Epigenetic modifications include DNA methylation, histone modification, microRNA and lncRNA regulations, and take part in many physiological and pathological processes. Recently, it has been found that natural compounds are essential in regulation of epigenetics. By influencing the expression and activities of genes related with epigenetics and altering the expression and functions of miRNAs, many natural compounds exhibit the biological and pharmaceutical activities in the prevention, diagnosis and treatment of many kinds of human diseases, such as cancer, diabetes and cardiovascular diseases. Here in this review, the effects of several natural compounds on epigenetics and the underlying mechanisms were summarized, providing a new insight into the role of natural compounds.
ChenT., LiE. (2004) Structure and function of eukaryotic DNA methyltransferases. Current Topics in Developmental Biology, 60, 55–89.
4.
DammannR.H., RichterA.M., JiménezA.P., WoodsM., KüsterM., WitharanaC. (2017) Impact of natural compounds on DNA methylation levels of the tumor suppressor gene RASSF1A in cancer. International Journal of Molecular Science, 18, pii: E2160.
5.
FeinbergA.P., IrizarryR.A., FradinD., AryeeM.J., MurakamiP., AspelundT., EiriksdottirG., HarrisT.B., LaunerL., GudnasonV., FallinM.D. (2010) Personalized epigenomic signatures that are stable over time and covary with body mass index. Science Translational Medicine, 2, 49ra67.
6.
WangX., ZhuH., SniederH., SuS., MunnD., HarshfieldG., MariaB.L., DongY., TreiberF., GutinB., ShiH. (2010) Obesity related methylation changes in DNA of peripheral blood leukocytes. BMC Medicine, 8, 87.
7.
MurphyS.K., YangH., MoylanC.A., PangH., DellingerA., AbdelmalekM.F., GarrettM.E., Ashley-KochA., SuzukiA., TillmannH.L., HauserM.A., DiehlA.M. (2013) Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease. Gastroenterology, 145, 1076–1087.
8.
DayehT., VolkovP., SalöS., HallE., NilssonE., OlssonA.H., KirkpatrickC.L., WollheimC.B., EliassonL., RönnT., BacosK., LingC. (2014) Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genetics, 10, e1004160.
9.
ZainaS., HeynH., CarmonaF.J., VarolN., SayolsS., CondomE., Ramírez-RuzJ., GomezA., GonçalvesI., MoranS., EstellerM. (2014) DNA methylation map of human atherosclerosis. Circulation-Cardiovascular Genetics, 7, 692–700.
10.
CoppietersN., DieriksB.V., LillC., FaullR.L., CurtisM.A., DragunowM. (2014) Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain. Neurobiology of Aging, 35, 1334–1344.
11.
OrtizL.M., LombardiP., TillhonM., ScovassiA.I. (2014) Berberine, an epiphany against cancer. Molecules, 19, 12349–12367.
12.
ChenX.W., DiY.M., ZhangJ., ZhouZ.W., LiC.G., ZhouS.F. (2012) Interaction of herbal compounds with biological targets: A case study with berberine. Scientific World Journal, 2012, 708292.
13.
TillhonM., Guamán OrtizL.M., LombardiP., ScovassiA.I. (2012) Berberine: New perspectives for old remedies. Biochemical Pharmacology, 84, 1260–1267.
14.
KongW., WeiJ., AbidiP., LinM., InabaS., LiC., WangY., WangZ., SiS., PanH., WangS., WuJ., WangY., LiZ., LiuJ., JiangJ.D. (2004) Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nature Medicine, 10, 1344–1351.
15.
TangL.Q., WeiW., ChenL.M., LiuS. (2006) Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. Journal of Ethnopharmacology, 108, 109–115.
16.
YaoJ., KongW., JiangJ. (2015) Learning from berberine: Treating chronic diseases through multiple targets. Science China-Life Science, 58, 854–859.
ZouK., LiZ., ZhangY., ZhangH.Y., LiB., ZhuW.L., ShiJ.Y., JiaQ., LiY.M. (2017) Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacologica Sinica, 38, 157–167.
19.
ZhuX., BianH., GaoX. (2016) The potential mechanisms of berberine in the treatment of nonalcoholic fatty liver disease. Molecules, 21, pii: E1336.
20.
ChangX., YanH., FeiJ., JiangM., ZhuH., LuD., GaoX. (2010) Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. Journal of Lipid Research, 51, 2504–2515.
21.
ZhangL., MiaoX.J., WangX., PanH.H., LiP., RenH., JiaY.R., LuC., WangH.B., YuanL., ZhangG.L. (2016) Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells. Scientific Report, 6, 28116.
22.
JinP., ZhangC., LiN. (2015) Berberine exhibits antitumor effects in human ovarian cancer cells. Anticancer Agents in Medicinal Chemistry, 15, 511–516.
23.
QingY., HuH., LiuY., FengT., MengW., JiangL., SunY., YaoY. (2014) Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter. Cell Biology International, 38, 563–570.
24.
HuangY., SongH., HuH., CuiL., YouC., HuangL. (2012) Trichosanthin inhibits DNA methyltransferase and restores methylation-silenced gene expression in human cervical cancer cells. Molecular Medicine Report, 6, 872–878.
25.
PanF.P., ZhouH.K., BuH.Q., ChenZ.Q., ZhangH., XuL.P., TangJ., YuQ.J., ChuY.Q., PanJ., FeiY., LinS.Z., LiuD.L., ChenL. (2016) Emodin enhances the demethylation by 5-Aza-CdR of pancreatic cancer cell tumor-suppressor genes P16, RASSF1A and ppENK. Oncology Report, 35, 1941–1949.
26.
NabaviS.F., RussoG.L., DagliaM., NabaviS.M. (2015) Role of quercetin as an alternative for obesity treatment: you are what you eat!Food Chemistry, 179, 305–310.
27.
WangL.S., KuoC.T., ChoS.J., SeguinC., SiddiquiJ., StonerK., WengY.I., HuangT.H., TichelaarJ., YearsleyM., StonerG.D., HuangY.W. (2013) Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells. Nutrition and Cancer, 65, 118–125.
28.
FarghaliH., KutinováCanová N., LekićN. (2013) Resveratrol and related compounds as antioxidants with an allosteric mechanism of action in epigenetic drug targets. Physiological Research, 62, 1–13.
29.
LewinskaA., WnukM., GrabowskaW., ZabekT., SemikE., SikoraE., Bielak-ZmijewskaA. (2015) Curcumin induces oxidation-dependent cell cycle arrest mediated by SIRT7 inhibition of rDNA transcription in human aortic smooth muscle cells. Toxicology Letters, 233, 227–238.
30.
DengY., LuX., WangL., LiT., DingY., CaoH., ZhangY., GuoX., YuG. (2014) Curcumin inhibits the AKT/NF-κB signaling via CpG demethylation of the promoter and restoration of NEP in the N2a cell line. AAPS Journal, 16, 649–657.
31.
KongD., ZhangD., ChuX., WangJ. (2018) Schizandrin A enhances chemosensitivity of colon carcinoma cells to 5-fluorouracil through up-regulation of miR-195. Biomedicine & Pharmacotherapy, 99, 176–183.
32.
ZhangM., HuoD.S., CaiZ.P., ShaoG., WangH., ZhaoZ.Y., YangZ.J. (2015) The effect of Schizandrol A-induced DNA methylation on SH-SY5YAB 1-40 altered neuronal cell line: a potential use in Alzheimer's Disease. Journal of Toxicology Environmental Health A, 78, 1321–1327.
33.
KaelinW.G.Jr., McKnightS.L. (2013) Influence of metabolism on epigenetics and disease. Cell, 153, 56–69.
34.
SenP., ShahP.P., NativioR., BergerS.L. (2016) Epigenetic mechanisms of longevity and aging. Cell, 166, 822–839.
35.
RenthalW., NestlerE.J. (2009) Histone acetylation in drug addiction. Seminars in Cell & Developmental Biology, 20, 387–394.
36.
MichalakE.M., VisvaderJ.E. (2016) Dysregulation of histone methyltransferases in breast cancer - Opportunities for new targeted therapies?Molecular Oncology, 10, 1497–1515.
37.
HsuJ.Y., SunZ.W., LiX., ReubenM., TatchellK., BishopD.K., GrushcowJ.M., BrameC.J., CaldwellJ.A., HuntD.F., LinR., SmithM.M., AllisC.D. (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell, 102, 279–291.
38.
AhnS.H., HendersonK.A., KeeneyS., AllisC.D. (2005) H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle, 4, 780–783.
39.
SargB., HelligerW., TalaszH., FörgB., LindnerH.H. (2006) Histone H1 phosphorylation occurs site-specifically during interphase and mitosis: identification of a novel phosphorylation site on histone H1. Journal of Bioligical Chemistry, 281, 6573–6580.
40.
MoyalL., LerenthalY., Gana-WeiszM., MassG., SoS., WangS.Y., EppinkB., ChungY.M., ShalevG., ShemaE., ShkedyD., SmorodinskyN.I., van VlietN., KusterB., MannM., CiechanoverA., Dahm-DaphiJ., KanaarR., HuM.C., ChenD.J., OrenM., ShilohY. (2011) Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Molecular Cell, 41, 529–542.
41.
ChoiJ.H., KwonH.J., YoonB.I., KimJ.H., HanS.U., JooH.J., KimD.Y. (2001) Expression profile of histone deacetylase 1 in gastric cancer tissues. Japanese Journal of Cancer Research, 92, 1300–1304.
42.
HalkidouK., GaughanL., CookS., LeungH.Y., NealD.E., RobsonC.N. (2004) Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate, 59, 177–189.
43.
WilsonA.J., ByunD.S., PopovaN., MurrayL.B., L'ItalienK., SowaY., ArangoD., VelcichA., AugenlichtL.H., MariadasonJ.M. (2006) Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. Journal of Biological Chemistry, 281, 13548–13558.
44.
ZhangZ., YamashitaH., ToyamaT., SugiuraH., AndoY., MitaK., HamaguchiM., HaraY., KobayashiS., IwaseH. (2005) Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Breast Cancer Research and Treatment, 94, 11–16.
45.
GräffJ., ReiD., GuanJ.S., WangW.Y., SeoJ., HennigK.M., NielandT.J., FassD.M., KaoP.F., KahnM., SuS.C., SamieiA., JosephN., HaggartyS.J., DelalleI., TsaiL.H. (2012) An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature, 483, 222–226.
46.
FröjdöS., DurandC., MolinL., CareyA.L., El-OstaA., KingwellB.A., FebbraioM.A., SolariF., VidalH., PirolaL. (2011) Phosphoinositide 3-kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. Molecular and Cellular Endocrinology, 335, 166–176.
47.
ChaiR., FuH., ZhengZ., LiuT., JiS., LiG. (2017) Resveratrol inhibits proliferation and migration through SIRT1 mediated post-translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Molecular Medicine Report, 16, 8037–8044.
48.
MaS., FengJ., ZhangR., ChenJ., HanD., LiX., YangB., LiX., FanM., LiC., TianZ., WangY., CaoF. (2017) SIRT1 activation by resveratrol alleviates cardiac dysfunction via mitochondrial regulation in diabetic cardiomyopathy mice. Oxidative Medicine and Cellular Longevity, 2017, 4602715.
49.
KalaiarasiA., AnushaC., SankarR., RajasekaranS., John MarshalJ., MuthusamyK., RavikumarV. (2016) Plant isoquinoline alkaloid berberine exhibits chromatin remodeling by modulation of histone deacetylase to induce growth arrest and apoptosis in the A549 cell line. Journal of Agricultural and Food Chemistry, 64, 9542–9550.
50.
SunY., XiaM., YanH., HanY., ZhangF., HuZ., CuiA., MaF., LiuZ., GongQ., ChenX., GaoJ., BianH., TanY., LiY., GaoX. (2017) Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21. British Journal of Pharmacology, 175, 374–387.
51.
ZhuH.R., WangZ.Y., ZhuX.L., WuX.X., LiE.G., XuY. (2010) Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1alpha expression in experimental stroke. Neuropharmacology, 59, 70–76.
52.
MuruganR.S., VinothiniG., HaraY., NaginiS. (2009) Black tea polyphenols target matrix metalloproteinases, RECK, proangiogenic molecules and histone deacetylase in a rat hepatocarcinogenesis model. Anticancer Research, 29, 2301–2305.
53.
DebG., ThakurV.S., LimayeA.M., GuptaS. (2015) Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells. Molecular Carcinogenesis, 54, 485–499.
54.
BalasubramanyamK., VarierR.A., AltafM., SwaminathanV., SiddappaN.B., RangaU., KunduT.K. (2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. Journal of Biological Chemistry, 279, 51163–51171.
55.
LiuH.L., ChenY., CuiG.H., ZhouJ.F. (2005) Curcumin, a potent antitumor reagent, is a novel histone deacetylase inhibitor regulating BNHL cell line Raji proliferation. Acta Pharmacologica Sinica, 26, 603–609.
56.
YangY.H., ZhaoM., LiW.M., ChenY.Y., KangB., LuY.Y. (2006) Expression of programmed cell death 5 gene involves in regulation of apoptosis in gastric tumor cells. Apoptosis, 11, 993–1001.
57.
Schneider-StockR., GhantousA., BajboujK., SaikaliM., DarwicheN. (2012) Epigenetic mechanisms of plant-derived anticancer drugs. Frontiers in Bioscience (Landmark Ed), 17, 129–173.
58.
DruesneN., PagniezA., MayeurC., ThomasM., CherbuyC., DuéeP.H., MartelP., ChaumontetC. (2004) Diallyl disulfide (DADS) increases histone acetylation and p21 (waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis, 25, 1227–1236.
59.
DruesneN., PagniezA., MayeurC., ThomasM., CherbuyC., DuéeP.H., MartelP., ChaumontetC. (2004) Repetitive treatments of colon HT-29 cells with diallyl disulfide induce a prolonged hyperacetylation of histone H3 K14. Annals of the New York Academy of Sciences, 1030, 612–621.
60.
DongY., XuS., LiuJ., PonnusamyM., ZhaoY., ZhangY., WangQ., LiP., WangK. (2018) Non-coding RNA-linked epigenetic regulation in cardiac hypertrophy. International Journal of Biological Sciences, 14, 1133–1141.
61.
KaikkonenM.U., LamM.T., GlassC.K. (2011) Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovascular Research, 90, 430–440.
62.
PeschanskyV.J., WahlestedtC. (2014) Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics, 9, 3–12.
63.
LinQ., MaL., LiuZ., YangZ., WangJ., LiuJ., JiangG. (2011) Targeting microRNAs: a new action mechanism of natural compounds. Oncotarget, 8, 15961–15970.
64.
EstellerM. (2011) Non-coding RNAs in human disease. Nature Reviews Genetics, 12, 861–874.
65.
LovatF., ValeriN., CroceC.M. (2011) MicroRNAs in the pathogenesis of cancer. Seminars in Oncology, 38, 724–733.
RatovitskiE.A. (2017) Anticancer natural compounds as epigenetic modulators of gene expression. Current Genomics, 18, 175–205.
68.
AyatiS.H., FazeliB., Momtazi-BorojeniA.A., CiceroA.F.G., PirroM., SahebkarA. (2017) Regulatory effects of berberine on microRNome in cancer and other conditions. Critical Reviews in Oncology Hematology, 116, 147–158.
69.
ChangW. (2017) Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities. European Journal of Pharmacology, 795, 8–12.
70.
Pandima DeviK., RajavelT., DagliaM., NabaviS.F., BishayeeA., NabaviS.M. (2017) Targeting miRNAs by polyphenols: Novel therapeutic strategy for cancer. Seminars in Cancer Biology, 46, 146–157.
71.
NwaeburuC.C., AbukiwanA., ZhaoZ., HerrI. (2017) Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer. Molecular Cancer, 16, 23.
72.
DuF., FengY., FangJ., YangM. (2015) MicroRNA-143 enhances chemosensitivity of Quercetin through autophagy inhibition via target GABARAPL1 in gastric cancer cells. Biomedicine & Pharmacotherapy, 74, 169–177.
73.
WeiD., YangL., LvB., ChenL. (2017) Genistein suppresses retinoblastoma cell viability and growth and induces apoptosis by upregulating miR-145 and inhibiting its target ABCE1. Molecular Vision, 23, 385–394.
74.
MaJ., ZengF., MaC., PangH., FangB., LianC., YinB., ZhangX., WangZ., XiaJ. (2016) Synergistic reversal effect of epithelial-to-mesenchymal transition by miR-223 inhibitor and genistein in gemcitabine-resistant pancreatic cancer cells. American Journal of Cancer Research, 6, 1384–1395.
75.
LiuT., LiuX., LiW. (2016) Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy. Oncotarget, 7, 40800–40815.
76.
SongC., JiY., ZouG., WanC. (2015) Tetrandrine down-regulates expression of miRNA-155 to inhibit signal-induced NF-κB activation in a rat model of diabetes mellitus. International Journal of Clinical Experimental Medicine, 8, 4024–4030.
77.
NingP., PengY., LiuD.W., HuY.H., LiuY., LiuD.M. (2016) Tetrandrine induces microRNA differential expression in human hypertrophic scar fibroblasts in vitro. Genetics and Molecular Research, 15, doi: 10.4238/gmr.15017288.
