Skip to main content
SpringerLink
Log in

Evaluation of nitric oxide inhibition effect in LPS-stimulated RAW 264.7 macrophages by phytochemical constituents from Mesua beccariana, Mesua congestiflora, and Mesua ferrea

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

This study was conducted to evaluate the anti-inflammatory properties of the secondary metabolites and extracts from Mesua species by using nitric oxide inhibition and protein denaturation assays. Our phytochemical investigations on three species of Mesua plants, Mesua beccariana, M. congestiflora, and M. ferrea have resulted in sixteen pure metabolites. The anti-inflammatory effects of the crude extracts, as well as the pure metabolites were evaluated against mouse leukemic monocyte RAW 264.7 macrophage cell line and protein denaturation assay. All the crude extracts exhibited concentration dependent inhibition of the anti-inflammatory activity against RAW 264.7 cells. The effects of the crude extracts on inhibition of egg albumin denaturation were also evaluated. The crude extracts of M. beccariana and M. congestiflora showed significant inhibition of protein denaturation as compared to the reference drug, diclofenac sodium. Among the pure constituents tested, three xanthones, macluraxanthone (7), α-mangostin (10) and mesuarianone diacetate B (13) possessed significant in-vitro anti-inflammatory properties against RAW 264.7 cells with IC50 values of less than 16.0 μM. The structure-activity relationship study of these xanthone was predicted based on the anti-inflammatory effects. It is deduced that xanthone derivatives which have trihydroxylated prenylated, diprenylated and indirectly prenylated and acetylated substituent groups on the xanthone skeleton contributed remarkable anti-inflammatory activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

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 

  • Ahmad F, Khan RA, Rasheed S (1992) Study of analgesic and anti-inflammatory activity from plant extracts of Lactuca scariola and Artemisia absinthium. J Islamic Acad Sci 5:111–114

    Google Scholar 

  • Awang K, Chan G, Litaudon M, Ismail NH, Martin MT, Gueritte F (2010) 4-phenylcoumarins from Mesua elegans with acetylcholinesterase inhibitory activity. Bioorg Med Chem 18:7873–7877

    Article  CAS  PubMed  Google Scholar 

  • Bogdan C, Röllinghoff M, Diefenbach A (2000) The role of nitric oxide in innate immunity. Immunol Rev 173:17–26

    Article  CAS  PubMed  Google Scholar 

  • Chahar MK, Kumar DSS, Lokesh T, Manohara KP (2012) In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua ferrea L. Seed oil. Int Immunopharmacol 13:386

    Article  CAS  PubMed  Google Scholar 

  • Chandra S, Chatterjee P, Dey P, Bhattacharya S (2012) Evaluation of in vitro anti-inflammatory activity of coffee against the denaturation of protein. Asian Pacific Journal of Tropical Biomedicine 2:S178–S180

  • Dennis TJ, Kumar KA (1998) Constituents of Mesua ferrea. Fitoterapia 69:291–304

    CAS  Google Scholar 

  • Ee GCL, Mah SH, Rahmani M, Taufiq-Yap YH, Teh SS, Lim YM (2011) A new furanoxanthone from the stem bark of Calophyllum inophyllum. J Asian Nat Prod Res 13:956–960

    Article  CAS  PubMed  Google Scholar 

  • Garg S, Sharma K, Ranjan R, Attri P (2009) Evaluation of antioxidant activity and hepatoprotective efficacy of methanolic extract of Mesua ferrea Linn leaves in experimentally challenged mice. Int J PharmTech Res 1:1692–1696

    Google Scholar 

  • Gell PGH, Benacerraf B (1959) Studies on hypersensitivity delayed hypersensitivity to denatured proteins in guinea pigs. Immunology 2:64–70

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ialenti A, Ianaro A, Moncada S, Rosa MD (1992) Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol 211:177–182

    Article  CAS  PubMed  Google Scholar 

  • Jalalpure SS, Mandavkar YD, Khalure PR, Shinde GS, Shelar PA, Shah AS (2011) Antiarthritic activity of various extracts of Mesua ferrea Linn. Seed. J Ethnopharmacol 138:700–704

    Article  PubMed  Google Scholar 

  • Kanterman J, Sade-Feldman M, Baniyash M (2012) New insights into chronic inflammation-induced immunosuppression. Sem Cancer Biol 22:307–318

    Article  CAS  Google Scholar 

  • Kondo Y, Takano F, Hojo H (1993) Inhibitory effect of bisbenzylisoquinoline alkaloids on nitric oxide production in activated macrophages. Biochem Pharmacol 46:1887–1892

    Article  CAS  PubMed  Google Scholar 

  • Kundu JK, Surh Y-J (2008) Inflammation: Gearing the journey to cancer. Mutat Res 659:15–30

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Hyun E-A, Yoon WJ, Kim BH, Rhee MH, Kang HK, Cho JY, Yoo ES (2006) In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J Ethnopharmacol 103:208–216

    Article  PubMed  Google Scholar 

  • Mahavorasirikul W, Viyanant V, Chaijaroenkul W, Itharat A, Na-Bangchang K (2010) Cytotoxic activity of thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med 10:55

    Article  PubMed  PubMed Central  Google Scholar 

  • Maki-Petaja KM, Wilkinson IB (2012) Inflammation and large arteries: Potential mechanisms for inflammation-induced arterial stiffness. Artery Res 6:59–64

    Article  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    CAS  PubMed  Google Scholar 

  • Murakami A, Gao G, Kim OK, Omura M, Yano M, Ito C, Furukawa H, Jiwajinda S, Koshimizu K, Ohigashi H (1999) Identification of coumarins from the fruit of citrus hystrix dc as inhibitors of nitric oxide generation in mouse macrophage RAW 264.7 cells. J Agric Food Chem 47:333–339

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa T, Yokozawa T (2002) Direct scavenging of nitric oxide by green tea. Food Chem Toxicol 40:1745–1750

    Article  CAS  PubMed  Google Scholar 

  • Narender PD, Rao GB, Rao SE, Rao MT, Praneeth V (2012) Quantification of phytochemical constituents and in-vitro antioxidant activity of Mesua ferrea leaves. Asian Pac J Trop Biomed 2:S539–S542

    Article  Google Scholar 

  • Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff A (2007) Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol 179:7121–7129

    Article  CAS  PubMed  Google Scholar 

  • Opie EL (1962) On the relation of necrosis and inflammation to denaturation of proteins. J Exp Med 115:597–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajesh KP, Manjunatha H, Krishna V, Swamy BEK (2013) Potential in vitro antioxidant and protective effects of Mesua ferrea linn. Bark extracts on induced oxidative damage. Ind Crop Prod 47:186–198

    Article  CAS  Google Scholar 

  • Singha S, Adhikari U, Chandra G (2011) Smoke repellency and mosquito larvicidal potentiality of Mesua ferra L. Leaf extract against filarial vector Culex quinquefasciatus Say. Asian Pac J Trop Biomed 1:S119–S123

  • Suh N, Honda T, Finlay HJ, Barchowsky A, Williams C, Benoit NE, Xie Q-W, Nathan C, Gribble GW, Sporn MB (1998) Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Am Assoc Cancer Res 58:717–723

    CAS  Google Scholar 

  • Taira J, Nanbu H, Ueda K (2009) Nitric oxide-scavenging compounds in Agrimonia pilosa Ledeb on LPS-induced RAW264.7 macrophages. Food Chem 115:1221–1227

    Article  CAS  Google Scholar 

  • Teh SS, Ee GCL, Mah SH, Ahmad Z (2016) Structure–activity relationship study of secondary metabolites from Mesua beccariana, Mesua ferrea and Mesua congestiflora for anti-cholinesterase activity. Med Chem Res 25:819–823

    Article  CAS  Google Scholar 

  • Teh SS, Ee GCL, Mah SH, Lim YM, Ahmad Z (2013) Cytotoxicity and structure-activity relationships of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards nine human cancer cell lines. Molecules 18:1985–1994

    Article  CAS  PubMed  Google Scholar 

  • Teh SS, Ee GCL, Mah SH, Lim YM, Rahmani M (2012) Mesua beccariana (Clusiaceae), a source of potential anti-cancer lead compounds in drug discovery. Molecules 17:10791–10800

    Article  CAS  PubMed  Google Scholar 

  • Umapathy E, Ndebia EJ, Meeme A, Adam B, Menziwa P, Nkeh-Chungag BN, Iputo JE (2010) An experimental evaluation of Albuca setosa aqueous extract on membrane stabilization, protein denaturation and white blood cell migration during acute inflammation. J Med Plants Res 4:789–795

    Google Scholar 

  • Verotta L, Lovaglio E, Vidari G, Finzi PV, Neri MG, Raimondi A, Parapini S, Taramelli D, Riva A, Bombardelli E (2004) 4-alkyl- and 4-phenylcoumarins from Mesua ferrea as promising multidrug resistant antibacterials. Phytochem 65:2867–2879

    Article  CAS  Google Scholar 

  • Wadsworth TL, Koop DR (1999) Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem Pharmacol 57:941–949

    Article  CAS  PubMed  Google Scholar 

  • Walsh NC, Crotti TN, Goldring SR, Gravallese EM (2005) Rheumatic diseases: The effects of inflammation on bone. Immunol Rev 208:228–251

    Article  CAS  PubMed  Google Scholar 

  • Zhou HY, Shin EM, Guo LY, Youn UJ, Bae K, Kang SS, Zou LB, Kim YS (2008) Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NFκb, JNK and p38 MAPK inactivation. Eur J Pharmacol 586:340–349

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge financial support from UPM and MOSTI under the Agri Science Fund. The SBC is also acknowledged.

Author information

Authors and Affiliations

  1. Energy and Environment Unit, Engineering and Processing Division, Malaysian Palm Oil Board, 43000, Kajang, Selangor, Malaysia

    Soek Sin Teh

  2. Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Gwendoline Cheng Lian Ee

  3. School of Biosciences, Taylor’s University, Lakeside Campus, 47500, Subang Jaya, Selangor, Malaysia

    Siau Hui Mah

Authors
  1. Soek Sin Teh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gwendoline Cheng Lian Ee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siau Hui Mah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gwendoline Cheng Lian Ee.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teh, S., Ee, G. & Mah, S. Evaluation of nitric oxide inhibition effect in LPS-stimulated RAW 264.7 macrophages by phytochemical constituents from Mesua beccariana, Mesua congestiflora, and Mesua ferrea . Med Chem Res 26, 3240–3246 (2017). https://doi.org/10.1007/s00044-017-2017-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-017-2017-4

Keywords

Search

Navigation