved or beneficially changed by administration of the composition of the present invention.

In the present invention, "improvement" means any action that at least reduces the degree of symptoms of cancer, increases apoptosis of cancer cells, or inhibits proliferation.

In the present invention, "pharmaceutical composition" means that it is prepared for the purpose of preventing or treating a disease, and can be administered in various dosage forms, whether orally or parenterally, during actual clinical administration. It can be prepared using diluents or excipients such as extenders, binders, wetting agents, disintegrating agents, surfactants, and the like.

In addition, pharmaceutically acceptable additives may be further included according to each formulation, and pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, and calcium hydrogen phosphate. , Lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, white sugar, dextrose, sorbitol and talc can be used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the mixed extract of the present invention, such as starch, calcium carbonate, water It can be prepared by mixing Sucrose, Lactose, or gelatin. In addition, lubricants such as magnesium stearate talc may be used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, are included. Can.

Preparations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

The composition of the present invention may be administered orally or parenterally depending on the desired method, and when administered parenterally, it is used for external or intraperitoneal injection, intracutaneous injection, subcutaneous injection, intravenous injection, intramuscular injection, or intramuscular injection. You can choose The dosage may vary in range depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate and disease severity.

The composition of the present invention can be administered in a pharmaceutically effective amount. The pharmaceutically effective amount is sufficient to treat the disease at a reasonable benefit/risk ratio applicable to medical treatment and means an amount that does not cause side effects, and the effective dose level is the patient's health condition, type of disease, severity, The activity of the drug, the sensitivity to the drug, the method of administration, the time of administration, the route of administration and the rate of excretion, the duration of treatment, factors including the drug used in combination or co- and other factors well known in the medical field can be determined. In addition, the pharmaceutical composition of the present invention may be used alone or in combination with other pharmacologically active compounds that exhibit a prophylactic, therapeutic, or ameliorating effect of cancer or in an appropriate collection.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be administered single or multiple. Considering all of the above factors, it is important to administer an amount capable of obtaining a maximum effect in a minimum amount without causing side effects, and can be easily determined by those skilled in the art.

Another aspect of the present invention for achieving the above object includes the mallow extract, a fraction thereof, a compound represented by Formula 1 separated therefrom, or a pharmaceutically acceptable salt of the compound as an active ingredient, preventing cancer Or provide a therapeutic food composition. The mallow, extract, fraction and cancer are as described above.

In the present invention, the term "food" includes, for example, various foods, beverages, gums, teas, vitamin complexes, health function (sex) foods, and the like, and includes all foods in the ordinary sense. The food can be prepared in the form of tablets, granules, powders, capsules, liquid solutions and pills, etc. according to a known manufacturing method, and the content of the extract according to the present invention is 0.0001 based on the total weight of the food composition according to the formulation It can be adjusted to 100% by weight. There are no particular limitations on other components except the mallow extract of the present invention, a fraction or a compound derived therefrom as an active ingredient, and may include various conventional flavoring agents or natural carbohydrates as additional components.

The "health function (sex) food" is the same term as food for special health use (FoSHU), and means food with high medical and medical effects processed to efficiently exhibit bio-control functions in addition to nutrition. do. The "function (sex)" means to obtain a useful effect for health use, such as adjusting nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method conventionally used in the art, and may be prepared by adding raw materials and ingredients conventionally added in the art. In addition, the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as food. The health functional food composition of the present invention can be manufactured in various types of formulations, and unlike general medicines, it has no side effects that may occur when taking medicines for a long time using food as a raw material, and has excellent portability.

Specifically, the health functional food is a food prepared by adding the composition of the present invention to food materials such as beverages, teas, spices, gums, confectionery, or by encapsulation, powdering, suspension, etc. It means to bring about an effect, but unlike general medicines, it has the advantage that there is no side effect that can occur when taking medicines for a long time using food as a raw material.

The health functional food composition may further include a physiologically acceptable carrier, and the type of the carrier is not particularly limited, and any carrier commonly used in the art may be used. In addition, the health functional food composition is commonly used in food compositions, and may include, without limitation, additional ingredients that can improve odor, taste, vision, etc., and can be selected according to the type of food and used in an appropriate amount.

Another aspect of the present invention for achieving the above object is a novel compound, (2S)-1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride ((2S)- 1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride, Compound 5). The compound may be derived from a mallow extract or a fraction thereof. The mallow, extract, fraction is as described above.

Another aspect of the present invention for achieving the above object provides a method for producing a compound represented by Formula 1, comprising the step of separating the compound represented by Formula 1 from the mallow extract or fraction. The mallow, extract, fraction and the compound represented by Formula 1 are as described above.

The mallow extract of the present invention, a fraction thereof, and a compound represented by Formula 1 isolated therefrom show cytotoxicity against various cancer cells and induce apoptosis, thus preventing, improving or treating cancer pharmaceutical compositions, food compositions Etc.

Figure 1 shows the structure of the glycosyl glyceride (glycosyl glyceride) compounds 1 to 13 isolated from the malting surface in the present invention.
Figure 2 shows the results of apoptosis analysis when treated with AGS (human gastric cancer cells) of maternal n-butanol fractions, compounds 1, 2 and 11.
FIG. 3 shows the protein (PARP, caspase-3, Bax and Bcl-2) related to apoptosis when treated with maternal n-butanol fractions, compounds 1, 2 and 11 to AGS (human gastric cancer cells). It shows the result of measuring the expression level.

Hereinafter, the present invention will be described in more detail through the following examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1: Materials, reagents and instruments

1-1: plant material

The ground part of Malva verticillata used in this example was collected from a commercial farm in Namyangju-si, Korea in April 2016, and the sample sample (KHU20160419) is stored in the Natural Product Chemistry laboratory at Kyunghee University.

1-2: reagents and instruments

The silica gel (SiO ₂ ) and octadecyl SiO ₂ (ODS) resins used in column chromatography (CC) are Kiesel gel 60 (Merck, Darmstadt, Germany) and Lichroprep RP-18 (40-60 μm, Merck), respectively. Thin layer chromatography (TLC) analysis was performed using Kiesel gel 60 F ₂₅₄ and RP-18 F _254S (Merck) TLC plates, and the compound was Spectroline Model ENF-240 C/F (Spectronics Corporation, Westbury, NY, USA). It was detected using a UV lamp and 10% H ₂ SO ₄ solution. Nuclear magnetic resonance (NMR) spectra were recorded using a 400 MHz FT-NMR spectrometer (Varian Inova AS-400, Palo Alto, CA, USA). Deuterium (deuterium) solvent Merck Co. Ltd and Sigma Aldrich Co. Ltd (St, Louis, MO, USA). IR spectra were obtained from the Perkin Elmer Spectrum One FT-IR spectrometer (Buckinghamshire, England). Fab atom mass spectrometry (FAB-MS) was recorded with JEOL JMS-700 (Tokyo, Japan). Gas chromatography mass spectrometry (GC-MS) was recorded with Shimadzu GC-MSQP2010 Plus (Kyoto, Japan). Optical rotation was measured with a JASCO P-1010 digital polarimeter (Jasco, Tokyo, Japan).

Example 2: Preparation of mallow extract and fraction

The upper part of the dry mallow (3.1 kg) was extracted with 80% methanol (MeOH, 54.0 L Х 5) at room temperature for 24 hours. The extract was filtered through filter paper and evaporated under reduced pressure at 43° C. to give 794 g of extract.

The obtained methanol extract was suspended in water (2L), and extracted successively with ethyl acetate (EtOAc, 2L Х 4) and n-butanol (n-BuOH, 2L Х 4). Each layer was concentrated to give ethyl acetate fraction (MVE, 80 g), n-butanol fraction (MVB, 77 g) and water fraction (MVW, 637 g).

Example 3: Isolation and identification of compounds from mallow n-butanol fraction

3-1: Separation of compound from mallow n-butanol fraction

The n-butanol fraction of Example 2 (MVB, 77 g) was applied to silica gel column chromatography (CC) (φ10 Х 15 cm), and chloroform (CHCl ₃ )-methanol (MeOH)-water (H ₂ O) (25 : 3: 1 → 22: 3: 1 → 20: 3: 1 → 18: 3: 1 → 15: 3: 1 → 12: 3: 1, each eluting with 18.8L, 14 fractions (MVB-1 To MVB-14).

Fraction MVB-6 (3.6 g, elution volume/total volume (V _e /V _t ) 0.053-0.096) was applied to ODS CC (φ4.5 Х 6 cm) and acetone-water (3: 2 → 2: 1, all eluted with 3.6L) to obtain 11 fractions (MVB-6-1 to MVB-6-11). Of these, fraction MVB 6-4 (659.4 mg, V _e /V _t 0.031-0.092) was applied to silica gel CC (φ2.5 Х 15 cm) and chloroform-methanol-water (20:3:1, 1.4L). Compound 3 purified by eluting with 11 fractions (MVB-6-4-1 to MVB-6-4-11) [MVB6-4-10, 21.2 mg, V _e /V _t 0.286-0.514, TLC ( Kiesel gel 60 F254) R _f 0.38, chloroform-methanol-water (10:3:1), TLC (RP-18 F254S) Rf 0.74, methanol-water (3:1)] was obtained.

Fraction MVB-7 (5.0 g, V _e /V _t 0.098-0.126) was applied to ODS CC (φ4.5 Х 5 cm) and methanol-water (1: 1 → 2: 1 → 6: 1 → 8: 1, Separated by eluting with 3.8 L), Compound 5 [MVB-7-9, 84.2 mg, V _e /V _t 0.212- purified with 22 fractions (MVB-7-1 to MVB-6-22) 0.217, TLC (Kiesel gel 60 F254) R _f 0.90, chloroform-methanol-water (7:3:1), TLC (RP-18 F254S) Rf 0.70, methanol-water (5:1)], compound 6 [MVB -7-12, 142.8 mg, V _e /V _t 0.323-0.366, TLC (Kiesel gel 60 F254) R _f 0.90, chloroform-methanol-water (7:3:1), TLC (RP-18 F254S) Rf 0.41 , Methanol-water (5:1)], compound 12 [MVB-7-18, 34.0 mg, V _e /V _t 0.737-0.750, TLC (Kiesel gel 60 F254) R _f 0.90, chloroform-methanol-water (7 :3:1), TLC (RP-18 F254S) Rf 0.52, methanol-water (14:1)], and compound 13 [MVB-7-20, 586.2 mg V _e /V _t 0.787-0.842, TLC (Kiesel gel 60 F254) R _f 0.90, chloroform-methanol-water (7:3:1), TLC (RP-18 F254S) Rf 0.24, methanol-water (14:1)] was obtained.

Fraction MVB-8 (3.5 g, V _e /V _t 0.128-0.383) was applied to ODS CC (φ4.5 Х 8 cm) and methanol-water (3: 1 → 4: 1 → 5: 1 → 6: 1, Separated by eluting with 1.0 L each, 17 fractions (MVB-8-1 to MVB-8-17) were obtained. Of these, MVB-8-17 (879.3 mg, V _e /V _t 0.602-1.000) was applied to ODS CC (φ4 Х 8 cm) and eluted with acetone-water (3: 1, 3.0 L), 13 fractions Compound 8 purified with (MVB-8-17-1 to MVB-8-17-13) [MVB-8-17-10, 26.0 mg, V _e /V _t 0.480-0.580, TLC (Kiesel gel 60 F254 ) R _f 0.35, chloroform-methanol-water (10:3:1), TLC (RP-18 F254S) R _f 0.20, methanol-water (2:1)].

Fraction MVB-9 (4.0 g, V _e /V _t 0.385-0.557) was applied to ODS CC (φ4 Х 6 cm) and methanol-water (3: 2 → 2: 1 → 2.5: 1 → 3: 1 → 5: 1, 3.6L) and eluted to separate, Compound 2 [MVB-9-10, 44.4 mg V _e /V _t 0.602-0.668 with 16 fractions (MVB-9-1 to MVB-9-16) , TLC (Kiesel gel 60 F254) R _f 0.25, chloroform-methanol-water (8:3:1), TLC (RP-18 F254S) R _f 0.28, methanol-water (5:1)].

Fraction MVB-9-5 (383.9mg, V _e /V _t 0.116-0.263) was applied to ODS CC (φ2.5 Х 6cm) and eluted with acetone-water (2:3, 4.0L), resulting in 14 fractions Compound 11 purified with (MVB-9-5-1 to MVB-9-5-14) [MVB-9-5-9, 96.3 mg V _e /V _t 0.602-0.668, TLC (Kiesel gel 60 F254) R _f 0.25, chloroform-methanol-water (8:3:1), TLC (RP-18 F254S) R _f 0.48, acetone-water (2:1)].

Fraction MVB-11 (8.7 g, V _e /V _t 0.560-0.755) was applied to ODS CC (φ4.5 Х 8 cm) and methanol-water (2: 1 → 4: 1 → 6: 1, 3.0 L each) As a result of eluting and separating, Compound 10 purified with 16 fractions (MVB-11-1 to MVB-11-16) [MVB-11-10, 732.4 mg V _e /V _t 0.582-0.629, TLC (Kiesel gel 60 F254) R _f 0.71, chloroform-methanol-water (65:35:10), TLC (RP-18 F254S) R _f 0.18, methanol-water (4:1)] was obtained.

Fraction MVB-11-6 (1.5 g, V _e /V _t 0.102-0.289) was applied to silica gel CC (φ3.5 Х 15 cm) and eluted with chloroform-methanol (5:2 → 2:1, all 1.5L). As a result of separation, 10 fractions (MVB-11-6-1 to MVB-11-6-10) were obtained. Among them, the fraction MVB-11-6-5 (263.0mg, V _e /V _t 0.240-0.473) was applied to ODS CC (φ3 Х 5cm) and methanol-water (3: 2 → 1: 1, all 1.8L) After separation by elution), compound 9 purified with 12 fractions (MVB-11-6-5-1 to MVB-11-6-5-12) [MVB-11-6-5-10, 38.8 mg V _e /V _t 0.502-0.746, TLC (Kiesel gel 60 F254) R _f 0.18, chloroform-methanol (2:1), TLC (RP-18 F254S) R _f 0.50, methanol-water (3:1)] Was obtained.

Fraction MVB-11-16 (1.8 g, V _e /V _t 0.998-1.000) was applied to silica gel CC (φ4 Х 15 cm) and ethyl acetate (EtOAc)-n-butanol (n-BuOH)-water (7: 3 : 1 → 2: 5: 1, all were eluted and separated, and 14 fractions (MVB-11-16-1 to MVB-11-16-14) were obtained. Among them, fraction MVB-11-16-7 (99.0 mg, V _e /V _t 0.120-0.237) was applied to ODS CC (φ2.5 Х 5 cm) and eluted with acetone-water (2:1, 0.46L). As a result of separation, compound 1 purified with 12 fractions (MVB-11-16-7-1 to MVB-11-16-7-12) [MVB-11-16-7-5, 23.8 mg V _e /V _t 0.110-0.209, TLC (Kiesel gel 60 F254) R _f 0.85, chloroform-methanol-water (6:4:1), TLC (RP-18 F254S) R _f 0.46, acetone-water (3:1) ].

Fraction MVB-12 (11.0 g, V _e /V _t 0.756-0.898) was applied to ODS CC (φ6.5 Х 5 cm) and methanol-water (1: 1 → 2: 1 → 3: 1 → 5: 1, Separated by eluting with 3.8 L), Compound 4 [MVB-12-10, 632.4 mg V _e /V _t 0.303-0.349 purified with 18 fractions (MVB-12-1 to MVB-12-18) , TLC (Kiesel gel 60 F254) R _f 0.50, chloroform-methanol-water (65:35:10), TLC (RP-18 F254S) R _f 0.78, methanol-water (5:1)].

Water fractions (MVW, 635 g) were applied to the anion HP-20 column (φ9 Х 30 cm) and methanol-water (0: 1 → 1: 4 → 2: 3 → 3: 2 → 4: 1 → 1: 0, each The result was eluted with 6.0L) to give 9 fractions (MVW -1 to MVW-9). Among them, the fraction MVW-7 (1.0 g, V _e /V _t 0.911-0.967) was applied to silica gel CC (φ4.5 Х 15 cm) and chloroform-methanol (40: 1 → 15: 1 → 10: 1 → 5 : 1, 5.6L each, eluted and separated. Compound 7 purified with 23 fractions (MVW-7-1 to MVW-7-23) [MVW-7-18, 22.8 mg V _e /V _t 0.476-0.500, TLC (Kiesel gel 60 F254) R _f 0.50, chloroform-methanol (5:1), TLC (RP-18 F254S) R _f 0.82, acetone-water (4:1)] was obtained.

3-2: Identification of isolated compounds 1 to 13

NMR, IR and FAB-MS and GC-MS analysis were performed on the compounds 1 to 13 obtained in Example 3-1 to identify the structures of each compound. Specifically, ¹ H (400 MHz) and ¹³ C (100 MHz) NMR results of Compounds 1, 2, and 5 are shown in Table 1 below.

[Table 1]

The results of analyzing Compound 1 are as follows.

-Pale yellow wax

-[a]D +30.8° (c 0.10, MeOH)

-IR (KBr, m) 3390, 1735, 1612, 1186 cm ^-1

-negative FAB-MS m/z 815 [MH] ^- , m/z 559 [MHR ₃ ] ^- , m/z 537 [MHR ₂ ]-, m/z 277 [R2-H] ^- , m/z 255 [ R ₃ -H] ^- , m/z 225 [the dehydrated product of the (6-deoxy-6-sulfo)-D-glucopyranose ion m/z 243], m/z 80 [SO ₃ ] ^-

-negative HR-FAB-MS m/z 815.4982 [MH] ^- (calcd for C ₄₃ H ₇₅ O ₁₂ S-, 815.4985)

-GC-MS t _R = 10.27 min (palmitic acid methyl ester), 13.76 min (linolenic acid methyl ester).

As a result of the analysis, Compound 1 is (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride ( (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride). Compound 1 is the first isolated and identified compound from natural raw materials.

The results of analyzing Compound 2 are as follows.

-Pale yellow wax

-[a]D +28.4° (c 0.10, MeOH)

-IR (KBr, v) 3386, 1732, 1610, 1178 cm ^-1

-positive FAB-MS m/z 861 [M+Na] ⁺

-negative FAB-MS m/z 837 [M-H]-, m/z 559

-[MHR _{2 or 3} ]-, m/z 277 [R ₂ or ₃ -H]-, m/z 225 [the dehydrated product of the (6-deoxy-6-sulfo)-D-glucopyranose ion m/z 243], m / z 80 [ SO 3] -, negative HR-FAB-MS m / z 837.4822 [MH] - (calcd for C 45 H 73 O 12 S -, 837.4828)

-GC-MS t _R =13.76 min (linolenic acid methyl ester).

As a result of the analysis, compound 2 was (2S)-1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2,3-di-O-linolenoyl glyceride ((2S) It was confirmed that -1-O-(6-deoxy-6-sulfo)-α-D-glucopyranosyl-2,3-di-O-linolenoyl Glyceride). Compound 2 is the first isolated and identified compound from natural raw materials.

The result of analyzing the compound 3 is as follows.

-Pale yellow wax

-[a]D +9.3° (c 0.10, MeOH)

-IR (KBr, m) 3379, 1725 cm ^-1

-positive FAB-MS m/z 515 [M+Na] ⁺

-GC-MS t _R = 11.06 min (palmitic acid).

As a result of the analysis, compound 3 was (2S)-1-O-β-D-galactopyranosyl-3-O-palmitoyl glyceride ((2S)-1-O-β-D-galactopyranosyl-3-O- palmitoyl glyceride).

The result of analyzing the compound 4 is as follows.

-Pale yellow wax

-[a]D +2.6° (c 0.10, MeOH)

-IR (KBr, m) 3383, 1723 cm ^-1

-positive FAB-MS m/z 543 [M+Na] ⁺

-GC-MS t _R = 14.36 min (stearic acid methyl ester)

As a result of the analysis, compound 4 was (2S)-1-O-β-D-galactopyranosyl-3-O-stearoyl glyceride ((2S)-1-O-β-D-galactopyranosyl-3-O -stearoyl glyceride).

The result of analyzing the compound 5 is as follows.

-Pale yellow wax

-[a]D +5.5° (c 0.10, MeOH)

-IR (KBr, m) 3380, 1722 cm ^-1 ;

-negative FAB-MS m/z 555 [M+Cl] ^- , m/z 339 [MH-180 (hexose + H ₂ O)] ^- , m/z 283 [R ₃ -H] ^- ,

-negative HR-FAB-MS m/z 555.3289 [M+Cl] ^- (calcd for C ₂₇ H ₅₂ O ₉ Cl, 555.3299)

-GC-MS t _R = 14.36 min (isostearic acid methyl ester)

As a result of the analysis, compound 5 was (2S)-1-O-β-D-galactopyranosyl-3-O-isostearoyl glyceride ((2S)-1-O-β-D-galactopyranosyl-3- O-isostearoyl glyceride). Compound 5 is a novel glycosyl glyceride compound, named malvaglycolipid A.

The result of analyzing compound 6 is as follows.

-Pale yellow wax

-[a]D +3.7° (c 0.10, MeOH)

-IR (KBr, m) 3386, 1722, 1612 cm ^-1

-positive FAB-MS m/z 537 [M+Na] ⁺

-GC-MS t _R = 13.76 min (linolenic acid methyl ester)

As a result of the analysis, compound 6 was (2S)-1-O-β-D-galactopyranosyl-3-O-linolenoyl glyceride ((2S)-1-O-β-D-galactopyranosyl-3-O -linolenoyl glyceride).

The result of analyzing the compound 7 is as follows.

-Pale yellow wax

-[a]D +26.4° (c 0.10, MeOH)

-IR (KBr, m) 3383, 1723 cm ^-1

-negative FAB-MS m/z 729 [MH] ^-

-GC-MS tR = 11.06 min (palmitic acid)

As a result of the analysis, compound 7 was (2S)-1-O-β-D-galactopyranosyl-2,3-di-O-palmitoyl glyceride ((2S)-1-O-β-D-galactopyranosyl- 2,3-di-O-palmitoyl glyceride).

The result of analyzing compound 8 is as follows.

-Pale yellow wax

-[a]D -4.0° (c 0.10, MeOH)

-IR (KBr, m) 3383, 1723, 1612 cm ^-1

-positive FAB-MS m/z 776 [M+H] ⁺

-GC-MS t _R = 13.76 min (linolenic acid methyl ester)

As a result of the analysis, compound 8 was (2S)-1-O-β-D-galactopyranosyl-2,3-di-O-linolenoyl glyceride ((2S)-1-O-β-D-galactopyranosyl -2,3-di-O-linolenoyl glyceride).

The result of analyzing compound 9 is as follows.

-Pale yellow wax

-[a]D +49.1° (c 0.10, MeOH)

-IR (KBr, m) 3383, 1723 cm ^-1

-positive FAB-MS m/z 655 [M+H] ⁺

-GC-MS t _R = 10.27 min (palmitic acid methyl ester)

As a result of the analysis, compound 9 was (2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-O-palmitoyl glyceride ((2S )-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-Opalmitoyl Glyceride).

The results of analyzing Compound 10 are as follows.

-Pale yellow wax

-[a]D +14.4° (c 0.10, MeOH)

-IR (KBr, m) 3386, 1722, 1610 cm ^-1

-positive FAB-MS m/z 677 [M+H] ⁺

-GC-MS t _R = 13.76 min (linilenic acid methyl ester)

As a result of the analysis, compound 10 was (2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-O-linolenoyl glyceride (( 2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-3-Olinolenoyl Glyceride).

The results of analyzing Compound 11 are as follows.

-Pale yellow wax

-[a]D -0.8° (c 0.10, MeOH)

-IR (KBr, m) 3383, 1723 cm ^-1

-Positive FAB-MS m/z 893 [M+H] ⁺

-GC-MS t _R = 10.27 min (palmitic acid methyl ester), 11.06 min (palmitic acid)

As a result of the analysis, Compound 11 was (2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-palmitoyl glycerol Ride ((2S)-1-O-6'-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-palmitoyl glyceride) was confirmed.

The result of analyzing the compound 12 is as follows.

-Pale yellow wax

-[a]D +7.0° (c 0.10, MeOH)

-IR (KBr, m) 3386, 1723, 1612 cm ^-1

-negative FAB-MS m/z 815 [M+Cl] ^-

-GC-MS t _R = 13.76 min (linilenic acid methyl ester), 14.36 min (stearic acid methyl ester)

As a result of the analysis, compound 12 was (2S)-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2-O-stearoyl-3-O- It was confirmed that linolenoyl glyceride ((2S)-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2-Ostearolyl-3-O-linolenoyl glyceride).

The result of analyzing compound 13 is as follows.

-Pale yellow wax

-[a]D +36.6° (c 0.10, MeOH)

-IR (KBr, m) 3389, 1722, 1615 cm ^-1

-Negative FAB-MS m/z 935 [MH] ^-

-GC-MS t _R = 13.76 min (linolenic acid methyl ester), 14.58 min (linolenic acid)

As a result of the analysis, compound 13 was (2S)-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-linolenoyl- It was confirmed that glyceride ((2S)-1-O-(6-O-α-D-galactopyranosyl)-β-D-galactopyranosyl-2,3-di-O-linolenoyl-glyceride).

Example 4: GC-MS analysis of fatty acids in glycerol glycerides

Each compound (1.0 mg) was dissolved in 2 ml of 20% potassium hydroxide (KOH)/methanol (MeOH) and heated in a water bath at 80° C. for 60 minutes. After cooling at room temperature, the reaction mixture was evaluated for disappearance of starting material on a TLC plate (n-hexane-EtOAc = 1:1), followed by neutralization by addition of an acidic cation-exchange resin (Dowex 50W, H ⁺ form) Filtered. Each filtrate was evaporated in vacuo and partitioned between ethyl acetate (EtOAc, 3 ml) and water (3 ml) fractions. The ethyl acetate fraction was then evaporated in vacuo, dissolved in 200 μl of ethyl acetate, and then filtered through a syringe filter (0.2 μm, 13 mm). The filtrate was stored at -4°C until GC-MS analysis.

For the GC-MS experiment, a DB-5 column (0.25 μm film thickness×0.25 mm diameter, 30 m length) was used. Helium gas was used as the carrier gas at a flow rate of 24.2 ml/min. The oven temperature was programmed to increase from 160°C to 320°C at a rate of 4°C/min and held for 15 minutes. The injector and detector temperatures were set to 280°C and 280°C, respectively. Sample solution (1 μl) was injected into the GC column at a 1:1 split ratio. Detection was performed by electron ionization (70 eV) and 4-pole mass spectrometry. Fatty acids were confirmed by comparing retention time and actual fatty acids and mass spectra with libraries (Wiley Library, version 2008, John Wiley & Sons Inc., Hoboken, NJ, USA).

Example 5: Analysis of anticancer effect of malt fraction and compounds 1 to 13

5-1: Cell culture

HepG2 (human liver cancer cells), AGS (human gastric cancer cells), HCT-15 (human colon cancer cells) and A549 (human lung cancer cell) cell lines were obtained from the Korean Cell Line Bank (KCLB), and 10% heat-inactivated bovine fetus DMEM and RPMI 1640 supplemented with serum and 1% penicillin streptomycin at 37°C, 5% CO₂ Cultured under air.

5-2: Cell survival analysis-confirm the apoptosis effect on cancer cells

To confirm the cytotoxicity of the malt fractions prepared in Examples 2 and 3 and various cancer cells of compounds 1 to 13, each fraction and isolated compounds 1 to 13 were added to HepG2, AGS, HCT-15 and A549 cell lines. Treatment with different concentrations and MTT analysis was performed.

Each cancer cell line was inoculated in a 96-well cell culture plate at 5 x 10 ³ cells/well in 100 µl. After 24 hours, cells were treated with various concentrations of fractions and compounds and incubated at 37° C. under 5% CO ₂ atmosphere for 24 hours. The analysis was performed by adding 10 μl of 5 mg/mL MTT reagent to the cells and incubating at 37° C. for 3 hours. Then, the supernatant of the culture medium was removed, 100 ml of DMSO was added to each well, and the plate was shaken for 5 minutes. Absorbance at 550 nm was measured using a multi-mode microplate reader (Tecan, Seoul, Korea). As a result, as can be seen from Table 2 below, it was confirmed that the viability of all four cell lines was significantly reduced in all fractions and compounds.

[Table 2]

In particular, n-butanol fractions, compounds 1, 2 and 11 exhibited significant cytotoxicity against AGS (human gastric cancer cells), and each IC ₅₀ value was 8.2±0.14 μg/ml, 33.7±0.64 μM, 11.1±0.07 μM, and 10.6±0.10 μM. From this, the mallow extract, its fraction, or a compound isolated therefrom, specifically the n-butanol fraction from the mallow surface, said compounds 1, 2 and 11 show cytotoxicity against various cancer cells, including AGS, to prevent cancer or It was found to have a therapeutic effect.

5-3: Measurement analysis of apoptosis-check the effect of apoptosis

To confirm the apoptosis-inducing effect of the malt fraction (n-butanol fraction) prepared in Examples 2 and 3 on AGS of compounds 1, 2, and 11, annexin V binding analysis and propidium iodide (PI ) Staining.

AGS cells were plated on a 6-well cell culture plate at 2 mL of 1×10 ⁵ cells/well and incubated at 37° C. in 5% CO ₂ atmosphere for 24 hours. Cell samples were then treated with various concentrations of n-butanol fraction and compounds 1, 2 and 11. After treatment for 24 hours, cells were harvested and analyzed using the Tali Apoptosis Assay Kit according to the manufacturer's instructions.

As a result, it was confirmed that the number of apoptotic cells increased as the concentrations of n-butanol fractions, compounds 1, 2 and 11 increased (FIG. 2). In other words, the n-butanol fraction in the terrestrial region, the compounds 1, 2 and 11 show not only cytotoxicity to cancer cells including AGS, but also an effect of inducing apoptosis of cancer cells, preventing or treating cancer It was found to have an effect.

5-4: Western blotting-analysis of apoptosis-related protein levels

The malt fractions (n-butanol fractions) prepared in Examples 2 and 3 and compounds 1, 2 and 11 were analyzed to control whether or not to regulate the expression of proteins (PARP, caspase-3, Bax and Bcl-2) related to apoptosis. . Specifically, PARP (poly (ADP-ribose) polymerase) is a proteolytic substrate of caspase that is cleaved in the apoptosis step, and the degradation of PARP is induced by activation of caspase-3, which leads to apoptosis. In addition, the ratio of the pro-apoptosis gene Bax and the anti-apoptosis gene Bcl2 (Bax/Bcl2) is an important factor in determining the stage of cell death.

AGS cells were placed in a 100 φ cell culture dish (1×10 ⁶ cells/plate in ⁶ mL) and cultured at 37° C. in 5% CO ₂ atmosphere. After 24 hours, cells were treated with various concentrations of compounds and incubated for 24 hours. Subsequently, the cells were harvested and protein extracts were prepared using a protein extraction kit (iNtRON Biotechnology, Seoul, Korea). Protein extracts (30 μg/μl) were separated by 12% SDS-PAGE. The protein was then transferred to a nitrocellulose (NC) membrane at 300 mA for 140 minutes. The transferred membrane was blocked and washed with skim milk for 2 hours in TBS containing 0.05% Tween 20 (TBS-T). Subsequently, the membrane was incubated with specific antibodies (PARP, caspase-3, Bax, Bcl-2 and β-actin, 1: 1000) overnight at 4° C., washed, and then incubated with secondary antibodies at room temperature. Target protein bands were visualized with EZ-Western Lumi Pico reagent according to the manufacturer's instructions.

As a result, PARP was dose-dependently degraded of the n-butanol fraction, compounds 1, 2 and 11, thereby reducing the expression of caspase-3 and caspase-3 in AGS cells. On the other hand, Bax was not affected by n-butanol fractions, compounds 2 and 11, but expression increased with treatment of compound 1, and Bcl-2 was expressed by treatment with n-butanol fractions, compounds 1, 2 and 11 Decreased (Figure 3).

As a result, the treatment of n-butanol fractions, compounds 1, 2 and 11 increased the Bax/Bcl-2 ratio to induce apoptosis, thus confirming that it inhibited the growth of AGS cells. In addition, sulfoquinovosyl glyceride compounds 1 and 2 are more resistant to HepG2, AGS, HCT-15, and A549 cells than other galactoglycosyl glyceride compounds (compounds 3 to 10, 12 and 13). It was confirmed that it has a high anti-cancer effect. From this, it was found that the n-butanol fraction of the terrestrial auricle, the compounds 1, 2, and 11 induce apoptosis of various cancer cells including AGS and thus have a prophylactic or therapeutic effect on cancer.

5-5: Statistical analysis

Each experiment was performed at least three times. Results are expressed as the mean±standard error of the mean (S.E.M.). Data were evaluated at a significance level of *p <0.05, **p <0.01 and ***p <0.001 using one-way ANOVA.

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be implemented in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the claims, which are described later, rather than the above detailed description, and all modified or modified forms derived from equivalent concepts thereof.

Claims (14)

As a pharmaceutical composition for preventing or treating cancer comprising n-butanol fraction of methanol extract of Malva verticillata as an active ingredient,
The cancer is stomach cancer, lung cancer, colorectal cancer or liver cancer pharmaceutical composition.
delete delete delete delete delete The pharmaceutical composition of claim 1, wherein the composition exhibits cytotoxicity against gastric cancer, lung cancer, colon cancer, or liver cancer cells.
delete According to claim 1, The composition is to induce apoptosis (apoptosis) of cancer cells, as a pharmaceutical composition,
The cancer is stomach cancer, lung cancer, colorectal cancer or liver cancer, the pharmaceutical composition.
As a food composition for preventing or improving cancer comprising n-butanol fraction of methanol extract of Malva verticillata as an active ingredient,
The cancer is gastric cancer, lung cancer, colorectal cancer or liver cancer food composition.
delete delete delete delete

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