Skip to main content
Top
Published in: Inflammopharmacology 2/2019

01-04-2019 | Original Article

Evaluation of the anti-inflammatory and urotoxicity ameliorative effects of γ-humulene containing active fraction of Emilia sonchifolia (L.) DC.

Authors: Gilcy George Kallivalappil, Girija Kuttan

Published in: Inflammopharmacology | Issue 2/2019

Login to get access

Abstract

In folklore medicine, the plant Emilia sonchifolia, belonging to the family Asteraceae, is used for treating tumour and inflammation. In our previous studies, we have done a thorough phytochemical investigation of E. sonchifolia with a report on its potent antimetastatic activity. Further, we isolated and characterised its active fraction (AFES) containing the major compound γ-humulene with an evaluation of the antiangiogenic effect of AFES (5 mg/kg b.wt.). In the first part of the present study, AFES in different concentrations was used for the assessment of its possible anti-inflammatory effect employing three in vivo inflammatory models. Further using the most effective concentration of AFES 5 mg/kg b.wt, its effect on proinflammatory cytokine levels was recorded along with a confirmatory gene expression analysis. The results manifested with a reduction in the paw oedema significantly decreased levels of proinflammatory cytokines, C-reactive protein, nitric oxide and also there was an efficient downregulation of cyclooxygenase-2 and inducible nitric oxide. Urotoxicity is one of the major side effects of conventional chemotherapy. So in the second part of the study, we used AFES in combination with the conventional therapeutic agent cyclophosphamide in vivo in mice. The effect of AFES on urotoxicity was assessed from various biochemical parameters, cytokine markers and finally with a histopathology of the bladder. The current study revealed the protective effects of AFES, implicating reduced levels of urea nitrogen, by revamping of glutathione and marker cytokine levels towards positive amelioration. The results obtained altogether proved the safeguarding effect of AFES in murine experimental models.
Literature
go back to reference Arjaans M, Schröder C, Oosting S, Dafni U (2016) VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside. Oncotarget 7:21247–21258CrossRefPubMedPubMedCentral Arjaans M, Schröder C, Oosting S, Dafni U (2016) VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside. Oncotarget 7:21247–21258CrossRefPubMedPubMedCentral
go back to reference Berlin L, Mu Hugh SL (1999) Physician’s drug handbook, 8th edn. Springhouse Corp, Springhouse Berlin L, Mu Hugh SL (1999) Physician’s drug handbook, 8th edn. Springhouse Corp, Springhouse
go back to reference Bhatia K, Kaur M, Atif F et al (2006) Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food Chem Toxicol 44:1744–1750CrossRefPubMed Bhatia K, Kaur M, Atif F et al (2006) Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food Chem Toxicol 44:1744–1750CrossRefPubMed
go back to reference Boscá L, Zeini M, Través P, Hortelano S (2005) Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology 208:249–258CrossRefPubMed Boscá L, Zeini M, Través P, Hortelano S (2005) Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology 208:249–258CrossRefPubMed
go back to reference Chang JY, Lewis A (1989) Pharmacological methods in the control of inflammation. A.R. Liss, New York Chang JY, Lewis A (1989) Pharmacological methods in the control of inflammation. A.R. Liss, New York
go back to reference Cole SP (1986) Rapid chemosensitivity testing of human lung tumor cells using the MTT assay. Cancer Chemother Pharmacol 17:259–263CrossRefPubMed Cole SP (1986) Rapid chemosensitivity testing of human lung tumor cells using the MTT assay. Cancer Chemother Pharmacol 17:259–263CrossRefPubMed
go back to reference Couto V, Vilela F, Dias D, dos Santos M (2011) Antinociceptive effect of extract of Emilia sonchifolia in mice. J Ethnopharmacol 134:348–353CrossRefPubMed Couto V, Vilela F, Dias D, dos Santos M (2011) Antinociceptive effect of extract of Emilia sonchifolia in mice. J Ethnopharmacol 134:348–353CrossRefPubMed
go back to reference Culling CFA (1974) Handbook of histopathological and histochemical techniques, 3rd edn. Butterworth-Heinemann, London Culling CFA (1974) Handbook of histopathological and histochemical techniques, 3rd edn. Butterworth-Heinemann, London
go back to reference Devi D, Lija Y, Cibin T et al (2006) Evaluation of the protective effects of Emilia sonchifolia Linn. (DC.) on perchlorate-induced oxidative damage. J Biol Sci 6:887–892CrossRef Devi D, Lija Y, Cibin T et al (2006) Evaluation of the protective effects of Emilia sonchifolia Linn. (DC.) on perchlorate-induced oxidative damage. J Biol Sci 6:887–892CrossRef
go back to reference Erickson D, Tomaszewski J, Kunselman A (2005) Do the national institute of diabetes and digestive and kidney diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol 173:93–97CrossRefPubMed Erickson D, Tomaszewski J, Kunselman A (2005) Do the national institute of diabetes and digestive and kidney diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol 173:93–97CrossRefPubMed
go back to reference Fernandes E, Passos G, Medeiros R (2007) Anti-inflammatory effects of compounds alpha-humulene and (−)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. J Pharmacol 569:228–236 Fernandes E, Passos G, Medeiros R (2007) Anti-inflammatory effects of compounds alpha-humulene and (−)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. J Pharmacol 569:228–236
go back to reference Firdous A, Kuttan G, Kuttan R (2015) Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action. Pharm Biol 53:961–967CrossRefPubMed Firdous A, Kuttan G, Kuttan R (2015) Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action. Pharm Biol 53:961–967CrossRefPubMed
go back to reference George GK, Kuttan G (2015) Immune response modulatory effect of Emilia sonchifolia (L.) DC: an in vivo experimental study. J Basic Clin Physiol Pharmacol 26:613–622 George GK, Kuttan G (2015) Immune response modulatory effect of Emilia sonchifolia (L.) DC: an in vivo experimental study. J Basic Clin Physiol Pharmacol 26:613–622
go back to reference George GK, Kuttan G (2016) Inhibition of pulmonary metastasis by Emilia sonchifolia (L.) DC: an in vivo experimental study. Phytomedicine 23:123–130CrossRefPubMed George GK, Kuttan G (2016) Inhibition of pulmonary metastasis by Emilia sonchifolia (L.) DC: an in vivo experimental study. Phytomedicine 23:123–130CrossRefPubMed
go back to reference Gilcy GK, Kuttan G (2016) Evaluation of antiangiogenic efficacy of Emilia sonchifolia (L.) DC on tumor-specific neovessel formation by regulating MMPs, VEGF, and proinflammatory cytokines. Integr Cancer Ther 15(4):NP1–NP12CrossRefPubMedPubMedCentral Gilcy GK, Kuttan G (2016) Evaluation of antiangiogenic efficacy of Emilia sonchifolia (L.) DC on tumor-specific neovessel formation by regulating MMPs, VEGF, and proinflammatory cytokines. Integr Cancer Ther 15(4):NP1–NP12CrossRefPubMedPubMedCentral
go back to reference Green LC, Wagner DA, Glogowski J et al (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138CrossRefPubMed Green LC, Wagner DA, Glogowski J et al (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138CrossRefPubMed
go back to reference Gupta R, DuBois R (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21CrossRefPubMed Gupta R, DuBois R (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21CrossRefPubMed
go back to reference Igbe I, Ching F, Eromon A (2010) Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation. Acta Pol Pharm Drug Res 67:81–85 Igbe I, Ching F, Eromon A (2010) Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation. Acta Pol Pharm Drug Res 67:81–85
go back to reference Lan Y, Wu Y, Wu K et al (2011) Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells. Oncol Rep 25:419–424PubMed Lan Y, Wu Y, Wu K et al (2011) Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells. Oncol Rep 25:419–424PubMed
go back to reference Lan Y, Chiang J, Huang W, Lu C (2012) Activations of both extrinsic and intrinsic pathways in HCT 116 human colorectal cancer cells contribute to apoptosis through p53-mediated ATM/Fas signaling by. Evid-Based Complement Altern Med 2012:1–13CrossRef Lan Y, Chiang J, Huang W, Lu C (2012) Activations of both extrinsic and intrinsic pathways in HCT 116 human colorectal cancer cells contribute to apoptosis through p53-mediated ATM/Fas signaling by. Evid-Based Complement Altern Med 2012:1–13CrossRef
go back to reference Laurence A, Tato C, Davidson T et al (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371–381CrossRefPubMed Laurence A, Tato C, Davidson T et al (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371–381CrossRefPubMed
go back to reference Lawson M, Vasilaras A, De Vries A (2008) Urological implications of cyclophosphamide and ifosfamide. Scand J Urol Nephrol 42:309–317CrossRefPubMed Lawson M, Vasilaras A, De Vries A (2008) Urological implications of cyclophosphamide and ifosfamide. Scand J Urol Nephrol 42:309–317CrossRefPubMed
go back to reference Lija Y, Biju P, Reeni A, Cibin T (2006) Modulation of selenite cataract by the flavonoid fraction of Emilia sonchifolia in experimental animal models. Phyther Res 20:1091–1095CrossRef Lija Y, Biju P, Reeni A, Cibin T (2006) Modulation of selenite cataract by the flavonoid fraction of Emilia sonchifolia in experimental animal models. Phyther Res 20:1091–1095CrossRef
go back to reference Maity T, Mandal S, Mukherjee P (1998) Studies on antiinflammatory effect of Cassia tora leaf extract (fam. Leguminosae). Phytotherapy 12:221–223CrossRef Maity T, Mandal S, Mukherjee P (1998) Studies on antiinflammatory effect of Cassia tora leaf extract (fam. Leguminosae). Phytotherapy 12:221–223CrossRef
go back to reference Manesh C, Kuttan G (2002) Alleviation of cyclophosphamide-induced urotoxicity by naturally occurring sulphur compounds. J Exp Clin cancer 21:509–517 Manesh C, Kuttan G (2002) Alleviation of cyclophosphamide-induced urotoxicity by naturally occurring sulphur compounds. J Exp Clin cancer 21:509–517
go back to reference Masella R, Varì R, D’Archivio M (2004) Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. J Nutr 134:785–791CrossRefPubMed Masella R, Varì R, D’Archivio M (2004) Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. J Nutr 134:785–791CrossRefPubMed
go back to reference Moron M, Depierre J, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78CrossRefPubMed Moron M, Depierre J, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78CrossRefPubMed
go back to reference Mühl H, Pfeilschifter J (2003) Anti-inflammatory properties of pro-inflammatory interferon-γ. Int Immunopharmacol 3:1247–1255CrossRefPubMed Mühl H, Pfeilschifter J (2003) Anti-inflammatory properties of pro-inflammatory interferon-γ. Int Immunopharmacol 3:1247–1255CrossRefPubMed
go back to reference Muko K, Ohiri F (2000) A preliminary study on the anti-inflammatory properties of Emilia sonchifolia leaf extracts. Fitoterapia 71:65–68CrossRefPubMed Muko K, Ohiri F (2000) A preliminary study on the anti-inflammatory properties of Emilia sonchifolia leaf extracts. Fitoterapia 71:65–68CrossRefPubMed
go back to reference Nguyen DX, Bos PD, Massagué J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284CrossRefPubMed Nguyen DX, Bos PD, Massagué J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284CrossRefPubMed
go back to reference Nworu C, Akah P, Okoye F (2012) Inhibition of pro-inflammatory cytokines and inducible nitric oxide by extract of Emilia sonchifolia L. aerial parts. Immunopharmacol Immunotoxicol 34:925–931CrossRefPubMed Nworu C, Akah P, Okoye F (2012) Inhibition of pro-inflammatory cytokines and inducible nitric oxide by extract of Emilia sonchifolia L. aerial parts. Immunopharmacol Immunotoxicol 34:925–931CrossRefPubMed
go back to reference Shylesh B, Padikkala J (2000) In vitro cytotoxic and antitumor property of Emilia sonchifolia (L.) DC in mice. J Ethnopharmacol 73:495–500CrossRefPubMed Shylesh B, Padikkala J (2000) In vitro cytotoxic and antitumor property of Emilia sonchifolia (L.) DC in mice. J Ethnopharmacol 73:495–500CrossRefPubMed
go back to reference Shylesh B, Nair S, Subramoniam A (2005) Induction of cell-specific apoptosis and protection from Dalton’s lymphoma challenge in mice by an active fraction from Emilia sonchifolia. Indian J Pharmacol 37:232–237CrossRef Shylesh B, Nair S, Subramoniam A (2005) Induction of cell-specific apoptosis and protection from Dalton’s lymphoma challenge in mice by an active fraction from Emilia sonchifolia. Indian J Pharmacol 37:232–237CrossRef
go back to reference Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 111:544–547CrossRefPubMed Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 111:544–547CrossRefPubMed
go back to reference Wood R, Eichel L, Messing E, Schwarz E (2001) Automated noninvasive measurement of cyclophosphamide-induced changes in murine voiding frequency and volume. Urology 57:115–116CrossRefPubMed Wood R, Eichel L, Messing E, Schwarz E (2001) Automated noninvasive measurement of cyclophosphamide-induced changes in murine voiding frequency and volume. Urology 57:115–116CrossRefPubMed
go back to reference Yang X, Ghoreschi K, Steward-Tharp S (2011) Opposing regulation of the Il17 locus through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12:247–254CrossRefPubMedPubMedCentral Yang X, Ghoreschi K, Steward-Tharp S (2011) Opposing regulation of the Il17 locus through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12:247–254CrossRefPubMedPubMedCentral
Metadata
Title
Evaluation of the anti-inflammatory and urotoxicity ameliorative effects of γ-humulene containing active fraction of Emilia sonchifolia (L.) DC.
Authors
Gilcy George Kallivalappil
Girija Kuttan
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 2/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-017-0423-3

Other articles of this Issue 2/2019

Inflammopharmacology 2/2019 Go to the issue