Helenalin

Last updated
Helenalin
Helenalin.svg
Names
IUPAC name
(8αH)-6α-Hydroxy-4-oxo-10α-ambrosa-2,11(13)-dieno-12,8-lactone
Systematic IUPAC name
(3aS,4S,4aR,7aR,8R,9aR)-4-Hydroxy-4a,8-dimethyl-3-methylidene-3,3a,4,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
KEGG
PubChem CID
UNII
  • InChI=1S/C15H18O4/c1-7-6-10-12(8(2)14(18)19-10)13(17)15(3)9(7)4-5-11(15)16/h4-5,7,9-10,12-13,17H,2,6H2,1,3H3/t7-,9+,10-,12-,13+,15+/m1/s1 X mark.svgN
    Key: ZVLOPMNVFLSSAA-XEPQRQSNSA-N X mark.svgN
  • InChI=1/C15H18O4/c1-7-6-10-12(8(2)14(18)19-10)13(17)15(3)9(7)4-5-11(15)16/h4-5,7,9-10,12-13,17H,2,6H2,1,3H3/t7-,9+,10-,12-,13+,15+/m1/s1
    Key: ZVLOPMNVFLSSAA-XEPQRQSNBI
  • O=C/2O[C@@H]3C[C@H]([C@@H]1/C=C\C(=O)[C@@]1(C)[C@@H](O)[C@@H]3C\2=C)C
Properties
C15H18O4
Molar mass 262.305 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Helenalin, or (-)-4-Hydroxy-4a,8-dimethyl-3,3a,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione, is a toxic sesquiterpene lactone which can be found in several plants such as Arnica montana and Arnica chamissonis Helenalin is responsible for the toxicity of the Arnica spp. Although toxic, helenalin possesses some in vitro anti-inflammatory and anti-neoplastic effects. Helenalin can inhibit certain enzymes, such as 5-lipoxygenase and leukotriene C4 synthase. For this reason the compound or its derivatives may have potential medical applications. [1] [2]

Contents

Structure and reactivity

Helenalin belongs to the group of sesquiterpene lactones which are characterised by a lactone ring. Beside this ring, the structure of helenalin has two reactive groups (α-methylene-γ-butyrolactone and a cyclopentenone group) that can undergo a Michael addition. [3] [4] The double bond in the carbonyl group can undergo a Michael addition with a thiol group, also called a sulfhydryl group. Therefore, helenalin can interact with proteins by forming covalent bonds to the thiol groups of cysteine-containing proteins/peptides, such as glutathione. This effect can disrupt the molecule's biological function. [2] Addition reactions can occur because thiol groups are strong nucleophiles; a thiol has a lone pair of electrons. [5]

Chemical derivatives

There are several derivatives of helenaline known within the same sesquiterpene lactone group; pseudoguaianolides. Most of these derivatives occur naturally, such as the compound dihydrohelenalin, but there are also some semi-synthetic derivatives known, such as 2β-(S-glutathionyl)-2,3-dihydrohelenalin. [1] [2] In general, most derivatives are more toxic than helenalin itself. Among these, derivatives with the shortest ester groups are most likely to contain a higher toxicity. [6] Other derivatives include 11α,13-dihydrohelenalin acetate, 2,3-dehydrohelenalin and 6-O-isobutyrylhelenalin. The molecular conformation differs between helenalin and its derivatives, which affects the lipophilicity and the accessibility of the Michael addition sites. Poorer accessibility results in a compounds with lower toxicity.[ citation needed ] Another possibility is that a derivative lacking one of the reactive groups, such as the cyclopentenone group, may have a lower toxicity.[ citation needed ]

Some biochemical effects of helenalin

Helenalin can target the p65 subunit (also called RelA) of the transcription factor NF-κB. It can react with Cys38 in RelA by Michael addition. Both reactive groups, α-methylene-γ-butyrolactone and cyclopentene, can react with this cysteine. [3] It was also found that helenalin can inhibit human telomerase, a ribonucleoprotein complex, by Michael addition. In this case also, both reactive groups of helenalin can interact with the thiol group of a cysteine and inhibit the telomerase activity. [7] Helenalin inhibits the formation of leukotrienes in human blood cells by inhibiting LTC4 synthase activity. Helenalin reacts with its cyclopentenone ring to the thiol group of the synthase. [2]

Metabolism

Helenalin inhibits cytochrome P450 enzymes by reacting with thiol groups, resulting in inhibition of the mixed-function oxidase system. These effects are important for the cytotoxicity of helenalin. The levels of glutathione, which contains sulfhydryl groups, are reduced in helenaline-treated cells, further increasing the toxicity of helenalin. Depending on the dose of helenalin, thiol-bearing compounds such as glutathione may provide some protection to cells from helenalin toxicity. It was also seen that helenalin increase CPK and LDH activities in serum and that it inhibits multiple enzymes of the liver involved in triglyceride synthesis. Therefore, helenaline causes acute liver toxicity, accompanied by a decrease in cholesterol levels. [8]

Helenalin also suppresses essential immune functions, such as those mediated by activated CD4+ T-cells, by multiple mechanisms. [9]

In vitro anti-inflammatory and anti-neoplastic effects

Helenalin and some of its derivatives have been shown to have potent anti-inflammatory and anti-neoplastic effects in vitro . Some studies have suggested that the inhibition by helenalin of platelet leukotriene C4 synthase, telomerase activity and transcription factor NF-κB contributes to helenalin's in vitro anti-inflammatory and anti-neoplastic activity [2] [7] [10] . [11] [12] The dose used varied per study. There is currently no in vivo evidence regarding helenalin's anti-inflammatory and anti-tumour effects, if any. The efficacy of helenalin for treatment of pain and swelling, when applied topically, is not supported by the current available evidence at doses of 10% or lower. For doses higher than 10%, more research is required whether those remain safe and are more efficient than the current available medications. [13]

Application

In former times, plant extracts containing helenalin were used as a herbal medicine for the treatment of sprains, blood clots, muscle strain and rheumatic complaints. [9] Currently helenalin is used topically in homeopathic gels and microemulsions. Helenalin is not FDA-approved for medical application. [14]

Toxicity

When applied topically on humans, helenalin can cause contact dermatitis in sensitive individuals. However, it is considered generally safe when applied this way. Oral administration of large doses of helenalin can cause gastroenteritis, muscle paralysis, and cardiac and liver damage. The toxicity of helenalin was studied in mammalian species such as mice, rat, rabbit and sheep, where the oral LD50 of helenalin was established between 85 and 150 mg/kg. [15] [16] It was shown in a mouse model that helenalin caused reduced levels of cholesterol. In a rat model, alcohol hepatic injury was prevented by helenalin administration. [8] [17] Parenteral administration showed a higher toxic effect when compared to oral administration. [18] [19]

Pharmacology

Helenalin has a variety of observed effects in vitro including anti-inflammatory and antitumour activities. [20] Helenalin has been shown to selectively inhibit the transcription factor NF-κB, which plays a key role in regulating immune response, through a unique mechanism. [21] In vitro, it is also a potent, selective inhibitor of human telomerase [7] —which may partially account for its antitumor effects—has anti-trypanosomal activity, [22] [23] and is toxic to Plasmodium falciparum . [24]

Animal and in vitro studies have also suggested that helenalin can reduce the growth of Staphylococcus aureus and reduce the severity of S. aureus infection. [25]

Related Research Articles

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

Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Some eicosanoids, such as prostaglandins, may also have endocrine roles as hormones to influence the function of distant cells.

<i>Arnica montana</i> Species of European flowering plant

Arnica montana, also known as wolf's bane, leopard's bane, mountain tobacco and mountain arnica, is a moderately toxic European flowering plant in the daisy family Asteraceae that has a large yellow flower head. The names "wolf's bane" and "leopard's bane" are also used for another plant, Aconitum, which is extremely poisonous.

<span class="mw-page-title-main">Leukotriene</span> Class of inflammation mediator molecules

Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.

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

Noscapine is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects.

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

Lactucopicrin (Intybin) is a bitter substance that has a sedative and analgesic effect, acting on the central nervous system. It is a sesquiterpene lactone, and is a component of lactucarium, derived from the plant Lactuca virosa, as well as being found in some related plants such as Cichorium intybus. It is also found in dandelion coffee.

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

Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.

An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor or leukotriene receptor antagonist and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.

Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme that in humans is encoded by the ALOX5 gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms essential fatty acids (EFA) substrates into leukotrienes as well as a wide range of other biologically active products. ALOX5 is a current target for pharmaceutical intervention in a number of diseases.

Cyclopentenone prostaglandins are a subset of prostaglandins (PGs) or prostanoids that has 15-deoxy-Δ12,14-prostaglandin J2 (15-d-Δ12,14-PGJ2), Δ12-PGJ2, and PGJ2 as its most prominent members but also including PGA2, PGA1, and, while not classified as such, other PGs. 15-d-Δ12,14-PGJ2, Δ12-PGJ2, and PGJ2 share a common mono-unsaturated cyclopentenone structure as well as a set of similar biological activities including the ability to suppress inflammation responses and the growth as well as survival of cells, particularly those of cancerous or neurological origin. Consequently, these three cyclopentenone-PGs and the two epoxyisoprostanes are suggested to be models for the development of novel anti-inflammatory and anti-cancer drugs. The cyclopenentone prostaglandins are structurally and functionally related to a subset of isoprostanes viz., two cyclopentenone isoprostanes, 5,6-epoxyisoprostane E2 and 5,6-epoxisoprostane A2.

Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the arachidonate 5-lipoxygenase enzyme, which is responsible for the production of inflammatory leukotrienes. The overproduction of leukotrienes is a major cause of inflammation in asthma, allergic rhinitis, and osteoarthritis.

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

Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today: topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.

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

Absinthin is a naturally produced triterpene lactone from the plant Artemisia absinthium (Wormwood). It constitutes one of the most bitter chemical agents responsible for absinthe's distinct taste. The compound shows biological activity and has shown promise as an anti-inflammatory agent, and should not be confused with thujone, a neurotoxin also found in Artemisia absinthium.

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

Gambogic acid is a xanthonoid that is derived from the brownish or orange resin from Garcinia hanburyi. Garcinia hanburyi is a small to medium-sized evergreen tree with smooth grey bark. It is native to Cambodia, southern Vietnam, and Thailand and has been successfully introduced in Singapore.

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

Withaferin A is a steroidal lactone, derived from Acnistus arborescens, Withania somnifera and other members of family Solanaceae. It is the first member of the withanolide class of ergostane type product to be discovered.

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

Celastrol (tripterine) is a chemical compound isolated from the root extracts of Tripterygium wilfordii and Tripterygium regelii. Celastrol is a pentacyclic nortriterpen quinone and belongs to the family of quinone methides. In mice, celastrol is an NR4A1 agonist that alleviates inflammation and induces autophagy. Also in mice, celastrol increase expression of IL1R1, which is the receptor for the cytokine interleukin-1 (IL-1). IL1R1 knock-out mice exposed to celastrol exhibit no leptin-sensitizing or anti-obesity effect.

Cynaropicrin is a sesquiterpene lactone of the guaianolide type found mainly in leaves of artichoke plants. It is one of the compounds that gives the artichoke its characteristic bitterness. It is found in artichoke leaves with an abundance of approximately 87 g/kg, but can hardly be found in other parts of the plant. Cynaropicrin makes up about 0.7% of leaf extracts of the artichoke. It exhibits a large diversity of bioactivities and shows properties such as anti-inflammatory, antifeedant and activation of bitter sensory receptors, but has not yet been used in medicine. Despite its pharmacologically beneficial properties, it can be toxic in higher doses. The compound has attracted attention in recent years as a potential anticancer drug.

<span class="mw-page-title-main">15-Hydroxyeicosatetraenoic acid</span> Chemical compound

15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15(S)-HETE, and 15S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15(S)-hydroperoxyeicosatetraenoic acid (15(S)-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15(S)-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5(S),15(S)-dihydroxy-eicosatetraenoic acid (5(S),15(S)-diHETE), 5-oxo-15(S)-hydroxyeicosatetraenoic acid (5-oxo-15(S)-HETE), a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15(S)-HETE and 15(S)-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.

<span class="mw-page-title-main">12-Hydroxyheptadecatrienoic acid</span> Chemical compound

12-Hydroxyheptadecatrienoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. It was discovered and structurally defined in 1973 by P. Wlodawer, Bengt I. Samuelsson, and M. Hamberg, as a product of arachidonic acid metabolism made by microsomes (i.e. endoplasmic reticulum) isolated from sheep seminal vesicle glands and by intact human platelets. 12-HHT is less ambiguously termed 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid to indicate the S stereoisomerism of its 12-hydroxyl residue and the Z, E, and E cis-trans isomerism of its three double bonds. The metabolite was for many years thought to be merely a biologically inactive byproduct of prostaglandin synthesis. More recent studies, however, have attached potentially important activity to it.

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

Helenin is a phytochemical mixture found in many plant species, including the Inula helenium (elecampane) of the family Asteraceae. It is a mixture of two isomeric sesquiterpene lactones, alantolactone and isoalantolactone.

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

Xanthatin, or (3aR,7S,8aS)-7-methyl-3-methylidene-6-[(E)-3-oxobut-1-enyl]-4,7,8,8a-tetrahydro-3aH-cyclohepta[b]furan-2-one (C15H18O3) is a major bioactive compound found in the leaves of the Xanthium strumarium (Asteracae) plant. It is classified as a natural sesquiterpene lactone. Xanthatin is believed to have anti-inflammatory, anti-tumour, anti-microbial, and anti-parasitic properties hence it is being researched for potential use in treatment of cancer and autoimmune diseases. While it has been used in traditional medicine for decades, its mechanisms and modern use haven’t been fully understood yet.

References

  1. 1 2 Perry NB, Burgess EJ, Rodríguez Guitián MA, Romero Franco R, López Mosquera E, Smallfield BM, Joyce NI, Littlejohn RP (May 2009). "Sesquiterpene lactones in Arnica montana: helenalin and dihydrohelenalin chemotypes in Spain". Planta Medica. 75 (6): 660–6. doi:10.1055/s-0029-1185362. PMID   19235681.
  2. 1 2 3 4 5 Tornhamre, Susanne; Schmidt, Thomas J.; Näsman-Glaser, Barbro; Ericsson, Inger; Lindgren, Jan Åke (2001). "Inhibitory effects of helenalin and related compounds on 5-lipoxygenase and leukotriene C 4 synthase in human blood cells". Biochemical Pharmacology. 62 (7): 903–911. doi:10.1016/S0006-2952(01)00729-8. PMID   11543725.
  3. 1 2 Widen JC, Kempema AM, Baur JW, Skopec HM, Edwards JT, Brown TJ, Brown DA, Meece FA, Harki DA (February 2018). "Helenalin Analogues Targeting NF-κB p65: Thiol Reactivity and Cellular Potency Studies of Varied Electrophiles". ChemMedChem. 13 (4): 303–311. doi:10.1002/cmdc.201700752. PMC   5894512 . PMID   29349898.
  4. ↑ Zwicker P, Schultze N, Niehs S, Albrecht D, Methling K, Wurster M, Wachlin G, Lalk M, Lindequist U, Haertel B (April 2017). "Differential effects of Helenalin, an anti-inflammatory sesquiterpene lactone, on the proteome, metabolome and the oxidative stress response in several immune cell types". Toxicology in Vitro. 40: 45–54. doi:10.1016/j.tiv.2016.12.010. PMID   27998807.
  5. ↑ Poole LB (March 2015). "The basics of thiols and cysteines in redox biology and chemistry". Free Radical Biology & Medicine. 80: 148–57. doi:10.1016/j.freeradbiomed.2014.11.013. PMC   4355186 . PMID   25433365.
  6. ↑ Beekman AC, Woerdenbag HJ, van Uden W, Pras N, Konings AW, Wikström HV, Schmidt TJ (March 1997). "Structure-cytotoxicity relationships of some helenanolide-type sesquiterpene lactones". Journal of Natural Products. 60 (3): 252–7. doi:10.1021/np960517h. PMID   9090867.
  7. 1 2 3 Huang PR, Yeh YM, Wang TC (September 2005). "Potent inhibition of human telomerase by helenalin". Cancer Letters. 227 (2): 169–74. doi:10.1016/j.canlet.2004.11.045. PMID   16112419.
  8. 1 2 Chapman DE, Roberts GB, Reynolds DJ, Grippo AA, Holbrook DJ, Hall IH, Chaney SG, Chang J, Lee KH (February 1988). "Acute toxicity of helenalin in BDF1 mice". Fundamental and Applied Toxicology. 10 (2): 302–12. doi:10.1016/0272-0590(88)90315-6. PMID   3356317.
  9. 1 2 Berges C, Fuchs D, Opelz G, Daniel V, Naujokat C (September 2009). "Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms". Molecular Immunology. 46 (15): 2892–901. doi:10.1016/j.molimm.2009.07.004. PMID   19656571.
  10. ↑ Hall IH, Starnes CO, Lee KH, Waddell TG (May 1980). "Mode of action of sesquiterpene lactones as anti-inflammatory agents". Journal of Pharmaceutical Sciences. 69 (5): 537–43. doi:10.1002/jps.2600690516. PMID   6247478.
  11. ↑ Lee KH, Hall IH, Mar EC, Starnes CO, ElGebaly SA, Waddell TG, Hadgraft RI, Ruffner CG, Weidner I (April 1977). "Sesquiterpene antitumor agents: inhibitors of cellular metabolism". Science. 196 (4289): 533–6. Bibcode:1977Sci...196..533L. doi:10.1126/science.191909. PMID   191909.
  12. ↑ Schröder H, Lösche W, Strobach H, Leven W, Willuhn G, Till U, Schrör K (March 1990). "Helenalin and 11 alpha,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways". Thrombosis Research. 57 (6): 839–45. doi:10.1016/0049-3848(90)90151-2. PMID   2116680.
  13. ↑ Brito, N; Knipschild, P; Doreste-Alonso, J (2014). "Systematic Review on the Efficacy of Topical Arnica montanafor the Treatment of Pain, Swelling and Bruises". Journal of Musculoskeletal Pain. 22 (2): 216–223. doi:10.3109/10582452.2014.883012. S2CID   76330596.
  14. ↑ "U.S. National Library of Medicine," [Online]. Available: https://clinicaltrials.gov/ct2/results?cond=&term=arnica+montana&cntry=&state=&city=&dist=. [Accessed 8 March 2018].
  15. ↑ Hall IH, Lee KH, Starnes CO, Muraoka O, Sumida Y, Waddell TG (June 1980). "Antihyperlipidemic activity of sesquiterpene lactones and related compounds". Journal of Pharmaceutical Sciences. 69 (6): 694–7. doi:10.1002/jps.2600690622. PMID   7205585.
  16. ↑ Witzel DA, Ivie W, Dollahite JW (July 1976). "Mammalian toxicity of helenalin, the toxic principle of Helenium microcephalum CD (smallhead sneezeweed)". American Journal of Veterinary Research. 37 (7): 859–61. PMID   937811.
  17. ↑ Lin X, Zhang S, Huang R, Wei L, Tan S, Liang S, Tian Y, Wu X, Lu Z, Huang Q (June 2014). "Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation". Fitoterapia. 95: 203–13. doi:10.1016/j.fitote.2014.03.020. PMID   24704336. (Retracted, see doi:10.1016/j.fitote.2024.106195, PMID   39217083 . If this is an intentional citation to a retracted paper, please replace {{ retracted |...}} with {{ retracted |...|intentional=yes}}.)
  18. ↑ B. H. Rumack, "POISINDEX(R) Information System Micromedex, Inc.", CCIS, vol. 172, 2017.
  19. ↑ A. H. Hall and B. H. Rumack, "TOMES(R) Information System Micromedex, Inc." CCIS, vol. 172, 2017
  20. ↑ Powis G, Gallegos A, Abraham RT, Ashendel CL, Zalkow LH, Grindey GB, Bonjouklian R (1994). "Increased intracellular Ca2+ signaling caused by the antitumor agent helenalin and its analogues". Cancer Chemotherapy and Pharmacology. 34 (4): 344–50. doi:10.1007/BF00686043. PMID   8033301. S2CID   22818483.
  21. ↑ Lyss G, Knorre A, Schmidt TJ, Pahl HL, Merfort I (December 1998). "The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65". The Journal of Biological Chemistry. 273 (50): 33508–16. doi: 10.1074/jbc.273.50.33508 . PMID   9837931.
  22. ↑ Jimenez-Ortiz V, Brengio SD, Giordano O, Tonn C, Sánchez M, Burgos MH, Sosa MA, et al. (February 2005). "The trypanocidal effect of sesquiterpene lactones helenalin and mexicanin on cultured epimastigotes". The Journal of Parasitology. 91 (1): 170–4. doi:10.1645/GE-3373. PMID   15856894. S2CID   42378778.
  23. ↑ Schmidt TJ, Brun R, Willuhn G, Khalid SA (August 2002). "Anti-trypanosomal activity of helenalin and some structurally related sesquiterpene lactones". Planta Medica. 68 (8): 750–1. doi:10.1055/s-2002-33799. PMID   12221603.
  24. ↑ François G, Passreiter CM (February 2004). "Pseudoguaianolide sesquiterpene lactones with high activities against the human malaria parasite Plasmodium falciparum". Phytotherapy Research. 18 (2): 184–6. doi:10.1002/ptr.1376. PMID   15022176. S2CID   3048612.
  25. ↑ Boulanger D, Brouillette E, Jaspar F, Malouin F, Mainil J, Bureau F, Lekeux P, et al. (January 2007). "Helenalin reduces Staphylococcus aureus infection in vitro and in vivo". Veterinary Microbiology. 119 (2–4): 330–8. doi:10.1016/j.vetmic.2006.08.020. PMID   17010538.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.