The silymarin composition… and why does it matter???

doi:10.1016/j.foodres.2017.07.017

Food Research International

Volume 100, Part 3, October 2017, Pages 339-353

https://doi.org/10.1016/j.foodres.2017.07.017 Get rights and content

Highlights

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This review describes all components of the medicinal plant Silybum marianum.
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Silymarin as crude extracts from S. marianum seeds contains flavonolignans.
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Variations of silymarin components due to cultivation and production are described.
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Silybum cultivars and chemoraces are discussed; analytical methods are reviewed.
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Use of seed fractions, e.g. fats, oils, vaxes, fibers, flour in food is discussed.

Abstract

The extract from milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin, contains a variety of flavonolignans and displays antioxidant, anti-inflammatory, immunomodulatory and hepatoprotective properties. As silybin is the main component of silymarin, the literature mainly focuses on this compound, ignoring all other components. This leads to problems in reproducibility of scientific results, as the exact composition of silymarin is often unknown and can vary to a certain degree depending on the processing, chemo-variety of the plant used and climatic conditions during the plant growth. There are studies dealing with the analytical separation and quantification of silymarin components as well as studies focused on silymarin content in clinically used drugs, in various plant parts, seasons, geographic locations etc. However, no comparison of detail flavonolignan profiles in various silymarin preparations is available to date. Also, as a result of the focus on the flavonolignans; the oil fraction, which contains linoleic, oleic and palmitic acids, sterols, tocopherol (vitamin E) and phospholipids, has been neglected. Due to all these factors, the whole plant is used e.g. as animal feed, the leaves can be eaten in salads and seed oil, besides culinary uses, can be also utilized for biodiesel or polymer production. Various HPLC separation techniques for the determination of the content of the flavonolignans have been vastly summarized in the present review.

Section snippets

Chemical compounds mentioned in this article

Silybin (PubChem CID: 31553)

Silymarin (PubChem CID: 7073228)

Silydianin (PubChem CID: 11982272)

Silychristin (PubChem CID: 441764)

Taxifolin (PubChem CID: 439533)

Isosilybin (PubChem CID: 3085830)

Oleic acid (PubChem CID: 445639)

Linoleic acid (PubChem CID: 5280450)

Palmitic acid (PubChem CID: 985)

Parameters affecting silymarin content and composition

Silymarin is the most frequently extracted from the whole pulverized seeds, or from the seed cake obtained by cold pressing the oil but it can also be obtained from whole plants (El Sherif, Khattab, Ibrahim, & Ahmed, 2013) or cultured cells of S. marianum (Cacho, Morán, Corchete, & Fernández-Tárrago, 1999). The silymarin content and composition strongly depends on S. marianum cultivar, geographical location of cultivation (soil physical properties, weather), and agronomic conditions (time of

Alternative use of milk thistle

Although S. marianum is mainly cultivated to produce silymarin for the production of food supplements and over the counter drugs, various parts of the plant can have also alternative use. For example, the whole milk thistle was found to be a promising crop for biomass production, which yielded more energy (275 GJ ha⁻¹) than globe artichoke and cultivated cardoon (Ledda, Deligios, Farci, & Sulas, 2013). However, the most promising for alternative use is milk thistle oil. Non-medical utilization of

Determination of flavonoids and flavonolignans in silymarin

HPLC-UV is the most widely and universal analytical method for the identification of flavonolignans in silymarin. Other analytical methods such as UV spectrometry, electromigration and electroanalytical methods, thin-layer chromatography and especially LC-MS are useful complementary methods for determination and quantification of the analytes (Csupor, Csorba, & Hohmann, 2016) but they are not suitable for ordinary use.

Conclusions

S. marianum is a versatile plant that can be utilized in a variety of ways. Not only seeds, but also other parts of the plant contain varying amounts of the flavonolignans. The amounts of silymarin (extract) obtained also varies depending on factors such as location, time of sowing and climate conditions. Silymarin is very popular and obviously efficient component of numerous nutraceuticals and preparations from S. marianum are also used in veterinary medicine and cosmetics. The seeds contain

Conflict of interest

The authors declare no conflict of interest.

Acknowledgement

The authors gratefully acknowledge the financial support of Czech Science Foundation (15-03037S), of the Ministry of Health of the Czech Republic (16-27317A) and COST Actions CM1307 “Targeted chemotherapy towards diseases caused by endoparasites” and FA1403 “Interindividual variation in response to consumption of plant food bioactives and determinants involved” co-funded by Czech Ministry of Education, Youth and Sports, projects LD15081 and LD15082, respectively.

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The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans – silybin, silychristin and silydianin − 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin (7) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin (7) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.
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Supercritical fluid extraction with carbon dioxide is nowadays one of the best approaches on an economic and ecological point of view for the extraction of natural compounds from plants. Besides, many seeds or fruits contain both lipids, as triglycerides, which can be used for food or cosmetic industries, and polyphenols which do have many bioprotective effects for the human health. By using successively pure carbon dioxide and carbon dioxide added with a polar modifier, either pure ethanol or a ethanol/water mixture, we achieved first the extraction of triglycerides of the milk thistle seeds, followed by the extraction of the flavonolignans, which are bioactive compounds. Effects of pressure (15 and 25 MPa) and temperature (40 and 60 °C) were studied on the lipids extraction efficiency. For flavonolignans, the polar compounds, the impact of modifier amount (pure ethanol from 10% to 40%) and water percentage in ethanol (5–15%) were compared. The duration of the two sequential steps to achieve the complete seed defatting and to increase the flavonolignan recovery were also studied. The complete lipids extraction was achieved with pure CO2 at 40 °C, 25 MPa for 30 min whereas the extraction of flavonolignans was achieved with 20% of modifier (wate/ethanol 15/85) during 90 min. The analysis of the triglyceride composition of milk thistle seed were studied by using supercritical fluid chromatography (SFC), whereas the analysis of flavonolignans was carried out by an improved Ultra-high-pressure liquid chromatography (UHPLC) method.
Foliar application of chitosan and titanium dioxide enhances silybin content by orchestrating miRNA and gene targets transcription in Milk thistle (Silybum marianum L.)
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Milk thistle (Silybum marianum L. Gaertn.) is an important herbaceous and annual plant that is used as a pharmaceutical for the remedy and prevention of liver diseases. Till now, there have been no reports of miRNAs’ involvement in the production of secondary metabolites in milk thistle. The present study was conducted with the aim of investigating the foliar application of chitosan and titanium dioxide (bulk and nano forms) on seed silybin content and the crosstalk of miRNAs and target genes. The ideal formulation [bulk and nanoparticles (NPs)] and concentration (0–100 mg L⁻¹) of titanium dioxide and chitosan applications for upregulating seed silybin content were investigated across ﬁve ecotypes. Additionally, the expression of miRNAs and their target genes involved in silybin biosynthesis were evaluated. Data revealed that foliar application of elicitors increased the content of silybin A, silybin B, and total silybin in all five ecotypes. The cultivar 'Budakalazi' had the best response compared to other ecotypes. The application of chitosan and TiO₂ decreased the expression of all five miRNAs in the phenological stage of immature seeds. In contrast, target gene expression was generally upregulated. miRNAs expression was generally linked to the phenological stage of mature seed, as miR156b, miR1438, and miR157a-5p were over-expressed, while miRNAs miR1873 and miR829.1 were down-regulated. In general, foliar application of Nano chitosan, especially at a concentration of 50 mg L⁻¹, increased the amount of silybin content by reducing the expression of most miRNAs, and upregulating the transcription of their target genes involved in silybin biosynthesis.
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The silymarin composition… and why does it matter???

Highlights

Abstract

Section snippets

Chemical compounds mentioned in this article

Parameters affecting silymarin content and composition

Alternative use of milk thistle

Determination of flavonoids and flavonolignans in silymarin

Conclusions

Conflict of interest

Acknowledgement

Industrial Crops and Products

Industrial Crops and Products

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences

Plant Science

Phytomedicine

Journal of Pharmaceutical and Biomedical Analysis

Industrial Crops and Products

Energy Conversion and Management

Journal of Pharmaceutical and Biomedical Analysis

Arabian Journal of Chemistry

Journal of Pharmaceutical and Biomedical Analysis

Free Radical Biology & Medicine

American Journal of Gastroenterology

Process Biochemistry

Process Biochemistry

Journal of Molecular Catalysis B: Enzymatic

Journal of Pharmaceutical and Biomedical Analysis

Industrial Crops and Products

Animal Feed Science and Technology

Journal of Molecular Catalysis B: Enzymatic

Food Research International

Journal of Chromatography A

Industrial Crops and Products

Journal of Chromatography A

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences

Process Biochemistry

European Journal of Pharmaceutics and Biopharmaceutics

Journal of Functional Foods

New Zealand Journal of Crop and Horticultural Science

Toxicology

Phytochemistry

Journal of Pharmaceutical and Biomedical Analysis

Journal of Photochemistry and Photobiology, B: Biology

Cancer Letters

Clinics in Dermatology

Pharmacological Research

Journal of Dermatological Science

Fuel Processing Technology

Poultry Science

Journal of Dairy Science

Evaluation of silymarin as a promising radioprotector

Zeitschrift für Naturforschung Section C: Journal of Biosciences

Accumulation of silymarin in milk thistle seeds under drought stress

Planta

Mechanistic study of the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle

Journal of Organic Chemistry

Silybum marianum: Non-medical exploitation of the species

Annals of Applied Biology

Properties of the seed oil of a dwarf cultivar of the pharmaceutical silymarin producing plant Silybum marianum (L.) Gaertn. developed in India

Indian Journal of Natural Products and Resources

Non-conventional lignans: Coumarinolignans, flavonolignans, and stilbenolignans

Silychristin: Skeletal alterations and biological activities

Journal of Natural Products

Chemistry of silybin

Natural Product Reports