This review is aimed at presenting relevant information on the therapeutic potential of essential oil sesquiterpenes with anti-inflammatory activity. The data reviewed provide a basis for seeking new anti-inflammatory drugs from natural products that do not exhibit the undesirable side effects often displayed by anti-inflammatory drugs. In this review the experimental models, possible mechanisms of action, and chemical structures of 12 sesquiterpenes are presented.
EdrisAE. (2007) Pharmaceutical and therapeutic potentials of essential oils and their individual volatile constituents: A review Phytotherapy Research, 21, 308–323.
2.
De SousaDP. (2012) Medicinal Essential Oils: Chemical, Pharmacological and Therapeutic Aspects, New York. 236.
3.
OliveiraFA, AndradeLN, De SousaEB, De SousaDP. (2014) Anti-ulcer activity of essential oil constituents. Molecules, 19, 5717–5747.
4.
SilveiraRDC, AndradeLN, De SousaDP. (2013) A review on anti-inflammatory activity of monoterpenes. Molecules, 18, 1227–1254.
5.
SobralMV, XavierAL, LimaTC, De SousaDP. (2014) Antitumor activity of monoterpenes found in essential oils. Scientific World Journal, 1–35.
6.
MedzhitovR. (2008) Origin and physiological roles of inflammation. Nature, 454, 428–435.
7.
BellinganG. (1999) Inflammatory cell activation in sepsis. British Medical Bulletin, 55, 12–29.
8.
SerhanCN. (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annual Review Immunology, 25, 101–137.
9.
SpiteM, SerhanCN. (2010) Novel lipid mediators promote resolution of acute inflammation. Impact of aspirin and statins. Circulation Research107, 1170–1184.
10.
MaloneyCG, KutcheraWA, AJbertineKH, MclntyreTM, PrescottSM, ZimmermanGA. (1998) Inflammatory agonists induce cyclo-oxygenase type 2 expression by human neutrophils. The Journal of Immunology, 160, 1402–1410.
Van der PollT, JansenPM, MontegutWJ, BraxtonCC, CalvanoSE, StackpoleSA, SmithSR, SwansonSW, HackCE, LowrySF, MoldawerLL. (1997) Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia. The Journal of Immunology, 158, 1971–1975.
13.
JooJH, JettenAM. (2010) Molecular mechanisms involved in farnesol-induced apoptosis. Cancer Letters, 287, 123–35.
14.
NavarathnaDH, NickersonKW, DuhamelGE, JerrelsTR, PetroTM. (2007) Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. Infection and Immunity, 75, 4001–1006.
15.
QamarW, SultanaS. (2008) Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: An initial step in lung chemoprevention. Chemico-Biological Interactions, 176, 79–87.
16.
CarpH, JanoffA. (1978) Possible mechanisms of emphysema in smokers: in vitro suppression of serum elastase-inhibitory capacity by fresh cigarette smoke and its prevention by antioxidants. American Review Respiratory Disease, 118, 617–621.
17.
PryorWA, StoneK. (1993) Oxidants in cigarette smoke: radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Annals of the New York Academy of Sciences, 686, 12–27.
18.
JaimesEA, De MasterEG, TianRX, RaijL. (2004) Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1031–1036.
19.
PryorWA, StanleyJP. (1975) A suggested mechanism for the production of malondialdehyde during the autoxidation of polyunsaturated fatty acids. Nonenzymatic production of prostaglandin endoperoxides during autoxidation. The Journal of Organic Chemistry, 40, 3615–3617.
20.
JahangirT, KhanTH, PrasadL, SultanaS. (2006) Farnesol prevents Fe-NTA mediated renal oxidative stress and early tumour promotion markers in rats. Human & Experimental Toxicology, 25, 235–242.
21.
KhanR, SultanaS. (2011) Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistarrats. Chemico-Biology Interactions, 192, 193–200.
22.
ArutiunianAV, ProkopenkoVM, BurmistrovSO, OparinaTI, FrolovaEV, ZabezhinskiMA, PopovichIG, AnisimovVN. (1997) Free-radical processes in blood serum, liver and large bowel during 1,2-dimethylhydrazine-induced carcinogenesis in rats. Voprosy Onkologii, 43, 618–622.
23.
RajeshkumarNV, KuttanR. (2003) Modulation of carcinogenic response and antioxidant enzymes of rats administered with 1,2-dimethylhydrazine bypicroliv. Cancer Letters, 191, 137–143.
24.
WenJ, YouKR, LeeSY, SongCH, KimDG. (2002) Oxidative stress-mediated apoptosis: the anticancer effect of the sesquiterpene lactone parthenolide. The Journal of Biology Chemistry, 277, 38954–38964.
25.
GhelardiniC, GaleottiN, Di Cesare MannelliL, MazzantiG, BartoliniA. (2001) Local anaesthetic activity of beta-caryophyllene. Farmaco, 56, 387–389.
26.
GertschJ, LeontiM, RadunerS, RaczI, ChenJZ, XieXQ, AltmannKH, KarsakM, ZimmerA. (2008) Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences, 105, 9099–9104.
27.
OrmeñoE, BaldyV, BalliniC, FernandezC. (2008) Production and diversity of volatile terpenes from plants on calcareous and siliceous soils: effect of soil nutrients. Journal of Chemical Ecology, 34, 1219–1229.
28.
OpdykeDLJ. (1973) Monographs on fragrance raw materials Food and Cosmetics Toxicology, 11, 1059–1060.
29.
Da SilvaSL, FigueiredoPM, YanoT. (2007) Chemotherapeutic potential of the volatile oils from Zanthoxylum rhoifolium Lam leaves. European Journal of Pharmacology, 8, 180–188.
30.
ZhengGQ, KenneyPM, LamLKT. (1992) Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents. Journal of Natural Products, 55, 999–1003.
31.
RussoEB: TamingTHC. (2011) Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects Ethan B Russo. British Journal of Pharmacology, 163, 1344–1364.
32.
AkolkarLV, KakkarKK, ChakreOJ. (1992) Second Supplementto Glossary of Indian Medicinal Plants with Active Principles. Part I. CSIR, New Delhi, Cheema, 72.
33.
DashGK, GanapathyS, SureshP, PandaSK, SahuSK. (2001) Analgesic and anti- inflammatory activity of Annona squamosa leaves. Indian Journal of Natural Products, 17, 32–35.
34.
ChavanMJ, WaktePS, ShindeDB. (2010) Analgesic and anti-inflammatory activity of caryophyllene oxide from Annona squamosa L. bark. Phytomedicine, 17, 149–151.
35.
AshtonJC. (2007) Cannabinoids for the treatment of inflammation. Current Opinion in Investigational Drugs, 8, 373–384.
36.
GuindonJ, HohmannAG. (2008) Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. British Journal of Pharmacology, 153, 319–334.
37.
PassosGF, FernandesES, CunhaFM, FerreiraJ, PianowskiLF, CamposMM, CalixtoJB. (2007) Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. Journal of Ethnopharmacology, 110, 323–333.
38.
SertieJA, BasileAC, PanizzaS, MatidaAK, ZelnikR. (1990) Antiinflammatory activity and sub-acute toxicity of artemetin Planta Medica, 56, 36–40.
39.
SertieJA, BasileAC, PanizzaS, OshiroTT, AzzoliniCP, PennaSC. (1991) Pharmacological assay of Cordia verbenacea. Part III. Oral and topical antiinflammatory activity and gastrotoxicity of a crude leaf extract. Journal of Ethnopharmacology, 31, 239–247.
40.
JorgeLIF, MarkamanBEO, GonzalezE, FerroVO. (1998) Identificaçño de Cordia verbenacea D.C. (erva baleeira) como fitoterápico. Revista Brasileira de Farmácia, 79, 69–71.
41.
De CarvalhoPM, RodriguesRF, SawayaAC, MarquesMO, ShimizuMT. (2004) Chemical composition and antimicrobial activity of the essential oil of Cordia verbenacea D.C. Journal of Ethnopharmacology, 95, 297–301.
42.
MoreauME, GarbackiN, MolinaroG, BrownNJ, MarceauF, AdamA. (2005) The kallikrein-kinin system: current and future pharmacological targets. Journal of Pharmacological Sciences, 99, 6–38.
43.
RegoliD, BarabeJ. (1980) Pharmacology of bradykinin and related kinins. Pharmacological Reviews, 32, 1–46.
44.
Leeb-LundbergLMF, MarceauF, Muller-EsterlW, PettiboneDJ. ZurawBL. (2005) International Union of Pharmacology. XLV Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacological Reviews, 57, 27–77.
45.
PassosGF, FernandesES, CamposMM, AraujoJG, PesqueroJL, SouzaGE, AvellarMC, TeixeiraMM, CalixtoJB. (2004) Kinin Bl receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx. The Journal of Immunology, 172, 1839–1847.
46.
RochaAC, FernandesES, PassosGF, CalixtoJB, CamposMM. (2005) Assessment of TNFalpha contribution to the functional upregulation of kinin B(l) receptors in the mouse paw after treatment with LPS. International Immunopharmacology, 5, 1593–1600.
47.
CamposMM, LealPC, YunesRA, CalixtoJB. (2006) Non-peptide antagonists for kinin Bl receptors: new insights into their therapeutic potential for the management of inflammatory and pain diseases. Trends in Pharmacological Sciences, 27, 646–651.
48.
MedeirosR, PassosGF, VitorCE, KoeppJ, MazzucoTL, PianowskiLF, CamposMM, CalixtoJB. (2007) Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. British Journal of Pharmacology, 151, 618–627.
49.
FernandesES, PassosGF, MedeirosR, CunhaFM, FerreiraJ, CamposMM, PianowskiLF, CalixtoJB. (2007) Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. European Journal of Pharmacology, 569, 228–236.
50.
BradleyPP, PriebatDA, ChristensenRD, RothsteinG. (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of Investigative Dermatology, 78, 206–209.
51.
RogerioAP, AndradeEL, LeiteDF, FigueiredoCP, CalixtoJB. (2009) Preventive and therapeutic anti-inflammatory properties of the sesquiterpene α-humulene in experimental airways allergic inflammation. British Journal of Pharmacology, 158, 1074–1087.
52.
TambeY, TsujiuchiH, HondaG, IkeshiroY, TanakaS. (1996) Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene. Planta Medica, 62, 469–470.
53.
KamatouGPP, ViljoenAM. (2010) A Review of the application and pharmacological properties of α-bisabolol and α-bisabolol-rich oils. Journal of the American Oil Chemists Society, 87, 1–7.
54.
CavalieriE, RigoA, BonifacioM, Carcereri de PratiA, GuardalbenE, BergaminiC, FatoR, PizzoloG, SuzukiH, VinanteF. (2011) Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells. Journal of Translation Medicine, 9, 45.
55.
CostarelliL, MalavoltaM, GiacconiR, CiprianoC, GaspariniN, TeseiS, PierpaoliS, OrlandoF, SuzukiH, PerbelliniL. (2010) In vivo effect of alpha-bisabolol, a nontoxic sesquiterpene alcohol, on the induction of spontaneous mammary tumors in HER-2/neu transgenic mice. Oncology Research, 18, 409–418.
56.
LeiteGO, LeiteLH, SampaioRS, ArarunaMK, De MenezesIR, Da CostaJG, CamposAR. (2011) (-)-α-Bisabolol attenuates visceral nociception and inflammation in mice. Fitoterapia, 82, 208–211.
57.
BragaPC, Dal SassoM, FontiE, CuliciM. (2009) Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell-free systems. Pharmacology, 83, 110–115.
58.
BhaskaranN, ShuklaS, SrivastavaJK, GuptaS. (2010) Chamomile: an anti-inflammatory agent inhibits inducible nitric oxide synthase expression by blocking RelA/p65 activity. International Journal of Molecular Medicine, 26, 935–940.
59.
SafahyiH, SabierajJ, SailerER, AmnionHPT. (1994) Chamazulene: an antioxidant-type inhibitor of leukotriene B4 formation. Planta Medica, 60, 410–413.
60.
SinghN, KulshresthaVK, GuptaMB, BhargavaKP. (1970) A pharmacological study of Cyperus rotundus. Indian Journal of Medical Research, 58, 103–109.
61.
JinJH, LeeDU, KimYS, KimHP. (2011) Anti-allergic activity of sesquiterpenes from the rhizomes of Cyperus rotundus. Archives Pharmacol Research, 34, 223–228.
62.
ZhuYP. (1998) Chinese materia medica: chemistry, pharmacology and applications. Harwood Academic Publishers, New York, 379–80.
63.
ChoiHG, LeeDS, LiB, ChoiYH, LeeSH, KimYC. (2012) Santamarin, a sesquiterpene lactone isolated from Saussurea lappa, represses LPS-induced inflammatory responses via expression of heme oxygenase-1 in murine macrophage cells. International Immunopharmacology, 13, 271–279.
64.
MinaminoT, ChristouH, HsiehCM, LiuY, DhawanV, AbrahamNG, PerrellaMA, MitsialisSA, KourembanasS. (2001) Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proceedings of the National Academy of Sciences, 98, 8798–8803.
65.
SuhGY, JinY, YiAK, WangXM, ChoiAM. (2006) CCAAT/enhancer-binding proteinmediates carbon monoxide-induced suppression of cyclooxygenase-2. American Journal of Respiratory Cell and Molecular Biology, 35, 220–226.
66.
OhGS, PaeHO, LeeBS, KimBN, KimJM, KimHR, JeonSB, JeonWK, ChaeHJ, ChungHT. (2006) Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaβ via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide. Free Radical Biology & Medicine, 41, 106–119.
67.
MotohashiH, YamamotoM. (2004) Nrf2-Keapl defines a physiologically important stress response mechanism. Trends in Molecular Medicine, 10, 549–557.
68.
JinM, LeeHJ, RyuJH, ChungKS. (2000) Inhibition of LPS-induced NO production and NF-kappaB activation by a sesquiterpene from Saussurea lappa. Archives of Pharmacology Research, 23, 54–58.
69.
GraeberMB, LiW, RodriguezML. (2011) Role of microglia in CNS inflammation FEBS Letters, 585, 3798–3805.
70.
AggarwalBB, KunnumakkaraAB, HarikumarKB, GuptaSR, TharakanST, KocaC, DeyS, SungB. (2009) Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?Annals of the New York Academy of Sciences, 1171, 59–76.
71.
JayasooriyaRG, KangCH, SeoMJ, ChoiYH, JeongYK, KimGY. (2011) Exopolysaccharide of Laetiporus sulphureus var. miniatus downregulates LPS-induced production of NO, PGE2, and TNF-α in BV2 microglia cells via suppression of the NF-κB pathway. Food and Chemical Toxicology, 49, 2758–2764.
72.
MagniP, RuscicaM, DozioE, RizziE, BerettaG, MaffeiFR. (2012) Parthenolide inhibits the LPS-induced secretion of IL-6 and TNF-α and NF-κB nuclear translocation in BV-2 microglia. Phytotherapy Research, 26, 1405–1409.
73.
SmithJA, DasA, RaySK, BanikNL. (2012) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin, 87, 10–20.
74.
ZhangG, HeJL, XieXY. (2012) Anti-inflammatory effects of aromatic-turmerone through blocking of NF-κB, JNK, and p38 MAPK signaling pathways in amyloid β-stimulated microglia. International Journal of Molecular Medicine, 30, 561–568.
75.
ZhangG., HeJ.L., XieX.Y, YuC. (2012) LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways. International Journal of Molecular Medicine, 30, 561–568.
76.
HanGQ, YangYJ, LiCL. (1987) The investigation of principles against platelet activating factor from Tussilago farfara L. Chinese Journal of Pharmaceutical Analysis, 19, 33–5.
ShanJJ, YangM, RenJW. (2006) Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice. Biological and Pharmaceutical Bulletin, 29, 455–459.
79.
LiuS, LiuH, YanW, ZhangL, BaiN, HoCT. (2004) Studies on l-O- acetylbritannilactone and its derivative, (2-O-butyloxime-3-phenyl)-propio-nyl-1-O-acetylbritannilactone ester. Bioorganic & Medicinal Chemistry Letters, 14, 1101–1104.
KalesnikoffJ, GalliSJ. (2008) New developments in mast cell biology. Nature Immunology, 9, 1215–1223.
82.
EvansJH, SpencerDM, ZweifachA, LeslieCC. (2001) Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. The Journal of Biological Chemistry, 276, 30150–30160.
83.
DuronioV, WelhamMJ, AbrahamS, DrydenP, SchraderJW. (1992) p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein. Proceedings of the National Academy of Sciences, 89, 1587–1591.
84.
LiW, HuangX, YangXW. (2012) New sesquiterpenoids from the dried flower buds of Tussilago farfara and their inhibition on NO production in LPS-induced RAW264.7 cells. Fitoterapia, 83, 318–322.
85.
LiYP, WangYM. (1988) Evaluation of tussilagone: a cardiovascular-respiratory stimulant isolated from Chinese herbal medicine. General Pharmacology, 19, 261–263.
86.
LimHJ, LeeHS, RyuJH. (2008) Suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from farfarae flos in BV-2 microglial cells. Archives of Pharmacol Research, 31, 645–652.
87.
HwangboC, LeeHS, ParkJ, ChoeJ, LeeJH. (2009) The anti-inflammatory effect of tussilagone, from Tussilago farfara, is mediated by the induction of heme oxygenase-1 in murine macrophages. International Immunopharmacology, 9, 1578–1584.
88.
JaeHR, YeonSJ, DongHS. (1999) A new bisabolene epoxide from Tussilago farfara, and inhibition of nitric oxide synthesis in LPS-activated macrophages. Journal of Natural Products, 62, 1437–1438.
89.
LiR, YangJJ, WangYF, SunQ, HuHB. (2014) Chemical composition, antioxidant, antimicrobial and anti-inflammatory activities of the stem and leaf essential oils from Piper flaviflorum from Xishuangbanna, SW China. Natural Product Communications, 9, 1011–1014.