Elderberry extract

Abstract

The present invention relates to a product containing an elderberry extract and an effect enhancer selected from a pepper extract, a ginger extract, a turmeric extract and a citrus plant extract.

Description

The invention relates to the field of food supplements. More particularly, the invention relates to a product containing a Holunder extract and an enhancer. The invention further relates to the use of at least one extract selected from a pepper extract, an ginger extract, a kuruma extract and a citrus plant extract for enhancing the effect of a holunder extract. Finally, the invention relates to the use of a product according to the invention for improving fat metabolism and to a product according to the invention for preventing and / or treating atherosclerosis.Atherosclerosis, the deposition of fatty and / or fibrous material in the atrium of the arteries, is the major cause of vascular disease. One cause of the deposition of cholesterol in the arteries is the accumulation of cholesterol in macrophages. Lipid-loaded macrophages - so-called foam cells - are already found in early atherosclerotic lesions, the so-called "fatty stretches", and are involved in the progression of the disease, since they lack a negative feedback regulation of cholesterol uptake. This results in cellular lipid overload, ultimately leading to apoptotic cell death, accompanied by the release into the atheroma of atherogenic and inflammatory components promoting both plaque growth and rupture.A therapeutic approach to reducing intimal cholesterol deposition is to increase reverse cholesterol transport (RCT) from macrophage foam cells to the liver to allow cholesterol to be excreted via bile and faeces, thereby preventing or even reversing atherogenesis. In this context, cholesterol efflux from macrophages to apolipoprotein (apo)A-I and HDL molecules is the first step of the atherosclerosis-protective RCT. Indeed, high cholesterol efflux capacity of human sera correlates with reduced intimal media thickness and lower incidence of cardiovascular events.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 überträgt cholesterol to low lipid HDL, ABCG1and SR-BI prefer lipid rich HDL. In macrophage foam cells, ABCA1 is considered to be the quantitatively most important transporter for cholesterol efflux.Products which are health-promoting are desirable, especially by improving fat metabolism and preventing or at least reducing the release of atherogenic and inflammatory components into the atheroma.Against this background, the present invention is based on the object of providing improved products and food supplements. In particular, the products and food supplements should help improve fat metabolism and / or prevent or treat atherosclerosis.According to the invention, this object is achieved by a product containing a Holunder extract and an action enhancer. The action enhancer is selected from a pepper extract, an ginger extract, a kurkuma extract and a citrus plant extract. In other words, according to the invention, the object is achieved by a product containing a Holunder extract and at least one extract selected from a pepper extract, an ginger extract, a kuruma extract and a citrus plant extract.The inventors have found that a Holunder extract increases ABCA1expression in macrophages and reduces foam cell formation without affecting hepatic lipogenesis. The inventors have further found that the effect of the elder extract can be enhanced by a pepper extract, an ginger extract, a kurkuma extract and / or a citrus plant extract.The Holunder extract is an extract from the Holunder (Sambucus nigra). The Holunder extract is preferably an aqueous extract of at least one selected from flowers and leaves of the Holunder.The pepper extract is an extract from the pepper (Piper nigrum), preferably piperine.The ginger extract is an extract from the ginger (Zingiber officinale), preferably from the rhizome of the ginger.The curcumin extract comprises a curcumin compound. Preferably, the curcumin extract is a curcumin compound, particularly preferably a curcumin-cyclodextrin complex, most particularly preferably a curcumin-gamma-cyclodextrin complex.The citrus plant extract is an extract from a citrus plant, preferably from a citrus fruit. Examples of citrus plants 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 recovered from dried citrus fruits including the peel using water and heat.Extraction methods for the preparation of an extract from vegetable material using extractants are generally known to the skilled person.The term "article of manufacture" preferably represents a composition produced by humans.The verbs "contain" and "comprise" and their conjugation also include the verb "consist of" and its conjugations.Preferred embodiments of the invention may be combined with each other as long as the context does not suggest otherwise. Preferred embodiments are also set forth 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 troche, a tablet, a dragee and a syrup.In a preferred embodiment, the product contains a pepper extract, preferably 4 mg to 200 mg pepper extract per 100 g of the product.In a preferred embodiment, the product contains an ginger extract, preferably 4 mg to 200 mg of ginger extract per 100 g of the product.In a preferred embodiment, the product contains an herbal extract, preferably 0.25 mg to 2 g of an herbal extract per 100 g of the product.In a preferred embodiment, the product contains a citrus plant extract.A pepper extract, an ginger extract, a kuruma extract and a citrus plant extract may, individually or in combination, enhance the effect of the elderberry extract.In a preferred embodiment, the product contains the pepper extract, the ginger extract and the kuruma extract, preferably in the respectively preferred quantity ranges.In a preferred embodiment, the product contains 4 mg to 200 mg of the pepper extract, 0.25 mg to 2 g of the kuruma extract, 4 mg to 200 mg of the ginger extract per 100 g of the product.Preferably, the product is suitable for oral ingestion, particularly human oral ingestion. This also means that the product contains essentially no alcoholic solvent (e.g. methanol, ethanol, propanol, butanol) and / or no organic solvent (<5% by weight, more preferably <1% by weight). In other words, the product contains a total of <5% by weight, more preferably <1% by weight, of alcohols and organic solvents.Preferably, the Holunder extract is prepared by extraction with an aqueous solvent. The extraction can be carried out using heat or as cold extraction.Preferably, the pollen extract is an extract of at least one component of the pollen selected from flowers and leaves.In a preferred embodiment, the product is a food supplement.In a preferred embodiment, the product is a product for the prevention and / or treatment of atherosclerosis.A further object of the present invention is to specify a use for at least one extract selected from a pepper extract, an ginger extract, a kuruma extract and a citrus plant extract.The object is achieved by the use of at least one extract selected from a pepper extract, an ginger extract, a kurkuma extract and a citrus plant extract for enhancing the effect of a holunder extract.Another object of the present invention is to provide a use for the product.The object is achieved by using the product to improve fat metabolism.The invention is explained in more detail below with the aid of an example.In this connection, FIG. 1 shows the effect of the Holunder extract alone and in combination with effect enhancers. Figure 1 shows the significant upregulation of ABCA1 gene expression in human macrophages by a Holunder extract in combination with an enhancer mixture (Figure 1A) or a citrus plant extract (Figure 1B).Since in macrophage foam cells ABCA1 is considered to be the quantitatively most important transporter for cholesterol efflux, it can be concluded that products of the invention are health promoting, improve lipid metabolism and prevent or at least reduce the release of atherogenic and inflammatory components into the atherosclerosis.Performing the Cell ExperimentHuman THP-1 monocytes differentiated into macrophages were treated for 24 hours i) without extract or with 250 μg / ml of Holunderextract (cold extracted Holunderbluts) in serum-reduced medium ii) alone or in combination with iii) of an action enhancer mixture (2 μg / ml of pepper extract, 15 μg / ml of ginger extract and 4 μg / ml of kurkumaextract) or iv) of an aqueous citrus plant extract with 424 μM total flavonoids (total flavonoids formed from the flavonoids narrutin, naringin, naringin-7-O-glucoside, hesperidin, neohesperidin, hesperetine-7-O-glucoside, Naringenin and hesperetine). TO901317 (10 μM), a pharmacological activator of the expression of ABCA1, served as reference.After 24 hours of cell treatment, the RNA was extracted and analyzed for ABCA1 expression by means of RT-qPCR. The results are shown in Fig. 1. Data are from two independent experiments, each performed in duplicate. Statistics were performed using a one-way ANOVA with multiple comparisons (1) all against control and (2) all against Holunderbluts 250 μg / ml. Significant p values are marked by * (≤ 0.05), ** (≤ 0.01), *** (≤ 0.001) or **** (≤ 0.0001); a * directly above a bar denotes significance to control, while a * in combination with a line denotes significance to Holunderbluts 250 μg / ml.Preparation of Holunder ExtractThe aqueous extract was prepared from Holunderbluts and leaves. For cold extraction, the plant parts were dried (50°C, 18h) and ground; 5g of these were dissolved in 30mL of bidisstalled 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×g, 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, using, for example, 70°C hot water as a solvent, no sonication is carried out, and the top shaking time is 10 minutes.Cell CultureHuman 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 NaHCO 3, 10 % FBS, 1% P / S (PAN Biotech), and 50 μM sterile filtered β-mercaptoethanol (Sigma Aldrich, Saint Louis, MO, USA). For subculture, the cells were pelleted by centrifugation (120×g, 7 min) and resuspended in fresh medium. For the experiments, differentiation was induced in macrophages by addition of 50 ng / ml phorbol 12-myristate 13-acetate (PMA; Sigma Aldrich) for 48 hours.Gene expression analysisOn day 0, 2.75×10 6 of THP-1 cells were seeded in 6-well plates (Greiner Bio-One GmbH). On day 2, the cells were washed once with PBS+ / + (Ca- and Mg-containing; PAN Biotech GmbH) and corresponding extracts or TO901317 (10 μM) in serum-reduced medium (1% FBS) were added.After incubation for 24 hours, the RNA was isolated using the RNeasy® Plus Mini Kit from QIAGEN (Hilden, Germany). The RNA isolation was followed by cDNA synthesis using the iScriptTM cDNA Synthesis Kit from Bio Rad Laboratories (Hercules, CA, US).Reverse transcription qPCR (RT-qPCR) was performed by a singleplex assay using the iQTM 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 home-keeping genes (RPL5 and GAPDH for THP-1 cells).

Claims

Product containing a Holunder extract, characterized in that the product contains an action enhancer selected from a pepper extract, an ginger extract, a kuruma extract and a citrus plant extract.Product according to at least claim 1 or at least according to the preamble of claim 1, characterized in that the product contains a pepper extract.Product according to at least one of the preceding claims, characterized in that the product contains an ginger extract.Product according to at least one of the preceding claims, characterized in that the product contains an extract of the turmeric substance.Product according to at least one of the preceding claims, characterized in that the product contains a citrus plant extract.Product according to at least one of the preceding claims, characterized in that the product is suitable for oral ingestion.Product according to at least one of the preceding claims, characterized in that the product is a food supplement.Product according to at least one of the preceding claims, characterized in that the Holunder extract is produced by extraction with an aqueous solvent.Product according to at least one of the preceding claims, characterized in that the product contains one or more constituents per 100 g of the product, which constituents are 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 kurkuma extract.Product according to at least one of the preceding claims, characterized in that the product contains the pepper extract, the ginger extract and the kuruma extract.Product according to at least one of the preceding claims, characterized in that the product contains 4 mg to 200 mg pepper extract, 4 mg to 200 mg g g gwer extract and 0.25 mg to 2 g of a kurkuma extract per 100 g of the product.Product according to at least one of the preceding claims, characterized in that the Holunder extract is an extract from at least one constituent of the Holunder selected from flowers and leaves.Use of at least one extract selected from a pepper extract, an ginger extract, a kurkuma extract and a citrus plant extract for enhancing the effect of a holunder extract.Use of a product according to any one of claims 1-12 for improving fat metabolism.Product according to any one of claims 1-12 for the prevention and / or treatment of atherosclerosis.

Images