Abstract
Aims and Objective: We investigated the inhibitory effects of fractions from Lycopus lucidus Turcz. leaves on genomic DNA oxidation, Nitric Oxide (NO) production, and Matrix Metalloproteinase (MMP) activity.
Materials and Methods: Oxidative damage of genomic DNA was detected after Fenton reaction with H2O2 using DNA electrophoresis. Western blotting was performed to compare the expression levels of MMP-2 in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 cells. Lipopolysacchride (LPS)-induced NO production in RAW 264.7 cells was measured using Griess reagent.
Results: All fractions (n-Hexane, 85% aq. MeOH, n-BuOH, and water fractions) from the leaves of L. lucidus Turcz. significantly inhibited intracellular production of reactive oxygen species (ROS) (p<0.05). Particularly, 85% aq. MeOH and n-BuOH fractions showed higher ROS inhibitory activity than the other fractions. n-Hexane, 85% aq. MeOH, n-BuOH and water (0.05 mg/mL) fractions significantly inhibited oxidative DNA damage by 57.97%, 68.48%, 58.97%, and 68.39%, respectively (p <0.05). Treatment of RAW 264.7 cells with each fraction reduced LPS-induced NO production in a dose-dependent manner (p<0.05). n-Hexane and 85% aq. MeOH fractions notably reduced MMP-2 secretion levels in the culture supernatants from HT-1080 cells.
Conclusion: Overall, these results indicated that L. lucidus Turcz. leaves can be exploited as plant based sources of antioxidants in the pharmaceutical, cosmetic, nutraceutical, and food industries.
Keywords: Lycopus lucidus Turcz., DNA oxidation, antioxidant, matrix metalloproteinase, reactive oxygen species (ROS), nitric oxide (NO).
Graphical Abstract
[1]
Sun, J.; Murata, T.; Shigemori, H. Inhibitory activities of phenylpropanoids from Lycopus lucidus on amyloid aggregation related to Alzheimer’s disease and type 2 diabetes. J. Nat. Med., 2020, 74(3), 579-583.
[http://dx.doi.org/10.1007/s11418-020-01398-6] [PMID: 32219646]
[http://dx.doi.org/10.1007/s11418-020-01398-6] [PMID: 32219646]
[2]
Lee, M.R.; Yang, H.J.; Park, K.I.; Ma, J.Y. Lycopus lucidus Turcz. ex Benth. Attenuates free fatty acid-induced steatosis in HepG2 cells and non-alcoholic fatty liver disease in high-fat diet-induced obese mice. Phytomedicine, 2019, 55, 14-22.
[http://dx.doi.org/10.1016/j.phymed.2018.07.008] [PMID: 30668424]
[http://dx.doi.org/10.1016/j.phymed.2018.07.008] [PMID: 30668424]
[3]
Shin, T.Y.; Kim, S.H.; Suk, K.; Ha, J.H.; Kim, I.; Lee, M.G.; Jun, C.D.; Kim, S.Y.; Lim, J.P.; Eun, J.S.; Shin, H.Y.; Kim, H.M. Anti-allergic effects of Lycopus lucidus on mast cell-mediated allergy model. Toxicol. Appl. Pharmacol., 2005, 209(3), 255-262.
[http://dx.doi.org/10.1016/j.taap.2005.04.011] [PMID: 15936049]
[http://dx.doi.org/10.1016/j.taap.2005.04.011] [PMID: 15936049]
[4]
Liu, J.; Bhuvanagiri, S.; Qu, X. The protective effects of lycopus lucidus turcz in diabetic retinopathy and its possible mechanisms. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 2900-2908.
[http://dx.doi.org/10.1080/21691401.2019.1640230] [PMID: 31307239]
[http://dx.doi.org/10.1080/21691401.2019.1640230] [PMID: 31307239]
[5]
Lee, J.W.; Lim, S.Y. Comparison of flavonoid content and antiopxidant effect of extracts from Stachys sieboldii Miq. and Lycopus lucidus Turcz. J. Life Sci., 2018, 28(7), 841-848.
[6]
Lu, Y.H.; Huang, J.H.; Li, Y.C.; Ma, T.T.; Sang, P.; Wang, W.J.; Gao, C.Y. Variation in nutritional compositions, antioxidant activity and microstructure of Lycopus lucidus Turcz. root at different harvest times. Food Chem., 2015, 183(183), 91-100.
[http://dx.doi.org/10.1016/j.foodchem.2015.03.033] [PMID: 25863615]
[http://dx.doi.org/10.1016/j.foodchem.2015.03.033] [PMID: 25863615]
[7]
Yu, J.Q.; Lei, J.C.; Zhang, X.Q.; Yu, H.D.; Tian, D.Z.; Liao, Z.X.; Zou, G.L. Anticancer, antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel. Food Chem., 2011, 126(4), 1593-1598.
[http://dx.doi.org/10.1016/j.foodchem.2010.12.027] [PMID: 25213932]
[http://dx.doi.org/10.1016/j.foodchem.2010.12.027] [PMID: 25213932]
[8]
Fu, X.; Bai, J.; Tan, X.; Chen, T.; Tang, W.; He, F. Antimicrobial activities and mechanism of the essential oil from Artemisia argyi Levl. Et Van. Var. argyi cv. Qiai. Ind. Crops Prod., 2018, 2018(125), 582-587.
[9]
Yamahana, H.; Takino, T.; Endo, Y.; Yamada, H.; Suzuki, T.; Uto, Y. A novel celecoxib analog UTX-121 inhibits HT1080 cell invasion by modulating membrane-type 1 matrix metalloproteinase. Biochem. Biophys. Res. Commun., 2020, 521(1), 137-144.
[http://dx.doi.org/10.1016/j.bbrc.2019.10.092] [PMID: 31629465]
[http://dx.doi.org/10.1016/j.bbrc.2019.10.092] [PMID: 31629465]
[10]
Kim, J.A.; Kong, C.S.; Seo, Y.W.; Kim, S.K. Sargassum thunbergii extract inhibits MMP-2 and -9 expressions related with ROS scavenging in HT1080 cells. Food Chem., 2010, 120(2), 418-425.
[http://dx.doi.org/10.1016/j.foodchem.2009.10.022]
[http://dx.doi.org/10.1016/j.foodchem.2009.10.022]
[11]
Kong, C.S.; Kim, Y.A.; Kim, M.M.; Park, J.S.; Kim, J.A.; Kim, S.K.; Lee, B.J.; Nam, T.J.; Seo, Y. Flavonoid glycosides isolated from Salicornia herbacea inhibit matrix metalloproteinase in HT1080 cells. Toxicol. In Vitro, 2008, 22(7), 1742-1748.
[http://dx.doi.org/10.1016/j.tiv.2008.07.013] [PMID: 18715546]
[http://dx.doi.org/10.1016/j.tiv.2008.07.013] [PMID: 18715546]
[12]
Huang, H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors (Basel), 2018, 18(10), 3249.
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739]
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739]
[13]
Chan, P.H. Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cereb. Blood Flow Metab., 2001, 21(1), 2-14.
[http://dx.doi.org/10.1097/00004647-200101000-00002] [PMID: 11149664]
[http://dx.doi.org/10.1097/00004647-200101000-00002] [PMID: 11149664]
[14]
D’Autréaux, B.; Toledano, M.B. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol., 2007, 8(10), 813-824.
[http://dx.doi.org/10.1038/nrm2256] [PMID: 17848967]
[http://dx.doi.org/10.1038/nrm2256] [PMID: 17848967]
[15]
Chen, Y.; Zheng, L.; Liu, J.; Zhou, Z.; Cao, X.; Lv, X.; Chen, F. Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways. Int. Immunopharmacol., 2014, 21(2), 447-455.
[http://dx.doi.org/10.1016/j.intimp.2014.05.026] [PMID: 24905636]
[http://dx.doi.org/10.1016/j.intimp.2014.05.026] [PMID: 24905636]
[16]
Lian, S.; Xia, Y.; Khoi, P.N.; Ung, T.T.; Yoon, H.J.; Kim, N.H.; Kim, K.K.; Jung, Y.D. Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells. Toxicol., 2015, 338, 104-116.
[http://dx.doi.org/10.1016/j.tox.2015.10.008] [PMID: 26514923]
[http://dx.doi.org/10.1016/j.tox.2015.10.008] [PMID: 26514923]
[17]
Paduch, R.; Walter-Croneck, A.; Zdzisińska, B.; Szuster-Ciesielska, A.; Kandefer-Szerszeń, M. Role of reactive oxygen species (ROS), metalloproteinase-2 (MMP-2) and interleukin-6 (IL-6) in direct interactions between tumour cell spheroids and endothelial cell monolayer. Cell Biol. Int., 2005, 29(7), 497-505.
[http://dx.doi.org/10.1016/j.cellbi.2005.01.007] [PMID: 15893483]
[http://dx.doi.org/10.1016/j.cellbi.2005.01.007] [PMID: 15893483]
[18]
Alicka, M.; Marycz, K. The effect of chronic inflammation nd oxidative and endoplasmic reticulum stress in the course of metabolic syndrome and its therapy. Stem Cells Int., 2018, 2018, 4274361.
[http://dx.doi.org/10.1155/2018/4274361] [PMID: 30425746]
[http://dx.doi.org/10.1155/2018/4274361] [PMID: 30425746]
[19]
Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 1999, 26(9-10), 1231-1237.
[http://dx.doi.org/10.1016/S0891-5849(98)00315-3] [PMID: 10381194]
[http://dx.doi.org/10.1016/S0891-5849(98)00315-3] [PMID: 10381194]
[20]
Sambrook, J.; Russell, D.W. Molecular Cloning: A Laboratory Manual, 3rd ed; Cold Spring Harbor Laboratory Press: NY, USA, 2001.
[21]
Kang, J.H. Oxidative damage of DNA induced by ferritin and hydrogen peroxide. Bull. Korean Chem. Soc., 2010, 31(10), 2873-2876.
[http://dx.doi.org/10.5012/bkcs.2010.31.10.2873]
[http://dx.doi.org/10.5012/bkcs.2010.31.10.2873]
[22]
Bae, J.Y.; Choi, M.; Park, I.D.; Lim, S.Y. Effect of Korean wine wste extraction on nitric oxide and cytokine product on lipopolysaccharide-induced inflammation. Bionature, 2018, 38(2), 105-113.
[23]
Nirmala, C.; Jasti, S.L.; Sawaya, R.; Kyritsis, A.P.; Konduri, S.D.; Ali-Osman, F.; Rao, J.S.; Mohanam, S. Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions. Int. J. Cancer, 2000, 88(5), 766-771.
[http://dx.doi.org/10.1002/1097-0215(20001201)88:5<766::AIDIJC13>3.0.CO;2-Y] [PMID: 11072246]
[http://dx.doi.org/10.1002/1097-0215(20001201)88:5<766::AIDIJC13>3.0.CO;2-Y] [PMID: 11072246]
[24]
Na, E.; Lee, J.W.; Lim, S.Y. Free radical scavenging, cytotoxic effects, and flavonoid content of fractions from leaves of Lycopus lucidus Turcz. J. Life Sci., 2019, 29(3), 337-344.
[25]
Stavrou, I.J.; Christou, A.; Kapnissi-Christodoulou, C.P. Polyphenols in carobs: A review on their composition, antioxidant capacity and cytotoxic effects, and health impact. Food Chem., 2018, 269, 355-374.
[http://dx.doi.org/10.1016/j.foodchem.2018.06.152] [PMID: 30100447]
[http://dx.doi.org/10.1016/j.foodchem.2018.06.152] [PMID: 30100447]
[26]
Amararathna, M.; Hoskin, D.W.; Rupasinghe, H.P.V. Anthocyanin-rich haskap (Lonicera caerulea L.) berry extracts reduce nitrosamine-induced DNA damage in human normal lung epithelial cells in vitro. Food Chem. Toxicol., 2020, 141, 111404.
[http://dx.doi.org/10.1016/j.fct.2020.111404] [PMID: 32413456]
[http://dx.doi.org/10.1016/j.fct.2020.111404] [PMID: 32413456]
[27]
Liu, H.; Peng, H.; Ji, Z.; Zhao, S.; Zhang, Y.; Wu, J.; Fan, J.; Liao, J. Reactive oxygen species-mediated mitochondrial dysfunction is involved in apoptosis in human nasopharyngeal carcinoma CNE cells induced by Selaginella doederleinii extract. J. Ethnopharmacol., 2011, 138(1), 184-191.
[http://dx.doi.org/10.1016/j.jep.2011.08.072] [PMID: 21924341]
[http://dx.doi.org/10.1016/j.jep.2011.08.072] [PMID: 21924341]
[28]
Poetsch, A.R. The genomics of oxidative DNA damage, repair, and resulting mutagenesis. Comput. Struct. Biotechnol. J., 2020, 18, 207-219.
[http://dx.doi.org/10.1016/j.csbj.2019.12.013] [PMID: 31993111]
[http://dx.doi.org/10.1016/j.csbj.2019.12.013] [PMID: 31993111]
[29]
Papi, S.; Ahmadizar, F.; Hasanvand, A. The role of nitric oxide in inflammation and oxidative stress. Immunopathologia Persa, 2019, 5(1), e8.
[http://dx.doi.org/10.15171/ipp.2019.08]
[http://dx.doi.org/10.15171/ipp.2019.08]
[30]
Sahni, S.; Hickok, J.R.; Thomas, D.D. Nitric oxide reduces oxidative stress in cancer cells by forming dinitrosyliron complexes. Nitric Oxide, 2018, 76(6), 37-44.
[http://dx.doi.org/10.1016/j.niox.2018.03.003] [PMID: 29522907]
[http://dx.doi.org/10.1016/j.niox.2018.03.003] [PMID: 29522907]
[31]
Möller, M.N.; Rios, N.; Trujillo, M.; Radi, R.; Denicola, A.; Alvarez, B. Detection and quantification of nitric oxide-derived oxidants in biological systems. J. Biol. Chem., 2019, 294(40), 14776-14802.
[http://dx.doi.org/10.1074/jbc.REV119.006136] [PMID: 31409645]
[http://dx.doi.org/10.1074/jbc.REV119.006136] [PMID: 31409645]
[32]
Chojnacka, K.; Lewandowska, U. Chemopreventive effects of polyphenol-rich extracts against cancer invasiveness and metastasis by inhibition of type IV collagenases expression and activity. J. Funct. Foods, 2018, 46, 295-311.
[http://dx.doi.org/10.1016/j.jff.2018.05.001]
[http://dx.doi.org/10.1016/j.jff.2018.05.001]
[33]
Mattos, B.R.; Bonacio, G.F.; Vitorino, T.R.; Garcia, V.T.; Amaral, J.H.; Dellalibera-Joviliano, R.; Franca, S.C.; Tanus-Santos, J.E.; Rizzi, E. TNF-α inhibition decreases MMP-2 activity, reactive oxygen species formation and improves hypertensive vascular hypertrophy independent of its effects on blood pressure. Biochem. Pharmacol., 2020, 180, 114121.
[http://dx.doi.org/10.1016/j.bcp.2020.114121] [PMID: 32592722]
[http://dx.doi.org/10.1016/j.bcp.2020.114121] [PMID: 32592722]
[34]
Panyathep, A.; Chewonarin, T.; Taneyhill, K.; Vinitketkumnuen, U.; Surh, Y.J. Inhibitory effects of dried longan (Euphoria longana Lam.) seed extract on invasion and matrix metalloproteinases of colon cancer cells. J. Agric. Food Chem., 2013, 61(15), 3631-3641.
[http://dx.doi.org/10.1021/jf3052863] [PMID: 23527961]
[http://dx.doi.org/10.1021/jf3052863] [PMID: 23527961]
Related Journals
Current Computer-Aided Drug Design
Article Metrics
14