Medicinal Chemistry Research

, Volume 24, Issue 5, pp 1952–1963 | Cite as

Bioassay directed isolation of a novel anti-inflammatory cerebroside from the leaves of Aerva sanguinolenta

  • Anurup Mandal
  • Durbadal Ojha
  • Asif Lalee
  • Sudipta Kaity
  • Mousumi Das
  • Debprasad ChattopadhyayEmail author
  • Amalesh SamantaEmail author
Original Research


This paper attempts to evaluate the anti-inflammatory potential and the possible mechanism of action of the leaf extracts and isolated compound(s) of Aerva sanguinolenta (Amaranthaceae), traditionally used in ailments related to inflammation. The anti-inflammatory activity of ethanol extract (ASE) was evaluated by acute, subacute and chronic models of inflammation, while a new cerebroside (‘trans’, ASE-1), isolated from the bioactive ASE and characterized spectroscopically, was tested by carrageenan-induced mouse paw oedema and protein exudation model. To understand the underlying mechanism, we measured the release of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG)E2, along with the cytokines like tumour necrosis factor (TNF)-α, and interleukins(IL)-1β, IL-6 and IL-12 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages. The results revealed that ASE at 400 mg/kg caused significant reduction of rat paw oedema, granuloma and exudative inflammation, while the inhibition of mouse paw oedema and exudative inflammation by ASE-1 (20 mg/kg) was comparable to that of the standard drug indomethacin (10 mg/kg). Interestingly, both ASE and ASE-1 showed significant inhibition of the expressions of iNOS2 and COX-2, and the down-regulation of the expressions of IL-1β, IL-6, IL-12 and TNF-α, in LPS-stimulated macrophages, via the inhibition of COX-2-mediated PGE2 release. Thus, our results validated the traditional use of A. sanguinolenta leaves in inflammation management.


Aerva sanguinolenta Cerebroside Anti-inflammatory COX-2 PGE2 



The authors are thankful to Dr. Basudeb Achari, former Emeritus Scientist, Indian Institute of Chemical Biology, India, for extending cooperation in structure elucidation of the isolated compound.

Conflict of interest

The authors declare that they have no conflict of interest.


This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Supplementary material

44_2014_1261_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2027 kb)


  1. Adhikari BS, Babu MM, Saklani PL, Rawat GS (2010) Medicinal plants diversity and their conservation status in Wildlife Institute of India (WII) Campus Dehradun. Ethnobot Leaflets 14:46–83Google Scholar
  2. Alam MM, Islam SA, Mohammed Y, Juyena NS, Hasim MA (2005) Comparative efficacy of two medicinal plant extracts and an antibiotic on wound healing. Pakistan J Biol Sci 8:740–743CrossRefGoogle Scholar
  3. Alcaraz MJ, Jimenez MJ (1988) Flavonoids as anti-inflammatory agents. Fitoterapia 59:25–38Google Scholar
  4. Betz M, Fox BS (1991) Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol 146:108–113PubMedGoogle Scholar
  5. Cateni F, Zilic J, Falsone G, Hollan F, Frausin F, Scarcia V (2003a) Preliminary biological assay on cerebroside mixture from Euphorbia nicaeensis All. Isolation and structure determination of five glucocerebrosides. Il Farmaco 58:809–817CrossRefPubMedGoogle Scholar
  6. Cateni F, Zilic J, Falsone G, Scialino G, Banfi E (2003b) New cerebrosides from Euphorbia peplis L.: antimicrobial activity evaluation. Bioorg Med Chem Lett 13:4345–4350CrossRefPubMedGoogle Scholar
  7. Cateni F, Zilic J, Zacchigna M (2008) Isolation and structure elucidation of cerebrosides from Euphorbia platyphyllos L. Sci Pharm 76:451–469CrossRefGoogle Scholar
  8. Chattopadhyay D, Khan MTH (2008) Ethnomedicines and ethnomedicinal phytophores against herpesviruses. Biotechnol Annu Rev 14:297–348CrossRefPubMedGoogle Scholar
  9. Chattopadhyay D, Arunachalam G, Mandal AB, Sur TK, Mandal SC (2002) Antimicrobial and anti-inflammatory activity of Mallotus peltatus leaf extract. J Ethnopharmacol 82(2–3):229–237CrossRefPubMedGoogle Scholar
  10. Chattopadhyay D, Mukherjee H, Bag P, Ojha D, Konreddy AK, Dutta S, Haldar P, Chatterjee T, Sharon A, Chakraborti S (2012) Inhibition of NO2, PGE2, TNF-α and iNOS expression by Shorea robusta L.: an ethnomedicine used for antiinflammatory and analgesic activity. Evidence-Based Complement Altern Med 2012, ID: 254849Google Scholar
  11. Colditz IG (1985) Margination and emigration of leucocytes. Surv Synth Pathol Res 4(1):44–68PubMedGoogle Scholar
  12. D’Arcy PF, Haward EM, Muggleton RW, Townsend SB (1960) The anti-inflammatory action of griseofulvin in experimental animals. J Pharm Pharmacol 12:659–665CrossRefPubMedGoogle Scholar
  13. Das S, Mukherjee H, Ahmed SKM, Haldar PK, Mandal AB, Mahapatra A, Mukherjee PK, Chakraborti S, Chattopadhyay D (2013) Evaluation of an ethnomedicinal combination containing Semecarpus kurzii and Hernandia peltata used for the management of inflammation. Pharm Biol 51(6):677–685CrossRefPubMedGoogle Scholar
  14. Dewanjee S, Dua TK, Sahu R (2013) Potential anti-inflammatory effect of Leea macrophylla Roxb. leaves: a wild edible plant. Food Chem Toxicol 59:514–520CrossRefPubMedGoogle Scholar
  15. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1β generation. Clin Exp Immunol 147(2):227–235PubMedCentralPubMedGoogle Scholar
  16. Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4:281–286CrossRefPubMedGoogle Scholar
  17. Gaddi A, Cicero AFG, Pedro EJ (2004) Clinical perspectives of anti-inflammatory therapy in the elderly: the lipoxigenase (LOX)/cyclooxigenase (COX) inhibition concept. Arch Gerontol Geriatr 38(3):201–212CrossRefPubMedGoogle Scholar
  18. Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A (2013) Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.). Med Chem Res 22:4347–4359CrossRefGoogle Scholar
  19. Griffon B, Cillard J, Chevanne M, Morel I, Cillard P, Sergent O (1998) Macrophage-induced inhibition of nitric oxide production in primary rat hepatocyte cultures via prostaglandin E2 release. Hepatology 28:1300–1308CrossRefPubMedGoogle Scholar
  20. Gupta M, Mazumder UK, Gomathi P, Selvan VT (2006) Antiinflammatory evaluation of leaves of Plumeria acuminata. BMC Complement Altern Med 6(1):36. doi: 10.1186/1472-6882-6-36 CrossRefPubMedCentralPubMedGoogle Scholar
  21. Harbrecht BG, Kim YM, Wirant EA, Simmons RL, Billiar TR (1997) Timing of prostaglandin exposure is critical for the inhibition of LPS- or IFN-gamma-induced macrophage NO synthesis by PGE2. J Leukoc Biol 61(6):712–720PubMedGoogle Scholar
  22. Heller A, Koch T, Schmeck J, Acker VK (1998) Lipid mediators in inflammatory disorders. Drugs 55:487–496CrossRefPubMedGoogle Scholar
  23. Hibbs JJB, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157(1):87–94CrossRefPubMedGoogle Scholar
  24. Ibrahim B, Sowemimo A, Van Rooyen A, Van de Venter VM (2012) Anti-inflammatory, analgesic and antioxidant activities of Cyathula prostrata (Linn.) Blume (Amaranthaceae). J Ethnopharmacol 141(1):282–289CrossRefPubMedGoogle Scholar
  25. Ishola IO, Agbaje OE, Narender T, Adeyemi OO, Shukla R (2012) Bioactivity guided isolation of analgesic and anti-inflammatory constituents of Cnestis ferruginea Vahl ex DC (Connaraceae) root. J Ethnopharmacol 142:383–389CrossRefPubMedGoogle Scholar
  26. Jalalpure SS, Patil MB, Prakash NS, Hemalata K, Manvi FV (2003) Hepatoprotective activity of the fruits of Piper longum Linn. Indian J Pharm Sci 65:363–366Google Scholar
  27. Kabir MH, Hasan N, Rahman MM, Rahman MA, Khan JA, Hoque NT, Bhuiyan MR, Mou SM, Jahan R, Rahmatullah M (2014) A survey of medicinal plants used by the Deb barma clan of the Tripura tribe of Moulvibazar district. Bangladesh. J Ethnobiol Ethnomed 6(10):19–47CrossRefGoogle Scholar
  28. Kang SS, Kim JS, Son KH, Kim HP, Chang HW (2001) Cyclooxygenase-2 inhibitory cerebrosides from Phytolaccae Radix. Chem Pharm Bull 49:321–323CrossRefPubMedGoogle Scholar
  29. Kasama T, Strieter RM, Standiford TJ, Burdick MD, Kunkel SL (1993) Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1α. J Exp Med 178(1):63–72CrossRefPubMedGoogle Scholar
  30. Klingemann HG, Tsoi MS, Storb R (1986) Inhibition of prostaglandin E2 restores defective lymphocyte proliferation and cell-mediated lympholysis in recipients after allogeneic marrow grafting. Blood 68:102–107PubMedGoogle Scholar
  31. Koo HJ, Lim KH, Jung HJ, Park EH (2006) Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J Ethnopharmacol 103:496–500CrossRefPubMedGoogle Scholar
  32. Lai PKK, Chan JYW, Wu SB et al (2014) Anti-inflammatory activities of an active fraction isolated from the root of Astragalus membranaceus in RAW 264.7 Macrophages. Phytother Res 28:395–404CrossRefPubMedGoogle Scholar
  33. Li S, Long C, Liu F, Lee S, Guo Q, Li R (2006) Herbs for medicinal baths among the traditional Yao communities of China. J Ethnopharmacol 108:59–67CrossRefPubMedGoogle Scholar
  34. Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–135PubMedGoogle Scholar
  35. Marotta P, Sautebin L, Di RM (1992) Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. Br J Pharmacol 107:640–641CrossRefPubMedCentralPubMedGoogle Scholar
  36. Mukherjee H, Ojha D, Bag P, Chandel HS, Chawla Sarkar M, Chatterjee TH, Chakraborti S, Chattopadhyay D (2013) Antiherpes activities of a triterpene acid of Achyranthes aspera: an Indian ethnomedicine. Microbiol Res 168:238–244CrossRefPubMedGoogle Scholar
  37. Nag Chaudhuri AK, Karmakar S, Roy D, Pal S, Pal M, Sen T (2005) Anti-inflammatory activity of Indian black tea (Sikkim variety). Pharmacol Res 51:169–175CrossRefPubMedGoogle Scholar
  38. Pullaiah T, Naidu KC (2003) Antidiabetic plants in India and herbal based antidiabetic research. Regency, New DelhiGoogle Scholar
  39. Rahmatullah M, Noman A, Hossan MS, Harun-Or-Rashid M, Rahman T, Chowdhury MH, Jahan R (2009) A survey of medicinal plants in two areas of Dinajpur district, Bangladesh including plants which can be used as functional foods. Am Eurasian J Sustainable Agric 3: 862–876. ISSN 1995-0748Google Scholar
  40. Schiatti P, Selva D, Galliani G, Baldoli E, Diena A, Leali M, Toja E (1986) Highly selective anti-inflammatory and analgesic activity of 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H-naphth [1, 2-d]imidazole, a new non-acidic molecule. Arzneim Forsch 36:102–109Google Scholar
  41. Srinivas Reddy K, Rajeev Reddy E, Ganapaty S (2011) Diuretic and anti-inflammatory activity of aqueous extract of Aerva sanguinolenta (L.) Blume. Int Res J Pharm 2: 65–67.
  42. Sur TK, Pandit S, Bhattacharya DK, Ashok CK, Mohanlakshmi S, Chattopadhyay D, Mondal SC (2002) Studies on anti-inflammatory activity of Betula alnoides bark. Phytother Res 16(7):669–671CrossRefPubMedGoogle Scholar
  43. Trebino CE, Stock JL, Gibbons CP et al. (2003) Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase. Proc Natl Acad Sci USA. 100(15): 9044–9049Google Scholar
  44. Williams TJ, Morley J (1973) Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature 246:215–217CrossRefPubMedGoogle Scholar
  45. Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18:7908–7916CrossRefPubMedGoogle Scholar
  46. Winter CA, Porter CA (1957) Effect of alterations in side chain upon anti-inflammatory and liver glycogen activities of hydrocortisone esters. J Am Pharm Assoc 46:515–519CrossRefGoogle Scholar
  47. Yamauchi R, Aizawa K, Inakuma T, Kato K (2001) Analysis of molecular species of glycolipids in fruit pastes of red bell pepper (Capsicum annuum L.) by high performance liquid chromatography-mass spectrometry. J Agric Food Chem 49:622–627CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Anurup Mandal
    • 1
  • Durbadal Ojha
    • 2
  • Asif Lalee
    • 1
  • Sudipta Kaity
    • 1
  • Mousumi Das
    • 1
  • Debprasad Chattopadhyay
    • 2
    Email author
  • Amalesh Samanta
    • 1
    Email author
  1. 1.Division of Microbiology, Department of Pharmaceutical TechnologyJadavpur UniversityKolkataIndia
  2. 2.ICMR virus unitID & BG HospitalKolkataIndia

Personalised recommendations