Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Toxicity and antitumor potential of Mesosphaerum sidifolium (Lamiaceae) oil and fenchone, its major component

Authors: Thaísa Leite Rolim, Déborah Ribeiro Pessoa Meireles, Tatianne Mota Batista, Tatyanna Kelvia Gomes de Sousa, Vivianne Mendes Mangueira, Renata Albuquerque de Abrantes, João Carlos Lima Rodrigues Pita, Aline Lira Xavier, Vicente Carlos Oliveira Costa, Leônia Maria Batista, Marcelo Sobral da Silva, Marianna Vieira Sobral

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

The essential oil from Mesosphaerum sidifolium (L’Hérit.) Harley & J.F.B.Pastore (syn. Hyptis umbrosa), Lamiaceae (EOM), and its major component, have been tested for toxicity and antitumor activity.

Methods

EOM was obtained from aerial parts of M. sidifolium subjected to hydro distillation, and gas chromatography-mass spectrometry was used to characterize the EOM chemical composition. The toxicity was evaluated using haemolysis assay, and acute toxicity and micronucleus tests. Ehrlich ascites carcinoma model was used to evaluate the in vivo antitumor activity and toxicity of EOM (50, 100 and 150 mg/kg), and fenchone (30 and 60 mg/kg) after 9 d of treatment.

Results

The EOM major components were fenchone (24.8%), cubebol (6.9%), limonene (5.4%), spathulenol (4.5%), β-caryophyllene (4.6%) and α-cadinol (4.7%). The HC50 (concentration producing 50% haemolysis) was 494.9 μg/mL for EOM and higher than 3000 μg/mL for fenchone. The LD50 for EOM was approximately 500 mg/kg in mice. The essential oil induced increase of micronucleated erythrocytes only at 300 mg/kg, suggesting moderate genotoxicity. EOM (100 or 150 mg/kg) and fenchone (60 mg/kg) reduced all analyzed parameters (tumor volume and mass, and total viable cancer cells). Survival also increased for the treated animals with EOM and fenchone. For EOM 150 mg/kg and 5-FU treatment, most cells were arrested in the G0/G1 phase, whereas for fenchone, cells arrested in the S phase, which represents a blockage in cell cycle progression. Regarding the toxicological evaluation, EOM induced weight loss, but did not induce hematological, biochemical or histological (liver and kidneys) toxicity. Fenchone induced decrease of AST and ALT, suggesting liver damage.

Conclusions

The data showed EOM caused in vivo cell growth inhibition on Ehrlich ascites carcinoma model by inducing cell cycle arrest, without major changes in the toxicity parameters evaluated. In addition, this activity was associated with the presence of fenchone, its major component.
Literature
1.
Singh S. R. cancer Stem cells: recent developments and future prospects. Cancer Lett. 2013;338(1):1–2.CrossRefPubMed
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2013;61:69–90.CrossRef
3.
Karolak-Wojciechowska J, Mrozek A, Amiel P, Brouant P, Barbe J, Acta Kasala ER, Bodduluru LN, Madana RM, Athira KV, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives. Toxicol Lett. 2015;233:214–25.CrossRef
4.
Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 1830;2013:3670–95.
5.
Moura APG, Beltrão DM, Pita JCLR, Xavier AL, Brito MT, Sousa TKGD, et al. Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity. Pharm Biol. 2016;54:3093–102.CrossRefPubMed
6.
Meireles DRP, Fernandes HMB, Rolim TL, Batista TM, Mangueira VM, Sousa TKG, Pita JCLR, Xavier AL, Beltrão DM, Tavares JF, Silva MS, Medeiros KKP, Sobral MV. Toxicity and antitumor efficacy of Croton Polyandrus oil against Ehrlich ascites carcinoma cells. Rev bras farmacogn. 2016;26:751–8.CrossRef
7.
Xavier AL, JCLR P, Brito MT, DRP M, Tavares JF, Maia SMS, JGS AEHA, MFFM D, Silva TG, HLF P, Sobral MV. Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia Microphylla. Zeitschrift fur Naturforschung. J Biosci. 2015;70:129–37.
8.
Bhalla Y, Gupta VK, Jaitak V. Anticancer activity of essential oils: a review. J Sci Food Agric. 2013;93:3643–53.CrossRefPubMed
9.
Souza CV, Lorenzi H. Botânica Sistemática. 2nd ed. São Paulo. Nova Odessa: Instituto Plantarum; 2008.
10.
Souza LKH, De Oliveira CMA, Ferri PH, et al. Antimicrobial activity of Hyptis Ovalifolia towards dermatophytes. Mem Inst Oswaldo Cruz. 2003;98:963–5. 2003CrossRefPubMed
11.
De Oliveira CMA, Silva MDRR, Kato L, Da Silva CC, Ferreira HD, Souza LKH. Chemical composition and antifungal activity of the essential oil of Hyptis Ovalifolia Benth. (Lamiaceae). J Braz Chem Soc. 2004;15:756–9.CrossRef
12.
Barbosa PPP, Ramos CP. Studies on the antiulcerogenic activity of the essential oil of Hyptis mutabilis Briq. In rats. Phytother Res. 1992;6:114–5.CrossRef
13.
Bueno AX, Moreira ATS, Silva FT, Estevam CS, Marchioro M. Effects of the aqueous extract from Hyptis pectinata leaves on rodent central nervous system. Rev bras farmacogn. 2006;16:317–23.CrossRef
14.
Bispo MD, Mourão RHV, Franzotti EM. Antinociceptive and antiedematogenic effects of the aqueous extract of Hyptis pectinata leaves in experimental animals. J Ethnopharmacol. 2001;76:81–6.CrossRefPubMed
15.
Falcão HS, Lima IO, Santos VL, Dantas HF, Diniz MFFM, Barbosa-Filho JM, Batista LM. Review of the plants with anti-inflammatory activity studied in Brazil. Rev bras farmacogn. 2005;15:381–91.CrossRef
16.
Ximenes RM, Melo AM, Magalhães LPM, Souza IA, Albuquerque JFC. Antitumor Activity of Leaves from Hyptis mutabilis (A. Rich.) Briq. (Lamiaceae) in Mice Bearing Tumor. Dataset Papers in Pharmacology. 2013;2013:1-3.
17.
Silva VA, Andrade LHC. O significado cultural das espécies botânicas entre indígenas de Pernambuco: o caso Xucuru. Biotemas. 2004;17:79–94.
18.
Fernandes A. Fitogeografia brasileira. Multgraf editora: Fortaleza; 1998.
19.
Matos FJA. Plantas da Medicina Popular do Nordeste: propriedades atribuídas e confirmadas. 1999. Editora da UFC, Fortaleza, p. 80.
20.
Adams RP. Identification of essential oil components by gas chromatography/ quadrupole mass spectroscopy. Carol Stream: Allured Publ. Corp; 2001. p. 456.
21.
Van Den Dool H, Kratz PD. A generalization of the retention index system including linear temperature programmed gas—liquid partition chromatography. J Chromatogr A. 1963;11:463–71.CrossRef
22.
Kang C, Munawir A, Cha M, Sohn E-T, Lee H, Kim JS, Yoon WD, Lim D, Kim E. Cytotoxicity and hemolytic activity of jellyfish Nemopilema nomurai (Scyphozoa: Rhizostomeae) venom. Comp Biochem Physiol. 2009;150:85–90.
23.
Ribeiro LR. In: Ribeiro L, Salvadori D, Marques E, editors. Teste do micronúcleo em medula óssea de roedores in vivo. Mutagênese Ambiental. Canoas: Editora da ULBRA; 2003. p. 173–6.
24.
Organisation for Economic Co-operation and Development (OECD). Acute oral toxicity. Guideline for testing of chemicals, vol. 423; 2001. p. 1–14.
25.
OECD. Mammalian erythrocyte micronucleus test. OECD guideline for testing of chemicals; 1997. p. 474.CrossRef
26.
Dolai N, Karmakar I, Kumar RBS, Kar B, Bala A, Haldar PK. Evaluation of antitumor activity and in vivo antioxidant status of Anthocephalus cadamba on Ehrlich ascites carcinoma treated mice. J Ethnopharmacol. 2012;142:865–70.CrossRefPubMed
27.
Maroni LC, Silveira ACO, Leite EA, Melo MM, Ribeiro AFC, Cassali GD, Souza CM, Souza-Fagundes EM, Caldas IR, Araújo MSS, Martins-Filho OA, Oliveira MC, Teixeira-Carvalho A. Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor. Exp Biol Med. 2012;237:973–84.CrossRef
28.
Pita JCLR, Xavier AL, Sousa TKGS, Vm M, Tavares JF, RJDO J, MVS C-B, et al. In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana. Molecules. 2012;17:9573–89.CrossRefPubMed
29.
Falcão DQ, Menezes FS. Ver. Bras. Farm. 2003;84:69–74.
30.
Zbidah M, Lupescu A, Herrmann T, Yang W, Foller M, Jilani K, Lang F. Effect of honokiol on erythrocytes. Toxicol in Vitro. 2013;27:1737–45.CrossRefPubMed
31.
Santos Júnior HM, et al. Evaluation of native and exotic Brazilian plants for anticancer activity. J Nat Prod. 2010;64:231–8.
32.
Mendanha SA, Moura SS, Anjos JLV, Valadares MC, Alonso A. Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity. Toxicol in Vitro. 2013;27:323–9.CrossRefPubMed
33.
Bakkali F, Averbeck S, Averbeck D, Idaomar M, et al. Biological effects of essential oils – a review. Food Chem Toxicol. 2008;46:446–75.CrossRefPubMed
34.
Algariri K, Atangwho IJ, Meng KY, Asmawi MZ, Sadikun A, Murugaiyah V. Antihyperglycaemic and toxicological evaluations of extract and fractions of Gynura Procumbens leaves. Trop Life Sci Res. 2014;1:75–93.
35.
Amelo W, Nagpal P, Makonnen E. Antiplasmodial activity of solvent fractions of methanolic root extract of Dodonaea Angustifolia in plasmodium berghei infected mice. BMC Complement Altern Med. 2014;1:1.
36.
Nai GA, De Oliveira MC, De Oliveira TG, Pereira LFF, Soares NDSL, Silva PG. Avaliação da genotoxicidade induzida pela administração repetida de anestésicos locais: um estudo experimental em ratos. Rev Bras Anestesiol. 2015;65:21–6.CrossRefPubMed
37.
Belcavello L, Cunha MRH, Andrade MA, Batitucci MCP. Citotoxicidade e danos ao DNA induzidos pelo extrato de Zornia diphylla, uma planta medicinal. Natureza on line. 2012;10:140–5.
38.
Ozaslan M, Karagoz ID, Kilic IH, Guldur ME. Ehrlich ascites carcinoma. Afr J Biotechnol. 2011;10:2375–8.
39.
Oliveira MLL, Melo AC. Hipertensão Portal não Cirrótica Associada à Oxaliplatina em Câncer Colorretal. Rev bras cancerol. 2011;57:57–61.
40.
Carvalho AA, Andrade LN, De Sousa ÉBV, De Sousa DP. Antitumor Phenylpropanoids Found in Essential Oils. BioMed Res Int. 2015;2015:1-21.
41.
Sobral MV, Xavier AL, Lima TC, De Sousa DP. Antitumor activity of Monoterpenes found in essential oils. Scientific World J. 2014;2014:1–35.CrossRef
42.
Chow HHS, Salazar D, Hakim IA. Pharmacokinetics of Perillic acid in humans after a single dose Administration of a Citrus Preparation Rich in d-limonene content cancer epidemiology. Cancer Epidemiol Biomarkers. 2002;11:1472–6.
43.
Loizzo MR, Tundis R, Menichini F, Saab AM, Statti GA. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif. 2008;41:1002–12.CrossRefPubMed
44.
45.
Kornberg RD, Lorch Y. Twenty-five years of the nucleosome fundamental particle of the eukaryotic chromosome. Cell. 1999;98:285–94.CrossRefPubMed
46.
Dickson MA, Schwartz GK. Development of cell cycle inhibitors for cancer therapy. Curr Opin Oncol. 2009;16:36–43.
47.
Xiao XY, Hao M, Yang XY, Ba Q, Li M, Ni SJ, Wang LS, Du X. Licochalcone a inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis. Cancer Lett. 2011;302:69–75.CrossRefPubMed
48.
Muller HR, Prado KB. Epigenetics: a new genetic field. Rubs. 2008;1:61–9.
49.
Darzynkiewicz’ S, Del Bino BG, Gorczyca W, Hotz MA, Lassota P, Traganos F. Features of apoptotic cells measured by flow Cytometry. Cytometry. 1992;13:795–808.CrossRef
50.
Franciscato C, STA L, Santurio JM, Wolkmer P, Maciel RM, de Paula MT, Garmatz BC, Costa MM. Pesq agropec bras. 2006;41:1573–7.CrossRef
51.
Miazzo R, Peralta MF, Magnoli C, Salvano M, Ferrero S, Chiacchiera SM, Carvalho ECQ, Rosa CAR, Dalcero A. Efficacy of sodium bentonite as a detoxifier of broiler feed contaminated with aflatoxin and fumonisin. Poult Sci. 2005;84:1–8.CrossRefPubMed
52.
Kodama T, Sendo F, Kobayashi H. Leukemoid reaction in BALB/c mice bearing transplanted tumors. Cancer Res. 1974;34:176–80.PubMed
53.
Okawa Y, Murata Y, Kobayashi M, Suzuki M, Suzuki S. Augmentation of host resistance to Candida albicans infection in ascites tumor-bearing mice. Microbiol Immunol. 1992;36:517–21.CrossRefPubMed
54.
Sato DYO, Wal R, De Oliveira CC, Cattaneo RII, Malvezzi M, Gabardo J, Buchi DF. Histopathological and immunophenotyping studies on normal and sarcoma 180-bearing mice treated with a complex homeopathic medication. Homeopathy. 2005;94:26–32.CrossRefPubMed
55.
Lins KO, Bezerra DP, Alves AP, Alencar NM, Lima MW, Torres VM, Farias WR, Pessoa C, De Moraes MO, Costa-Lotufo LV. Antitumor properties of a sulfated polysaccharide from the red seaweed Champia Feldmannii (Diaz-Pifferer). J Appl Toxicol. 2009;29:20–6.CrossRefPubMed
56.
Torti VR, Cobb AJ, Everitt JL, Marshall MW, Boorman GA, Buterworth BE. Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice. Toxicol Sci. 2001;64:269.CrossRefPubMed
Metadata
Title
Toxicity and antitumor potential of Mesosphaerum sidifolium (Lamiaceae) oil and fenchone, its major component
Authors
Thaísa Leite Rolim
Déborah Ribeiro Pessoa Meireles
Tatianne Mota Batista
Tatyanna Kelvia Gomes de Sousa
Vivianne Mendes Mangueira
Renata Albuquerque de Abrantes
João Carlos Lima Rodrigues Pita
Aline Lira Xavier
Vicente Carlos Oliveira Costa
Leônia Maria Batista
Marcelo Sobral da Silva
Marianna Vieira Sobral
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1779-z

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress induced by unpredictable chronic mild stress in rats

Research article

Hepatoprotective effect of Coreopsis tinctoria flowers against carbon tetrachloride-induced liver damage in mice

Research article

The Hippo signaling pathway: a potential therapeutic target is reversed by a Chinese patent drug in rats with diabetic retinopathy

Research article

The herbal formula KH-204 is protective against erectile dysfunction by minimizing oxidative stress and improving lipid profiles in a rat model of erectile dysfunction induced by hypercholesterolaemia

Research article

Coronary angiogenic effect of long-term administration of Nigella sativa

Research article

Association of lumbar spine stiffness and flexion-relaxation phenomenon with patient-reported outcomes in adults with chronic low back pain – a single-arm clinical trial investigating the effects of thrust spinal manipulation