IT202100007721A1 - Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attività statino-simile - Google Patents
Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attività statino-simile Download PDFInfo
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- IT202100007721A1 IT202100007721A1 IT102021000007721A IT202100007721A IT202100007721A1 IT 202100007721 A1 IT202100007721 A1 IT 202100007721A1 IT 102021000007721 A IT102021000007721 A IT 102021000007721A IT 202100007721 A IT202100007721 A IT 202100007721A IT 202100007721 A1 IT202100007721 A1 IT 202100007721A1
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- cholesterol
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- statin
- plant extracts
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- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 title claims description 12
- 230000000694 effects Effects 0.000 title claims description 12
- 239000000203 mixture Substances 0.000 title claims description 9
- 238000009472 formulation Methods 0.000 title claims description 7
- 239000000419 plant extract Substances 0.000 title claims description 6
- 210000002966 serum Anatomy 0.000 title claims description 4
- 102100029108 Elongation factor 1-alpha 2 Human genes 0.000 title description 4
- 101000841231 Homo sapiens Elongation factor 1-alpha 2 Proteins 0.000 title description 4
- 241000468081 Citrus bergamia Species 0.000 claims description 7
- 244000175448 Citrus madurensis Species 0.000 claims description 5
- 235000017316 Fortunella japonica Nutrition 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 9
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 9
- 241000196324 Embryophyta Species 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 235000010672 Monarda didyma Nutrition 0.000 description 5
- 244000003027 Bergamotto Species 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-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[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 3
- 241001672694 Citrus reticulata Species 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 150000002215 flavonoids Chemical class 0.000 description 3
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH 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)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 235000013628 Lantana involucrata Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000006677 Monarda citriodora ssp. austromontana Nutrition 0.000 description 1
- 244000179970 Monarda didyma Species 0.000 description 1
- 240000007673 Origanum vulgare Species 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SHCWOSSXLGIQEQ-UHFFFAOYSA-N brutieridin Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC(=O)CC(C)(O)CC(O)=O)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 SHCWOSSXLGIQEQ-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000031154 cholesterol homeostasis Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
Description
Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attivit? statino-simile
Campo tecnico dell?invenzione
La presente invenzione riguarda una formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attivit? statino-simile al fine di trattare livelli sierici elevati di colesterolo.
Stato dell?arte
Elevati livelli di colesterolo totale, colesterolo LDL e trigliceridi sono associati ad aterosclerosi e patologie delle coronarie. L?approccio terapeutico prevede l?uso di farmaci detti ?statine?, le quali comportano per? una serie di effetti collaterali. Il bergamotto (Citrus bergamia ) ? in grado di esercitare azione ipocolesterolemizzante, probabilmente dovuta ai flavonoidi in esso contenuti ( 2016). I flavonoidi glicosidici presenti nel succo di bergamotto, infatti, brutieridina e melitidina, sono noti per le loro propriet? ipocolesterolemizzanti ( , 2018). Miceli e collaboratori (2007), hanno dimostrato che la somministrazione di Citrus bergamia Risso & Poit (1ml/animale/giorno) comporta una diminuzione dei livelli sierici di colesterolo totale, colesterolo LDL e trigliceridi; di contro aumenta il valore del colesterolo ?buono? HDL ( , 2007). Il protocollo ? stato adattato da Sigma-Aldrich e da riferimenti bibliografici di letteratura ( 2015).
Valutazione dell?inbizione dell?attivit? dell?enzima HMGR
Al fine di valutare l?inibizione dell?attivit? dell?enzima HMGR, ? stato adattato una procedura sperimentale dal kit Sigma-Aldrich ( ). Il test ? stato condotto in vitro secondo protocolli validati dalla letteratura scientifica ( 2015). L?ossidazione dell?NADPH ? stata valutata spettrofotometricamente utilizzando l?HMG-CoA come substrato e l?HMGR come enzima di reazione.
Il 3-idrossi-3-metilglutaril-CoA reduttasi (HMGR) ? una glicoproteina transmembrana, localizzata nel reticolo endoplasmatico. Questo enzima catalizza la riduzione a quattro elettroni di HMG-CoA a coenzima A e mevalonato, la fase limitante il tasso di biosintesi degli steroli. L'attivit? di HMGR ? controllata attraverso sintesi, degradazione e fosforilazione al fine di mantenere la concentrazione dei prodotti derivati dal mevalonato. Oltre alla regolazione fisiologica dell'HMGR, l'enzima umano ? stato preso di mira con successo dai farmaci nel trattamento clinico dei livelli sierici elevati di colesterolo. Il controllo dei livelli sierici di colesterolo ha un importante ruolo terapeutico in quanto l'ipercolesterolemia porta spesso allo sviluppo di aterosclerosi e di conseguenza a patologie cardiovascolari, che potrebbero provocare infarto miocardico e ictus. Prove recenti suggeriscono che un disturbo dell'omeostasi del colesterolo contribuisce allo sviluppo di uno stato infiammatorio cronico.
Un?aliquota di Assay Buffer, NADPH, substrato HMG-CoA ed enzima HMGR sono stati miscelati in una micropiastra da 96 pozzetti, ed ? stata valutata l?assorbanza a 340 nm a 37?C dopo 10 minuti. La pravastatina, nota statina, ? stata utilizzata come controllo positivo. Le percentuali di inibizione sono state calcolate come segue:
Dove
A+ = campione con enzima e substrato
A-= campione con enzima e non substrato
C = controllo
Utilizzando l?Assay Kit HMGR della abbiamo valutato l?attivit? statino-simile di alcuni estratti vegetali, i quali contenuti di flavonoidi e polifenoli, andavano a mimare l?azione delle statine. Per ricercare le piante adatte allo studio, ? stata effettuata inizialmente una ricerca bibliografica di piante presenti sul territorio calabrese e poi messa a punto del protocollo per standardizzarne il metodo. Dopo aver valutato l?azione sinergica di Bergamotto e Origano, il Bergamotto ? stato valutato insieme al Mandarino cinese, calcolandone le percentuali di inibizione:
? %I Bergamotto (Citrus bergamia Risso & Poit) = 18%
? %I Mandarino cinese (Fortunella japonica L.) = 17%
Le concentrazioni testate di entrambe le piante sono state di 150 ?g/ml. Successivamente sono stati testati i mix delle due piante, per valutarne l?attivit? sinergica, il rapporto 80/20 ha evidenziato sinergismo d?azione:
? %I Bergamotto-Mandarino cinese 80/20 = 56%
Il sinergismo si ottiene quando, dall?interazione tra due piante, otteniamo una somma degli effetti, cio? un effetto maggiore rispetto agli effetti della singola pianta.
Claims (2)
1. Formulazione a base di estratti di piante comprendente estratti di Citrus bergamia Risso & Poit. e di Fortunella japonica caratterizzata dal fatto che detta formulazione prevede una miscela 80/20, cio? con 80% di Citrus bergamia . e 20% di Fortunella japonica L
2. Formulazione a base di estratti di piante comprendente estratti di Citrus bergamia . e di Fortunella japonica per uso atto a limitare i livelli sierici di colesterolo e loro attivit? statino-simile caratterizzata dal fatto che detta formulazione prevede una miscela 80/20, cio? con 80% di Citrus bergamia e 20% di Fortunella japonica L
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| IT102021000007721A IT202100007721A1 (it) | 2021-03-29 | 2021-03-29 | Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attività statino-simile |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT102021000007721A IT202100007721A1 (it) | 2021-03-29 | 2021-03-29 | Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attività statino-simile |
Publications (1)
| Publication Number | Publication Date |
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| IT202100007721A1 true IT202100007721A1 (it) | 2022-09-29 |
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|---|---|---|---|
| IT102021000007721A IT202100007721A1 (it) | 2021-03-29 | 2021-03-29 | Formulazione a base di estratti vegetali e suo uso per limitare i livelli sierici di colesterolo e loro attività statino-simile |
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| IT (1) | IT202100007721A1 (it) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002326947A (ja) * | 2002-03-11 | 2002-11-15 | Kao Corp | 脂肪分解促進剤 |
| JP2008253256A (ja) * | 2007-03-14 | 2008-10-23 | Nagaoka Koryo Kk | ポリフェノール類の重合体、並びにこれを含有した抗酸化剤およびリパーゼ阻害剤 |
| CN104815138A (zh) * | 2015-05-01 | 2015-08-05 | 温州高新技术产业开发区聚智汇科技信息咨询服务中心 | 一种枳实提取物、制剂及用途 |
| CN108066549A (zh) * | 2016-11-18 | 2018-05-25 | 江倩倩 | 一种治疗内分泌失调的药物 |
| EP3903801A1 (en) * | 2020-04-23 | 2021-11-03 | Naturextralab S.r.l. | Formulation comprising citrus bergamia l. and fortunella japonica extracts and its use to limit pancreatic lipase |
-
2021
- 2021-03-29 IT IT102021000007721A patent/IT202100007721A1/it unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002326947A (ja) * | 2002-03-11 | 2002-11-15 | Kao Corp | 脂肪分解促進剤 |
| JP2008253256A (ja) * | 2007-03-14 | 2008-10-23 | Nagaoka Koryo Kk | ポリフェノール類の重合体、並びにこれを含有した抗酸化剤およびリパーゼ阻害剤 |
| CN104815138A (zh) * | 2015-05-01 | 2015-08-05 | 温州高新技术产业开发区聚智汇科技信息咨询服务中心 | 一种枳实提取物、制剂及用途 |
| CN108066549A (zh) * | 2016-11-18 | 2018-05-25 | 江倩倩 | 一种治疗内分泌失调的药物 |
| EP3903801A1 (en) * | 2020-04-23 | 2021-11-03 | Naturextralab S.r.l. | Formulation comprising citrus bergamia l. and fortunella japonica extracts and its use to limit pancreatic lipase |
Non-Patent Citations (11)
| Title |
|---|
| BASKARAN G.SALVAMANI S.AHMAD S. A.SHAHARUDDIN NO. A.PATTIRAM P. DSHUKOR M.Y.: "HMG-CoA reductase inhibitor activity and phytocomponent investigation of Basella alba leaf extract treatment for hypercholesterolaemia", DRUG DESIGN, DEVELOPMENT AND THERAPHY, vol. 9, 2015, pages 509 - 517 |
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| LAMIQUIZ-MONEO ITZIAR ET AL: "Effect of bergamot on lipid profile in humans: A systematic review", CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, vol. 60, no. 18, 10 October 2020 (2020-10-10), XP002804791 * |
| LEONARDO DI DONNA ET AL: "Hypocholesterolaemic activity of 3-hydroxy-3-methyl-glutaryl flavanones enriched fraction from bergamot fruit (Citrus bergamia): In vivo studies", JOURNAL OF FUNCTIONAL FOODS, vol. 7, 1 February 2014 (2014-02-01), NL, pages 558 - 568, XP055194428, ISSN: 1756-4646, DOI: 10.1016/j.jff.2013.12.029 * |
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