Essential Oils and Their Major Compounds in the Treatment of Chronic Inflammation: A Review of Antioxidant Potential in Preclinical Studies and Molecular Mechanisms

Table 3

In vivo studies involving essential oils and antioxidant activity.

Essential oil and/or majority constituent	Animals (strain/sex), (per group)	Doses, route, and administration period	Antioxidant assays	Experimental model of inflammation	General results	Reference
Essential oil of ginger	Mice (Balb/c/), , 5, or 6	10, 50, 100, 250, 500, or 1000 mg/kg (i.p. or p.o.), single dose or 4 days	Lipid peroxidation, SOD and hydroxyl activity assay; DPPH and ABTS radical scavenging and FRAP assay; PMA-induced radical generation and dosage of SOD, CAT, and GSH in vivo	Formalin induced chronic inflammation	Scavenged superoxide, DPPH, hydroxyl radicals, and lipid peroxidation inhibition; Increase in SOD, GSH, and GR enzyme levels in blood and glutathione peroxidase and SOD enzymes in liver; Reduction in formalin-induced chronic inflammation	Jeena et al. 2013 [26]
Anethole	Mice (Swiss/M),	125, 250, or 500 mg/kg (p.o.), for until 7 days	MPO activity	Paw edema induced by complete Freund’s adjuvant	Inhibition of paw edema on all of the days analyzed; Inhibition of MPO activity and reduction of TNF-α, IL-1β, and IL-17 levels in acute and persistent inflammation models	Ritter et al. 2013 [25]
Essential oil of Nigella sativa L.	Rats (Sprague–Dawley),	500 mg/kg (p.o.), 3 times a 1 day	Determination of SOD, CAT activity, and MDA and NO levels	LPS induced inflammation	Increase in SOD and CAT, and reduction of MDA and NO in lung	Entok et al. 2014 [36]
Essential oil of Piper nigrum Linn	Mice (Balb/C), or 6	10, 50, 100, 250, 500, or 1000 mg/kg (i.p. or p.o.), 5 or 30 days.	Lipid peroxidation and SOD and hydroxyl activity assay; DPPH radical scavenging and FRAP assay; PMA-induced radical generation and dosage of SOD, CAT, and GSH in vivo	Formalin induced chronic inflammation	Scavenged SOD, DPPH, and hydroxyl radicals; inhibition of lipid peroxidation in vitro; Increase in SOD and GSH enzyme levels in blood of mice and CAT, SOD, and GSH enzymes in liver; Reduction of chronic inflammation in formalin test	Jeena et al., 2014 [35]
Linalool	Mice (C57BL/6J/M),	5, 15 or 25 mg/kg (s.c.)	ROS and SOD activity assay	Pasteurella multocida induced intranasal lung infection/inflammation	Increase in nuclear Nrf-2 protein amount and reduction in SOD expression; Reduction in TNF-α and IL-6 levels and decrease in neutrophil accumulation	Wu et al. 2014 [34]
Essential oil from blossoms of Citrus aurantium L.	Rats (Wistar/M),	5, 10, 20, 40, or 80 mg/kg (i.p.) for until 7 days	Measurement of NO	Cotton pellet-induced granuloma	Decrease in transudate and granuloma formation amount involving the nitric oxide pathway	Khodabakhsh et al. 2014 [33]
Essential oil of Camellia reticulata L.	Rats (Wistar/M),	200 or 400 mg/kg (p.o.) for 11 days	Colonic GSH content and lipid peroxides concentration	Enterocolitis induced by indomethacin	Decrease in macroscopic and microscopic scores for inflammation; Reduction in MPO and lipid peroxidation and increase in GSH content	Patil et al., 2014 [32]
Essential oil of Pistacia integerrima	Rats (Sprague-Dawley/F),	5-30 μg/mL; 10, 30, or 100 mg/mL; and 7, 5, 15, or 30 mg/kg (i.p.)	DPPH radical scavenging, lipoxygenase activity, and measurement of NO and MPO	LPS- and ovalbumin-induced bronchial inflammation	Inhibition of lipoxygenase enzyme and DPPH scavenging activity; Antiallergic activity by inhibition of mast cell degranulation; Reduction in total leucocyte, neutrophils, NO, total protein, and albumin levels in bronchoalveolar fluid and MPO levels in lung homogenates	Shirole et al. 2014 [31]
Essential oil of thyme	Rats (Sprague-Dawley/M),	7, 5, 15, or 30 mg/kg (i.p.) for 21 days	FRAP assay	Ulcer-forming induced by Shigella flexneri strain	Synergistic activity of thyme oil decreased the inflammation of the lamina propria and decreased the bacterial load in the colon; Increase in total antioxidant capacity time	Allam et al. 2015 [40]
Essential oil from leaves of Choisya ternata Kunth	Mice (Webster/M), , 6, 8 or 10	3-10 or 30 mg/kg (p.o.)	NO levels and trapping capacity of anthranilates	Formalin test and subcutaneous air pouch (SAP) model	Reduction in migration, exudate volume, and protein extravasation and reduced levels of NO, TNF-α, and IL-1β	Lin et al. 2014 [29]
Carvacrol	Rats (Sprague-Dawley/F), , 7, or 8	20, 40, or 80 mg/kg (p.o.) for 6 days	MDA and NO levels	LPS-induced peritoneal inflammation	Decrease in levels of TNF-α and IL-6, MDA, NO levels, and arginase activity levels	Kara et al., 2015 [39]
Cinnamaldehyde	Rats (Sprague-Dawley/M),	30, 60, or 90 (p.o.) 1x/day for 30 days	Determination of intracellular levels of ROS	LPS-induced cardiac dysfunction	Inhibition of cardiac dysfunction, inflammatory infiltration, and the levels of TNF-α, IL-1β, and IL-6 in LPS stimulated rats by blocking the TLR4, NOX4, MAPK, and autophagy signaling pathway	Zhao et al., 2016 [44]
Thymol	Rabbits (M),	3 or 6 mg/kg (p.o) for 8 weeks	DPPH and ABTS radical scavenging activity and measurement of MDA level in serum	Inflammatory process in aortic intimal thickening	High antioxidant activity in both tests; Reduction in TC, TG, LDL-C, and MDA levels; Reduction in VCAM-1 and MCP-1 levels and proinflammatory cytokines IL-1β, IL-6, and TNF-α	Yu et al. 2016 [45]
Eucalyptol	Mice (C57BL/6/M),	1, 3, and 10 mg/mL via inhalation (15 min/daily) for 5 days	NBT assay, SOD and CAT activity; Measurement of GSH and TBARS levels	Cigarette smoke exposure	Reduction in IL-1β, IL-6, and TNF-α levels; Decrease in NF-κB expression; Reduction in ROS, SOD, CAT, MDA, and GSH levels; Rare presence of leukocytes in alveolar septa	Kennedy-Feitosa et al., 2016 [46]
Carvacrol	Mice (Swiss/F), or 8	25, 75, or 150 mg/kg (i.p.) for 8 days	GSH, MDA, and NO levels	Intestinal mucositis induced by CPT-11 chemotherapy	Reduction in TNF-α, IL-1β, and KC levels; Decrease in MPO, NF-κB, COX-2, and oxidative stress (GSH, MDA, and NO levels)	Alvarenga et al. 2016 [47]
β-Elemene	Mice ApoE−/− (C57BL/6/M),	Not related	Measurement of eNOS and NO concentrations, ROS assay, enzyme activity SOD, CAT, GPx, GSH, and MDA	Atherosclerosis induced by high fat	Inhibition of atherosclerotic lesion size and increase in plaque stability; Reduction of vascular oxidative stress and preventing proinflammatory cytokine production; Improvement in NO levels, expression of eNOS, and phosphorylation of eNOSser1177 and Akt	Liu et al. 2017 [49]
Carvacrol	Rat (Fischer 344/M),	50 mg/kg (p.o.) for 7 days before and 7 days, after tumor induction	Antioxidant enzyme activities SOD, CAT, GPx, GR, GSH, vitamin E and vitamin C, and NO level and MDA contents	Colitis induced by DMH-associated colon cancer	Increase in SOD, CAT, and GSH levels and reduction in LPO, MPO, and NO; Suppression of proinflammatory mediators iNOS and IL-1β; Reduction in ulcer size	Arigesavan and Sudhandiran 2017 [51]
Essential oil of Zingiber cassumunar Roxb. in niosomes entrapped	Rats (Wistar/M),	12.5–400 μg/mL	DPPH radical scavenging	LPS-induced subcutaneous inflammatory assay	Inhibition of DPPH radical and decrease in skin temperature and blood flow, reducing tissue inflammation process	Leelarungrayub et al. 2017 [50]
Thymol in nanoparticles from natural lipids	Mice (C57B/6/M), or 12	5 mg/day (p.o.), 15 days	Anthralin-induced ear edema model	Imiquimod-induced psoriasis	Improved inflammation and healing, on anthralin model and imiquimod	Pivetta et al. 2018 [53]

eNOS: nitric oxide synthase; NO: nitric oxide; ROS: reactive oxygen species; SOD: superoxide dismutase; CAT: catalase; GPx: glutathione peroxidase; GSH: glutathione; GR: reductase glutathione; MDA: malondialdehyde; DMH: 1,2-dimethyl hydrazine; LPO: lipid peroxides; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1 beta; DPPH: 2,2-diphenyl-1-picrylhydrazyl radical; LPS: lipopolysaccharide; M: male; ABTS: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); TC: total cholesterol; TG: triglycerides; LDL: low-density lipoprotein; VCAM-1: vascular cell adhesion molecule-1; MCP-1: monocyte chemotactic protein-1 (MCP-1); NBT: nitroblue tetrazolium; TBARS: thiobarbituric acid; NF-κB: nuclear factor kappa B; MDA: malondialdehyde; CPT-11: irinotecan, Camptosar, Camptothecin-11; COX-2: cyclooxygenase; TNF-α: tumor necrosis factor alpha; IL-6: interleukin-6; IL-17: interleukin-17; FRAP: ferric reducing antioxidant power; MPO: myeloperoxidase; TNBS: trinitrobenzenesulphonic acid; Nrf-2: nuclear factor erythroid 2–related factor 2; PMA: phorbol-12-myristate-13-acetate.