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Anti-inflammatory of pyrrolizidine alkaloids from Heliotropium digynum

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Abstract

One new and six known pyrrolizidine alkaloids (1–7) were isolated from the 70% ethanol extract of the aerial parts of Heliotropium digynum (Forssk.) C. Chr. The chemical structure of the new compound, 7-Angeloylsincamidine N-Oxide (4) was determined by extensive 1D and 2D NMR spectroscopic analysis and HRESIMS. The absolute configuration of 4 was elucidated by comparing the experimental and electronic circular dichroism spectra. The anti-inflammatory activity of the ethanolic extract and compounds 1, 2, 4, and 6 were evaluated against the Nitric oxide production in lipopolysaccharide induced murine macrophages RAW 264.7 cells. The IC50 values of the tested compounds were 52.4, 85.1, 105.1, and 7.9 µM, respectively, while the % inhibition of the ethanolic extract at 25 µg/mL was 78.7%. A docking study was conducted to provide more explanation about the activity of the tested compounds.

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References

  • Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621

    Article  CAS  PubMed  Google Scholar 

  • Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alwahibi M, Buhkary N (2013) Morphological variation in Heliotropium digynum growing in four locations of the central region of Saudi Arabia. Afr J Plant Sci 7:85–92

    Article  Google Scholar 

  • Aqheel MA, Janardhan M, Durrai VS (2013) Evaluation of the anti hyperglycemic activity of methanolic extract of root of Heliotropium indicum in streptozotocin and alloxan induced diebetic rats. Indian J Res Pharm Biotechnol 5674:707–710

    Google Scholar 

  • Ara I, Bukhari NA, Solaiman D, Bakir MA (2012) Antimicrobial effect of local medicinal plant extracts in the kingdom of Saudi Arabia sereach for their metabolites by gas chromatography-mass spectrometric (GC-MS) analysis. J Med Plant Res 6:5688–5694

    CAS  Google Scholar 

  • Asibal CF, Gelbaum LT, Zalkow LH (1989) Pyrrolizidine alkaloids from Heliotropium rotundifolium. J Nat Prod 52:726–731

    Article  CAS  PubMed  Google Scholar 

  • Culvenor CCJ, Smith LW (1966) The alkaloids of Amsinckia species: A. intermedia Fisch. & Mey., A. hispida (Ruiz. & Pav.) Johnst. and A. lycopsoides Lehm. Aust J Chem 19:1955–1964

    Article  CAS  Google Scholar 

  • Dash GK, Abdullah MS (2013) A review on Heliotropium indicum L. (Boraginaceae). Int J Pharm Sci Res 4:1253–1258

    Google Scholar 

  • Farsam H, Yassa N, Sarkhail P, Shafiee A (2000) New pyrrolizidine alkaloids from Heliotropium crassifolium. Planta Med 66:389–391

    Article  CAS  PubMed  Google Scholar 

  • Field RA, Stegelmeier BL, Colegate SM, Brown AW, Green BT (2015) An in vitro comparison of the cytotoxic potential of selected dehydropyrrolizidine alkaloids and some N-oxides. Toxicon 97:36–45

    Article  CAS  PubMed  Google Scholar 

  • Fischmann TO, Hruza A, Niu XD, Fossetta JD, Lunn CA, Dolphin E, Prongay AJ, Reichert P, Lundell DJ, Narula SK, Weber PC (1999) Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol 6:233–242

    Article  CAS  PubMed  Google Scholar 

  • Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE, Francis P, Shenkin PS (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749

    Article  CAS  PubMed  Google Scholar 

  • Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49:6177–6196

    Article  CAS  PubMed  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Guenther R, Gilbert F, Zalat S, Salem KA (2005) Vegetation and Grazing in the St. Katherine Protectorate, South Sinai, Egypt. Egypt J Biol 7:55–66

    Google Scholar 

  • Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, Banks JL (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47:1750–1759

    Article  CAS  PubMed  Google Scholar 

  • Hammouda F, Risk A, Ismail SI, Atteya SZ, Ghaleb HA, Madkour MK, Poland AE, Wood G (1984) Poisonous plants contaminating edible ones and toxic substances in plant foods, part 3. Pyrrolizidine alkaloids from Heliotropium digynum Forssk.(=H. luteum, poir.). DiePharmazie 39:703–705

    CAS  Google Scholar 

  • Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119:203–221

    Article  CAS  PubMed  Google Scholar 

  • Hoang LS, Tran MH, Lee JS, To DC, Nguyen VT, Kim JA, Lee JH, Woo MH, Min BS (2015) Anti-inflammatory Activity of Pyrrolizidine Alkaloids from the Leaves of Madhuca pasquieri (Dubard). Chem Pharm Bull 63:481–484

    Article  CAS  Google Scholar 

  • Ibrahim LF, Kawashty SA, El-Eraky WI, Shabana MM, El-Negoumy SI (2000) A comparative study of the flavonoids, pharmacological and antimicrobial effects of Echium longifolium and Heliotropium digynum. Egypt J Physiol Sci 24:63–82

    CAS  Google Scholar 

  • Jacobson MP, Friesner RA, Xiang Z, Honig B (2002) On the role of crystal packing forces in determining protein side-chain conformations. J Mol Biol 320:597–608

    Article  CAS  PubMed  Google Scholar 

  • Jacobson MP, Pincus DL, Rapp CS, Day TJF, Honig B, Shaw DE, Friesner RA (2004) A hierarchical approach to all-atom protein loop prediction. Proteins 55:351–367

    Article  CAS  PubMed  Google Scholar 

  • Kyei S, Koffuor GA, Ramkissoon P, Ameyaw EO, Asiamah EA (2016) Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits. Int J Ophthalmol 9:528–535

    PubMed  PubMed Central  Google Scholar 

  • Logie CG, Grue MR, Liddell JR (1994) Proton NMR spectroscopy of pyrrolizidine alkaloid. Phytochemistry 37:43–109

    Article  CAS  Google Scholar 

  • Mcmillan K, Adler M, Auld DS, Baldwin JJ, Blasko E, Browne LJ, Chelsky D, Davey D, Dolle RE, Eagen KA, Erickson S, Feldman RI, Glaser CB, Mallari C, Morrissey MM, Ohlemeyer MHJ, Pan G, Parkinson JF, Phillips GB, Polokoff MA, Sigal NH, Vergona R, Whitlow M, Young TA, Devlin JJ (2000) Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry. Proc Natl Acad Sci USA 97:1506–1511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehrabani M, Ghannadi A, Sajjadi E, Ghassemi N, Shams-Ardakani M (2006) Toxic pyrrolizidine alkaloids of Echium amoenum Fisch. & Mey. Daru J Pharm Sci 14:122–127

    CAS  Google Scholar 

  • Reina M, Mericli A, Cabrera R, Gonzalez C (1995) A pyrrolizidine alkaloids from Heliotropium bovei. Phytochemistry 38:355–358

    Article  CAS  Google Scholar 

  • Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aid Mol Des 27:221–234

    Article  Google Scholar 

  • Shafiee A, Salimi M, Farsam H, Yassa N (2002) Pyrrolizidine alkaloids from Heliotropium dissitiflorum Boiss. Daru 10:168–170

    CAS  Google Scholar 

  • Singh B, Sahu PM, Jain SC, Singh S (2002a) Antineoplastic and antiviral screening of Pyrrolizidine Alkaloids from Heliotropium subulatum. Pharm Biol 40:581–586

    Article  CAS  Google Scholar 

  • Singh B, Sahu PM, Singh S (2002b) Antimicrobial activity of pyrrolizidine alkaloids from Heliotropium subulatum. Fitoterapia 73:153–155

    Article  CAS  PubMed  Google Scholar 

  • Wink M (2013) Evolution of secondary metabolites in legumes (Fabaceae). S Afr J Bot 89:164–175

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the Egyptian Government and National Center for Natural Products Research, School of Pharmacy, The University of Mississippi for the financial support. We are also thankful to Dr. Amira Gamal El-Deen, Cancer Biology Lab, National Research Center, Dokki, Giza, Egypt, for conducting the biological assay.

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Correspondence to Samir A. Ross.

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Aboelmagd, M., Elokely, K., Zaki, M.A. et al. Anti-inflammatory of pyrrolizidine alkaloids from Heliotropium digynum. Med Chem Res 27, 1066–1073 (2018). https://doi.org/10.1007/s00044-017-2128-y

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