Table 1 Agents/phytochemicals targeting the Wnt pathway

1

Andrographolide analogue, 3A.1

19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide

Andrographis

Significantly inhibits Wnt/β-catenin signaling T cell factor and lymphatic enhancer factor (TCF/LEF) promoter activity and increases the activity of GSK-3β kinase.

[130]

2

Crocin

Crocin

Saffron

Inhibit cell growth and invasive behavior of CRC cells by regulating Wnt pathway and E-cadherin

[131]

3

NDC

Non-digestible carbohydrates

Starch

The SCFA butyrate produced by colonic fermentation binds to the G protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes

[132]

4

EPLE

11α, 12α-epoxyleukamenin E

A new type of ent-kaurane diterpene isolated from sage

Mediates the down-regulation of Wnt target genes (such as c-Myc, Axin2 and Survivin), enters the β-catenin/TCF4 complex interface and blocks their interaction

[133]

5

YW2065

ND

Anthelmintic pyrvinium and the previous lead FX1128

Stabilize Axin-1 (a scaffold protein that regulates the degradation of β-catenin proteasome) to achieve its inhibitory activity on Wnt signaling

[134]

6

ND

Homoharringtonine

Cedarwood

STAT3 inhibition significantly reduces tumor ball formation and survival

[135]

7

ND

Nerigoside

Oleander

The ERK and GSK3β/β-catenin signaling pathways are significantly blocked, and the ERK /GSK3β/β-catenin signaling pathway is inhibited

[136]

8

TSN

Toosendanin

Neem Tree

Induces G1 phase arrest and causes caspase-dependent cell apoptosis, inhibits Wnt/β-catenin signal in CRC cells

[137]

9

ND

Fucoidan

Brown algae

Activating the Hippo pathway and down-regulating the β-catenin pathway to induce tumor cell apoptosis reduces the expression of β-catenin C-Myc, CyclinD1 and Survivin

[138]

10

ES

Esculetin

Coumarin compounds

Inhibition of Axin2 contributes to E-cadherin-mediated Wnt signal suppression, targeting Axin2/E-cadherin axis

[139]

11

ND

Silibinin

Milk thistle

Significantly reduces the transcriptional activity of β-catenin-dependent T cell factor-4 (TCF-4) and the protein expression of β-catenin target genes (such as c-Myc and cyclin D1), and also reduces cyclin Dependent Kinase 8 (CDK8)

[140]

12

5-ASA

Mesalamine

5-aminosalicylic acid

The membrane expression of adhesion molecules E-cadherin and β-catenin is restored, and the inhibition of PAK1 expression can prevent tumor progression in the occurrence of colorectal cancer

[141]

13

ND

Curcumin

Turmeric

The regulation of Wnt pathway and E-cadherin inhibits the growth and invasion behavior of CRC cells

[142]

14

RSV

Resveratrol

Knotweed

Reduce inflammation and accelerate healing to prevent infection and fight cancer

[143]

15

AGE

3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18 (19)-dien-28-oic acid β-d-glucopyranosyl ester

Sanguisorba officinalisA

Induces cell death through apoptosis pathway and autophagy, and inhibits cell proliferation through G0-G1 cell cycle arrest mediated by Wnt signaling pathway

[144]

16

TPs

Tea polyphenols

Tea

Regulate the Wnt/β-catenin pathway and the 67 kDa laminin receptor pathway to inhibit proliferation and promote cell apoptosis, improve the immune system and reduce inflammation by adjusting the composition of the intestinal microbiota

[145]

17

A/A

Anthocyanins/anthocyanidins

Grape seed

Attenuate Wnt signal and inhibit the proliferation of abnormal epithelial cells, mediated apoptosis

[146]

18

Pal

Palmatine

Cork

Less inhibition of Wnt/β-catenin signaling pathway

[147]

19

ND

Crocin

Saffron

Inhibit the expression of pain-related molecules through the Wnt5a/−catenin pathway

[148]

20

DOP

Dendrobium officinale Polysaccharides

Dendrobium officinale

Down-regulate the gene expression of Wnt2β, Gsk3β, PCNA, CyclinD1 and β-catenin, as well as the protein expression of Wnt2β, PCNA and β-catenin, by regulating the Wnt/β-catenin pathway and changing endogenous metabolites

[149]

21

ND

Baicalein

Scutellaria

By inhibiting EMT, this may be due to the down-regulation of SATB1 and Wnt/β-catenin pathway

[150]

22

ND

Potato glycoalkaloids

Potato

By inhibiting the normal function of JNK in the Wnt/PCP pathway, it increases the possibility of neural tube defects, which leads to neural tube defects.

[151]

23

ND

Biejiajian Pills

ND

Significantly reduce the expression of β-catenin, cyclin D1 and MMP-2 proteins in the cytoplasm and nucleus, and reduce the activity of β-catenin/TCF4 complex

[152]

24

ND

Triptolide

Diterpene Triepoxide

Inhibit the phosphorylation of LRP6 to inhibit the activation of WNT1, FZD1 and disheveled (DSH) in the cancer cell lines MIA PaCa-2 and S2-VP10, and at the same time by inhibiting its glycosylation

[153]

25

NCTD

Norcantharidin

Cantharidin

Cytoplasmic translocation that prevents β-catenin from entering the nucleus

[154]

26

APS

Astragalus polysaccharide

Astragalus

Decrease the expression level of Snail and vimentin, increase the expression of E-cadherin, down-regulate the expression of Wn​​t1, β-catenin and downstream targets

[155]

27

CAFG

Caviunin 7-O-[β-D-apiofuranosyl-(1–6)-β-D-glucopyranoside

Dalbergia

Participate in the p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to mediate Wnt/β-catenin signaling, thereby reducing the phosphorylation of GSK3-β and subsequent nuclear accumulation of β-catenin

[156]

28

ND

Decane tetracyclic triterpenes

Poria

Inhibition of Wnt significantly attenuates epithelial-mesenchymal transition and extracellular matrix production/β-catenin pathway activation and Smad3 phosphorylation, effectively blocking RAS

[157]

29

ND

Astaxanthin

Carrot

Down-regulate key regulatory enzymes IKKβ and GSK-3β to inhibit NF-κB and Wnt signaling, down-regulate the expression of anti-apoptotic Bcl-2, p-Bad and survivin, and up-regulate pro-apoptotic Bax and Bad to induce caspase Mitochondrial apoptosis

[158]

30

ND

Paclitaxel

PacificYew

Blocking the combination of ErbB1 and ErbB2, trabecular bone loss and bone marrow obesity, involving the conversion of osteogenic/adipogenic potential, and altering the Wnt/β-catenin signaling pathway

[159]

31

ND

Methanolic extracts of the P. patens

Pasqueflower

Change the key signal molecules required for cell cycle progression to enhance cell apoptosis, relieve cell proliferation, differentiation and progression to tumor phenotype

[160]

32

DIO

Diosgenin

Dioscorea

Mediates the expression of important molecules in the Wnt pathway, inhibits the loss of alveolar bone after OVX and inhibits bone formation and osteoclastogenesis

[161]

33

PASI

Paeonoside

Peony

Inhibition of BMP2 and Wnt3a pathways are weakened, accompanied by a decrease in RUNX2 expression in the nucleus

[162]

34

ND

Carnosic acid

Rosemary

Targets transcriptionally active (“carcinogenic”) form of β-catenin for proteasomal degradation in an H1-dependent manner

[163]

35

ND

Maclurin

Mulberry twigs

Inhibit Src/FAK and ERK signals to activate GSK3-β, thereby inhibiting nuclear accumulation of β-catenin

[164]