Anti-inflammatory and cytotoxicity assay of Cardamom-based nutraceuticals in comparison with 1,8 -Cineol
Abstract
Aim: To investigate anti-inflammatory, cytotoxic effects and viability of Recovereez- 51% 1,8-Cineol and 1,8-Cineol (natural), and to determine safety for both of the compounds and its use in new product range of nutraceuticals.
Methodology: Cell line was divided into two groups; one was treated with Recovereez(R) and another one with 1,8-Cineol(C). The ELISA assay method was used to measure the COX, LOX, MPO, NO, and nitrate levels. Cellular viability was performed by observing cells under the inverted phase contrast microscope, followed by MTT assay.
Results: R&C showed a reduction in levels of inflammatory markers such as IL-6, IL-1β, TNF-α, LOX, MPO, COX, iNOS, and nitrate levels. The inhibition as observed in the levels of COX and LOX enzymes were 65%±0.1 and 59%±0.3µg/ml, and 72%±0.3 and 67%±0.4µg/ml for R&C, respectively. iNOS production showed inhibition by 70%±0.3 and 65%±0.8µg/ml and NO production were reduced by 193 and 209.5µg/ml by R&C, respectively. Again, there was a decrease in the activity of MPO by 0.35 and 0.39U/ml for R&C, respectively. The results were significant with p<0.001 compared to the Diclofenac sodium. Cell viability of 60% was observed upon treating L929 cells with R&C.
Conclusion: R&C exerted an anti-inflammatory effect on RAW 264.7 cells without exerting cytotoxicity in a dose-dependent manner. Therefore, Recovereez could be used as an alternative treatment or to prevent inflammatory diseases. Moreover, R&C are expected to treat different types of cancer. The findings could potentially lead to the discovery of safe and effective bioactive compounds that can prevent or cure the occurrence of cancerous cells.
Keywords: dietary supplements, nutraceutical, COX, anti-inflammation, cancer
Keywords:
dietary supplements, nutraceutical, COX, anti-inflammation, cancerDOI
https://doi.org/10.22270/jddt.v13i10.5978References
https://en.wikipedia.org/wiki/Cardamom [Accessed on: 03-05-2023]
Kaushik P, Goyal P, Chauhan A, Chauhan G. In Vitro Evaluation of Antibacterial Potential of Dry Fruit Extracts of Elettaria cardamomum Maton (Chhoti Elaichi). Iran J Pharm Res. 2010;9(3):287-292.
World Health Organization. WHO Traditional Medicine Strategy: 2014-2023. WHO Press; Geneva, Switzerland: 2013.
Almeer RS, Alnasser M, Aljarba N, AlBasher GI. Effects of Green cardamom (Elettaria cardamomum Maton) and its combination with cyclophosphamide on Ehrlich solid tumors. BMC Complement Med Ther. 2021;21(1):133. Published 2021 Apr 29. https://doi.org/10.1186/s12906-021-03305-2 PMid:33926427 PMCid:PMC8086365
Frencken JE, Sharma P, Stenhouse L, Green D, Laverty D, Dietrich T. Global epidemiology of dental caries and severe periodontitis - a comprehensive review. J Clin Periodontol. 2017; 44 (Suppl. 18): S94-S105. https://doi.org/10.1111/jcpe.12677
Souissi M, Azelmat J, Chaieb K, Grenier D. Antibacterial and anti-inflammatory activities of cardamom (Elettaria cardamomum) extracts: Potential therapeutic benefits for periodontal infections. Anaerobe. 2020;61:102089. https://doi.org/10.1016/j.anaerobe.2019.102089 PMid:31430531
Juergens L, Racké K, Tuleta I, Stoeber M, Juergens U. Anti-inflammatory effects of 1,8-cineole (eucalyptol) improve glucocorticoid effects in vitro: A novel approach of steroid-sparing add-on therapy for COPD and asthma. Synergy. 2017;5. https://doi.org/10.1016/j.synres.2017.08.001
Hendry ER, Worthington T, Conway BR, Lambert PA. Antimicrobial efficacy of eucalyptus oil and 1, 8-cineole alone and in combination with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm cultures. Journal of antimicrobial chemotherapy. 2009 Dec 1;64(6):1219-25. https://doi.org/10.1093/jac/dkp362 PMid:19837714
Juergens UR, Dethlefsen U, Steinkamp G, Gillissen A, Repges R, Vetter H. Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: a double-blind placebo-controlled trial. Respir Med. 2003;97(3):250-256. https://doi.org/10.1053/rmed.2003.1432 PMid:12645832
Tian Y, Zhou S, Takeda R, Okazaki K, Sekita M, Sakamoto K. Anti-inflammatory activities of amber extract in lipopolysaccharide-induced RAW 264.7 macrophages. Biomed Pharmacother. 2021;141:111854. https://doi.org/10.1016/j.biopha.2021.111854 PMid:34229253
Vutakuri N, Somara S. Natural and herbal medicine for breast cancer using Elettaria cardamomum (L.) Maton. International Journal of Herbal Medicine. 2018;6, 91-96.
Goodarzi M, Hamidiyan H, Bigdeli M. Separation of 1,8-cineol from essentil oil of Eucalyptus globulus and synthesis of new derivatives and antifungal activity of against Candida albicans. Biochemical and Cellular Archives. 2017;17. 487-491.
Juergens UR. Anti-inflammatory properties of the monoterpene 1.8-cineole: current evidence for co-medication in inflammatory airway diseases. Drug Res (Stuttg). 2014;64(12):638-646. https://doi.org/10.1055/s-0034-1372609 PMid:24831245
Worth H, Schacher C, Dethlefsen U. Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: a placebo-controlled double-blind trial. Respir Res. 2009;10(1):69. Published 2009 Jul 22. https://doi.org/10.1186/1465-9921-10-69 PMid:19624838 PMCid:PMC2720945
Beer AM, Zagorchev P, Draganova-Filipova M and Lukanov J. Effects of 1,8-Cineole on the Activity of Cyclooxygenase and Cyclooxygenase 1 and Cyclooxygenase 2 Isoforms. Natural Products Chemistry & Research. 2017;05. https://doi.org/10.4172/2329-6836.1000253
Yadav N, Chandra H. Suppression of inflammatory and infection responses in lung macrophages by eucalyptus oil and its constituent 1,8-cineole: Role of pattern recognition receptors TREM-1 and NLRP3, the MAP kinase regulator MKP-1, and NFκB. PLoS One. 2017;12(11):e0188232.. https://doi.org/10.1371/journal.pone.0188232 PMid:29141025 PMCid:PMC5687727
Walker MC, Gierse JK. In vitro assays for cyclooxygenase activity and inhibitor characterization. Methods Mol Biol. 2010;644:131-144. https://doi.org/10.1007/978-1-59745-364-6_11 PMid:20645170
Axelrod B, Cheesbrough TM, Laakso S. Lipoxygenase from Soybeans: EC 1.13.11.12 Linoleate: Oxygen Oxidoreductase. Methods in Enzymology. 1981;71, 441-451. https://doi.org/10.1016/0076-6879(81)71055-3
Salter M, Duffy C, Garthwaite J, Strijbos PJ. Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. J.Neurochem. 1996; 66: 1683-1690. https://doi.org/10.1046/j.1471-4159.1996.66041683.x PMid:8627326
Lepoivre M, Chenais B, Yapo A, Lemaire G, Thelander L, Tenu JP. Alterations of ribonucleotide reductase activity following induction of the nitrite generating pathway in adenocarcinoma cells. J Biol Chem. 1990; 265: 14143-14149. https://doi.org/10.1016/S0021-9258(18)77279-7 PMid:2117605
Talarico LB, Zibetti RGM, Faria PCS, Scolaro LA, Duarte MER, Noseda MD, Pujol CA, Damonte EB. Anti-herpes simplex virus activity of sulfated galactans from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulate. International Journal of Biological Macromolecules. 2004; 34: 63-71. https://doi.org/10.1016/j.ijbiomac.2004.03.002 PMid:15178011
Vaziri ND. Causal link between oxidative stress, inflammation, and hypertension. Iran J Kidney Dis. 2008;2(1):1-10.
Govindappa M, Sadananda TS, Channabasava R, Vinay R. In vitro anti-inflammatory, lipoxygenase, xanthine oxidase and acetycholinesterase inhibitory activity of Tecoma stans (L.) Juss. Ex kunth. International Journal of Pharma and Bio Sciences. 2011;2. 275-285.
Skaper SD, Facci L, Zusso M, Giusti P. An Inflammation-Centric View of Neurological Disease: Beyond the Neuron [published correction appears in Front Cell Neurosci. 2020 Feb 03;13:578]. Front Cell Neurosci. 2018;12:72. https://doi.org/10.3389/fncel.2018.00072 PMid:29618972 PMCid:PMC5871676
Stephenson J, Nutma E, van der Valk P, Amor S. Inflammation in CNS neurodegenerative diseases. Immunology. 2018;154(2):204-219. https://doi.org/10.1111/imm.12922 PMid:29513402 PMCid:PMC5980185
Paoletti R, Bolego C, Poli A, Cignarella A. Metabolic syndrome, inflammation and atherosclerosis. Vasc Health Risk Manag. 2006;2(2):145-152. https://doi.org/10.2147/vhrm.2006.2.2.145 PMid:17319458 PMCid:PMC1993992
Van Amersfoort ES, Van Berkel TJ, Kuiper J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev. 2003;16(3):379-414. https://doi.org/10.1128/CMR.16.3.379-414.2003 PMid:12857774 PMCid:PMC164216
Higuchi M, Higashi N, Taki H, Osawa T. Cytolytic mechanisms of activated macrophages. Tumor necrosis factor and L-arginine-dependent mechanisms act synergistically as the major cytolytic mechanisms of activated macrophages. J Immunol. 1990;144(4):1425-1431. https://doi.org/10.4049/jimmunol.144.4.1425 PMid:2303713
Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci. 2004;74(17):2157-2184. https://doi.org/10.1016/j.lfs.2003.09.047 PMid:14969719 PMCid:PMC7126989
Nagasaka R, Chotimarkorn C, Shafiqul IM, Hori M, Ozaki H, Ushio H. Anti-inflammatory effects of hydroxycinnamic acid derivatives. Biochem Biophys Res Commun. 2007;358(2):615-619. https://doi.org/10.1016/j.bbrc.2007.04.178 PMid:17499610
Patel K, Jain A, Patel D. Medicinal significance, pharmacological activities, and analytical aspects of anthocyanidins 'delphinidin': A concise report. Journal of Acute Disease. 2013;2. 169-178. https://doi.org/10.1016/S2221-6189(13)60123-7
Nørregaard R, Kwon TH, Frøkiær J. Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Kidney Res Clin Pract. 2015;34(4):194-200. https://doi.org/10.1016/j.krcp.2015.10.004 PMid:26779421 PMCid:PMC4688592
Nguyen HT, Vu TY, Chandi V, Polimati H, Tatipamula VB. Dual COX and 5-LOX inhibition by clerodane diterpenes from seeds of Polyalthia longifolia (Sonn.) Thwaites. Sci Rep. 2020;10(1):15965. Published 2020 Sep 29. https://doi.org/10.1038/s41598-020-72840-8 PMid:32994508 PMCid:PMC7524750
Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 2003;54(4):469-487.
Malayil D, House NC, Puthenparambil D, Job JT, Narayanankutty A. Borassus flabellifer haustorium extract prevents pro-oxidant mediated cell death and LPS-induced inflammation. Drug Chem Toxicol. 2022;45(4):1716-1722. https://doi.org/10.1080/01480545.2020.1858854 PMid:33307839
Zhang L, Chen J, Liao H, Li C, Chen M. Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model. Journal of Functional Foods. 2020;75, 104217. https://doi.org/10.1016/j.jff.2020.104217
Yang M, Wang Y, Patel G, et al. In vitro and in vivo anti-inflammatory effects of different extracts from Epigynum auritum through down-regulation of NF-κB and MAPK signaling pathways. J Ethnopharmacol. 2020;261:113105. https://doi.org/10.1016/j.jep.2020.113105 PMid:32590114
Baek SH, Park T, Kang MG, Park D. Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages. Molecules. 2020;25(18):4089. https://doi.org/10.3390/molecules25184089 PMid:32906766 PMCid:PMC7570554
Yang EJ, Jang S, Hyun KE, Jung EY, Kim SY, Hyun CG. Anti-Inflammatory Activity of Sonchus oleraceus Extract in Lipopolysaccharide-Stimulated RAW264.7 Cells. Biomed Pharmacol J. 2018;11(4). https://doi.org/10.13005/bpj/1546
Eddouks M, Chattopadhyay D, Zeggwagh NA. Animal models as tools to investigate antidiabetic and anti-inflammatory plants. Evid Based Complement Alternat Med. 2012;2012:142087. https://doi.org/10.1155/2012/142087 PMid:22899950 PMCid:PMC3414199
Gorgulu S, Yagci G, Kaymakcioglu N, et al. Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. Dig Dis Sci. 2006;51(3):480-487. https://doi.org/10.1007/s10620-006-3159-2 PMid:16614956
Khan AQ, Khan R, Qamar W, et al. Caffeic acid attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced NF-κB and COX-2 expression in mouse skin: abrogation of oxidative stress, inflammatory responses and proinflammatory cytokine production. Food Chem Toxicol. 2012;50(2):175-183. https://doi.org/10.1016/j.fct.2011.10.043 PMid:22036979
Chen W, Tumanov S, Kong SMY, et al. Therapeutic inhibition of MPO stabilizes pre-existing high risk atherosclerotic plaque. Redox Biol. 2022;58:102532. https://doi.org/10.1016/j.redox.2022.102532 PMid:36375379 PMCid:PMC9663534
Published
Abstract Display: 405 
PDF Downloads: 461 PDF Downloads: 98 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.