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CN-121974967-A - Orange ketone lignan glycoside compound separated from saffron and its use in resisting non-alcoholic fatty liver

CN121974967ACN 121974967 ACN121974967 ACN 121974967ACN-121974967-A

Abstract

The invention discloses an aureoco lignan glycoside compound separated from saffron and application thereof in resisting non-alcoholic fatty liver. The aureonolignan glycoside compound shown in the structural formula I or pharmaceutically acceptable salt thereof: I. The compound can obviously reduce ALP, AST, ALT, TG, TC, LDL-C level in serum of golden mice of a non-alcoholic fatty liver model, can obviously raise APN and HDL-C level, and has obvious non-alcoholic fatty liver resisting activity. The invention discloses application of a neohesperidin lignan glycoside compound in preparation of a blood lipid reducing medicament. The invention discloses application of a neohesperidin lignan glycoside compound in preparation of a medicine for resisting non-alcoholic fatty liver.

Inventors

  • WEI RONGRUI
  • MA QINGE

Assignees

  • 武汉轻工大学

Dates

Publication Date
20260505
Application Date
20260121

Claims (10)

  1. 1. The aureonolignan glycoside compound shown in the structural formula I or pharmaceutically acceptable salt thereof: ; I。
  2. 2. A method for preparing the aureolignan glycoside compound according to claim 1, which is characterized by comprising the following steps: Extracting the saffron by heating and refluxing with 90-100% ethanol for 3-5 times and 3-5 hours each time to obtain an extracting solution, extracting the residue by heating and refluxing with 60-80% ethanol for 3-5 times and 3-5 hours each time to obtain an extracting solution, and combining the extracting solutions to obtain a saffron total extracting solution; Step (2), concentrating and drying the saffron total extract under reduced pressure to obtain a dry total thick paste; Uniformly suspending the saffron total thick paste in water, and sequentially extracting with petroleum ether, ethyl acetate and n-butanol to obtain petroleum ether extract, ethyl acetate extract and n-butanol extract respectively; Step (4), subjecting the n-butanol extract to macroporous adsorption resin column, and sequentially performing gradient elution with 15%, 30%, 50% and 100% ethanol to obtain 4 fractions A, B, C and D; step (5), performing normal phase silica gel column chromatography on the fraction B, and performing gradient elution by taking methylene dichloride and methanol with the volume ratio of = 20:1 → 1:1 as eluent to obtain 4 subfractions including subfractions B-1, subfractions B-2, subfractions B-3 and subfractions B-4; Step (6), loading the subfraction B-3 on a Sephadex LH-20 gel column, eluting with 80% -100% methanol to obtain 3 secondary fractions, namely secondary fraction B-3-1, secondary fraction B-3-2 and secondary fraction B-3-3; Step (7), loading the secondary fraction B-3-2 on a Toyopearl HW-40C gel column, eluting with 85% -95% methanol to obtain 3 small fractions, namely small fraction B-3-2-1, small fraction B-3-2-2 and small fraction B-3-2-3; and (8) performing preparative liquid chromatography separation on the small fraction B-3-2-2 to obtain the aureocone lignan glycoside compound.
  3. 3. The method for preparing the aureolignan glycoside compound according to claim 2, wherein in the step (2), the temperature of the reduced pressure concentration and drying is 45-55 ℃.
  4. 4. The method for preparing the aureolignan glycoside compound according to claim 2, wherein in the step (4), the macroporous adsorption resin is D101 macroporous adsorption resin.
  5. 5. The method for producing A aureolignan glycoside compound according to claim 2, wherein in the step (8), the conditions for liquid chromatography are YMC-Pack ODS-A column (250X 20mm, 5 μm), mobile phase 15-40% methanol, absorption wavelength 150-400 nm, flow rate 2-4 m/min.
  6. 6. The use of the aureonolignan glycoside compound according to claim 1 for the preparation of a hypolipidemic agent.
  7. 7. The use of the aureonolignan glycoside compound according to claim 1 for the preparation of a medicament for treating non-alcoholic fatty liver disease.
  8. 8. A pharmaceutical composition is characterized in that the pharmaceutical composition takes the aureonolignan glycoside compound as the active ingredient, and is prepared into a pharmaceutically acceptable dosage form with pharmaceutically acceptable auxiliary materials.
  9. 9. The pharmaceutical composition of claim 8, wherein the dosage form is a tablet, a capsule, a granule, a pill, an oral liquid, or a suspension.
  10. 10. Use of the aureolignan glycoside compound according to claim 1 for the preparation of a health food for helping to maintain a healthy level of blood lipids (cholesterol/triglycerides).

Description

Orange ketone lignan glycoside compound separated from saffron and its use in resisting non-alcoholic fatty liver Technical Field The invention belongs to the technical field of medicines, and in particular relates to a neohesperidin lignan glycoside compound separated from saffron, a preparation method thereof and application thereof in preparing medicines for resisting non-alcoholic fatty liver. Technical Field The Tibetan monascus is functional monascus obtained by taking fruits of highland barley of Gramineae as raw materials, inoculating monascus and then performing solid state fermentation, and has the characteristic of both medicine and food. The Tibetan monascus is used as an important Tibetan medicine, is recorded in the 'compendium of materia medica' and the 'Chinese medical dictionary', has various effects of promoting blood circulation, activating blood circulation to remove stasis, soothing liver and regulating qi, helping digestion, strengthening spleen and stomach and the like, and is suitable for treating hypochondriac pain and chest distress caused by liver depression and qi stagnation, abdominal distention and anorexia and stomachache caused by spleen and stomach qi stagnation and the like. Early researches found that the saffron contains rich chemical components including flavonoids, lignans, alkaloids, monascus pigments, monacolins, lactones, polysaccharides, statins, sterols, enzymes and the like. Modern pharmacological researches show that the saffron has multiple effects of resisting aging, resisting tumor, resisting inflammation, resisting fatigue, resisting convulsion, protecting liver, reducing blood fat, reducing blood pressure, reducing blood sugar and the like, and especially the researches on protecting liver are favored by people. Therefore, the saffron has potential development value in preventing and treating liver diseases. Disclosure of Invention In order to further extract the potential medicinal value of the saffron for protecting the liver, the invention selects the saffron as a research object, separates the saffron from the saffron to obtain a neohesperidin lignan glycoside compound, and adopts the modern spectrum technology (NMR, MS, IR, UV and the like) to analyze and identify the chemical structure of the neohesperidin lignan glycoside compound. Meanwhile, the invention adopts a biochemical method to detect the blood lipid index (TG, TC, LDL-C, HDL-C) of the golden yellow mice and the liver function index (ALP, AST, ALT, APN) of the golden yellow mice to evaluate the anti-nonalcoholic fatty liver effect of the compound, the compound can obviously reduce ALP, AST, ALT, TG, TC, LDL-C level in serum of the golden yellow mice of a nonalcoholic fatty liver model, can obviously raise APN and HDL-C level, and has obvious anti-nonalcoholic fatty liver activity. The invention aims to provide a neohesperidin lignan glycoside compound separated from saffron, a preparation method of the compound and application of the compound in preparing medicaments for resisting non-alcoholic fatty liver. In order to achieve the above purpose, the present invention adopts the following technical scheme: neoaureonolignan glycoside compound (marked as compound I) or pharmaceutically acceptable salt thereof, which is separated from saffron as shown in formula I: I Chemical name of compound I (7E) -5-hydroxy-6-rutinoside-8- (12, 13-dimethyl-11-carbonyl-pentalactone) -9' ' - (3 ' ',4' ' -dihydroxy-styryl) -9' ' - (4 ' -hydroxy-phenyl) -orange-one. The molecular formula of the compound I is C 41H42O18. The invention also provides a preparation method of the aureolignan glycoside compound, which comprises the following steps: Extracting the saffron by heating and refluxing with 90-100% ethanol for 3-5 times and 3-5 hours each time to obtain an extracting solution, extracting the residue by heating and refluxing with 60-80% ethanol for 3-5 times and 3-5 hours each time to obtain an extracting solution, and combining the extracting solutions to obtain a saffron total extracting solution; Step (2), concentrating and drying the saffron total extract under reduced pressure to obtain a dry total thick paste; Uniformly suspending the saffron total thick paste in water, and sequentially extracting with petroleum ether, ethyl acetate and n-butanol to obtain petroleum ether extract, ethyl acetate extract and n-butanol extract respectively; Step (4), subjecting the n-butanol extract to macroporous adsorption resin column, and sequentially performing gradient elution with 15%, 30%, 50% and 100% ethanol to obtain 4 fractions A, B, C and D; step (5), performing normal phase silica gel column chromatography on the fraction B, and performing gradient elution by taking methylene dichloride and methanol with the volume ratio of = 20:1 → 1:1 as eluent to obtain 4 subfractions including subfractions B-1, subfractions B-2, subfractions B-3 and subfractions B-4; Step (6), loading the subfraction B-3 on a Sephadex LH-20