CN110621327A - 含有阳春砂提取物的预防及治疗改善脂肪肝的组成物 - Google Patents
含有阳春砂提取物的预防及治疗改善脂肪肝的组成物 Download PDFInfo
- Publication number
- CN110621327A CN110621327A CN201880026613.9A CN201880026613A CN110621327A CN 110621327 A CN110621327 A CN 110621327A CN 201880026613 A CN201880026613 A CN 201880026613A CN 110621327 A CN110621327 A CN 110621327A
- Authority
- CN
- China
- Prior art keywords
- amomum villosum
- fatty liver
- extract
- villosum extract
- preventing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 244000141331 Amomum villosum Species 0.000 title claims abstract description 86
- 208000010706 fatty liver disease Diseases 0.000 title claims abstract description 60
- 231100000240 steatosis hepatitis Toxicity 0.000 title claims abstract description 54
- 208000004930 Fatty Liver Diseases 0.000 title claims abstract description 53
- 206010019708 Hepatic steatosis Diseases 0.000 title claims abstract description 53
- 239000000203 mixture Substances 0.000 title claims abstract description 18
- 210000002472 endoplasmic reticulum Anatomy 0.000 claims abstract description 37
- 230000014509 gene expression Effects 0.000 claims abstract description 26
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 24
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 17
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 241000699670 Mus sp. Species 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 claims description 33
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 claims description 33
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 claims description 33
- 210000004027 cell Anatomy 0.000 claims description 18
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 claims description 10
- 101150112743 HSPA5 gene Proteins 0.000 claims description 10
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 claims description 10
- 101150028578 grp78 gene Proteins 0.000 claims description 10
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 claims description 9
- 108010074436 Sterol Regulatory Element Binding Protein 1 Proteins 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 108020004999 messenger RNA Proteins 0.000 claims description 6
- 108010039731 Fatty Acid Synthases Proteins 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 150000003626 triacylglycerols Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 22
- 230000002401 inhibitory effect Effects 0.000 abstract description 18
- 230000005764 inhibitory process Effects 0.000 abstract description 10
- 238000001727 in vivo Methods 0.000 abstract description 9
- 238000000338 in vitro Methods 0.000 abstract description 8
- 230000007246 mechanism Effects 0.000 abstract description 6
- 230000035882 stress Effects 0.000 description 32
- 210000004185 liver Anatomy 0.000 description 20
- 239000003814 drug Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 108091008038 CHOP Proteins 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 9
- 238000011740 C57BL/6 mouse Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 102100029145 DNA damage-inducible transcript 3 protein Human genes 0.000 description 7
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000000411 inducer Substances 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 208000008589 Obesity Diseases 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 238000003570 cell viability assay Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- 239000004576 sand Substances 0.000 description 6
- 102100026839 Sterol regulatory element-binding protein 1 Human genes 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 description 4
- 206010016262 Fatty liver alcoholic Diseases 0.000 description 4
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 3
- 108010018763 Biotin carboxylase Proteins 0.000 description 3
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 description 2
- 102000052651 Pancreatic hormone Human genes 0.000 description 2
- 101800001268 Pancreatic hormone Proteins 0.000 description 2
- 108010035430 X-Box Binding Protein 1 Proteins 0.000 description 2
- 102100038151 X-box-binding protein 1 Human genes 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000003520 lipogenic effect Effects 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 2
- 231100000956 nontoxicity Toxicity 0.000 description 2
- 239000004025 pancreas hormone Substances 0.000 description 2
- 229940032957 pancreatic hormone Drugs 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- 206010036067 polydipsia Diseases 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 2
- 229960004245 silymarin Drugs 0.000 description 2
- 235000017700 silymarin Nutrition 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 2
- 229960001661 ursodiol Drugs 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 241001127714 Amomum Species 0.000 description 1
- 241001571352 Amomum longiligulare Species 0.000 description 1
- 101710186200 CCAAT/enhancer-binding protein Proteins 0.000 description 1
- 241001070941 Castanea Species 0.000 description 1
- 235000014036 Castanea Nutrition 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 206010059186 Early satiety Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241001071917 Lithospermum Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 229920009405 Polyvinylidenefluoride (PVDF) Film Polymers 0.000 description 1
- 235000011158 Prunus mume Nutrition 0.000 description 1
- 244000018795 Prunus mume Species 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 1
- 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- -1 Tetrazolium salt Chemical class 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 241000234299 Zingiberaceae Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000002293 adipogenic effect Effects 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 108010070004 glucose receptor Proteins 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000007449 liver function test Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000006676 mitochondrial damage Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Mycology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nutrition Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及含有有效成分阳春砂提取物的预防及治疗改善脂肪肝的组成物。本发明涉及预防及治疗改善脂肪肝的组成物，其特征为用水提取所述阳春砂提取物，以老鼠经口给药基准含100～500mg/kg所述阳春砂提取物。本发明提供含有有效成分阳春砂提取物的预防及治疗改善脂肪肝的组成物，阳春砂提取物对脂肪肝生成的抑制效能及其机制具有在生物体外和生物体内抑制TG、抑制内质网应激相关基因的表达、抑制脂肪合成相关基因表达的效能。
Description
技术领域
本发明涉及含有有效成分阳春砂提取物的预防及治疗改善脂肪肝的组成物。
本发明提供一种含有有效成分阳春砂提取物的预防及治疗改善脂肪肝的组成物，其特征是用水提取所述阳春砂提取物，阳春砂提取物对脂肪肝生成的抑制效能及其机制具有在生物体外和生物体内抑制肝内TG、抑制ER压力相关遗传基因表达、抑制脂肪合成相关遗传基因表达的效能。
背景技术
一般健康的肝脏的脂肪比率为5％，蓄积比这个比率多的脂肪的肝称为脂肪肝。最近随着营养状态变好、成人病增加，脂肪肝患者增加。脂肪肝是一种由于脂肪的过度摄取导致肝内脂肪蓄积、合成及无法进行正常的脂肪代谢而发病的疾病。
脂肪肝可以分为由过量饮酒引起的酒精性脂肪肝和由肥胖、糖尿病、高血脂症、药物引起的非酒精性脂肪肝。酒精性脂肪肝是因为过量摄入酒精时在肝内促进脂肪合成且无法进行正常的能量代谢而发生。
即，脂肪肝的主要原因为饮酒和肥胖，有时与血液中脂肪类的浓度高的高血脂症或糖尿病等疾病相伴出现，肾上腺皮质激素类药(类固醇类激素类药)或女性激素类药等药剂也可能成为原因。
脂肪肝大部分没有症状，外观上看起来健康，可能感到疲劳感和全身倦怠感、或者右上腹部的不舒服或轻微的疼痛。因此，与明显表现发病的情况相比，大部分通过血液检查进行肝功能检查或超声波检查中出现诊断出异常的情况多。
这种脂肪肝的治疗方法根据酒精、非酒精脂肪肝而不同。
由于酒精性脂肪肝是过量饮酒导致发病，因此，作为酒精性脂肪肝的治疗方法，首先通过生活习惯改善，从戒酒开始，掌握健康状态，持续进行管理。其次，除了戒或减少酒的方法以外，作为治疗剂使用抗氧化剂(维生素E、维生素B、C)。使用肝细胞保护剂即熊脱氧胆酸(urosodeoxycholic acid，UDCA)或水飞蓟素(silymarin)等护肝。
非酒精性脂肪肝的治疗方法，有改善生活习惯、手术治疗、药物疗法等。
脂肪肝患者的70～80％为肥胖，其余相当数的患者为超重。因此，减少体重来提高胰岛素敏感性，进而使脂肪肝好转，最近有只要减重大约5％左右，就改善胰岛素抵抗，肝功能数值好转的报告。因此，生活习惯的改善比什么都重要。
其次，过去不太使用肥胖手术疗法，但最近随着高度肥胖患者增加，在高度肥胖(体脂量指数>40Kg/m2)、或体脂量指数为35Kg/m2以上且伴随糖尿或高血压等危险因子的情况下，推荐手术疗法。手术包括：1)诱导早期饱腹感，减少食物摄入的手术(gastricbanding)；(2)将小肠迂回诱导吸收不良的手术(jejunoileal bypass)；3)为得到上述两种全部效果的手术(Roux-en-Y gastric bypass,bilopancreatic diversion)。
最后，药物疗法使用糖尿病治疗剂及胰导素抵抗改善药物，抗氧化剂及肝细胞保护剂、高血脂症治疗药物。使用糖尿病治疗剂及胰导素抵抗改善药物，增加葡萄糖受体，促进肌肉中糖的吸收，促进脂肪细胞的分化，减少肝内脂肪沉积，对脂肪肝及脂肪肝炎的治疗有效果。另外，为了减少脂肪肝疾病的发生机制之一的氧化应激，正在研究抗氧化剂使用，有报道称通过使用高血脂症治疗剂对相关脂肪肝有效能。
但是，实际情况是脂肪肝药物学治疗中有效的药物几乎不存在，推荐运动和饮食疗法。另外，使用上述药物时，反而有关于乳酸症、对肌肉的线粒体损伤、炎症、纤维化等多种副作用的报告。相对来说，脂肪肝在初期是可以通过饮食调节恢复的轻疾，但是持续长时间时，肝受损伤，肝有可能无法恢复，是可怕的疾病。因此，这种脂肪肝的药剂选择，应考虑短期及长期服用时均没有副作用。
鉴于上述情况，本申请人利用阳春砂(Amomum villosum Loureiro)提取物提出本发明，其没有副作用，长期服用也没有毒性，对预防、治疗改善脂肪肝有效果。
砂仁指生姜科(Zingiberaceae)所属的绿壳砂(Amomum villosum Loureirovar.xanthioides T.L.Wu et Senjen)或阳春砂(Amomum villosum Loureiro)的成熟的果实或种子的块，本发明中使用阳春砂的果实作为材料。
阳春砂主要产于中国福建、广东、广西、云南，绿壳砂主要产于柬埔寨、印度、老挝、缅甸、泰国、越南等中南半岛区域和中国的广西、云南的部分地区。(摘自中国植物志(Floraof China,v24:347-356.2000))。由于产地不同，古代将绿壳砂别称为“缩砂仁”。
另外，目前的情况是中国认证为正品但在韩国视为假货的海南砂(Amomumlongiligulare T.L.Wu)的果实也大量流通。但是，申等(SHEN Li WANG Yang JIANG Ku etal.Comparison of HPLC Fingerprints of Amomum villosum Lour.，Amomurn villosumLour.var.xanthioides T.L.Wu et Senjen and Amomum longiligulare T.L.Wu.中国药学杂志.2016:51(12)；1039-1043.)经RP-HPLC研究结果，表示3种砂仁在成分上显示高的类似度，但是海南砂和阳春砂的化学成分类似，相反绿壳砂与前两种有明显的差异，需要对其进行详细的药理和临床效能的比较。
脂肪肝被认为是肥胖、糖尿病等代谢疾病的前一阶段或征兆，脂肪肝的发生可用二次打击模型(two-hit working model)说明。肝的脂肪层相当于第一次打击，所述第一次打击产生的炎症、饱和脂肪酸等肝损伤导致的第二次打击使肝变成脆弱的状态。最近的研究中，利用诸如GRP78、CHOP、XBP-1的内质网应激标记物(ER stress marker)证明了内质网应激在这样的过程中为二次打击的主要原因，因此为了防止脂肪肝的恶化，研究减少内质网应激的方法变得重要。
对此，本研究为了证明阳春砂提取物的预防及改善脂肪肝的效能，利用由脂肪肝的化学性诱导因子——衣霉素(tunicamycin)引起内质网应激(Endoplasmic reticulum(ER)stress)的HepG2细胞和C57BL/6老鼠模型，在生物体外和生物体内，证明了阳春砂提取物的效能，从而完成了本发明。
另外，根据现有文献，大韩民国注册专利公报第10-1431610号记载有作为有效成分包含乌梅及紫草提取物的用于预防或治疗肥胖、异常血脂症、脂肪肝或糖尿的药剂学组成物，大韩民国注册专利公报第10-1206543号记载有含栗壳提取物的组成物对预防或治疗脂肪肝有效果。
但是，上述现有技术文献使用不同于阳春砂的其它天然物揭示效能，在这一点上区别于本发明。
发明内容
技术课题
本发明的技术课题是提供一种含有有效成分阳春砂提取物的用于预防及治疗改善脂肪肝的组成物。
本发明的技术课题是提供一种含有有效成分阳春砂提取物的预防及治疗改善脂肪肝的组成物，关于阳春砂提取物对基于内质网应激的脂肪肝生成的抑制效能及其机制，通过在生物体外和生物体内给药作为内质网应激诱导剂的衣霉素，确认了抑制内质网应激相关GRP78、CHOP基因表达、抑制脂肪合成相关SREBP-1的表达的脂肪肝预防效能。
课题解决方案
本发明提供一种含有有效成分阳春砂提取物的用于预防及治疗改善脂肪肝的组成物，从而解决技术课题。
本发明的用于预防及治疗改善脂肪肝的组成物，所述阳春砂提取物以老鼠经口给药基准含100～500mg/kg，从而解决技术课题。
本发明的用于预防及治疗改善脂肪肝的组成物，所述阳春砂提取物是用水提取的，从而解决技术课题。
本发明的用于预防及治疗改善脂肪肝的组成物，其特征在于，所述阳春砂提取物在HepG2细胞和老鼠中抑制基于衣霉素的脂肪生成，在老鼠中抑制内质网应激相关基因GRP78、CHOP的蛋白质及mRNA表达，抑制脂肪肝合成相关基因乙酰辅酶A羧化酶ACC(acetylCoA carboxylase)、脂肪酸合成酶FAS(fatty acid synthase)、固醇调节元件结合蛋白SREBP(sterol regulatory element binding protein)-1的蛋白质及mRNA表达，从而解决技术课题。
本发明的用于预防及治疗改善脂肪肝的组成物，所述阳春砂提取物对由内质网应激引起的脂肪肝的生成有抑制效果。
本发明的用于预防及改善改善脂肪肝及肝疾病的保健功能食品组成物，作为有效成分含有阳春砂提取物，从而解决技术课题。
发明效果
根据本发明的实验例，为了确认阳春砂提取物的预防及治疗改善脂肪肝的效能，在生物体外和生物体内确认了肝内脂肪蓄积抑制效能。
根据本发明的实验例，进行阳春砂提取物处理之后进行内质网应激诱导剂——衣霉素处理来确认的结果，在HepG2细胞及C57BL/6老鼠中有意义地抑制了基于衣霉素的TG含量的增加。另外，抑制内质网应激相关GRP78、CHOP基因表达，抑制脂肪合成相关SREBP-1的表达。
由此，证明了阳春砂提取物对由衣霉素诱导内质网应激及脂肪合成引起的脂肪肝生成的效能。据此，本发明人开发出基于阳春砂提取物的预防及治疗改善脂肪肝的效能组成物，完成了本发明。
附图说明
图1是通过本发明的实验例表示随浓度的阳春砂提取物细胞内毒性的图表。
图2是通过本发明的实验例表示随浓度的阳春砂提取物细胞内抑制TG生成的图表。
图3是通过本发明的实验例表示随浓度的阳春砂提取物对动物抑制TG生成的图表。
图4是通过本发明的实验例表示阳春砂提取物对由衣霉素引起的内质网应激相关基因表达的影响的图表。
图5是通过本发明的实验例表示阳春砂提取物对由衣霉素引起的脂肪合成相关基因表达的影响的图表。
具体实施方式
本说明书及权利要求书中使用的用语或词语不应限定解释为通常或词典上的意义，根据发明人为了用最优选的方法说明自己的发明可以适当定义用语的概念的原则，应解释为符合本发明的技术思想的意义和概念。
因此，本说明书中记载的实施例、参照例及附图中所述的事项不过是本发明的最优选的一例，不代表本发明的全部技术思想，因此应当理解在本申请提出的时刻，可能存在代替它们的多样的等同物和变形例。
实验例1.阳春砂提取物的脂肪肝生成抑制效能评价
1)试剂
药草阳春砂购于CoreSciences公司(首尔，韩国)。衣霉素购于Sigma-Aldrich(St.Louis，MO，美国)，抗葡萄糖调节蛋白(anti-glucose regulated protein 78)GRP78、同源蛋白(homolog protein)CHOP、抗x盒结合蛋白-1(anti-X-box-biding protein-1)XBP-1购于圣克鲁兹生物技术(Santa Cruz Biotechnology)(Santa Cruz，CA，美国)。细胞活力测定试剂(cell viability assay reagent)即EZ-cytoxy购于西格玛奥德里奇公司(Sigma-Aldrich)。
2)提取阳春砂的步骤
用水提取阳春砂得到提取物的步骤。根据设计条件，可以使用其它溶媒，根据提取溶媒的种类，可以不同地设计提取温度、提取时间、溶媒的量及残留成分处理方式等。提取溶媒也可以使用多样的溶媒，可提取的溶媒有水、乙醇、甲醇、脂油、甘油、马油、乙酸乙酯、丙酮、丁醇及异丙醇等。本发明中优选用水提取阳春砂。
3)细胞活力实验
为了评价肝疾病效能，人肝癌细胞株HepG2(Human hepatocellular carcinomacell line)购自美国菌种保藏中心ATCC(American Type Culture Collection)。(Manassas，VA，美国)。HepG2细胞在10％热灭活胎牛血清FBS(heat-inactivated fetalbovine serum)、用1％抗菌素(antibiotics)加强的杜尔贝科氏最低必需伊格尔氏培养基DMEM(Dulbecco's minimum Eagle's essential medium)中培养。
作为细胞活力测定试剂(Cell viability assay reagent)使用EZ-cytoxy。通过吸光度测量由四氮唑盐(Tetrazolium salt)生成的甲瓒(formazan)。为了解阳春砂提取物的细胞毒性，在HepG2细胞中利用作为细胞活力分析试剂的EZ-cytoxy确认了各浓度100、200、500、1000μg/ml的阳春砂提取物对细胞的毒性。
图1是通过本发明的实验例表示随浓度的阳春砂提取物的细胞内毒性的图表。
其结果，在1000μg/ml浓度下确认了50～60％的细胞生存率，在100～500μg/ml的浓度下未显出有意义的细胞毒性。由此确认了高浓度阳春砂提取物有毒性，据此，本发明中使用了100～500μg/ml的浓度。在本发明中，1000μg/ml以上浓度由于细胞毒性高而从实验中排除，实验组分为分别给药阳春砂提取物100、200、500μg/ml的3组。
4)阳春砂提取物的细胞内TG抑制效能评价
人体肝癌细胞株HepG2为肝细胞，为评价细胞内TG抑制效能而选择。HepG2细胞在10％在10％热灭活胎牛血清FBS、用1％抗菌素加强的杜尔贝科氏最低必需伊格尔氏培养基DMEM中培养。
为了调查阳春砂对由于内质网应激增加的甘油三酯TG的抑制效果，培养16小时HepG2细胞，培养液包括含各浓度100、200、500μg/ml的阳春砂提取物的组和对照组。3小时之后处理衣霉素(2μg/ml)，持续培养24小时。
为了测量培养后TG含量，HepG2细胞在体积比(v/v/v)8:4:3的氯仿-甲醇-水溶液(chlorofor-methanol-H2O solution)中均质化。在常温下培养1小时后，进行转速3000rpm的10分钟(min)圆心分离。去除上层液后，将沉淀物干燥24小时。在乙醇中溶解后，利用TG试剂盒(AM 157S-K与AM202-K，Asan Pharmaceutical,韩国)检查肝甘油三酯TG，标准化为蛋白质(protein)浓度。
图2是通过本发明的实验例表示随浓度的阳春砂提取物抑制细胞内TG生成的图表。
其结果，进行了衣霉素处理的组与对照组相比，甘油三酯TG的含量有意义地增加。但是，进行阳春砂提取物预处理的组中，浓度相关地抑制了由衣霉素引起的TG的增加。即在生物体外的TG分析结果，确认了阳春砂提取物在HepG2细胞中浓度相关地抑制由衣霉素诱发的TG水平的增加。通过这种结果，可知阳春砂提取物在HepG2细胞中具有减少细胞内TG水平的效果。
5)老鼠模型中阳春砂提取物对肝TG水平的效果
为了在生物体内模型中确认阳春砂提取物的生物体外对由内质网应激引起的甘油三酯蓄积抑制效果，向C57BL/6老鼠给药多种浓度的阳春砂提取物之后，给药衣霉素，并测量了蓄积于肝的甘油三酯的量。
动物为24～26g的C57BL/6老鼠(8周龄)购买于Central Lab.Animal Inc.公司(首尔，韩国)。老鼠随机地分为5组(n＝6)：非给药对照组(control group)，培养对照组(衣霉素单独处理组)，衣霉素和阳春砂提取物100mg/kg给药组，衣霉素和阳春砂提取物200mg/kg给药组，衣霉素和阳春砂提取物500mg/kg给药组。为了适应环境，利用三天在动物饲养室充分供给一般混合饲料和水。
阳春砂提取物经口给药7天。第7天以腹腔注射给药衣霉素(1mg/kg体重)24小时。动物实验得到圆光大学动物实验伦理委员会(Wonkwang University Animal ExperimentEthics Committee)的承认，实验室动物的使用和管理遵循机构指引。
按照下列步骤，从肝提取肝脂(Hepatic lipid)。肝组织(liver tissue)在体积比2：1的氯仿甲醇溶液中均质化，在常温培育一小时后，进行转速3000rpm的10分钟圆心分离。去除上层液之后，沉淀物干燥24小时。在乙醇中溶解后，肝甘油三酯TG利用TG试剂盒(AM157S-K和AM 202-K(Asan制药，韩国)检查，标准化为蛋白质浓度。
图3是通过本发明的实验例表示随浓度的阳春砂提取物抑制动物的TG生成的图表。
其结果，衣霉素组中，肝的TG含量与对照组相比增加2倍以上，但是进行了阳春砂提取物处理的组浓度相关地抑制了由衣霉素引起的肝内的脂肪蓄积。即，在生物体内实验中，对C57BL/6老鼠预处理阳春砂提取物并注射24小时衣霉素之后，测量肝TG水平来进行了确认，肝TG水平在衣霉素注射后显著增加。但是，阳春砂提取物浓度相关地减少了这种TG水平的增加。通过这种结果，在生物体内模型中也可以确认阳春砂提取物的甘油三酯蓄积抑制效果。
6)阳春砂提取物对由衣霉素引起的内质网应激相关基因表达产生的影响
本发明中为了确认基于阳春砂提取物的脂肪肝改善是否与内质网应激的减少有关，测量了内质网应激标志物相关基因GRP78、CHOP蛋白质和mRNA量。
为调查阳春砂提取物对内质网应激的抑制效果，向C57BL/6老鼠给药7天多种浓度的阳春砂提取物。然后，作为药物内质网应激诱导剂(pharmaceutical ER stressinducer)给药衣霉素，测量肝内与内质网应激相关的基因GRP78、CHOP蛋白质和mRNA量。
利用包含cDNA模板(template)、引物(primer)、SYBR Green PCR Master MIX的反应混合物和利用7500快速RT-PCR系统，测量实时PCR，总RNA是利用TRlzol(英杰公司(Invitrogen)，德国达姆施塔特)从实验鼠中分离。
另外，蛋白质(40μg per well)通过8％凝胶的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(sodium dodecyl sulfate-polyacrylamide gel electrophoresis)SDS-PAGE分离，用聚偏二氟乙烯(polyvinylidene difluoride)PVDF薄膜转移。封闭的薄膜与内质网应激的标志物78-kDa葡萄糖调节蛋白(GRP78；BiP)&C/EBP的同源蛋白(CHOP)的初级抗体一起培养。蛋白质使用增强化学发光蛋白印迹检测试剂盒(安玛西亚(Amersham)公司，瑞典乌普萨拉)检查。
图4是通过本发明的实验例表示阳春砂提取物对由衣霉素引起的内质网应激相关基因表达的影响的图表。
其结果，与衣霉素对照组相比，给药阳春砂提取物之后给药衣霉素的组之间，GRP78、CHOP蛋白质和mRNA的表达比对照组有意义地减少。这可以确认阳春砂提取物对肝细胞中药物内质网应激诱导剂的抑制效能。
7)阳春砂对由衣霉素引起的脂肪合成相关基因表达的影响
为了明确阳春砂提取物的肝保护效果的机制，调查阳春砂提取物对脂肪生成的效果。
即，为了确认阳春砂提取物对内质网应激诱发甘油三酯的抑制效果机制，向C57BL/6老鼠给药7天各浓度阳春砂提取物。然后，给药作为内质网应激诱导剂的衣霉素，测量了已知为与肝内脂肪合成相关基因的乙酰辅酶A羧化酶AC、脂肪酸合酶FAS、固醇调节元件结合蛋白SREBP-1表达量。
图5是通过本发明的实验例表示阳春砂提取物对由衣霉素引起的脂肪合成相关基因表达的影响的图表。
其结果，与衣霉素给药对照组相比，在阳春砂提取物给药组中，已知为诱导肝内脂肪合成的基因ACC和FAS mRNA有意义地减少。另外，对ACC和FAS的表达造成影响的已知为阳春砂转录因子的SREBP-1的表达比衣霉素给药对照组有意义地减少。
在先的研究中，已知内质网应激激活主要的脂肪形成转录因子SREBP-1，从而增加诸如ACC和FAS的致脂基因的表达。因此，可以确认阳春砂提取物抑制由内质网应激促进的SREBP-1的表达，进而抑制诸如FAS、ACC的致脂基因，从而改善脂肪肝。
8)统计处理
数据表示为平均数(S.E.M.)的平均数±标准差表示。统计上重要的差异点是通过单因素方差分析测量后进行邓肯多重范围检验。在统计分析中小于等于0.05的p值视为有意义。
9)考察
为了确认阳春砂提取物预防及治疗改善脂肪肝的效能，在生物体外和生物体内确认了甘油三酯蓄积抑制效能。
首先，在HepG2细胞，阳春砂提取物到浓度500μg/ml为止未出现毒性。因此，进行各浓度的阳春砂提取物处理之后进行内质网应激诱导剂——衣霉素处理来确认的结果，阳春砂提取物在HepG2细胞及C57BL/6老鼠有意义地抑制由衣霉素引起的TG含量的增加。
另外，抑制内质网应激相关GRP78、CHOP基因的表达，抑制脂肪合成相关SREBP-1的表达。由此，证明了阳春砂提取物对由衣霉素诱导内质网应激及脂肪合成引起的脂肪肝生成的效能。由此，本发明开发出阳春砂提取物的预防及治疗改善脂肪肝的效能组成物。
Claims (1)
1.一种用于预防或改善由内质网应激引起的脂肪肝生成的保健功能组成物，其特征在于，作为有效成分含有阳春砂提取物，所述阳春砂提取物是用水提取的，以老鼠经口给药基准含100～500mg/kg所述阳春砂提取物，所述阳春砂提取物在HepG2细胞和老鼠中抑制由衣霉素诱发的甘油三酯的生成，在老鼠中抑制内质网应激相关基因GRP78、CHOP的蛋白质及mRNA表达，抑制脂肪肝合成相关基因乙酰辅酶A羧化酶ACC、脂肪酸合酶FAS、固醇调节元件结合蛋白SREBP-1的蛋白质及mRNA表达。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170098490A KR101952648B1 (ko) | 2017-08-03 | 2017-08-03 | 양춘사 추출물을 함유하는 지방간 예방 및 치료 개선 조성물 |
| KR10-2017-0098490 | 2017-08-03 | ||
| PCT/KR2018/008718 WO2019027244A2 (ko) | 2017-08-03 | 2018-07-31 | 양춘사 추출물을 함유하는 지방간 예방 및 치료 개선 조성물 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110621327A true CN110621327A (zh) | 2019-12-27 |
Family
ID=65232953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880026613.9A Withdrawn CN110621327A (zh) | 2017-08-03 | 2018-07-31 | 含有阳春砂提取物的预防及治疗改善脂肪肝的组成物 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP3616705A4 (zh) |
| JP (1) | JP2020518664A (zh) |
| KR (1) | KR101952648B1 (zh) |
| CN (1) | CN110621327A (zh) |
| WO (1) | WO2019027244A2 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102643099B1 (ko) * | 2020-01-31 | 2024-03-05 | 주식회사 일원바이오 | 양춘사 및 백출 복합 추출물을 유효성분으로 함유하는 고지혈증 또는 동맥경화의 예방, 개선 또는 치료용 조성물 |
| KR20230114999A (ko) | 2022-01-26 | 2023-08-02 | 주식회사 일원바이오 | 양춘사 추출물을 유효성분으로 함유하는 대장염의 예방, 개선 또는 치료용 조성물 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101391079A (zh) * | 2008-11-06 | 2009-03-25 | 徐朝阳 | 治疗脂肪肝的中药 |
| CN102068648A (zh) * | 2009-11-20 | 2011-05-25 | 林绥 | 对酒精性肝损伤有辅助治疗作用的保健胶囊及其制备方法 |
| CN103735561A (zh) * | 2014-01-15 | 2014-04-23 | 蚌埠医学院 | 内质网应激诱导小鼠急性肝损伤模型的建立方法 |
| CN104689218A (zh) * | 2015-03-31 | 2015-06-10 | 周冠旻 | 一种治疗脂肪肝的中药组合物 |
| CN105435205A (zh) * | 2016-01-12 | 2016-03-30 | 济南超舜中药科技有限公司 | 一种治疗脂肪肝的中药汤剂及其制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001022934A2 (en) * | 1999-09-24 | 2001-04-05 | Yng Wong Quing Non | Delivery of small doses of ingestible treatments |
| CN101401918B (zh) * | 2008-11-06 | 2011-06-01 | 韩海林 | 一种治疗脂肪肝的中药组合物 |
| KR101206543B1 (ko) | 2009-01-29 | 2012-11-30 | 한국생명공학연구원 | 율피 추출물을 포함하는 지방간의 예방 또는 치료용 조성물 |
| CN102860516A (zh) * | 2012-10-22 | 2013-01-09 | 纪显玥 | 一种保肝健胃解酒中药保健食品及制备方法 |
| KR101431610B1 (ko) | 2013-01-30 | 2014-08-18 | 호서대학교 산학협력단 | 오매 및 자초 추출물을 유효성분으로 포함하는 비만, 이상지방혈증, 지방간 또는 당뇨의 예방 또는 치료용 약제학적 조성물 |
| CN104351610B (zh) * | 2014-10-23 | 2019-08-09 | 吉林省现代中药工程研究中心有限公司 | 一种抑制酒精吸收、促进酒精代谢的保健口服液及制备方法 |
| CN104397676A (zh) * | 2014-11-17 | 2015-03-11 | 威海桦众节能设备有限公司 | 一种解酒保肝护肝的保健食品 |
| CN104435977B (zh) * | 2014-11-18 | 2017-08-01 | 西双版纳傣族自治州民族医药研究所 | 一种用于治疗肝损伤的药物及其制备方法 |
| CN106139108A (zh) * | 2016-08-31 | 2016-11-23 | 梁小荣 | 防治荷兰侏儒兔膨胀病的中药制剂及制备方法 |
| KR101952644B1 (ko) * | 2017-09-21 | 2019-05-23 | 국가식품클러스터지원센터 | 양춘사 추출물을 함유하는 비만 예방, 개선 또는 치료 조성물 |
-
2017
- 2017-08-03 KR KR1020170098490A patent/KR101952648B1/ko active IP Right Grant
-
2018
- 2018-07-31 JP JP2020509412A patent/JP2020518664A/ja active Pending
- 2018-07-31 CN CN201880026613.9A patent/CN110621327A/zh not_active Withdrawn
- 2018-07-31 WO PCT/KR2018/008718 patent/WO2019027244A2/ko unknown
- 2018-07-31 EP EP18841028.6A patent/EP3616705A4/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101391079A (zh) * | 2008-11-06 | 2009-03-25 | 徐朝阳 | 治疗脂肪肝的中药 |
| CN102068648A (zh) * | 2009-11-20 | 2011-05-25 | 林绥 | 对酒精性肝损伤有辅助治疗作用的保健胶囊及其制备方法 |
| CN103735561A (zh) * | 2014-01-15 | 2014-04-23 | 蚌埠医学院 | 内质网应激诱导小鼠急性肝损伤模型的建立方法 |
| CN104689218A (zh) * | 2015-03-31 | 2015-06-10 | 周冠旻 | 一种治疗脂肪肝的中药组合物 |
| CN105435205A (zh) * | 2016-01-12 | 2016-03-30 | 济南超舜中药科技有限公司 | 一种治疗脂肪肝的中药汤剂及其制备方法 |
Non-Patent Citations (4)
| Title |
|---|
| LONGQUAN YU，等: "Effects of Some Chinese Spices on Body Weights, Plasma Lipids, Lipid Peroxides, and Liver Lipids in Mice", 《FOOD SCIENCE AND TECHNOLOGY RESEARCH》 * |
| SEONG,ROH JONG，等: "Comparison of Gangjihwan and Combination of Gangjihwan and Gamisochehwan in the Improvement Effects of Nonalcoholic Fatty Liver Disease in a High Fat Diet-Fed NAFLD Mouse Model", 《THE JOURNAL OF HERBAL FORMULA SCIENCE》 * |
| ZHANG, DANYAN，等: "Extraction, characterization and biological activities of polysaccharides from Amomum villosum", 《CARBOHYDRATE POLYMERS》 * |
| 陆山红，等: "砂仁的化学及药理研究进展 ", 《中药药理与临床》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019027244A3 (ko) | 2019-03-28 |
| EP3616705A2 (en) | 2020-03-04 |
| WO2019027244A2 (ko) | 2019-02-07 |
| JP2020518664A (ja) | 2020-06-25 |
| KR101952648B1 (ko) | 2019-02-27 |
| KR20190014700A (ko) | 2019-02-13 |
| EP3616705A4 (en) | 2020-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ho et al. | Anti-aging herbal medicine—how and why can they be used in aging-associated neurodegenerative diseases? | |
| Pirozzi et al. | Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD | |
| SHAFQAT ZAIDI et al. | Effect of Kalahari Cactus Extract on Appetitte, Body Weight And Lipid Profile In Cafeteria Diet Induced Obesity In Experimental Animal | |
| EP2206509B1 (en) | Method of producing aloe vera extract | |
| Yang et al. | ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract | |
| Huang et al. | Poria cocos water extract ameliorates the behavioral deficits induced by unpredictable chronic mild stress in rats by down-regulating inflammation | |
| Lin et al. | The chloroform extract of Cyclocarya paliurus attenuates high-fat diet induced non-alcoholic hepatic steatosis in Sprague Dawley rats | |
| Rondanelli et al. | A systematic review on the effects of botanicals on skeletal muscle health in order to prevent sarcopenia | |
| KR101952644B1 (ko) | 양춘사 추출물을 함유하는 비만 예방, 개선 또는 치료 조성물 | |
| Choi et al. | Combined treatment of Betulinic acid, a PTP1B inhibitor, with Orthosiphon stamineus extract decreases body weight in high-fat–fed mice | |
| Solikhah et al. | Effect of Muntingia calabura L. leaf extract on blood glucose levels and body weight of alloxan-induced diabetic mice | |
| EP2992933B1 (en) | Ginsenoside f2 for prophylaxis and treatment of liver disease | |
| Kim et al. | Anti-obesity effects of pectinase and cellulase enzyme‑treated Ecklonia cava extract in high‑fat diet‑fed C57BL/6N mice | |
| Patel et al. | Aphrodisiac activity of ethanolic extract of Pedalium murex Linn fruit | |
| Kobayashi et al. | Ternatin, a cyclic peptide isolated from mushroom, and its derivative suppress hyperglycemia and hepatic fatty acid synthesis in spontaneously diabetic KK-Ay mice | |
| CN110621327A (zh) | 含有阳春砂提取物的预防及治疗改善脂肪肝的组成物 | |
| Ambadasu et al. | Effect of Caralluma fimbriata extract on appetite and lipid profile in rats fed with hypercalorie/cafeteria diet. | |
| Choi et al. | Anti‐aging effects of Schisandrae chinensis Fructus extract: improvement of insulin sensitivity and muscle function in aged mice | |
| Lee et al. | Anti-inflammatory effects of Allium cepa L. peel extracts via inhibition of JAK-STAT pathway in LPS-stimulated RAW264. 7 cells | |
| Moreno et al. | Inhibition of lipid metabolic enzymes using Mangifera indica extracts | |
| Rouag et al. | The effect of oral gavage (force-feeding) administration of fenugreek seeds (Trigonella foenum-graecum L.) on biochemical and neurobehavioural parameters in male Wistar rats | |
| Lee et al. | Licorice extract suppresses adipogenesis through regulation of mitotic clonal expansion and adenosine monophosphate‐activated protein kinase in 3T3‐L1 cells | |
| Park et al. | Dioscorea nipponica extracts enhance recovery from skeletal muscle atrophy by suppressing NF-κB expression | |
| KR20040062832A (ko) | 비만 치료 또는 예방용 및, 비만과 관련된 유전자,단백질, 세포 발현 조절용 한약 추출물을 포함하는약제학적 조성물 | |
| CN106822095A (zh) | 一种防治脂肪肝和肥胖的药物及其在制药中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20191227 |
|
| WW01 | Invention patent application withdrawn after publication |