In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types of chronic diseases, such as diabetes, hypertension, chronic pain, and general inflammation. Despite its widespread use, little is known about the medicinal properties of the plants of this genus. In this study, we evaluate the antioxidant and anti-inflammatory of T. subulata leaf extract in an in vitro model of inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We observed that cotreatment with T. subulata leaf extract was able to reduce the oxidative stress in cells due to inflammatory response. More importantly, we observed that the leaf extract was able to directly modulate inflammatory response by altering activity of members of the mitogen-activated protein kinase pathways. Our results demonstrate for the first time that T. subulata have antioxidant and anti-inflammatory properties, which warrant further investigation of the medicinal potential of this species.
Get full access to this article
View all access options for this article.
References
1.
DauchetL, AmouyelP, HercbergS, DallongevilleJ: Fruit and vegetable consumption and risk of coronary heart disease: A meta-analysis of cohort studies. J Nutr, 2006; 136:2588–2593.
2.
TohillBC, SeymourJ, SerdulaM, Kettel-KhanL, RollsBJ: What epidemiologic studies tell us about the relationship between fruit and vegetable consumption and body weight. Nutr Rev, 2004; 62:365–374.
3.
CookeLJ, et al.: Demographic, familial and trait predictors of fruit and vegetable consumption by pre-school children. Public Health Nutr, 2004; 7:295–302.
4.
de Carvalho Nilo BituV. et al.: Ethnopharmacological study of plants sold for therapeutic purposes in public markets in Northeast Brazil. J Ethnopharmacol, 2015; 172:265–272.
5.
BritoNJN, et al.: Antioxidant activity and protective effect of Turnera ulmifolia Linn. var. elegans against carbon tetrachloride-induced oxidative damage in rats. Food Chem Toxicol, 2012; 50:4340–4347.
6.
KumarS, TanejaR, SharmaA: The genus Turnera: A review update. Pharm Biol, 2005; 43:383–391.
7.
Estrada-ReyesR, Carro-JuárezM, Martínez-MotaL: Pro-sexual effects of Turnera diffusa Wild (Turneraceae) in male rats involves the nitric oxide pathway. J Ethnopharmacol, 2013; 146:164–172.
8.
Soriano-MelgarLDAA, et al.: Antioxidant and trace element content of damiana (Turnera diffusa Willd) under wild and cultivated conditions in semi-arid zones. Ind Crops Prod, 2012; 37:321–327.
9.
Garza-JuárezA, Salazar-CavazosMDLL, Salazar-ArandaR, Pérez-MeseguerJ, de TorresNW: Correlation between chromatographic fingerprint and antioxidant activity of Turnera diffusa (Damiana). Planta Med, 2011; 77:958–963.
10.
TakebayashiJ, et al.: Reassessment of antioxidant activity of arbutin: Multifaceted evaluation using five antioxidant assay systems. Free Radic Res, 2010; 44:473–478.
11.
Avelino-FloresMDC, Cruz-LópezM. del C, Jiménez-Montejo FE, Reyes-Leyva J: Cytotoxic activity of the methanolic extract of Turnera diffusa Willd on breast cancer cells. J Med Food, 2015; 18:299–305.
12.
ZhaoJ, DasmahapatraAK, KhanSI, KhanIA: Anti-aromatase activity of the constituents from damiana (Turnera diffusa). J Ethnopharmacol, 2008; 120:387–393.
13.
GalvezJ, et al.: Intestinal antiinflammatory activity of a lyophilized infusion of Turnera ulmifolia in TNBS rat colitis. Fitoterapia, 2006; 77:515–520.
14.
SzewczykK, ZidornC: Ethnobotany, phytochemistry, and bioactivity of the genus Turnera (Passifloraceae) with a focus on damiana—Turnera diffusa. J Ethnopharmacol, 2014; 152:424–443.
LiuZ, LenardoMJ: Reactive oxygen species regulate autophagy through redox-sensitive proteases. Dev Cell, 2007; 12:484–485.
17.
VernonPJ, TangD: Eat-Me: Autophagy, phagocytosis, and reactive oxygen species signaling. Antioxid Redox Signal, 2012; 18:120918063726003.
18.
AzadMB, ChenY, GibsonSB: Regulation of autophagy by reactive oxygen species (ROS): Implications for cancer progression and treatment. Antioxid Redox Signal, 2009; 11:777–790.
19.
ChenY, AzadMB, GibsonSB: Superoxide is the major reactive oxygen species regulating autophagy. Cell Death Differ, 2009; 16:1040–1052.
20.
GutteridgeJM, HalliwellB: Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci, 2000; 899:136–147.
HalliwellB: Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence?. Lancet, 1994; 344:721–724.
23.
MittalM, SiddiquiMR, TranK, ReddySP, MalikAB: Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal, 2014; 20:1126–1167.
24.
KhodrB, KhalilZ: Modulation of inflammation by reactive oxygen species: Implications for aging and tissue repair. Free Radic Biol Med, 2001; 30:1–8.
25.
DraperHH, et al.: A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Radic Biol Med, 1993; 15:353–363.
26.
LevineRL, et al.: Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol, 1990; 186:464–478.
AebiH: Catalase in vitro. Methods Enzymol, 1984; 105:121–126.
29.
Misra HaraP, FridovichI: The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem, 1972; 247:3170–3175.
30.
WangH, JosephJA: Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med, 1999; 27:612–616.
31.
De Bittencourt PasqualiMA, et al.: Vitamin A (retinol) downregulates the receptor for advanced glycation endproducts (RAGE) by oxidant-dependent activation of p38 MAPK and NF-kB in human lung cancer A549 cells. Cell Signal, 2013; 25:939–954.
32.
SkehanP, et al.: New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst, 1990; 82:1107–1112.
33.
MukhtarM, et al.: Antiviral potentials of medicinal plants. Virus Res, 2008; 131:111–120.
34.
HalliwellB: Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res, 1996; 25:57–74.
35.
López-AlarcónC, DenicolaA: Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays. Anal Chim Acta, 2013; 763:1–10.
36.
SperanzaPR, SeijoJG, GrelaIA, Sol NeffaVG: Chloroplast DNA variation in the Turnera sidoides L. complex (Turneraceae): Biogeographical implications. J Biogeogr, 2007; 34:427–436.
37.
SzewczykK, ZidornC: Ethnobotany, phytochemistry, and bioactivity of the genus Turnera (Passifloraceae) with a focus on damiana—Turnera diffusa. J Ethnopharmacol, 2014; 152:424–443.
MillerNJ, Rice-EvansCA: Factors influencing the antioxidant activity determined by the ABTS.+ radical cation assay. Free Radic Res, 1997; 26:195–199.
41.
Ruiz-LarreaMB, et al.: Antioxidant activity of phytoestrogenic isoflavones. Free Radic Res, 1997; 26:63–70.
42.
RoleiraFMF, et al.: Plant derived and dietary phenolic antioxidants: Anticancer properties. Food Chem, 2015; 183:235–258.
43.
Fernández-MorianoC, Gómez-SerranillosMP, CrespoA: Antioxidant potential of lichen species and their secondary metabolites. A systematic review. Pharm Biol, 2015; 54:1–17.
44.
CostaG, FranciscoV, LopesMC, CruzMT, BatistaMT: Intracellular signaling pathways modulated by phenolic compounds: Application for new anti-inflammatory drugs discovery. Curr Med Chem, 2012; 19:2876–2900.
45.
WangG, et al.: The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death. Cell Death Dis, 2013; 4:e746.
46.
MorettiE, et al.: Effect of quercetin, rutin, naringenin and epicatechin on lipid peroxidation induced in human sperm. Reprod Toxicol, 2012; 34:651–657.
47.
AwadN. et al.: N-acetyl-cysteine (NAC) attenuates LPS-induced maternal and amniotic fluid oxidative stress and inflammatory responses in the preterm gestation. Am J Obstet Gynecol, 2011; 204:450.e15–e20.
48.
WangH, et al.: N-Acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice. Acta Pharmacol Sin, 2007; 28:1803–1809.
49.
ZhouR, YazdiAS, MenuP, TschoppJ: A role for mitochondria in NLRP3 inflammasome activation. Nature, 2011; 469:221–225.
50.
PasqualiMAB, et al.: Retinol and retinoic acid modulate catalase activity in Sertoli cells by distinct and gene expression-independent mechanisms. Toxicol In Vitro, 2008; 22:1177–1183.
51.
GelainDP, et al.: Retinol increases catalase activity and protein content by a reactive species-dependent mechanism in Sertoli cells. Chem Biol Interact, 2008; 174:38–43.
52.
BindoliA, FukutoJM, FormanHJ: Thiol chemistry in peroxidase catalysis and redox signaling. Antiox Redox Signal, 2008; 10:1549–1564.
53.
WinterbournCC, HamptonMB: Thiol chemistry and specificity in redox signaling. Free Radic Biol Med, 2008; 45:549–561.
54.
BourdonE, BlacheD: The importance of proteins in defense against oxidation. Antioxid Redox Signal, 2001; 3:293–311.
55.
ChengX, KuCH, SiowRCM: Regulation of the Nrf2 antioxidant pathway by microRNAs: New players in micromanaging redox homeostasis. Free Radic Biol Med, 2013; 64:4–11.
56.
ChappleSJ, SiowRCM, MannGE: Crosstalk between Nrf2 and the proteasome: Therapeutic potential of Nrf2 inducers in vascular disease and aging. Int J Biochem Cell Biol, 2012; 44:1315–1320.
57.
VeitF, PakO, BrandesRP, WeissmannN: Hypoxia-dependent reactive oxygen species signaling in the pulmonary circulation: Focus on ion channels. Antioxid Redox Signal, 2015; 22:537–552.
58.
HöhnTJA, GruneT: The proteasome and the degradation of oxidized proteins: Part II—protein oxidation and proteasomal degradation. Redox Biol, 2013; 2:99–104.
59.
HöhnTJA, GruneT: The proteasome and the degradation of oxidized proteins: Part III-redox regulation of the proteasomal system. Redox Biol, 2014; 2:388–394.
60.
GruneT, MerkerK, SandigG, DaviesKJA: Selective degradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun, 2003; 305:709–718.
61.
DaviesKJA: Degradation of oxidized proteins by the 20S proteasome. Biochimie, 2001; 83:301–310.
62.
GelainDP, et al.: Serum heat shock protein 70 levels, oxidant status, and mortality in sepsis. Shock, 2011; 35:466–470.
63.
AndradesMÉ, et al.: Plasma glycation levels are associated with severity in sepsis. Eur J Clin Invest, 2012; 42:1055–1060.
64.
ShonW-J, LeeY-K, ShinJH, ChoiEY, ShinD-M: Severity of DSS-induced colitis is reduced in Ido1-deficient mice with down-regulation of TLR-MyD88-NF-kB transcriptional networks. Sci Rep, 2015; 5:17305.
GeorgopoulosNT, et al.: A novel mechanism of CD40-induced apoptosis of carcinoma cells involving TRAF3 and JNK/AP-1 activation. Cell Death Differ, 2006; 13:1789–1801.
67.
FreundA, OrjaloAV, DesprezP-Y, CampisiJ: Inflammatory networks during cellular senescence: Causes and consequences. Trends Mol Med, 2010; 16:238–246.
68.
RyterSW, XiS, HartsfieldCL, ChoiAMK: Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells. Antioxid Redox Signal, 2002; 4:587–592.
69.
GaestelM, KotlyarovA, KrachtM: Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov, 2009; 8:480–499.
