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Volume 32, Issue 9
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Ranunculin, a glucoside, serves as a chemotaxonomic marker in Ranunculaceae plants. When these plants are damaged, an enzyme β−glucosidase triggers the conversion of ranunculin into protoanemonin through hydrolysis. Subsequently, protoanemonin undergoes cyclodimerization to form anemonin. The inherent instability of ranunculin and the rapid dimerization of protoanemonin render them unsuitable for use in biological assays. Conversely, anemonin stands out as the optimal molecule for bioassays and demonstrates diverse biological properties, including anti-inflammatory, anti-infective, and anti-oxidant effects. Among these, anemonin exhibits the greatest promise in addressing arthritis, cerebral ischemia, and ulcerative colitis. Its potential medical uses are enhanced by its capacity to inhibit nitric oxide synthesis and successfully counteract lipopolysaccharide-induced inflammation. This review describes the chemistry and biological properties of anemonin and its precursors, including discussions on extraction, isolation, synthesis, and investigations into bioactivity and pharmacokinetics.

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2024-02-28
2025-04-13

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References

  1. HillR. Van HeyningenR. Ranunculin: The precursor of the vesicant substance of the buttercup.Biochem. J.195149333233510.1042/bj049033214858339
     [Google Scholar]
  2. NeagT. OlahN.K. HanganuD. BenedecD. PriponF.F. ArdeleanA. TomaC.C. The anemonin content of four different ranunculus species.Pak. J. Pharm. Sci.201831Supp. 52027203230393208
     [Google Scholar]
  3. HsiehP.W. ChangF.R. YenH.F. WuY.C. Anemonin and two norsesquiterpenes from Drymaria diandra. Biochem. Syst. Ecol.200331554154310.1016/S0305‑1978(02)00182‑5
     [Google Scholar]
  4. JiangL. ChiC. YuanF. LuM. HuD. WangL. LiuX. Anti-inflammatory effects of anemonin on acute ulcerative colitis via targeted regulation of protein kinase C-θ.Chin. Med.20221713910.1186/s13020‑022‑00599‑335346284
     [Google Scholar]
  5. SouthwellI.A. TuckerD.J. Protoanemonin in Australian Clematis.Phytochemistry19933351099110210.1016/0031‑9422(93)85030‑U
     [Google Scholar]
  6. MoriartyR.M. RomainC.R. KarleI.L. KarleJ. The structure of anemonin.J. Am. Chem. Soc.196587143251325210.1021/ja01092a047
     [Google Scholar]
  7. MahranG. SaberA. El-AlfyT. Spectrophotometric determination of protoanemonin, anemonin and ranunculin in Ranunculus sceleratus L.Planta Med.196816332332810.1055/s‑0028‑10999155734279
     [Google Scholar]
  8. MaresD. Antimicrobial activity of protoanemonin, a lactone from ranunculaceous plants.Mycopathologia198798313314010.1007/BF004376483587338
     [Google Scholar]
  9. JhaA.K. SitN. Extraction of bioactive compounds from plant materials using combination of various novel methods: A review.Trends Food Sci. Technol.202211957959110.1016/j.tifs.2021.11.019
     [Google Scholar]
  10. NachmanR.J. OlsenJ.D. Ranunculin: A toxic constituent of the poisonous range plant bur buttercup (Ceratocephalus testiculatus).J. Agric. Food Chem.19833161358136010.1021/jf00120a0526655145
     [Google Scholar]
  11. NonoN.R. NzowaK.L. BarboniL. TapondjouA.L. Drymaria cordata (Linn.) willd (caryophyllaceae): Ethnobotany, pharmacology and phytochemistry.Adv. Biol. Chem.20144216016710.4236/abc.2014.42020
     [Google Scholar]
  12. LouaarS. AkkalS. DuddeckH. MakhloufiE. AchouriA. MedjroubiK. Secondary metabolites of Ranunculus bulbosus. Chem. Nat. Compd.201248116616710.1007/s10600‑012‑0193‑5
     [Google Scholar]
  13. AliI. KhatoonS. AmberF. AbbasQ. IsmailM. EngelN. AhmadV.U. Isolation of anemonin from Pulsatilla wallichiana and its biological activities.J. Chem. Soc. Pak.201941232533310.52568/000742/JCSP/41.02.2019
     [Google Scholar]
  14. NazirS. LiB. TahirK. KhanA. KhanZ. KhanS. Antimicrobial activity of five constituents isolated from Ranunculus muricatus. J. Med. Plants Res.20134734383443
     [Google Scholar]
  15. KarleI.L. KarleJ. The crystal and molecular structure of anemonin, C10H8O4.Acta Crystallogr.196620455555910.1107/S0365110X66001233
     [Google Scholar]
  16. BennM. YellandL.J. ParvezM. Ranunculin.Acta Crystallogr. Sect. E Struct. Rep. Online20106610o250310.1107/S160053681003484721587499
     [Google Scholar]
  17. JinF. NarkowiczC. JacobsonG.A. Protoanemonin content variation between Clematis spp.: Leaf, stem and root.Nat. Prod. Commun.2013821934578X130080010.1177/1934578X130080022023513731
     [Google Scholar]
  18. SaidiR. GhrabF. KallelR. FekiA.E. BoudawaraT. ChesnéC. AmmarE. JarrayaR.M. Tunisian Clematis flammula essential oil enhances wound healing: GC-MS analysis, biochemical and histological assessment.J. Oleo Sci.201867111483149910.5650/jos.ess1805630404969
     [Google Scholar]
  19. SirakB. MannL. RichterA. AsresK. ImmingP. In vivo antimalarial activity of leaf extracts and a major compound isolated from Ranunculus multifidus forsk.Molecules20212620617910.3390/molecules2620617934684762
     [Google Scholar]
  20. BonoraA. Dall’OlioG. BruniA. Separation and quantitation of protoanemonin in ranunculaceae by normal- and reversed-phase HPLC.Planta Med.198551536436710.1055/s‑2007‑96952117342584
     [Google Scholar]
  21. RoderickW.R. Naturally occurring oxygen ring compounds (Dean, F. M.).J. Chem. Educ.196441951910.1021/ed041p519.3
     [Google Scholar]
  22. BonoraA. Dall’OlioG. DoniniA. BruniA. An hplc screening of some italian ranunculaceae for the lactone protoanemonin.Phytochemistry19872682277227910.1016/S0031‑9422(00)84700‑7
     [Google Scholar]
  23. BruniA. BonoraA. Dall’OlioG. Protoanemonin detection in Caltha palustris. J. Nat. Prod.19864961172117310.1021/np50048a058
     [Google Scholar]
  24. BaerH. HoldenM. SeegalB.C. The nature of the antibacterial agent from Anemone pulsatilla. J. Biol. Chem.19461621656810.1016/S0021‑9258(17)41459‑121010893
     [Google Scholar]
  25. MartínM. RománL. DomínguezA. In vitro activity of protoanemonin, an antifungal agent.Planta Med.1990561666910.1055/s‑2006‑9608862356244
     [Google Scholar]
  26. ShawE. A synthesis of protoanemonin; The tautomerism of acetylacrylic acid and of penicillic acid.J. Am. Chem. Soc.194668122510251310.1021/ja01216a02420282388
     [Google Scholar]
  27. GrundmannC. KoberE. An improved synthesis of protoanemonin.J. Am. Chem. Soc.19557782332233310.1021/ja01613a092
     [Google Scholar]
  28. SugaT. HirataT. The biosynthesis of protoanemonin in Ranunculus glaber Makino.Chem. Lett.19732763764010.1246/cl.1973.637
     [Google Scholar]
  29. SugaT. HirataT. HorikawaT. WakiN. The genuine precursor for the biosynthesis of protoanemonin in Ranunculus glaber. Chem. Lett.19743101201120210.1246/cl.1974.1201
     [Google Scholar]
  30. SugaT. HirataT. OkamotoE. KataokaM. Biosynthesis of protoanemonin in Ranunculus glaber. The stereochemistry of the hydrogen elimination in the formation of the double bond of protoanemonin.Chem. Lett.19776670971010.1246/cl.1977.709
     [Google Scholar]
  31. TschescheR. WirthW. WelmarK. 5-Hydroxylevulinic acid, a new intermediate in the biosynthesis of protoanemonin.Phytochemistry19812081835183910.1016/0031‑9422(81)84015‑0
     [Google Scholar]
  32. CardellachJ. EstopaC. FontJ. Moreno-MañasM. OrtuñoR.M. Sánchez-FerrandoF. ValleS. VilamajoL. Studies on structurally simple α,β-butenolides-I.Tetrahedron198238152377239410.1016/0040‑4020(82)87016‑6
     [Google Scholar]
  33. CampsP. CardellachJ. FontJ. OrtuñoR.M. PonsatiO. Studies on structurally simple α,β-butenolides—II.Tetrahedron198238152395240210.1016/0040‑4020(82)87017‑8
     [Google Scholar]
  34. FangZ. ZhouJ. HuangL. Studies of the total synthesis of (-)-ranunculin.Yao Xue Xue Bao19892431821882816373
     [Google Scholar]
  35. CottierL. DescotesG. SoroY. Synthesis of acetylated ranunculin diastereoisomers and δ–glucosyloxy–γ–oxo esters from α or β glucosylmethylfurfural.J. Carbohydr. Chem.2005241557110.1081/CAR‑200049688
     [Google Scholar]
  36. LichtenthalerF.W. MartinD. WeberT. SchiweckH. Studies on ketoses, 7 – 5-(α-D-glucosyloxymethyl) furfural: preparation from isomaltulose and exploration of its ensuing chemistry.Liebigs Ann. Chem.19931993996797410.1002/jlac.1993199301154
     [Google Scholar]
  37. AlibésR. FontJ. MuláA. OrtuñoR.M. Studies on structurally simple α,β-butenolides. XI. a new and convenient synthesis of protoanemonin.Synth. Commun.199020172607261510.1080/00397919008051468
     [Google Scholar]
  38. BlascoR. WittichR.M. MallavarapuM. TimmisK.N. PieperD.H. From xenobiotic to antibiotic, formation of protoanemonin from 4-chlorocatechol by enzymes of the 3-oxoadipate pathway.J. Biol. Chem.199527049292292923510.1074/jbc.270.49.292297493952
     [Google Scholar]
  39. AlonsoD. OrtiJ. BranchadellV. OlivaA. OrtunoR.M. BertranJ. FontJ. 5-Methylene-2(5H)-furanone as a dienophile in Diels-Alder cycloadditions: site-selectivity and regioselectivity.J. Org. Chem.199055103060306310.1021/jo00297a021
     [Google Scholar]
  40. BangS.C. KimY. YunM.Y. AhnB.Z. 5-Arylidene-2(5H)-furanone derivatives: Synthesis and structure-activity relationship for cytotoxicity.Arch. Pharm. Res.200427548549410.1007/BF0298012015202552
     [Google Scholar]
  41. MahajanV.A. Design and synthesis of β-substituted-γ-methylenefuranones, related lignan analogues and synthetic studies towards saintopin.PhD thesis, University of Pune. 2025, 1-283.
     [Google Scholar]
  42. KataokaH. YamadaK. SugiyamaN. The photo-synthesis of anemonin from protoanemonin.B.C.S.J.19653811
     [Google Scholar]
  43. HirabayashiT. YokotaK. Oligomerization of protoanemonin with n-butyllithium.Polym. J.198921434134610.1295/polymj.21.341
     [Google Scholar]
  44. StamosI.K. HowieG.A. ManniP.E. HawsW.J. ByrnS.R. CassadyJ.M. Synthesis and structures of dilactones related to anemonin.J. Org. Chem.197742101703170910.1021/jo00430a008
     [Google Scholar]
  45. StamosI.K. CassadyJ.M. A trilactone related to anemonin.J. Heterocycl. Chem.19963331001100210.1002/jhet.5570330376
     [Google Scholar]
  46. HakanA. KaragözY. Ranunculus sericeus Banks Sol. extract fractions possess antibacterial and antifungal activity.E.A.J.S20184915
     [Google Scholar]
  47. HuangY.H. LeeT.H. ChanK.J. HsuF.L. WuY.C. LeeM.H. Anemonin is a natural bioactive compound that can regulate tyrosinase-related proteins and mRNA in human melanocytes.J. Dermatol. Sci.200849211512310.1016/j.jdermsci.2007.07.00817766092
     [Google Scholar]
  48. DuanH. ZhangY. XuJ. QiaoJ. SuoZ. HuG. MuX. Effect of anemonin on NO, ET-1 and ICAM-1 production in rat intestinal microvascular endothelial cells.J. Ethnopharmacol.2006104336236610.1016/j.jep.2005.09.03416257161
     [Google Scholar]
  49. XiaoK. CaoS.T. JiaoL.F. LinF.H. WangL. HuC.H. Anemonin improves intestinal barrier restoration and influences TGF-β1 and EGFR signaling pathways in LPS-challenged piglets.Innate Immun.201622534435210.1177/175342591664822327189428
     [Google Scholar]
  50. MaZ. YuP. LiX. DaiF. JiangH. LiuJ. Anemonin reduces hydrogen peroxide-induced oxidative stress, inflammation and extracellular matrix degradation in nucleus pulposus cells by regulating NOX4/NF-κB signaling pathway.J. Orthop. Surg. Res.202318118910.1186/s13018‑023‑03679‑836899420
     [Google Scholar]
  51. FostokS.F. EzzeddineR.A. HomaidanF.R. Al-SaghirJ.A. SalloumR.G. SalibaN.A. TalhoukR.S. Interleukin-6 and Cyclooxygenase-2 downregulation by fatty-acid fractions of Ranunculus constantinopolitanus. BMC Complement. Altern. Med.2009914410.1186/1472‑6882‑9‑4419917107
     [Google Scholar]
  52. WangZ. HuangJ. ZhouS. LuoF. XuW. WangQ. TanQ. chenL. WangJ. ChenH. ChenL. XieY. DuX. Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL -1β/ NF -κB pathway.J. Cell. Mol. Med.201721123231324310.1111/jcmm.1322728643466
     [Google Scholar]
  53. HouH. PengQ. WangS. ZhangY. CaoJ. DengY. WangY. SunW. WangH. Anemonin attenuates RANKL-induced osteoclastogenesis and ameliorates LPS-induced inflammatory bone loss in mice via modulation of NFATc1.Front. Pharmacol.202010169610.3389/fphar.2019.0169632116686
     [Google Scholar]
  54. NingY. RaoY. YuZ. LiangW. LiF. Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian.Pharmazie201671313413827183707
     [Google Scholar]
  55. MisraS.B. DixitS.N. Antifungal principle of Ranunculus sceleratus. Econ. Bot.198034436236710.1007/BF02858312
     [Google Scholar]
  56. BrodersenR. KjærA. The antibacterial action and toxicity of some unsaturated lactones.Acta Pharmacol. Toxicol.19462210912010.1111/j.1600‑0773.1946.tb02603.x20277024
     [Google Scholar]
  57. SirakB. AsresK. HailuA. DubeM. ArnoldN. HäberliC. KeiserJ. ImmingP. In vitro antileishmanial and antischistosomal activities of Anemonin isolated from the fresh leaves of Ranunculus multifidus forsk.Molecules20212624747310.3390/molecules2624747334946555
     [Google Scholar]
  58. JiaD. HanB. YangS. ZhaoJ. Anemonin alleviates nerve injury after cerebral ischemia and reperfusion (i/r) in rats by improving antioxidant activities and inhibiting apoptosis pathway.J. Mol. Neurosci.201453227127910.1007/s12031‑013‑0217‑z24443273
     [Google Scholar]
  59. QiaoL. LiuY. LiC. GeJ. LiT. Regulation of iRhom-2/Tumor necrosis factor-α converting enzyme pathway and oxidative stress protects the renal injury with anemonin in streptozotocin-induced diabetic nephropathy neonatal rat model.Pharmacology20191045-625826610.1159/00050163131344701
     [Google Scholar]
  60. PirvuL. StefaniuA. NeaguG. PintilieL. Studies on Anemone nemorosa L. extracts; Polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies.Open Chem.202220129931210.1515/chem‑2022‑0137
     [Google Scholar]
  61. Villegas PañedaA.G. Ramírez ApanM.T.O. Synthesis and cytotoxic evaluation of protoanemonin and three brominated derivatives.Rev. Colomb. Quim.2020493131810.15446/rcq.v49n3.87159
     [Google Scholar]
  62. LeeT.H. HuangN.K. LaiT.C. YangA.T.Y. WangG.J. Anemonin, from Clematis crassifolia, potent and selective inducible nitric oxide synthase inhibitor.J. Ethnopharmacol.2008116351852710.1016/j.jep.2007.12.01918281171
     [Google Scholar]
  63. NingY.M. RaoY.F. LiangW.Q. Influence of permeation enhancers on transdermal permeation of anemonin.Zhongguo Zhongyao Zazhi200732539339617511142
     [Google Scholar]
  64. ButnariuM. Biodiversity of the phytoconstituents in some plant species potentially toxic.J. Biodivers. Endanger. Species201751110.4172/2332‑2543.1000e127
     [Google Scholar]
  65. WinkM. Mode of action and toxicology of plant toxins and poisonous plants.Mitt. Julius. Kühn-Inst200942193112
     [Google Scholar]
  66. TurnerN.J. Counter-irritant and other medicinal uses of plants in ranunculaceae by native peoples in british columbia and neighbouring areas.J. Ethnopharmacol.198411218120110.1016/0378‑8741(84)90038‑26387285
     [Google Scholar]
  67. CalderonA. FontJ. Ortun¯oR.M. Studies on structurally simple αβ-butenolides. IV. behaviour of protoanemonin as electrophile towards alcohols and thiols.Tetrahedron198440193787379410.1016/S0040‑4020(01)88808‑6
     [Google Scholar]
  68. BigorraJ. FontJ. JaimeC. OrtuñoR.M. Sanchez-FerrandoF. Studies on structurally simple butenolides. V. reactions of protoanemonin with piperidine and -nucleophiles.Tetrahedron198541235577558710.1016/S0040‑4020(01)91359‑6
     [Google Scholar]
  69. TeixeiraR. BarbosaL. MalthaC. RochaM. BezerraD. Costa-LotufL. PessoaC. MoraesM. Synthesis and cytotoxic activity of some 3-benzyl-5-arylidenefuran-2(5H)-ones.Molecules20071251101111610.3390/1205110117873844
     [Google Scholar]
  70. RoscaM.G. HoppelC.L. Mitochondrial dysfunction in heart failure.Heart Fail. Rev.201318560762210.1007/s10741‑012‑9340‑022948484
     [Google Scholar]
  71. SchrenkD. MerzK.H. JochimsK. Feasibility study of nonclinical safety assessments on homeopathic preparations using the example of protoanemonin in Pulsatilla pratensis L.Regul. Toxicol. Pharmacol.201366110410810.1016/j.yrtph.2013.03.00423535118
     [Google Scholar]
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Ranunculin, Protoanemonin, and Anemonin: Pharmacological and Chemical Perspectives
Curr. Med. Chem. 32, 1659 (2025); https://doi.org/10.2174/0109298673294080240221115830
/content/journals/cmc/10.2174/0109298673294080240221115830
/content/journals/cmc/10.2174/0109298673294080240221115830
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  • Article Type:     Review Article
Keyword(s): biological activities; cerebral ischemia; medicinal plants; natural products; nitric oxide; Ranunculaceae

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