Elderberry extract

Abstract

The present invention relates to a product containing elderberry extract and a potentiator selected from pepper extract, ginger extract, curcuma extract and citrus plant extract.

Description

[0001] Elderberry extract

[0002] Description

[0003] The invention relates to the field of dietary supplements. In particular, the invention relates to a product containing an elderberry extract and an effect enhancer. The invention further relates to the use of at least one extract selected from a pepper extract, a ginger extract, a turmeric extract, and a citrus plant extract to enhance the effect of an elderberry extract. Finally, the invention relates to the use of a product according to the invention for improving lipid metabolism and to a product according to the invention for the prevention and / or treatment of arteriosclerosis.

[0004] Atherosclerosis, the deposition of fatty and / or fibrous material in the intima of the arteries, is the main cause of vascular disease. One cause of cholesterol deposition in the arteries is the accumulation of cholesterol in macrophages. Lipid-laden macrophages—so-called foam cells—are found in early atherosclerotic lesions, the so-called "fatty streaks," and are involved in disease progression because they lack negative feedback regulation of cholesterol uptake. This leads to cellular lipid overload, which ultimately leads to apoptotic cell death, accompanied by the release of atherogenic and inflammatory components into the atheroma, which promote both plaque growth and rupture.

[0005] One therapeutic approach to reduce intimal cholesterol deposition is to increase reverse cholesterol transport (RCT) from macrophage foam cells to the liver, allowing cholesterol to be excreted via bile and feces, thereby preventing or even reversing atherogenesis. In this context, cholesterol efflux from macrophages to apolipoprotein (apo)AI and HDL molecules is the first step in atheroprotective RCT. Indeed, a high cholesterol efflux capacity of human sera correlates with reduced intima-media thickness and a lower incidence of cardiovascular events.

[0006] At the molecular level, cholesterol efflux from macrophages is initiated by the transfer of cholesterol to apoA-I and HDL particles via the ATP-binding cassette (ABC) transporters ABCA1, ABCG1, and the scavenger receptor class B type 1 (SR-BI). While ABCA1 transfers cholesterol to lipid-poor HDL, ABCG1 and SR-BI prefer lipid-rich HDL. In macrophage foam cells, ABCA1 is considered the quantitatively most important transporter for cholesterol efflux.

[0007] Products that promote health are desirable, in particular by improving lipid metabolism and preventing or at least reducing the release of atherogenic and inflammatory components into the atheroma.

[0008] Against this background, the present invention aims to provide improved products and dietary supplements. In particular, the products and dietary supplements are intended to help improve lipid metabolism and / or prevent or treat arteriosclerosis.

[0009] According to the invention, this object is achieved by a product containing an elderberry extract and an effect enhancer. The effect enhancer is selected from a pepper extract, a ginger extract, a turmeric extract, and a citrus plant extract. In other words, according to the invention, the object is achieved by a product containing an elderberry extract and at least one extract selected from a pepper extract, a ginger extract, a turmeric extract, and a citrus plant extract.

[0010] The inventors have found that an elderberry extract increases ABCAl expression in macrophages and reduces foam cell formation without impairing hepatic lipogenesis. The inventors have further found that the effect of the elderberry extract can be enhanced by a pepper extract, a ginger extract, a turmeric extract, and / or a citrus plant extract.

[0011] Elderberry extract is an extract from the elderberry (Sambucus nigra). Elderberry extract is preferably an aqueous extract of at least one component selected from elderberry flowers and leaves.

[0012] The pepper extract is an extract from pepper (Piper nigrum), preferably piperine.

[0013] Ginger extract is an extract from ginger (Zingiber officinale), preferably from the rhizome of ginger.

[0014] The turmeric extract comprises a curcumin compound. The turmeric extract is preferably a curcumin compound, more preferably a curcumin-cyclodextrin complex, most preferably a curcumin-gamma-cyclodextrin complex.

[0015] The citrus plant extract is an extract from a citrus plant, preferably from a citrus fruit. Examples of a citrus plant are Citrus aurantium var. amara L., Citrus sinensis, and Citrus paradisi. The citrus plant extract is preferably an aqueous extract from a citrus fruit. For example, the extract can be obtained from dried citrus fruits including peel using water and heat.

[0016] Extraction processes for producing extracts from plant material using extraction agents are generally known to those skilled in the art.

[0017] The term "product" preferably represents a man-made composition.

[0018] The verbs "contain" and "comprise" and their conjugations also include the verb "consist of" and its conjugations.

[0019] Preferred embodiments of the invention can be combined with one another, unless the context indicates otherwise. Preferred embodiments are also specified in the claims. In a preferred embodiment, the product is selected from a solution, an emulsion, a suspension, a powder, a granulate, a capsule, a pastille, a tablet, a coated tablet, and a syrup.

[0020] In a preferred embodiment, the product contains a pepper extract, preferably 4 mg to 200 mg of pepper extract per 100 g of the product.

[0021] In a preferred embodiment, the product contains a ginger extract, preferably 4 mg to 200 mg ginger extract per 100 g of the product.

[0022] In a preferred embodiment, the product contains a turmeric extract, preferably 0.25 mg to 2 g of a turmeric extract per 100 g of the product.

[0023] In a preferred embodiment, the product contains a citrus plant extract.

[0024] A pepper extract, a ginger extract, a turmeric extract and a citrus plant extract can, individually or in combination, enhance the effect of the elderberry extract.

[0025] In a preferred embodiment, the product contains the pepper extract, the ginger extract and the turmeric extract, preferably in the respective preferred amount ranges.

[0026] In a preferred embodiment, the product contains 4 mg to 200 mg of pepper extract, 0.25 mg to 2 g of turmeric extract, 4 mg to 200 mg of ginger extract per 100 g of the product.

[0027] Preferably, the product is suitable for oral administration, in particular for oral administration by humans. This also means that the product contains essentially no alcoholic solvent (e.g., methanol, ethanol, propanol, butanol) and / or no organic solvent (< 5% w / w, more preferably < 1% w / w). In other words, the product contains a total of < 5% w / w, more preferably < 1% w / w, of alcohols and organic solvents. Preferably, the elderberry extract is produced by extraction with an aqueous solvent. The extraction can be carried out using heat or as a cold extraction.

[0028] Preferably, the elderberry extract is an extract of at least one component of the elderberry selected from flowers and leaves.

[0029] In a preferred embodiment, the product is a dietary supplement.

[0030] In a preferred embodiment, the product is a product for the prevention and / or treatment of arteriosclerosis.

[0031] A further object of the present invention is to provide a use for at least one extract selected from a pepper extract, a ginger extract, a turmeric extract and a citrus plant extract.

[0032] The object is achieved by using at least one extract selected from a pepper extract, a ginger extract, a turmeric extract and a citrus plant extract to enhance the effect of an elderberry extract.

[0033] A further object of the present invention is to provide a use for the product.

[0034] The task is solved by using the product to improve fat metabolism.

[0035] The invention is further explained below using an example.

[0036] Figure 1 shows the effect of elderberry extract alone and in combination with enhancers. Figure 1 shows the significant upregulation of ABCA1 gene expression in human macrophages by elderberry extract in combination with an enhancer mixture (Figure 1A) or a citrus plant extract (Figure 1B). Since ABCA1 is considered the quantitatively most important transporter for cholesterol efflux in macrophage foam cells, it can be concluded that products according to the invention are health-promoting, improve lipid metabolism, and prevent or at least reduce the release of atherogenic and inflammatory components into the atheroma.

[0037] Conducting the cell experiment

[0038] Human THP-1 monocytes differentiated into macrophages were treated for 24 hours with i) no extract or with 250 pg / ml elderberry extract (cold-extracted elderflower) in reduced-serum medium, ii) alone or in combination with iii) an enhancing mixture (2 pg / ml pepper extract, 15 pg / ml ginger extract, and 4 pg / ml turmeric extract), or iv) an aqueous citrus plant extract containing 424 pM total flavonoids (total flavonoids formed from the flavonoids narirutin, naringin, naringenin 7-O-glucoside, hesperidin, neohesperidin, hesperetin 7-O-glucoside, naringenin, and hesperetin). TO901317 (10 pM), a pharmacological activator of ABCA1 expression, served as a reference.

[0039] After 24 hours of cell treatment, RNA was extracted and analyzed for ABCAl expression using RT-qPCR. The results are shown in Fig. 1. Data were obtained from two independent experiments, each performed in duplicate. Statistics were performed using a one-way ANOVA with multiple comparisons (1) all versus control and (2) all versus elderflower 250 pg / ml. Significant p-values ​​are indicated by * (< 0.05), ** (< 0.01), *** (< 0.001), or **** (< 0.0001); a * directly above a bar indicates significance versus control, while a * combined with a line indicates significance versus elderflower 250 pg / ml.

[0040] Production of elderberry extract

[0041] The aqueous extract was prepared from elderflowers and leaves. For cold extraction, the plant parts were dried (50°C, 18 h) and ground.

[0042] 5 g of this was dissolved in 30 mL of double-distilled water at room temperature, shaken, and sonicated for 30 min. After shaking, the samples were incubated for 2 hours at room temperature in an overhead shaker and centrifuged (3157 xg, 10 min, RT). The supernatant was collected, the residue was rinsed with water, shaken and centrifuged, and both supernatants were combined. The final volume of the plant extract was 50 mL. Aliquots of the extracts were stored at -80°C until further use. A hot extract can be prepared accordingly, for example, using 70°C water as the solvent, without sonication, and shaking overhead for 10 minutes.

[0043] Cell culture

[0044] Human THP-1 monocytes (ATCC®: TIB-202TM) were cultured in RPMI 1640 with 2 mM L-glutamine, 1 mM sodium pyruvate, 10 mM HEPES, 4.5 g / L glucose, 1.5 g / L NaHCCH, 10% FBS, 1% P / S (PAN Biotech), and 50 pM sterile-filtered ß-mercaptoethanol (Sigma Aldrich, Saint Louis, MO, USA). For subculturing, cells were pelleted by centrifugation (120 xg, 7 min) and resuspended in fresh medium. For the experiments, differentiation into macrophages was induced by adding 50 ng / ml phorbol 12-myristate 13-acetate (PMA; Sigma Aldrich) for 48 hours.

[0045] Gene expression analysis

[0046] On day 0, 2.75 x 10 6 THP-l cells were seeded in 6-well plates (Greiner Bio-One GmbH). On day 2, the cells were washed once with PBS+ / + (containing Ca and Mg; PAN Biotech GmbH) and appropriate extracts or TO901317 (10 pM) in serum-reduced medium (1% FBS) were added.

[0047] After 24 hours of incubation, RNA was isolated using the RNeasy® Plus Mini Kit from QIAGEN (Hilden, Germany). RNA isolation was followed by cDNA synthesis using the iScript™ cDNA Synthesis Kit from Bio Rad Laboratories (Hercules, CA, US).

[0048] Reverse transcription qPCR (RT-qPCR) was performed using a singleplex assay with iQ™ SYBR® Green Supermix (Bio-Rad Laboratories). Gene expression was analyzed according to standard protocols. Gene expression was normalized to the average expression level of two housekeeping genes (RPL5 and GAPDH for THP-1 cells).

Claims

Claims 1. Product containing an elderberry extract, characterized in that the product contains an effect enhancer selected from a pepper extract, a ginger extract, a turmeric extract and a citrus plant extract.

2. Product at least according to claim 1 or at least according to the preamble of claim 1, characterized in that the product contains a pepper extract.

3. Product according to at least one of the preceding claims, characterized in that the product contains a ginger extract.

4. Product according to at least one of the preceding claims, characterized in that the product contains a turmeric extract.

5. Product according to at least one of the preceding claims, characterized in that the product contains a citrus plant extract.

6. Product according to at least one of the preceding claims, characterized in that the product is suitable for oral administration.

7. Product according to at least one of the preceding claims, characterized in that the product is a food supplement.

8. Product according to at least one of the preceding claims, characterized in that the elderberry extract is prepared by extraction with an aqueous solvent.

9. Product according to at least one of the preceding claims, characterized in that the product contains, per 100 g of the product, one or more ingredients selected from 4 mg to 200 mg of pepper extract, 4 mg to 200 mg of ginger extract and 0.25 mg to 2 g of turmeric extract.

10. Product according to at least one of the preceding claims, characterized in that the product contains the pepper extract, the ginger extract and the turmeric extract.

11. Product according to at least one of the preceding claims, characterized in that the product contains 4 mg to 200 mg of pepper extract, 4 mg to 200 mg of ginger extract and 0.25 mg to 2 g of a turmeric extract per 100 g of the product.

12. Product according to at least one of the preceding claims, characterized in that the elderberry extract is an extract of at least one component of the elderberry selected from flowers and leaves.

13. Use of at least one extract selected from a pepper extract, a ginger extract, a turmeric extract and a citrus plant extract to enhance the effect of an elderberry extract.

14. Use of a product according to any one of claims 1-12 for improving lipid metabolism.

15. Product according to any one of claims 1-12 for the prevention and / or treatment of arteriosclerosis.

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