Advertisement

Medicinal Chemistry Research

, Volume 26, Issue 1, pp 93–100 | Cite as

TNF-α and IL-6 inhibitory effects of cyclic dipeptides isolated from marine bacteria Streptomyces sp

  • Yedukondalu Nalli
  • Shilpa Gupta
  • Vidushi Khajuria
  • Varun P. Singh
  • Mehak Sajgotra
  • Zabeer Ahmed
  • Narsinh L. Thakur
  • Asif AliEmail author
Original Research

Abstract

Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. The anti-inflammatory cytokines are a series of immune regulatory molecules that control the pro inflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. The aim of the present study is to probe the anti-inflammatory potential of the crude extract and the bioactive metabolite isolated from marine bacteria Streptomyces sp. on key inflammatory mediators like tumor necrosis factor-α and interleukin-6. Here, we isolated ten known pyrazine-1,4-dione substituted cyclic dipeptide by semi-preparative HPLC and studied their anti-inflammatory activities against tumor necrosis factor-α and interleukin-6. Compound 3, 4, 5, 7 and 8 showed good inhibition of the both the cytokines in lipopolysaccharide-stimulated macrophages. The study reveal that compound 7 was to be specific inhibitor for tumor necrosis factor-α which efficiently inhibited tumor necrosis factor-α release in a dose-dependent manner and decreased lipopolysaccharide induced tumor necrosis factor-α production in human peripheral blood mononuclear cells in both the in vitro and in vivo experiments.

Keywords

TNF-α IL-6 Streptomyces sp Cyclic dipeptides 

Notes

Acknowledgments

The authors are grateful to the University grant commission (UGC-New Delhi) and CSIR for providing financial support having the Grant No. ITR-0001 for the work of YN, and SM. YK, SG and VK acknowledge AcSIR for their enrolment in Ph. D program. VK also acknowledge DST for INSPIRE Fellowship. We are also thankful to Deeαpika Singh for recording the NMR experiments.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2016_1730_MOESM1_ESM.docx (6 mb)
Supplementary Information

References

  1. Akyol S, Tanriverdi T, Hanci M (2012) Do immunologic events in degenerative disc tissue alter the peripheral immune tolerance? World Spinal Column J 3:45–49Google Scholar
  2. Ali A et al (2013) Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp. Immunol Lett 150:79–86CrossRefPubMedGoogle Scholar
  3. Ammon HPT (2010) Modulation of the immune system by Boswellia serrata extracts and boswellic acids. Phytomedicine 17:862–867CrossRefPubMedGoogle Scholar
  4. Cronan JM, Davidson TR, Singleton FL, Colwell RR, Cardellina JH (1998) Plant growth promoters isolated from a marine bacterium associated with Palythoa sp. Nat Prod Lett 11:271–278CrossRefGoogle Scholar
  5. De Vries DJ, Beart PM (1995) Fishing for drugs from the sea: status and strategies. Trends Pharmacol Sci 16:275–279CrossRefPubMedGoogle Scholar
  6. Debitus C et al (1998) Quinolones from a bacterium and tyrosine metabolites from its host sponge, Suberea creba from the coral sea. J Mar Biotechnol 6:136–141PubMedGoogle Scholar
  7. Fdhila F, Vázquez V, Sánchez JL, Riguera R (2003) dd-Diketopiperazines: antibiotics active against vibrio anguillarum isolated from marine bacteria associated with cultures of pecten maximus. J Nat Prod 66:1299–1301CrossRefPubMedGoogle Scholar
  8. Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A (2007) Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNF-α, IL-1β, NO and MAP kinases. Int Immunopharmacol 7:473–482CrossRefPubMedGoogle Scholar
  9. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415CrossRefPubMedPubMedCentralGoogle Scholar
  10. Jahromi MM, Millward BA, Demaine AG (2000) A polymorphism in the promoter region of the gene for interleukin-6 is associated with susceptibility to type 1 diabetes mellitus. J Interferon Cytokine Res 20:885–888CrossRefPubMedGoogle Scholar
  11. Jayatilake GS, Thornton MP, Leonard AC, Grimwade JE, Baker BJ (1996) Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas aeruginosa. J Nat Prod 59:293–296CrossRefPubMedGoogle Scholar
  12. Lam KS (2006) Discovery of novel metabolites from marine actinomycetes. Curr Opin Microbiol 9:245–251CrossRefPubMedGoogle Scholar
  13. Lin WC, Lin JY (2011) Five bitter compounds display different anti-inflammatory effects through modulating cytokine secretion using mouse primary splenocytes in vitro. J Agric Food Chem 59:184–192CrossRefPubMedGoogle Scholar
  14. Lovering F, Zhang Y (2005) Therapeutic potential of TACE inhibitors in stroke. Curr Drug Targets CNS Neurol Disord 4:161–168CrossRefPubMedGoogle Scholar
  15. Papa Gobbi R et al (2016) A galectin-specific signature in the gut delineates Crohn’s disease and ulcerative colitis from other human inflammatory intestinal disorders. BioFactors 42:93–105PubMedGoogle Scholar
  16. Park YC, Gunasekera SP, Lopez JV, Mccarthy PJ, Wright AE (2006) Metabolites from the marine-derived fungus Chromocleista sp. Isolated from a deep-water sediment sample collected in the Gulf of Mexico. J Nat Prod 69:580–584CrossRefPubMedGoogle Scholar
  17. Remsing LL et al (2003) Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis. J Am Chem Soc 125:5745–5753CrossRefPubMedPubMedCentralGoogle Scholar
  18. Rosler N, Wichart I, Jellinger KA (2001) Intra vitam lumbar and post mortem ventricular cerebrospinal fluid immunoreactive interleukin-6 in Alzheimer’s disease patients. Acta Neurol Scand 103:126–130CrossRefPubMedGoogle Scholar
  19. Rudi A, Kashman Y, Benayahu Y, Schleyer M (1994) Amino acid derivatives from the marine sponge Jaspis digonoxea. J Nat Prod 57:829–832CrossRefPubMedGoogle Scholar
  20. Ruiz-Alcaraz AJ et al. (2011) Peritoneal macrophage priming in cirrhosis is related to ERK phosphorylation and IL-6 secretion. Eur J Clin Invest 41:8–15CrossRefPubMedGoogle Scholar
  21. Selmaj K, Raine CS, Cannella B, Brosnan CF (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949–954CrossRefPubMedPubMedCentralGoogle Scholar
  22. Smolen JS, Steiner G (2003) Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2:473–488CrossRefPubMedGoogle Scholar
  23. Solanki R, Khanna M, Lal R (2008) Bioactive compounds from marine actinomycetes. Indian J Microbiol 48:410–431CrossRefPubMedGoogle Scholar
  24. Such J et al (2001) Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. Dig Dis Sci 46:2360–2366CrossRefPubMedGoogle Scholar
  25. Sujatha P, Bapi Raju KV, Ramana T (2005) Studies on a new marine streptomycete BT-408 producing polyketide antibiotic SBR-22 effective against methicillin resistant Staphylococcus aureus. Microbiol Res 160:119–126CrossRefPubMedGoogle Scholar
  26. Takaya Y et al (2007) Antioxidant constituents in distillation residue of awamori spirits. J Agric Food Chem 55:75–79CrossRefPubMedGoogle Scholar
  27. Williams PG et al (2007) Saliniketals A and B, bicyclic polyketides from the marine actinomycete Salinispora arenicola. J Nat Prod 70:83–88CrossRefPubMedGoogle Scholar
  28. Wu SJ, Fotso S, Li F, Qin S, Laatsch H (2007) Amorphane sesquiterpenes from a marine Streptomyces sp. J Nat Prod 70:304–306CrossRefPubMedGoogle Scholar
  29. Yuan G, Wahlqvist ML, He G, Yang M, Li D (2006) Natural products and anti-inflammatory activity. Asia Pac J Clin Nutr 15:143–152PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yedukondalu Nalli
    • 1
    • 2
  • Shilpa Gupta
    • 2
    • 3
  • Vidushi Khajuria
    • 2
    • 3
  • Varun P. Singh
    • 4
  • Mehak Sajgotra
    • 1
    • 2
  • Zabeer Ahmed
    • 2
    • 3
  • Narsinh L. Thakur
    • 5
  • Asif Ali
    • 1
    • 2
    Email author
  1. 1.Natural Product Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammu- TawiIndia
  2. 2.Academy of Scientific and Innovative ResearchCSIR-Indian Institute of MedicineJammu-TawiIndia
  3. 3.Inflammation Pharmacology DivisionCSIR-Indian Institute of Integrative MedicineJammu-TawiIndia
  4. 4.Medicinal Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  5. 5.Chemical Oceanography DivisionCSIR-National Institute of OceanographyGoaIndia

Personalised recommendations