Year | Extract/component | Studying model/cell line | Epigenetic targets | Dose characteristics | Gene modified/epigenetic alterations | Outcome | References |
---|---|---|---|---|---|---|---|
Brain tumor | |||||||
2013 | Curcumin | U87 and U251 cells | DNA | •30 μM curcumin for 4 days •10, 20, and 40 μM curcumin for 4 days | •Curcumin induces hypomethylation at 17 CpG sites on the RANK promoter •Curcumin inhibits the activity of DNMT1 | Results in RANK gene activation in epigenetic modification in human glioblastoma cells | [31] |
2014 | Tetramethylpyrazine | SH-SY5Y cells | Histone | •80 μM tetramethylpyrazine for 3 or 5 days | •Tetramethylpyrazine enhances the recruitment of ac-H3 and ac-H4 to the TopoIIβ gene promoter region | Promotes SH-SY5Y cells to differentiate toward post-mitotic neurons | [52] |
2018 | Leonurus sibiricus transgenic roots extract | U87MG and grade IV glioma cells | DNA; Histone | •Treat the cells with the extraction for 24 h | •The extract downregulates the expression of UHRF1 and DNMT1 | Influences epigenetic regulation | [65] |
2018 | Rhaponticum carthamoides transformed roots extract | U87MG and grade IV glioma cells | DNA; Histone | •Treat the cells with the extraction for 24 h | •The extract downregulates the expression of UHRF1 and DNMT1 | Influences epigenetic regulation | [66] |
2019 | Calebin-A | STS26T, ST8814, T265, and S462-TY cells | Histone | •12.5 and 25 μM calebin-A •Calebin-A for 8 or 24 h | •Calebin-A decreases H3 histone acetylation •Reduces HAT activity | Epigenetic control of survivin and hTERT genes | [28] |
Thoracic tumor | |||||||
2008 | Nordihydroguaiaretic acid | T47D and RKO cells | DNA | •0–100 μM nordihydroguaiaretic acid for 72 or 144 h | •Nordihydroguaiaretic acid reverses p161NK4a CpG island hypermethylation | Induces cell cycle arrest in the G1 phase and a senescence-like state in cells | [112] |
2008 | Nordihydroguaiaretic acid | SKBR3 and MDA-MB-435 cells | DNA | •0–100 μM nordihydroguaiaretic acid for 7 days | •Nordihydroguaiaretic acid reverses methylation-silenced E-cadherin gene hypermethylation | Reactivates the expression of E-cadherin | [44] |
2012 | Thymus serpyllum extract | MDA-MB-231 cells | DNA; Histone | •250 and 500 μg/mL extract for 72 h | •The extract inhibits the DNMT and HDAC activities | Influences epigenetic regulation | [113] |
2012 | Tanshinone I | MCF-7 cells | Histone | •3 μM tanshinone I for 48 h | •Tanshinone I reduces ac-H3 associated with the primer 4-amplified area in Aurora A gene DNA promoter | Downregulates Aurora A gene expression | [71] |
2014 | Kazinol Q | MDA-MB-231 cells | DNA | •1, 2.5, 5, and 10 μM kazinol Q for 48 h | •Kazinol Q inhibits DNMT1 activity and reactivates the expression of a DNA methylation-silenced gene, E-cadherin | Inhibits cell viability | [37] |
2016 | Tien-Hsien Liquid | MCF-7 cells | DNA | •0–6 mg/mL Tien-Hsien Liquid for 72 h | •Tien-Hsien Liquid downregulates the protein level of DNMT1 and DNMT3a | Influences epigenetic regulation | [114] |
2016 | Jinfukang | A549 cells | Histone | •Treat the cells with Jinfukang for 48 h | •Jinfukang downregulates the H3K4me3 modification levels at SUSD2, PTN, GLIS2, CCND2, MYC, EGFR, and TM4SF4 genes, whereas those at BCL2A1, IL31RA, WISP2, TNFAIP6, and TMEM158 genes are upregulated | Inhibits cell proliferation | [75] |
2017 | Z-ligustilide | MDA-MB-231 cells | Histone | •50 μM Z-ligustilide for 72 h | •Z-ligustilide increases the enrichment of ac-H3 (K9/14) in the ERα promoter, and significantly reduces HDAC1, HDAC2, and HDAC4/5/7 at the ERα promoter | Induces cell cycle arrest and apoptosis | [115] |
2018 | Nimbolide | MDA-MB-231 and MCF-7 cells | Histone | •0–2.5 μM nimbolide for 48 h | •Nimbolide decreases HDAC2 and increases H3K27ac | Induces apoptosis, autophagy, cytoplasmic vacuolization and formation of autophagosomes | [43] |
2019 | Cucurbitacin B | MDA-MB-231, MCF-10A, and MCF-7 cells | DNA | •0–5 μM cucurbitacin B for 48 h | •Cucurbitacin upregulates DNMT1, as well as increases methylation in c-Myc, cyclin D1, and survivin promoters | Downregulates the expression of oncogenes, c-Myc, cyclin D1, and survivin | [30] |
2020 | Luteolin | MCF7-TamR cells | Histone | •10 and 20 μM luteolin | •Luteolin increases the expression of MLL3, increases the global level of H3K4me1, decreases the global level of H3K4ac, and increases the monomethylation level of H3K4 in the Ras gene enhancer and promoter region | Inactivates PI3K/AKT/mTOR pathway through repression of the Ras gene and thus causes apoptosis in tamoxifen-resistant breast cancer cells | [74] |
2020 | Cotinus coggygria Scop. extract | MCF-7 cells | DNA | •40.6 μg/mL Cotinus coggygria Scop. extract for 3, 24, 48, or 72 h | •Inhibits the expression of DNMT1 and DNMT3a | Causes S phase cell cycle arrest and triggers apoptosis, reduces colony formation, induces DNA damage, affects cellular thermodynamic parameters | [116] |
2021 | Valeric acid | MCF-7 cells | DNA; Histone | •0–10 μM valeric acid for 48 h | •Reduces HDAC activity and a global DNA hypomethylation | Decreases the breast cancer cell proliferation | [54] |
2021 | Luteolin | BT-20 and MDA-MB-231 cells | Histone | •10, 20 and 30 μM luteolin | •Luteolin decreases the level of H3K27ac and H3K56ac in the MMP-9 promoter region 2 and 3 in the BT-20 cells, and increases H3K27ac and H3K56ac on the MMP-2 and MMP-9 promoter region in MDA-MB-231 cells | Inhibits the proliferation and metastasis of androgen receptor-positive triple-negative breast cancer cells | [73] |
Digestive system tumor | |||||||
2010 | N-butylidenephthalide | HepG2 and J5 HCC cells | DNA | •50 μg/mL of n-butylidenephthalide for 48 h •25 μg/mL n-butylidenephthalide combined with 6.25–25 μM 1,3-bis(2-chloroethyl)-1-nitrosourea for 48 h | •N-butylidenephthalide downregulates the mRNA and protein level of MGMT •The combination treatment enhances methylation of the MGMT promoter | Inhibits the expression of MGMT and enhances apoptosis | [42] |
2019 | Ginkgo biloba extract | B6C3F1/N mice | DNA | •0, 200, 600, and 2000 mg/kg Ginkgo biloba extract, 5 days a week for 104 weeks | •The Ginkgo biloba extract-exposed affects the methylation of the hepatocellular carcinoma gene promoter | Influences epigenetic regulation | [117] |
2019 | Aged citrus peel extract | AML-12 cells | DNA; Histone | •0–100 μg/mL aged citrus peel extract for 72 h •50–1000 μg/mL aged citrus peel extract | •Aged citrus peel extract decreases the protein expression of HDAC8, DNMT1 and DNMT3a, enhances the protein expression of JMJD3 and UTX, and demethylates Nrf2 promoter •Inhibits CpG methyltransferase activity | Attenuates APAP-induced hepatic injury through the reactivation of NRF2 pathway in mouse AML-12 hepatocytes | [118] |
2019 | Supercritical CO2 extract of Azadirachta indica; Nimbolide | HCT116 and HT29 | DNA; Histone | •40 and 75 μg/mL supercritical CO2 extract of Azadirachta indica for 48 or 96 h •5 and 10 μM nimbolide for 48 or 96 h | •Inhibits HDAC and DNMT activity and expression in both cell lines •Increases acetylation of H3K9, H3K14, H3K18, and H3K27 in the p16 promoter region and decreases methylation levels of H3K9me3 and H3K27me3 in HCT116 cells | Restores the expression p16 | [80] |
2020 | Silibinin | RT4, 5637, and T24 cells | DNA | •50 μM silibinin for 24 h | •Silibinin induces global DNA hypomethylation | Influences epigenetic regulation | [50] |
2020 | Valeric acid | Hep3B, SNU-449, and HepG2 cells | Histone | •850 μM valeric acid for 24, 48, or 72 h | •Valeric acid inhibits HDAC1, HDAC2 and HDAC3 activity | Suppresses liver cancer development | [119] |
2021 | Oleanolic acid | MKN-45 cells | DNA | •0–40 μM oleanolic acid for 24 h | •Oleanolic acid selectively reduced the expression of TET3 in IL-1β-treated MKN-45 cells | Leads to DNA hypomethylation | [45] |
2021 | Hesperetin | Nude mice with MKN45 cells MKN-45 and HGC-27 cells | Histone | •Mice: 50 mg/kg hesperetin for 1 week •Cell: 0–100 μM hesperetin for 48 h | •Hesperetin decreases H3K79me2 and H3K79me3 levels in mice •Inhibits H3K79 methylation and reduces the abundance of Dot1L protein in the cells | Decreases the mobility of gastric cancer cells and inhibits the abundance of DOT1L | [78] |
2021 | Curcumol | HepG2 and SMMC-7721 cells | Histone | •60 μM curcumol for 48 h | •Curcumol increases the expression of H3K27me3 and H3K9me3 in HepG2 cells, decreases H3K27me3 expression in SMMC-7721 cells, and downregulates EZH2 | Downregulates lncRNA Hotair in turn downregulated EZH2, thereby disrupting trimethylation of H3K9 and H3K27 specifically catalyzed by EZH2, and regulating histone modification to inhibit tumor growth and metastasis | [32] |
2022 | Baicalin | BALB/c nude mouse and HepG2 cells | DNA | •Mice: 20 or 50 mg/kg baicalin for 28 days •Cell: 50 mg/L baicalin for 24 h | •Baicalin downregulates the m6A/A, SAM/SAH, and m6A (2854) levels of HKDC1 in the tumor tissue of the BALB/c mice •Downregulates the total DNA 5mC and RNA m6A levels, upregulates SAM/SAH, and suppresses the RNA m6A (2854) of HKDC1 in HepG2 cells | Inhibits the progression of T2D-induced liver tumors by regulating the HKDC1/JAK2/STAT1/caspase-3 pathway | [27] |
2022 | Phyllanthus debilis methanolic extract | HT-29 cells | DNA | •0.1 mg/mL Phyllanthus debilis methanolic extract for 24 h | •Phyllanthus debilis extract increases the Alu DNA methylation and LINE-1 methylation | Anticancer effects | [120] |
Urogenital tumor | |||||||
2012 | Trichosanthin | HeLa and CaSki cells | DNA | •0, 20, 40, and 80 μg/mL for 48 h | •Trichosanthin inhibits DNMT1 enzyme activity and DNMT1 expression | Induces gene demethylation of both HeLa and CaSki cells | [121] |
2012 | Triptolide | Du145 | Histone | •0, 25, 50, 100 nM triptolide for 24 h | •Triptolide decreases histone H3K27me3 methylation and downregulates EZH2 | Influences epigenetic regulation | [122] |
2013 | Z-Ligustilide; Radix Angelicae Sinensis | TRAMP C1 cells | DNA | •50 µM Z-Ligustilide or 8.5 µg/mL Radix Angelicae Sinensis for 3 days | •Z-Ligustilide or Radix Angelicae Sinensis treatment reduces the methylation levels of the first five CpG of the NRF2 promoter and inhibits DNA methyltransferase in vitro | Results in the re-expression of NRF2 and NRF2 target genes | [90] |
2013 | Triptolide | PC-3 cells | Histone | •0–1 µM triptolide for 24 h | •Triptolide decreases the expression of EZH2 | Results in increased mRNA levels of target genes (ADRB2, CDH1, CDKN2A, and DAB2IP), and decreased mRNA levels of gene (cyclinD1) | [83] |
2014 | Zyflamend | CWR22Rv1 cells | Histone | •200 µg/mL zyflamend for 0–60 min •200 μg/ml zyflamend for 24 h | •Zyflamend downregulates the expression of all class I and II HDACs, and upregulates the histone acetyltransferase complex CBP/ p300 •Increases histone 3 acetylation | Promotes the increased expression of the tumor suppressor p21 gene | [123] |
2015 | Allicin | MIA PaCa-2 cells | Histone | •100 and 200 µM allicin for 24 h | •Allicin reduces the level of H3K9me, and increases the level of H3S10ph and H3K14ac | Modulates apoptosis and represses gene expression | [26] |
2017 | Triptolide | PC-3 cells | Histone | •0–100 nM triptolide for 24 h or 100 nM triptolide for 0–24 h | •Triptolide enhances H3K27me3 levels by downregulating JMJD3 and UTX and enhances H3K9me3 level through upregulation of SUV39H1 | Influences epigenetic regulation | [86] |
2019 | Oldenlandia diffusa extract | A2780cis cells | Histone | •40 µg/mL and 160 µg/mL for 48 h | •Oldenlandia diffusa extract downregulates the epigenetic regulator KDM1B | Overcomes resistance to cisplatin in CRC by modulating epigenetic regulation | [92] |
Blood tumor | |||||||
2010 | Triptolide | U266 cells | Histone | •20, 80, and 160 nM triptolide for 48 h •20, 80, and 160 nM triptolide for 24 h | •Triptolide decreases the expression of histone H3K4me3, H3K27me3 and H3K36me3 •Decreases histone methyltransferases SMYD3, EZH2 and NSD1 | Induces epigenetic alterations | [53] |
2010 | Triptolide | RPMI8226 cells | Histone | •0–160 nM triptolide for 48 h | •Triptolide decreases histone H3K9me3 and H3K27me3 and downregulates histone methyltransferase SUV39H1 and EZH2 | Induces epigenetic alterations by regulating histone lysine methylation | [124] |
2011 | Tien-Hsien Liquid | NB4 cells | DNA | •0–3 mg/mL Tien-Hsien Liquid for 72 h | •Tien-Hsien Liquid downregulates DNMT1 | Influences epigenetic regulation | [125] |
2012 | Triptolide | RPMI8226 cells | Histone | •50, 100, and 150 nM triptolide for 48 h | •Triptolide suppresses the expression of H3K4me2, H3K9me2 and H3K36me2 and alters the expression of histone demethylase LSD1 and JMJD2B | Restores epigenetic changes by regulating the histone demethylases LSD1 and JMJD2B | [98] |
2015 | Triptolide | KM3 cells | Histone | •0–160 nM triptolide for 48 h | •Triptolide blocks the accumulation of H3K4me3 on c-Myc and VEGFA promoters | Decreases the expression of c-Myc and VEGFA genes | [102] |
2016 | Acanthopanax senticosus | HL-60 and HL60/ADM cells | Histone | •100 μg/mL Acanthopanax senticosus for 6 h •100 μg/mL Acanthopanax senticosus for 0–24 h | •Acanthopanax senticosus decreases HDAC enzyme activity •Increases histone ac-H3 | Induces apoptosis of leukemia cells, cell cycle arrest, and FasL expression by promoting histone H3 acetylation | [126] |
2020 | Zaluzanin D | PMA differentiated human monocytic THP-1 cells | DNA | •0.35 mM zaluzanin D for 24 h | •Zaluzanin D reduces hypomethylation of the MMP9 gene promoter region caused by PMA activation | Influences the epigenetic machinery | [55] |
2021 | Z-ligustilide | Acute myeloid leukemia cells | Histone | •50 μM Z-ligustilide for 1 h •50 μM Z-ligustilide for 6 h | •Z-ligustilide increases the enrichment of ac-H3 (K9/14) in the Nur77 and NOR-1 promoters •Increases p300 acetyltransferase and decreases HDACs, including HDAC1 and HDAC4/5/7 and MTA1, recruitment to the Nur77 promoter region | Restores the expression of both Nur77 and NOR-1 | [56] |
Other chronic diseases | |||||||
2012 | Parthenolide | JB6P + cells | Histone | •5 and 10 μM parthenolide for 24 h | •Parthenolide inhibits HDAC1 and increases dimethylation level of H3 (K9/K4) on p21 and cyclin D1 promoters | Epigenetically modulates p21 and cyclin D1 expression | [47] |
2019 | Moringa isothiocyanate | JB6P + cells | DNA | •2.5 μM Moringa isothiocyanate and/or 10 ng/mL 12-O-tetradecanoylphorbol-13-acetate for 5 days | •Moringa isothiocyanate reverses methylation changes in those genes (hyper- or hypomethylation) that occur in response to TPA | Affects the progression of skin carcinogenesis | [40] |
2015 | Esculetin | Type 2 diabetic rats | Histone | •50 and 100 mg/kg/day esculetin for 2 weeks | •Inhibits H3K4me2, H3K36me2, H3K79me2, H3S10ph, H3S28ph, H3T3ph, H3K27ac and H3K56ac, and decreases H2AK119ub and H2BK120ub in hearts of IR and type 2 diabetic rats | Restores normal levels of allowed PTHMs and H2A/H2Bub in the hearts of IR and diabetic hearts | [106] |
2017 | Esculetin | Type 2 diabetic rats | Histone | •50 and 100 mg/kg/day esculetin for 2 weeks | •Esculetin reverses the modification in H2BK120ub and decreases the mRNA levels of Usp16 and Usp22 | Intervenes H2Bub system | [33] |
2017 | Esculetin | Type 2 diabetic rats | Histone | •50 mg/kg/day esculetin for 6 weeks | •Esculetin reduces H3K9ac, H2AK119ub and H2BK120ub level | Influences epigenetic regulation | [107] |
2021 | Naringenin and Hesperetin | INS-1 cells and C57BLKS/Leprdb mice | Histone | •Cell: 100 μM naringenin or hesperetin for 24 h •Mice: 50 mg/kg/day naringenin or 50 mg/kg/day hesperetin for 6 weeks | •Naringenin and hesperetin suppress the acetylation of H3K18 and H3K27 and inhibit the activity of p300, and hesperetin suppresses H3K27 acetylation in the transcriptional regulatory region of Txnip gene in INS-1 cells •Inhibit the acetylation of H3K18 and H3K27 in the islets of the C57BLKS/Leprdb mouse | Reduces the expression of TXNIP | [41] |
2020 | Hesperetin | RAW 264.7 cells | Histone | •100 μM hesperetin overnight | •Suppresses the acetylation of RelA/p65 by inducing SIRT1 expression | Reduces NF-κB activity | [127] |
2022 | Kaempferol | 3T3-L1 cells | Histone | •100 μM kaempferol | •Kaempferol decreases H3K27me3 deposition in the promoter region of Adipoq, Fabp4, and Lpl genes | Suppresses the expression of PPARγ target genes (Adipoq, Fabp4, and Lpl) | [38] |
2020 | Bacopa monniera extraction | Male Swiss albino mice | DNA; Histone | •120 mg/kg Bacopa monniera extract | •Reduces the expression of HDACs, and decreases the activity of DNMT and HDAC enzyme and global DNA methylation | Reverses epigenetic changes in scopolamine induced amnesia as well as able to recover levels of synaptic proteins | [128] |
2019 | Piperine | 3T3-L1 cells | Histone | •50 μM for piperine 8 days | •Piperine decreases the enrichment of H3K27me3 PPARγ, and H3K9ac, and increase EZH2 | Augments the expression of Ezh2-associated lipolytic genes | [48] |
2021 | Sophora flavescens (SF)-F2 | PBMCs | DNA | •22.5 μg/mL Sophora flavescens (SF)-F2 for 3 days | •Sophora flavescens (SF)-F2 combination with dexamethasone downregulates the Foxp3 promoter methylation at CpG | Counteracts dexamethasone-induced immuno-suppression | [129] |
2021 | Hydroxysafflor yellow A | hBMSCs | Histone | •10 μM hydroxysafflor yellow A for 48 h | •Hydroxysafflor yellow A increases the protein level of KDM7A and decreases the occupancy of H3K27me2 on beta-catenin promoter | Increases β-catenin expression | [35] |
2020 | Astragalus polysaccharide | Specific pathogen-free Female Sprague–Dawley rats | DNA | •150 mg/kg/day astragalus polysaccharide for 8 weeks | •Astragalus polysaccharide alters the DNA methylation group of the colon epithelium and induces promoter DNA methylation changes in genes involved in calcium homeostasis, osteocast/osteoblast balance, Wnt signaling, and hormone-related processes | Influences epigenetic regulation | [130] |
2011 | Multiglycosides of Tripterygium wilfordii Hook f extract | 68 days male mice | Histone | •7.5–22.5 mg/kg/day multiglycosides of Tripterygium wilfordii Hook f extract for 40 days | •Reduces the dimethylation levels of histone H3K9 in germ cells | Inhibits the process of spermatogenesis | [131] |
2020 | Qian Yang Yu Yin Granule | The renal damage model of spontaneously hypertensive rats HEK293T cells | DNA; Histone | •Mice: 2.1 or 8.4 g/kg/d Qian Yang Yu Yin Granule for 8 weeks •Cell: 0.5 or 10 μg/mL | •Qian Yang Yu Yin Granule suppresses protein expression of NNMT and ac-cortactin and increased protein expression of H3K4me3 •Inhibits the production of NNMT and SAH mRNA, and promotes the production of SAM and SIRT1, and upregulates DNA methylation | Protects against hypertension-induced renal injury in spontaneously hypertensive rats and inhibited cells proliferation induced by Ang II | [132] |
2021 | Juglanin | High fat diet-fed mice | Histone | •7.5–30 mg/kg juglanin for 16 weeks | •Juglanin suppresses the expression of HDAC3 from mRNA and protein levels | Suppresses the activation of NF-κB/HDAC3 signaling in kidney of HFD-challenged mice | [36] |
2012 | Yang-Gan-Wan | Hepatic stellate cells isolated from C57Bl/6 and Coll-GFP mice | Histone | •Yang-Gan-Wan for 7 days | •Yang-Gan-Wan suppresses the expression of PRC2 components, EZH2, SUZ12, and EED, and increases H3K4me2 and H3ac at the PPARγ promoter locus | Prevents and reverses hepatic stellate cell activation | [133] |
2020 | Sennoside A | HSC-T6 cells | DNA | •10 μM sennoside A for 48 h | •Sennoside A blunts the activity of DNMT1 in TGF-β1-treated HSC-T6 cells | Inhibits activation and proliferation of HSC-T6 cells by targeting DNMT1 | [109] |
2021 | Sennoside A | RAW264.7 cells | DNA | •Sennoside A 20 nM for 24 h | •Sennoside A decreases the activity of DNMT1 in LPS-treated RAW264.7 cells and inhibits SOCS1 hypermethylation mediated by DNMT1 | Enhances SOCS1 expression | [49] |
2014 | Luteolin | THP-1 cells | Histone | •3, 6 and 10 μM luteolin for 48 h | •Luteolin downregulates HAT activity, upregulates HDAC activity and decreases the levels of acetyl CBP/p300 in high-glucose conditions | Affects NF-κB and p65 activation and interaction between p300 and NF-κB under hyperglycemic conditions in monocytes | [39] |
2017 | Osthole | PDLSCs | Histone | •10 μM osthole for 7 days | •Osthole increases the expression of KAT5, MOZ, MORF and ELP3, and increases the level of acetylation of H3K9 and H3K14 | Reverses defective osteogenesis of P-PDLSCs | [46] |
2013 | Cannabidiol and cannabigerol | HaCaT cells | DNA | •0.5 μM cannabidiol or 0.5 μM cannabigerol for 5 days | •Cannabidiol and cannabigerol enhance DNMT1 expression | Increase global DNA methylation levels and decrease the expression of all the genes examined in the differentiated HaCaT cells by increasing the DNA methylation of the keratin 10 gene | [29] |
2021 | Cannabidiol, luteolin, and piceatannol | CPEK cells | DNA | •10 μM cannabidiol, 25 μM luteolin, and 25 μM piceatannol for 8 h | •Increase the percentage of methylation in ccl2 CpG sites | Manage chronic inflammation through nutraceuticals that modulate DNA methylation | [134] |
2022 | Cooked rhubarb | Young male Sprague–Dawley rats | DNA | •3 g/kg/day cooked rhubarb for 8 weeks | •Regulates the level of DNA methylation and expression of IL-1α and IL-10 genes | Reduces pathological tissue damage caused by chronic alcohol exposure | [135] |