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Lipoxygenase inhibitors from the latex of Calotropis Procera

Abstract

A radical-scavenging, guided phytochemical study of the latex of Calotropis Procera afforded five lignans (15), including a new one (4). The structural determination was accomplished using 1D- and 2D-NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and correlation with known compounds. Among the isolated compounds, acylated lignans (35) showed stronger antioxidant activity than non-acylated derivatives (1,2). Anti-inflammatory activity was evaluated by determining the inhibitory potential against 5- and 15-lipoxygenase enzymes. The highest anti-inflammatory activity was observed in compound 4, with IC50s values of 7.6 µM and 2.7 µM against 5-LOX and 15-LOX, respectively.

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References

  1. Abdel-Mageed WM, Milne BF, Wagner M, Schumacher M, Sandor P, Pathom-aree W, Goodfellow M, Bull AT, Horikoshi K, Ebel R, Diederich M, Fiedler HP, Jaspars M (2010) Dermacozines, a new phenazine family from deep-sea dermacocci isolated from a Mariana Trench sediment. Org Biomol Chem 8:2352–2362

    CAS  Article  PubMed  Google Scholar 

  2. Abdel-Mageed WM, Backheet EY, Khalifa AA, Ibraheim ZZ, Ross SA (2012) Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis. Fitoterapia 83:500–507

    CAS  Article  PubMed  Google Scholar 

  3. Abdel-Mageed WM, Bayoumi SAH, Radwan AA, Salem-Bekhit MM, Abd-Alrahman SH, Basudan OA, Sayed HM (2014) Simmondsia chinensis: a rich source of bioactive flavonoids and lignans. Ind Crops Prod 60:99–103

    CAS  Article  Google Scholar 

  4. Al-Qarawi AA, Mahmoud OM, Sobaih MA, Haroun EM, Adam SE (2001) A preliminary study on the anthelmintic activity of Calotropis procera latex against Haemonchus contortus infection in Najdi sheep. Vet Res Commun 25:61–70

    CAS  Article  PubMed  Google Scholar 

  5. Ansari SH, Ali M (2001) Norditerpenic ester and pentacyclic triterpenoids from root bark of Calotropis procera (Ait) R. Br Pharmazie 56:175–177

    CAS  PubMed  Google Scholar 

  6. Arya S, Kumar VL (2005) Antiinflammatory efficacy of extracts of latex of Calotropis procera against different mediators of inflammation. Mediators Inflamm 2005:228–232

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bai LP, Ho HM, Ma DL, Yang H, Fu WC, Jiang ZH (2013) Aminoglycosylation can enhance the G-quadruplex binding activity of epigallocatechin. PLoS ONE 8:e53962

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Begum N, Sharma B, Pandey RS (2010) Evaluation of Insecticidal Efficacy of Calotropis Procera and Annona Squamosa Ethanol Extracts Against Musca Domestica. J Biofert Biopest 1:1–6

    Google Scholar 

  9. Choedon T, Mathan G, Arya S, Kumar VL, Kumar V (2006) Anticancer and cytotoxic properties of the latex of Calotropis procera in a transgenic mouse model of hepatocellular carcinoma. World J Gastroenterol 12:2517–2522

    PubMed  PubMed Central  Google Scholar 

  10. Cuvelier ME, Richard H, Berset C (1992) Comparison of the antioxidative activity of some acid-phenols: structure-activity relationship. Biosci Biotechnol Biochem 56:324–325

    CAS  Article  Google Scholar 

  11. Dewan S, Kumar S, Kumar VL (2000) Antipyretic effect of latex of Calotropis procera. Indian J Pharmacol 32:252

    Google Scholar 

  12. Dong-Mei W, Wen-Jun P, Yong-Hong W, Yu-Juan Z, Shan-Shan W (2012) A New Isorhamnetin Glycoside and Other Phenolic Compounds from Callianthemum taipaicum. Molecules 17:4595–4603

    Article  Google Scholar 

  13. Doshi H, Satodiya H, Thakur MC, Parabia F, Khan A (2011) Phytochemical screening and biological activity of Calotropis Procera (Ait). R. Br. (Asclepiadaceae) against selected bacteria and Anopheles stephansi Larvae. Int J Plant Res 1:29–33

    Article  Google Scholar 

  14. Farzin MP, Kothari IL, Parabia MH (2008) Antibacterial activity of solvent fractions of crude water decoction of apical twigs and latex of Calotropis procera (Ait.) R. Br. Nat Prod Radiance 7:30–34

    Google Scholar 

  15. Gill SS, Tuteja N (2010) Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants. Plant Physiol Biochem 48:909–930

    CAS  Article  PubMed  Google Scholar 

  16. Gupta VK, Sharma SK (2006) Plants as natural antioxidants. Nat Prod Radiance 5:326–334

    Google Scholar 

  17. Harne S, Sharma A, Dhaygude M, Joglekar S, Kodam K, Hudlikar M (2012) Novel route for rapid biosynthesis of copper nanoparticles using aqueous extract of Calotropis procera L. latex and their cytotoxicity on tumor cells. Colloids Surf B Biointerfaces 95:284–288

    CAS  Article  PubMed  Google Scholar 

  18. Ibraheim ZZ, Abdel-Mageed WM, Dai H, Guo H, Zhang L, Jaspars M (2012) Antimicrobial antioxidant daucane sesquiterpenes from Ferula hermonis Boiss. Phytother Res 26:579–586

    CAS  Article  PubMed  Google Scholar 

  19. Joshi R, Sharma A, Jat BL (2009) Analysis of antioxidant activity in extracts of Calotropis procera (Ait.) R. Br. J Appl Biosci 17:899–903

    Google Scholar 

  20. Kamel HS, Nagy M, Heidi Z, Johannes FI, Bernd S (2010) Secondary metabolites from Calotropis procera (Aiton). Phytochem Lett 3:212–216

    Article  Google Scholar 

  21. Kareem SO, Akpan I, Ojo OP (2008) Antimicrobial activities of Calotropis procera on selected pathogenic microorganisms. African J Biomed Res 11:105–110

    Google Scholar 

  22. Kawo AH, Mustapha A, Abdullahi BA, Rogo LD, Gaiya ZA, Kumurya AS (2009) Phytochemical properties and antibacterial activities of the leaf and latex extracts of Calotropis procera (Ait. F.). Bayero J Pure Appl Sci 2:34–40

    Google Scholar 

  23. Khasawneh MA, Elwy HM, Fawzi NM, Hamza AA, Chevidenkandy A, Hassan AH (2011) Antioxidant activity, lipoxygenase inhibitory effect and polyphenolic compounds from Calotropis procera (Ait.) R. Br. Res J Phytochem 5:80–88

    CAS  Article  Google Scholar 

  24. Kirley MC, Mary ASL, Edilberto RS (2010) Amburosides C-H and 6-O-Protocatechuoyl Coumarin from Amburana cearensis. J Braz Chem Soc 21:1746–1753

    Article  Google Scholar 

  25. Kohyama N, Nagata T, Fujimoto SI, Sekiya K (1997) Inhibition of arachidonate lipoxygenase activities by 2-(3,4-dihydroxyphenyl)ethanol, a phenolic compound from olives. Biosci Biotech Biochem 61:347–350

    CAS  Article  Google Scholar 

  26. Kumar VL, Roy S (2009) Protective effect of latex of Calotropis procera in Freund’s complete adjuvant induced monoarthritis. Phytother Res 23:1–5

    CAS  Article  PubMed  Google Scholar 

  27. Kumar S, Dewan S, Sangraula H, Kumar VL (2001) Anti-diarrhoeal activity of the latex of Calotropis procera. J Ethnopharmacol 76:115–118

    CAS  Article  PubMed  Google Scholar 

  28. Larhsini M, Markouk M, Jaouhari JT, Bekkouche K, Lazrek HB, Jana M (2002) The antipyretic activity of some Moroccan medicinal plants. Phytother Res 16:97–98

    Article  Google Scholar 

  29. Mabalirajan U, Rehman R, Ahmad T, Kumar S, Leishangthem GD, Singh S, Dinda AK, Biswal S, Agrawal A (2013) 12/15-lipoxygenase expressed in non-epithelial cells causes airway epithelial injury in asthma. Sci Rep 3:1540–1550

    PubMed  PubMed Central  Google Scholar 

  30. Mahajan RT, Badgujar SB (2008) Phytochemical investigation of some lactiferous plants belonging to Khandesh region of Maharashtra. Ethnobot Leaflets 12:1145–1152

    Google Scholar 

  31. Mathew S, Abraham TE, Zakaria ZA (2015) Reactivity of phenolic compounds towards free radicals under in vitro conditions. J Food Sci Technol. doi:10.1007/s13197-014-1704-0

    Google Scholar 

  32. Matsunami K, Otsuka H, Kondo K, Shinzato T, Kawahata M, Yamaguchi K, Takeda Y (2009) Absolute configuration of (+)-pinoresinol 4-O-[6′’-O-galloyl]-beta-d-glucopyranoside, macarangiosides E, and F isolated from the leaves of Macaranga tanarius. Phytochemistry 70:1277–1285

    CAS  Article  PubMed  Google Scholar 

  33. Meena AK, Yadav MM, Niranjan US, Singh B, Nagariya AK, Sharma K, Gaurav A, Sharma S, Rao MM (2010) A review of Calotropis procera Linn and its ethnobotany, phytochemical and pharmacological profile. Drug Invent Today 2:185–190

    Google Scholar 

  34. Mijatovic T, Van Quaquebeke E, Delest B, Debeir O, Darro F, Kiss R (2007) Cardiotonic steroids on the road to anti-cancer therapy. BBA Rev Cancer 1776:32–57

    CAS  Google Scholar 

  35. Moursy LE (1997) Insecticidal activity of Calotropis procera extracts of the flesh fly, Sarcophaga haemorrhoidalis fallen. J Egypt Soc Parasitol 2:505–514

    Google Scholar 

  36. Nadia HM, Miaomiao L, Wael MA, Lamya HA, Huanqin D, Mady AI, Gamal B, Ronald JQ, Xueting L, Lixin Z, Ahmed AMS (2015) Cytotoxic cardenolides from the latex of Calotropis procera. Bioorg Med Chem Lett 25:4615–4620

    Article  Google Scholar 

  37. Natella F, Nardini M, di Felice M, Scaccini C (1999) Benzoic and cinnamic acid derivatives as antioxidants: structure-activity relation. J Agric Food Chem 47:1453–1459

    CAS  Article  PubMed  Google Scholar 

  38. Ouyang MA, Wein YS, Zhang ZK, Kuo YH (2007) Inhibitory Activity against Tobacco Mosaic Virus (TMV) Replication of Pinoresinol and Syringaresinol Lignans and Their Glycosides from the Root of Rhus javanica var. roxburghiana. J Agric Food Chem 55:6460–6465

    CAS  Article  PubMed  Google Scholar 

  39. Parhira S, Yang ZF, Zhu GY, Chen QL, Zhou BX, Yu-Tao WYT, Liu L, Bai LP, Jiang ZH (2014) In Vitro anti-influenza virus activities of a New Lignan Glycoside from the Latex of Calotropis gigantea. PLoS ONE 9:e104544

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rackova L, Oblozinsky M, Kostalova D, Kettmann V, Bezakova L (2007) Free radical scavenging activity and lipoxygenase inhibition of Mahonia aquifolium extract and isoquinoline alkaloids. J Inflammation 4:15–21

    Article  Google Scholar 

  41. Ramos MV, Bandeira GP, De Freitas CD, Nogueira NA, Alencar NM, De Sousa PA, Carvalho AF (2006) Latex constituents from Calotropis procera (R. Br.) display toxicity upon egg hatching and larvae of Aedes aegypti (Linn.). Mem Inst Oswaldo Cruz 101:503–510

    Article  PubMed  Google Scholar 

  42. Ramos MV, Aguiar VC, Melo VMM, Mesquita RO, Silvestre PP, Oliveira JS, Macedo NM, Alencar NM (2007) Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R. Br. J Ethnopharmacol 111:115–122

    CAS  Article  PubMed  Google Scholar 

  43. Ramos MV, Oliveira JS, Figueiredo JG, Figueireido IS, Kumar VL, Bitencourt FS, Cunha FQ, Oliveira RS, Bomfim LR, Vitor LFJ, Alencar NM (2009) Involvement of NO in the inhibitory effect of Calotropis procera latex protein fractions on leukocyte rolling, adhesion and infiltration in rat peritonitis model. J Ethnopharmacol 125:387–392

    CAS  Article  PubMed  Google Scholar 

  44. Rehman AU, Malik A, Riaz N, Ahmed H, Nawaz SA, Choudhary MI (2005) Lipoxygenase Inhibiting Constituents from Indigofera hetrantha. Chem Pharm Bull 53:263–266

    Article  Google Scholar 

  45. Rioux N, Castonguay A (1998) Inhibitors of lipoxygenase: a new class of cancer chemopreventive agents. Carcinogenesis 19:1393–1400

    CAS  Article  PubMed  Google Scholar 

  46. Roy S, Sehgal R, Padhy BM, Kumar VL (2005) Antioxidant and protective effect of latex of Calotropis procera against alloxan-induced diabetes in rats. J Ethnopharmacol 102:470–473

    CAS  Article  PubMed  Google Scholar 

  47. Sabrin RMI, Gamal AM, Lamiaa AS, Laetitia MYB, Robert K, Diaa TAY (2015) Calotroposides H-N, new cytotoxic oxypregnane oligoglycosides from the root bark of Calotropis procera. Steroids 96:63–72

    Article  Google Scholar 

  48. Sangraula H, Dewan S, Kumar VL (2002) Evaluation of anti-inflammatory activity of latex of Calotropis procera in different models of inflammation. Inflammopharmacology 9:257–264

    Article  Google Scholar 

  49. Sehgal R, Arya S, Kumar VL (2005) Inhibitory effect of extracts of latex of Calotropis procera against Candida albicans: A preliminary study. Indian J Pharmacol 37:334–335

    Article  Google Scholar 

  50. Setty SR, Quereshi AA, Swamy AHM, Patil T, Prakash T, Prabhu K, Veeran G (2007) Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats. Fitoterapia 78:451–454

    Article  Google Scholar 

  51. Sharma P, Sharma JD (2000) In-vitro schizonticidal screening of Calotropis procera. Fitoterapia 71:77–79

    CAS  Article  PubMed  Google Scholar 

  52. Shivkar YM, Kumar VL (2003) Anthelmintic activity of latex of Calotropis procera. Pharm Biol 41:263–265

    Article  Google Scholar 

  53. Silva MCC, Silva AB, Teixeira FM, Sousa PCP, Rondon RMM, Junoir JERH, Sampiao LRL, Oliveira SL, Holonda ANM, Vasconcelos SMM (2010) Therapeutic and biological activities of Calotropis procera (Ait.) R. Br. Asian Pac J Trop Med 3:332–336

    Article  Google Scholar 

  54. Soares de Oliveira J, Pereira Bezerra D, Teixeira de Freitas CD, Delano BMFJ, Odorico de Moraes M, Pessoa C, Costa-Lotufo LV, Ramos MV (2007) In vitro cytotoxicity against different human cancer cell lines of laticifer proteins of Calotropis procera (Ait.) R. Br. Toxicol in Vitro 21:1563–1573

    CAS  Article  PubMed  Google Scholar 

  55. Takeshi D, Takako I, Sansei N (1985) The constituents of Eucommia ulmoides Oliv II. Isolation and structures of three new lignan glycosides. Chem Pharm Bull 33:3651–3657

    Article  Google Scholar 

  56. Tappel AL (1962) Methods in Enzymology, vol 5. Academic Press, New York, p 539

    Google Scholar 

  57. Vernon ES, Cathy AH, Ernest TH, Levy K, Ronald AL, James AC, Caroline CS, Gary JK (1999) Lipoxygenase Inhibitors as Potential Cancer Chemopreventives. Cancer Epidemiol Biomarkers Prev 8:467–483

    Google Scholar 

  58. Wagner M, Abdel-Mageed WM, Ebel R, Bull AT, Goodfellow M, Fiedler HP, Jaspars M (2014) Dermacozines H-J isolated from a deep-sea strain of Dermacoccus abyssi from Mariana Trench sediments. J Nat Prod 77:416–420

    CAS  Article  PubMed  Google Scholar 

  59. Walther M, H-g Holzhütter, Kuban RJ, Wiesner R, Rathmann J, Kühn H (1999) The Inhibition of Mammalian 15-Lipoxygenases by the anti-inflammatory drug ebselen: dual-type mechanism involving covalent linkage and alteration of the iron ligand sphere. Mol Pharmacol 56:196–203

    CAS  PubMed  Google Scholar 

  60. Wisastra R, Dekker FJ (2014) Inflammation, cancer and oxidative lipoxygenase activity are intimately Linked. Cancers 6:1500–1521

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. Yamagami C, Akamatsu M, Motohashi N, Hamada S, Tanahashi T (2005) Quantitative structure-activity relationship studies for antioxidant hydroxybenzalacetones by quantum chemical- and 3-D-QSAR(CoMFA) analyses. Bioorg Med Chem Lett 15:2845–2850

    CAS  Article  PubMed  Google Scholar 

  62. Yesmin MN, Uddin SN, Mubassara S, Akond MA (2008) Antioxidant and antibacterial activities of Calotropis procera Linn. Am Eurasian J Agric Environ Sci 4:550–553

    Google Scholar 

  63. Yves D, Christine B, Daniel D, Chi CC, Jean PF, John WG, Jocelyne G, John HH, Cyryl SM (1994) Naphthalenic lignan lactones as selective, nonredox 5-lipoxygenase inhibitors. Synthesis and biological activity of (methoxyalkyl)thiazole and methoxytetrahydropyran hybrids. J Med Chem 37:512–518

    Article  Google Scholar 

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Acknowledgments

The authors would like to extend their sincere appreciation to the deanship of Scientific Research at King Saud University for its funding of this research through Research Group Project no. RGP-VPP-326.

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Correspondence to Xueting Liu, Lixin Zhang or Ahmed A. M. Shoreit.

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Abdel-Mageed, W.M., Mohamed, N.H., Liu, M. et al. Lipoxygenase inhibitors from the latex of Calotropis Procera . Arch. Pharm. Res. (2016). https://doi.org/10.1007/s12272-016-0725-9

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Keywords

  • Calotropis procera
  • Lignans
  • Antioxidants
  • Anti-inflammatory
  • Lipoxygenase inhibitors