Epigallocatechin-3-gallate (EGCG) |
Cardiovascular |
EGCG inhibits macrophage accumulation and inflammation response in the skin wounds of STZ-induced diabetes mellitus |
EGCG reduces expression of Notch-1 and 2 in wound tissues of diabetic mice |
[299] |
In RAW 264.7, EGCG limits LPS-mediated release of proinflammatory IL-1β
|
EGCG reduces expression of Notch-1 and 2 and of Notch target gene HES1. EGCG binds Notch-1 and limits its activity |
In HUVECs, EGCG induces expression of iNOS and eNOS and inhibits oxLDL-mediated apoptosis |
EGCG restores the expression of Jagged-1 and of target proteins (MATH1, HES1, and HES5) |
[276] |
Jagged-1 is the key effector of EGCG-protective effect against oxLDL-induced endothelial dysfunction |
EGCG attenuates the HFD-induced accumulation of atherosclerotic plaque in ApoE-deficient mice |
EGCG protects ApoE-KO mice from atherosclerosis through the Jagged-1/Notch-1 pathway |
Cancer |
EGCG inhibits the self-renewal capacity of head and neck squamous carcinoma (HNSC) cancer stem cells (CSCs) by suppressing their sphere forming capacity and attenuates the expression of stem cell markers. EGCG augments cisplatin-mediated chemosensitivity |
EGCG decreases HNSC CSC traits by inhibiting the Notch-1 pathway |
[225] |
Norisoboldine |
Cardiovascular |
Norisoboldine suppresses VEGF-induced HUVEC migration |
Norisoboldine induces VEGF-mediated migration through activation of Notch-1 |
[301] |
Docosahexaenoic acid (DHA) |
Cardiovascular |
DHA significantly decreases VSMC migration/proliferation induced by IL-1β as well as fibrinolytic/MMP activity |
DHA increases Notch-3 expression and HES1 transcription and enhances γ-secretase complex activity |
[300] |
Diosgenin |
Cardiovascular |
Diosgenin reduces the HFD-induced atherogenesis in rat aorta |
Diosgenin prevents nuclear translocation of NICD in aorta and in differentiated macrophage cells |
[302] |
Berberine (BBR) |
Cardiovascular |
BBR significantly improves cardiac function recovery and decreases myocardial apoptosis, infarct size, serum creatine kinase, and lactate dehydrogenase levels in rats following myocardial IRI |
Both in vitro and in vivo, BBR upregulates NICD translocation and HES1 expression |
[304] |
In H9C2, BBR attenuates simulated IRI-induced myocardial apoptosis |
In vitro, antiapoptotic effect of BBR is blocked by Notch-1 or HES1 siRNA |
Polydatin |
Cardiovascular |
Following myocardial IRI, polydatin preserves cardiac function, ameliorates myocardial oxidative/nitrative stress damage, and reduces myocardial infarct size in STZ-induced diabetic rats |
Polydatin exerts cardioprotection against diabetic myocardial IRI by activating myocardial Notch-1/HES1 signaling. DAPT blunts the beneficial effects of polydatin |
[305] |
2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) |
Cardiovascular |
TSG significantly improves cardiac function and suppresses IRI-induced myocardial apoptosis |
Both in vitro and in vivo, TSG upregulates NICD and HES1 expression |
[306] |
In H9C2, TSG pretreatment dose-dependently decreases simulated IRI-induced apoptosis |
In vitro, antiapoptotic effect of TSG is blocked by DAPT |
Honokiol |
Cancer |
Honokiol inhibits the growth of melanospheres formed by CSC |
In vitro, Honokiol downregulates Notch-2, HES1, and cyclin D1 expression |
[285] |
Withaferin-A |
Cancer |
In three colon cancer cell lines, Withaferin-A mediates c-Jun-NH(2)-kinase-mediated apoptosis |
Withaferin-A inhibits Notch-1 signaling |
[286] |
Tricin and p-coumaric acid |
Cancer |
Tricin and p-coumaric acid inhibits the growth of CSCs and VEGF and HIF1α expression |
Tricin and p-coumaric acid inhibits Dll-1 and Notch-1 expression |
[287] |
Curcumin |
Cancer |
Curcumin inhibits hepatocellular cancer cell (HCC) proliferation |
Curcumin decreases NICD expression in HCC |
[289] |
Curcumin treatment results in a 40% decrease in tumor growth in a nude mouse xenograft model |
Curcumin inhibits proliferation and colony formation in esophageal cancer cell lines and upregulates expression of let-7a miRNA |
Curcumin reduces Notch-1 activation and expression of Jagged-1 and HES1 |
[288] |
Curcumin reduces expression of Notch-1-specific microRNAs (miR-21 and miR-34a) and upregulates tumor suppressor let-7a miRNA |
Curcumin decreases markers associated with CSCs in Burkitt lymphoma and acute myeloid leukemia cells |
Curcumin reduces expression of Notch-1 and cyclin D1 |
[93] |
Resveratrol |
Cancer |
Resveratrol increases apoptosis and suppresses proliferation in MOLT-4 acute lymphoblastic leukemia cells |
Resveratrol reduces NICD levels in a dose-dependent manner and inhibits the expression of HES1 |
[293] |
Cardiovascular |
Resveratrol inhibits phenotypic switching of neointimal VSMCs after balloon injury in rats |
Resveratrol decreases Notch-1, Jagged-1, Hey1, and Hey2 mRNA in balloon-injured arteries at 7 days |
[303] |
All-trans retinoic acid (ATRA) |
Cancer |
ATRA exerts a strong antimigratory action in the HER2-positive SKBR3 cell line |
ATRA inhibits Notch-1 pathway |
[295] |
Oroxylin A |
Cancer |
Oroxylin A inhibits the hypoxia-induced invasion and migration of ERα-positive breast cancer cells |
Oroxylin A inhibits NICD translocation into the nucleus |
[296] |
Alpinetin |
Cancer |
Alpinetin suppresses the proliferation and invasiveness of glioma stem cells (GSCs) and induces their apoptosis |
Alpinetin reduces Notch-1 activity. Notch reactivation, by using recombinant Jagged-1, rescues the effect of alpinetin on GSCs |
[297] |
Cowanin |
Cancer |
Cowanin shows potent cytotoxicity against human leukemic HPB-ALL cells |
Cowanin degrades nicastrin, a component of γ-secretase, thus hampering Notch-1 activation |
[298] |