Silychristin

Last updated
Silychristin
Silychristin A 1996.gif
Silychristin B 1996.gif
Names
IUPAC name
Silychristin A = (2R,3R)-3,5,7-trihydroxy-2-((2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydrobenzofuran-5-yl)chroman-4-one Silychristin B = (2R,3R)-3,5,7-trihydroxy-2-((2S,3R)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydrobenzofuran-5-yl)chroman-4-one
Other names
Silichristin, Silicristin, Silycristin
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 251-720-9
KEGG
PubChem CID
UNII
  • InChI=1S/C25H22O10/c1-33-18-6-10(2-3-15(18)28)23-14(9-26)13-4-11(5-17(30)25(13)35-23)24-22(32)21(31)20-16(29)7-12(27)8-19(20)34-24/h2-8,14,22-24,26-30,32H,9H2,1H3/t14-,22+,23+,24-/m1/s1
    Key: BMLIIPOXVWESJG-LMBCONBSSA-N
  • COC1=C(C=CC(=C1)[C@H]2[C@@H](C3=C(O2)C(=CC(=C3)[C@@H]4[C@H](C(=O)C5=C(C=C(C=C5O4)O)O)O)O)CO)O
Properties
C25H22O10
Molar mass 482.4 g/mol
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H302
P264, P270, P301+P312, P330, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Silychristin (also known as silichristin) is a natural product and one of the constituents of silymarin, the standardized, active extract of the fruit of milk thistle, Silybum marianum . [1] [2] It is the second most abundant constituent in silymarin, after silybin. [3] Silychristin is a flavonolignan, along with many other silymarin constituents (such as silybin, isosilybin, silydianin, etc.), meaning it is composed up of a flavonoid and a lignan. [3] It is estimated that up to 65–80% of silymarin extract is made up of flavonolignans, like silychristin, which give silymarin its well known potent antioxidant and hepatoprotective properties. [4] [5] Silychristin can exist as two stereoisomers, silychristin A (2R, 3S) and silychristin B (2S, 3R). The marianum variety of S. marianum (purple corollas) includes silychristin A as a major flavonolignan constituent, while the lesser known and studied albiflorum variety (white corollas) includes unique flavonolignans, including silyhermin, (–)-silandrin, and (+)-silymonin. [6]

Contents

Toxicity

Several studies have documented the potentially dangerous effects of silychristin and of the silymarin mixture in general on the thyroid system. All of the flavonolignan compounds found in the silymarin mixture seem to block the uptake of thyroid hormones into the cells by selectively blocking the MCT8 transmembrane transporter. [7] The authors of this study noted that especially silychristin seems to be perhaps the most powerful and selective inhibitor known so far for the MCT8 transporter. [7] Due to the essential role played by the thyroid hormone in human metabolism in general it is believed that the intake of silymarin can lead to disruptions of the thyroid system. [7] Because the thyroid hormones and the MCT8 as well are known to play a critical role during early and fetal development, the administration of silymarin during pregnancy is especially thought to be dangerous, potentially leading to the Allan–Herndon–Dudley syndrome, a brain development disorder that causes both moderate to severe intellectual disability and problems with speech and movement. [8]

Biosynthesis

Natural flavonolignans, which include silychristin, are biosynthesized by the oxidative coupling of a flavonoid and a phenylpropanoid moiety. The flavonoid moiety can be any number of flavonoids, including taxifolin, naringenin, luteolin, etc., while the pheylpropanoid moiety includes coniferyl alcohol, a monolignol, in most all flavonolignans. The two biosynthetic precursors specifically for silychristin are taxifolin and coniferyl alcohol, which are both biosynthesized via the phenylpropanoid pathway, a pathway which converts phenylalanine into 4-coumaroyl-CoA. [9] Phenylpropanoid Pathway.gif

Still much is not known today about the specific enzymes and mechanism of the biosynthesis of silychristin and its related flavononlignan counterparts in S. marianum. The most widely accepted hypothesis for the biosynthesis of flavonolignans is via an oxidative radicalization of both the flavonoid precursor and coniferyl alcohol, followed by coupling of the two radicals, and then proton transfer(s) in order to aromatize the intermediate to get the final product. Although the enzyme catalyzing this oxidative coupling of flavonolignans has not yet been fully characterized, peroxidase enzymes have been hypothesized as likely candidates because they are radical generators. [9] Proposed Silychristin Biosynthesis.gif

Related Research Articles

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Thiamine Chemical compound

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, which cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Food sources of thiamine include whole grains, legumes, and some meats and fish. Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine. Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy. Other uses include the treatment of maple syrup urine disease and Leigh syndrome. They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.

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Flavonoid Class of plant and fungus secondary metabolites

Flavonoids are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.

Polyphenol Class of chemical compounds

Polyphenols are a large family of naturally occurring organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some of which have been used historically as dyes and for tanning garments.

Hepatotoxicity Liver damage caused by a drug or chemical

Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.

<i>Silybum</i> Genus of plants

Silybum is a genus of two species of thistles in the daisy family. The plants are native to the Mediterranean regions of Europe, North Africa, and the Middle East. One species has been introduced elsewhere, including in North America. The name "milk thistle" derives from a feature of the leaves, which are prominently banded with splashes of white. Historically, these milky bands were said to be Mother Mary's milk, and this is the origin of another common name, St. Mary's thistle. The most widespread species is Silybum marianum.

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Silibinin Chemical compound

Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. The mixture exhibits a number of pharmacological effects, particularly in the fatty liver, non-alcoholic fatty liver, non-alcoholic steatohepatitis, and there is great clinical evidence for the use of silibinin as a supportive element in alcoholic and Child–Pugh grade 'A' liver cirrhosis. However, despite its several beneficial effects on the liver, silibinin and all the other compounds found in silymarin, especially silychristin seem to act as potent disruptors of the thyroid system by blocking the MCT8 transporter. The long term intake of silymarin can lead to some form of thyroid disease and if taken during pregnancy, silymarin can cause the development of the Allan–Herndon–Dudley syndrome. Although this information is not being taken into consideration by all regulatory bodies, several studies now consider silymarin and especially silychristin to be important inhibitors of the MCT8 transporter and a potential disruptor of the thyroid hormone functions.

Quercetin Chemical compound

Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods.

<i>Silybum marianum</i> Species of plant of genus Silybum in family Asteraceae

Silybum marianum is a species of thistle. It has various common names including milk thistle, blessed milkthistle, Marian thistle, Mary thistle, Saint Mary's thistle, Mediterranean milk thistle, variegated thistle and Scotch thistle. This species is an annual or biennial plant of the family Asteraceae. This fairly typical thistle has red to purple flowers and shiny pale green leaves with white veins. Originally a native of Southern Europe through to Asia, it is now found throughout the world.

Hesperidin Chemical compound

Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the word "hesperidium", for fruit produced by citrus trees.

<i>Amanita ocreata</i> Species of poisonous fungus in the genus Amanita endemic to western North America

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Taxifolin Chemical compound

Taxifolin (5,7,3',4'-flavan-on-ol), also known as dihydroquercetin, belongs to the subclass flavanonols in the flavonoids, which in turn is a class of polyphenols.

Flavonolignans are natural phenols composed of a part flavonoid and a part phenylpropane.

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References

  1. "Silicristin - an overview :ScienceDirect Topics". www.sciencedirect.com. Skin Aging Handbook. Retrieved 2020-11-22.
  2. Johannes, Jörg; Jayarama-Naidu, Roopa; Meyer, Franziska; Wirth, Eva Katrin; Schweizer, Ulrich; Schomburg, Lutz; Köhrle, Josef; Renko, Kostja (2016-04-01). "Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8". Endocrinology. 157 (4): 1694–1701. doi: 10.1210/en.2015-1933 . PMID   26910310.
  3. 1 2 Biedermann, D.; Buchta, M.; Holečková, V.; Sedlák, D.; Valentová, K.; Cvačka, J.; Bednárová, L.; Křenková, A.; Kuzma, M.; Škuta, C.; Peikerová, Ž.; Bartůněk, P.; Křen, V., Silychristin: Skeletal Alterations and Biological Activities. Journal of Natural Products2016, 79 (12), 3086–3092.
  4. Kawaguchi-Suzuki, M.; Frye, R. F.; Zhu, H.-J.; Brinda, B. J.; Chavin, K. D.; Bernstein, H. J.; Markowitz, J. S., The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity. Drug Metabolism and Disposition2014, 42 (10), 1611–1616.
  5. Zhu, H.-J.; Brinda, B. J.; Chavin, K. D.; Bernstein, H. J.; Patrick, K. S.; Markowitz, J. S., An Assessment of Pharmacokinetics and Antioxidant Activity of Free Silymarin Flavonolignans in Healthy Volunteers: A Dose Escalation Study. Drug Metabolism and Disposition2013, 41 (9), 1679–1685.
  6. Ahmed, H. S.; Mohamed, W. R.; Moawad, A. S.; Owis, A. I.; Ahmed, R. R.; AbouZid, S. F., Cytotoxic, hepatoprotective and antioxidant activities of Silybum marianum variety albiflorum growing in Egypt. Natural Product Research2019, 1–5.
  7. 1 2 3 Johannes J, Jayarama-Naidu R, Meyer F, Wirth EK, Schweizer U, Schomburg L, Köhrle J, Renko K (2016). "Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8". Endocrinology. 157 (4): 1694–2301. doi: 10.1210/en.2015-1933 . PMID   26910310.
  8. "Allan-Herndon-Dudley syndrome". Genetic and Rare Diseases Information Center (GARD). Retrieved 2021-05-06.
  9. 1 2 AbouZid, S. F.; Ahmed, H. S.; Moawad, A. S.; Owis, A. I.; Chen, S.-N.; Nachtergael, A.; McAlpine, J. B.; Brent Friesen, J.; Pauli, G. F., Chemotaxonomic and biosynthetic relationships between flavonolignans produced by Silybum marianum populations. 2017, 119, 175–184.