Ginsenoside

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The chemical structure of the ginsenoside Rg1, a member of the dammarane family of molecules. Ginsenoside Rg1.png
The chemical structure of the ginsenoside Rg1, a member of the dammarane family of molecules.

Ginsenosides or panaxosides are a class of natural product steroid glycosides and triterpene saponins. Compounds in this family are found almost exclusively in the plant genus Panax (ginseng), which has a long history of use in traditional medicine that has led to the study of pharmacological effects of ginseng compounds. As a class, ginsenosides exhibit a large variety of subtle and difficult-to-characterize biological effects when studied in isolation. [1]

Contents

Ginsenosides can be isolated from various parts of the plant, though typically from the roots, and can be purified by column chromatography. [2] The chemical profiles of Panax species are distinct; although Asian ginseng, Panax ginseng, has been most widely studied due to its use in traditional Chinese medicine, there are ginsenosides unique to American ginseng (Panax quinquefolius) and Japanese ginseng (Panax japonicus). Ginsenoside content also varies significantly due to environmental effects. [3]

Classification

Ginsenosides are named according to their retention factor in thin layer chromatography (TLC). They can be broadly divided into two groups based on the carbon skeletons of their aglycones: the four-ring dammarane family, which contains the majority of known ginsenosides, and the oleanane family. The dammaranes further subdivided into 2 main groups, the protopanaxadiols and protopanaxatriols, [4] with other smaller groups such as the ocotillol-type pseudoginsenoside F11 and its derivatives. [3]

Chemical structure

Most known ginsenosides are classified as members of the dammarane family. The structure of these dammarane ginsenosides consists of a 4-ring, steroid-like structure. To each ginsenoside is bound at least 2 or 3 hydroxyl groups at the carbon-3 and -20 positions or the carbon-3, -6, and -20 positions respectively. In protopanaxadiols, sugar groups attach to the 3-position of the carbon skeleton, while in comparison sugar groups attach to the carbon-6 position in protopanaxatriols. Well known protopanaxadiols include Rb1, Rb2, Rg3, Rh2, and Rh3. Well known protopanaxatriols include Rg1, Rg2, and Rh1. [5]

Ginsenosides that are a member of the oleanane family are pentacyclic, composed of a five ring carbon skeleton. [6]

Biosynthesis

The biosynthetic pathway of ginsenosides is not entirely characterized, though as steroids they derive from pathways that lead to the synthesis of isoprene units. A proposed pathway converts squalene to 2,3-oxidosqualene via the action of squalene epoxidase, at which point dammaranes can be synthesized through dammarenediol synthase, oleananes through beta-amyrin synthase, and another class of molecules, the phytosterols, through cycloartenol synthase. [4]

In the proposed pathway, squalene is synthesized from the assembly of two farnesyl diphosphate (FPP) molecules. Each molecule of FPP is in turn the product of two molecules of dimethylallyl diphosphate and two molecules of isopentenyl diphosphate (IPP). IPP is produced by the mevalonic pathway in the cytosol of a ginseng plant cell and by the methylerythritol phosphate pathway in the plant's plastid. [7]

Ginsenosides likely serve as mechanisms for plant defense. [7] [8] Ginsenosides have been found to have both antimicrobial and antifungal properties. Ginsenoside molecules are naturally bitter-tasting and discourage insects and other animals from consuming the plant. [7]

Metabolism

Ginseng is generally consumed orally as a dietary supplement, and thus its component ginsenosides may be metabolized by gut flora. For example, ginsenosides Rb1 and Rb2 are converted to 20-b-O-glucopyranosyl-20(S)-protopanaxadiol or 20(S)-protopanaxadiol by human gut bacteria. [9] This process is known to vary significantly between individuals. [10] In some cases the metabolites of ginsenosides may be the biologically active compounds. [8]

Biological effects

Most studies of the biological effects of ginsenosides have been in cell culture or animal models and thus their relevance to human biology is unknown. Effects on the cardiovascular system, central nervous system and immune system have been reported, primarily in rodents. Antiproliferative effects have also been described. [1] [8]

Many studies suggest that ginsenosides have antioxidant properties. Ginsenosides have been observed to increase internal antioxidant enzymes and act as a free-radical scavenger. [5] Ginsenosides Rg3 and Rh2 have been observed in cell models as having an inhibitory effect on the cell growth of various cancer cells while studies in animal models have suggested that ginsenosides have neuroprotective properties and could be useful in treating neurodegenerative disease such as Alzheimer's and Parkinson's diseases. [5]

Two broad mechanisms of action have been suggested for ginsenoside activity, based on their similarity to steroid hormones. They are amphiphilic and may interact with and change the properties of cell membranes. [1] Some ginsenosides have also been shown to be partial agonists of steroid hormone receptors. It is not known how these mechanisms yield the reported biological effects of ginsenosides. The molecules as a class have low bioavailability due to both metabolism and poor intestinal absorption. [8]

See also

Related Research Articles

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Steroid Any organic compound having sterane as a core structure

A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes which alter membrane fluidity; and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol (opisthokonts) or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.

Salvinorin A Chemical compound

Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.

Terpene Class of oily organic compounds found in plants

Terpenes are a class of natural products consisting of compounds with the formula (C5H8)n. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes are further classified by the number of carbons: monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), as examples. The terpene, alpha-pinene, is a major component of the common solvent, turpentine.

Ginseng Root of a plant used in herbal preparations

Ginseng is the root of plants in the genus Panax, such as Korean ginseng, South China ginseng, and American ginseng, typically characterized by the presence of ginsenosides and gintonin.

Saponins, also selectively referred to as triterpene glycosides, are bitter-tasting usually toxic plant-derived organic chemicals that have a foamy quality when agitated in water. They are widely distributed but found particularly in soapwort, a flowering plant, and the soapbark tree. They are used in soaps, medicinals, fire extinguishers, speciously as dietary supplements, for synthesis of steroids, and in carbonated beverages. Structurally, they are glycosides, sugars bonded to another organic molecule, usually a steroid or triterpene, a steroid building block. Saponins are both water and fat soluble, which gives them their useful soap properties. Some examples of these chemicals are glycyrrhizin, licorice flavoring; and quillaia, a bark extract used in beverages.

Cytochrome P450 Class of enzymes

Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.

<span class="mw-page-title-main">Squalene</span> Chemical compound

Squalene is an organic compound. With the formula (C5H8)6, it is a triterpene. It is a colourless oil although impure samples appear yellow. It was originally obtained from shark liver oil (hence its name, as Squalus is a genus of sharks). All plants and animals produce squalene as a biochemical intermediate. An estimated 12% of bodily squalene in humans comes from the sebum. Squalene has a role in topical skin lubrication and protection.

<span class="mw-page-title-main">Triterpene</span> Class of chemical compounds

Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squalene, the precursor to all steroids.

Farnesyl-diphosphate farnesyltransferase Class of enzymes

Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins.

<i>Panax notoginseng</i> Species of flowering plant

Panax notoginseng is a species of the genus Panax, and it is commonly referred to in English as Chinese ginseng or notoginseng. In Chinese it is called tiánqī, tienchi ginseng, sānqī or sanchi, three-seven root, and mountain plant. P. notoginseng belongs to the same scientific genus as Panax ginseng. In Latin, the word panax means "cure-all", and the family of ginseng plants is one of the best-known herbs.

Protopanaxadiol Chemical compound

Protopanaxadiol (PPD) is an organic compound characterizing a group of ginsenosides. It is a dammarane-type tetracyclic terpene sapogenin found in ginseng and in notoginseng.

Protopanaxatriol Chemical compound

Protopanaxatriol (PPT) is an organic compound characterizing a group of ginsenosides. It is a dammarane-type tetracyclic triterpene sapogenins found in ginseng and in notoginseng.

American ginseng Species of flowering plant

American ginseng is a herbaceous perennial plant in the ivy family, commonly used as an herb in traditional Chinese medicine. It is native to eastern North America, though it is also cultivated in China. Since the 18th century, American ginseng has been primarily exported to Asia, where it is highly valued for its cooling and sedative medicinal effects. It is considered to represent the cooling yin qualities, while Asian ginseng embodies the warmer aspects of yang.

Amyrin Chemical compound

The amyrins are three closely related natural chemical compounds of the triterpene class. They are designated α-amyrin (ursane skeleton), β-amyrin (oleanane skeleton) and δ-amyrin. Each is a pentacyclic triterpenol with the chemical formula C30H50O. They are widely distributed in nature and have been isolated from a variety of plant sources such as epicuticular wax. In plant biosynthesis, α-amyrin is the precursor of ursolic acid and β-amyrin is the precursor of oleanolic acid. All three amyrins occur in the surface wax of tomato fruit. α-Amyrin is found in dandelion coffee.

The squalene/phytoene synthase family represents proteins that catalyze the head-to-head condensation of C15 and C20 prenyl units (i.e. farnesyl diphosphate and genranylgeranyl diphosphate). This enzymatic step constitutes part of steroid and carotenoid biosynthesis pathway. Squalene synthase EC (SQS) and Phytoene synthase EC (PSY) are two well-known examples of this protein family and share a number of functional similarities. These similarities are also reflected in their primary structure. In particular three well conserved regions are shared by SQS and PSY; they could be involved in substrate binding and/or the catalytic mechanism. SQS catalyzes the conversion of two molecules of farnesyl diphosphate (FPP) into squalene. It is the first committed step in the cholesterol biosynthetic pathway. The reaction carried out by SQS is catalyzed in two separate steps: the first is a head-to-head condensation of the two molecules of FPP to form presqualene diphosphate; this intermediate is then rearranged in a NADP-dependent reduction, to form squalene:

Dammarenediol II synthase (EC 4.2.1.125, dammarenediol synthase, 2,3-oxidosqualene (20S)-dammarenediol cyclase, DDS, (S)-squalene-2,3-epoxide hydro-lyase (dammarenediol-II forming)) is an enzyme with systematic name (3S)-2,3-epoxy-2,3-dihydrosqualene hydro-lyase (dammarenediol-II forming). This enzyme catalyses the following chemical reaction

Pseudoginsenoside F11 Chemical compound

Pseudoginsenoside F11 is a chemical natural product found in American ginseng but not in Asian ginseng, although it has similar properties to the Asian ginseng compound ginsenoside Rf. The molecule is a triterpenoid saponin member of the dammarane family and contains a four-ring rigid skeleton. Compounds in the ginsenoside family are found almost exclusively in plants of the genus Panax. A wide variety of difficult-to-characterize in vitro effects have been reported for the compounds in isolation. Pseudoginsenoside F11 and its derivatives are sometimes referred to as having an ocotillol-type skeleton structure.

Oxidosqualene cyclase

Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.

Ginsenoside Rb1 Chemical compound

Ginsenoside Rb1 (or Ginsenoside Rb1 or GRb1 or GRb1) is a chemical compound belonging to the ginsenoside family.

References

  1. 1 2 3 Attele, AS; Wu, JA; Yuan, CS (1 December 1999). "Ginseng pharmacology: multiple constituents and multiple actions". Biochemical Pharmacology. 58 (11): 1685–93. doi:10.1016/s0006-2952(99)00212-9. PMID   10571242.
  2. ↑ Fuzzati, N (5 December 2004). "Analysis methods of ginsenosides". Journal of Chromatography B. 812 (1–2): 119–33. doi:10.1016/j.jchromb.2004.07.039. PMID   15556492.
  3. 1 2 Qi, LW; Wang, CZ; Yuan, CS (June 2011). "Ginsenosides from American ginseng: chemical and pharmacological diversity". Phytochemistry. 72 (8): 689–99. doi:10.1016/j.phytochem.2011.02.012. PMC   3103855 . PMID   21396670.
  4. 1 2 Liang, Y; Zhao, S (July 2008). "Progress in understanding of ginsenoside biosynthesis". Plant Biology (Stuttgart). 10 (4): 415–21. doi:10.1111/j.1438-8677.2008.00064.x. PMID   18557901.
  5. 1 2 3 Lü, J.-M.; Yao, Q.; Chen, C. (2009). "Ginseng Compounds: An Update on Their Molecular Mechanisms and Medical Applications". Current Vascular Pharmacology. 7 (3): 293–302. doi:10.2174/157016109788340767. PMC   2928028 . PMID   19601854.
  6. ↑ Shibata, S (Dec 2001). "Chemistry and Cancer Preventing Activities of Ginseng Saponins and Some Related Triterpenoid Compounds". J Korean Med Sci. 16 (Suppl): S28–S37. doi:10.3346/jkms.2001.16.S.S28. PMC   3202208 . PMID   11748374.
  7. 1 2 3 Kim, Yu-Jin; Zhang, Dabing; Yang, Deok-Chun (2015-11-01). "Biosynthesis and biotechnological production of ginsenosides". Biotechnology Advances. 33 (6, Part 1): 717–735. doi:10.1016/j.biotechadv.2015.03.001. PMID   25747290.
  8. 1 2 3 4 Leung, KW; Wong, AS (11 June 2010). "Pharmacology of ginsenosides: a literature review". Chinese Medicine. 5: 20. doi:10.1186/1749-8546-5-20. PMC   2893180 . PMID   20537195.
  9. ↑ Bae, Eun-Ah; Han, Myung Joo; Choo, Min-Kyung; Park, Sun-Young; Kim, Dong-Hyun (2002-01-01). "Metabolism of 20(S)- and 20(R)-Ginsenoside Rg3 by Human Intestinal Bacteria and Its Relation to in Vitro Biological Activities". Biological and Pharmaceutical Bulletin. 25 (1): 58–63. doi: 10.1248/bpb.25.58 . PMID   11824558.
  10. ↑ Christensen, LP (2009). Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Advances in Food and Nutrition Research. Vol. 55. pp. 1–99. doi:10.1016/S1043-4526(08)00401-4. ISBN   9780123741202. PMID   18772102.
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