Table 2.
Potential of cardamonin in the prevention and treatment of chronic diseases.
| Chronic Diseases | In vitro/In vivo In silico/Ex vivo | Model | Mechanism | References |
|---|---|---|---|---|
| Cancers | ||||
| Breast Cancer | In vitro | SUM190, MCF-7, Cama-1 | ↓Colony forming ability, CSCs, ALDH1, Sox 2, ↓c-myc, OCT4, ↓SMYD3, IL-6, IL-8, MCP-1, NF-κB, IκB, STAT3 NANOG, EZH2, SETDB1 | Jia et al. (2016) |
| In vivo | SUM190 xenograft | ↓Tumor growth, CSCs, ALDH1, Sox 2, OCT4, ↓NANOG | Jia et al. (2016) | |
| In vitro | MCF-7, MDA-MB-231,BT-549 | ↓Cell proliferation ↓Colony formation, ↑apoptosis, G2/M phase arrest, ↑Bax/Bcl-2, ↓β-catenine ↑E-cadherin, ↓N-cadherin, snail, slug, vimentin, ↓Wnt/β-catenin, cyclin D1, c-Myc, VEGF, CDK-4, ↓Akt-GSK3β | Shrivastava et al. (2017) | |
| In vivo | 4T1 induced tumor | ↓Tumor growth | Shrivastava et al. (2017) | |
| In vitro | MDA-MB-231, MCF-7 | ↓Cell proliferation, Bcl-2, GSH, ↑caspase-3, Bax, PARP, ROS, Apoptosis, ↑Foxo3a, p21, p27, Bim, p-JNK, G2/M phase arrest | Kong et al. (2019) | |
| In vivo | MDA-MB-231 xenograft | ↓Tumor growth, cyclin D1, Bim, ↑caspase-3, p-JNK, FOXO3a, p21, p27 | Kong et al.(2019) | |
| In vitro | MDA-MB-231 MCF-7, BT-549 | ↓Cell viability, ↑Apoptosis, Bax, caspase 3, ↓Bcl-2, ↓HIF-1α, PDHK1, LDHA, ↑OXPHOS, ↑ROS, ↓Nrf2, HO-1, NQO-1, mTOR/p70S6K | Jin et al. (2019) | |
| In vivo | MDA-MB-231 xenograft | ↓Tumor growth, Bcl-2/Bax, ↓HIF-1α, ↓LDHA, p-PI3K, p-AKT, p-mTOR, p-P70S6K, ↓angiogenesis;, ↑caspase-3, | Jin et al. (2019) | |
| CRC | In vitro | HCT-8 | ↓Cell viability | Jin et al. (2019) |
| In vitro | SW480, LS1748, SW480, DLD-1, HCT116 | ↓Wnt/β-catenin, cyclin D1, c-myc, ↑G2/M phase arrest, cell viability | Park et al. (2013) | |
| In vitro | HT-29 | ↓Cell proliferation, clonogenicity, migrationA | Memon et al. (2014) | |
| In vitro | HCT116 | ↓Cell proliferation, ↑G2/M phase arrest, autophagy, ↑p53/JNK | Kim et al. (2015) | |
| In vitro | HCT15, HCT116 SW480, SW620 | ↓Cell proliferation; ↑Apoptosis, S phase arrest, ROS, MD, Bax, p-JNK, p-p38 | James et al. (2017) | |
| In vivo | AOM induced CRC | ↓Tumor incidence, multiplicity, ↓NF-κB, p65, Ki-67, β-catenin | James et al. (2017) | |
| In vitro | HCT-116 | ↓Cell viability, ↑apoptosis, caspase-3/9, Bax, ↓c-myc, Oct4, cyclin E, NF-κB, TSP50 | Lu et al. (2018) | |
| In vitro | HT-29, SW-460 | ↓Cell viability, IL-1β, TNF-α, ↓STAT1, STAT3, STAT5 | Hou et al. (2019) | |
| In vivo | DSS + AOM induced CACC | ↓IL-1β, TNF-α, p-JAK2, p-STAT1 ↓p-STAT3, p-STAT5 | Hou et al. (2019) | |
| Fibrosarcoma | In vitro | HT-1080 | ↓Tgase-2, ↓MMP-2, ↓NF- κB, ↓MMP-9, ↓cell migration & invasion | Park et al., (2013) |
| Gastric Cancer | In vitro | MGC803 | ↓Cell viability | Jin et al. (2019) |
| In vitro | BGC-823, BGC-823/5-FU | ↓Cell viability, ↑apoptosis, G2/M phase arrest, ↓CD44, ALDH1, OCT4, C-myc, β-catenin/TCF4 ↓cyclinD1, P-glycoprotein, Wnt | Hou et al. (2020) | |
| In vivo | BGC-823/5-FU xenograft | ↓Tumor weight, volume | Hou et al. (2020) | |
| In vitro | AGS | ↓Cell viability, ↑apoptosis, Bax, caspase-3, ↓Bcl-2 ↓colony formation, CDK1, Cyclin B1, CDC25 ↑p21, ↓cell migration, invasion, ↑E-cadherin, ↓snail, ↓α-SMA, STAT3, vimentin, | Wang et al. (2019a) | |
| HCC | In vitro | HepG2 | ↓Cell viability, ↑G1 phase arrest, apoptosis, ↑caspase-3/7, −8, −9, Fas, TRAIL, H1F, FADD, ↑DR4, DR5, CD95, cyt c, p-p53, ↓ HSP-60, -27, −70, ↓XIAP, catalase, clusterin, survivin, TNF-α, NF-κB, ↑ROS | Badroon et al. (2020) |
| Leukemia | In vitro | WEHI-3 | ↑ROS, Ca2+, caspase-3, -8 and -9, Bax, cyt c, AIF, Endo G, GRP78, caspase-12, Fas, Fas-Ligand, FADD, DAP, TMBIM4, ATG5; ↓Bcl-2, DDIT3, DDIT4, BAG6, BRAT1 | Liao et al. (2019) |
| In vivo | WEHI-3 xenograft | ↑CD19, ↓Mac-3, CD3, CD11b, ↑phagocytosis of macrophages, cytotoxicity of NK cells, ↑survival rate | Liao et al. (2020) | |
| Lung Cancer | In vitro | A549, NCI-H1299, NCI-H460, NCI-H1688, NCI-H446, primary cell line 1,2 | ↓Cell viabilityB | He et al. (2014) |
| In vitro | A549, NCI-H460 | ↑Apoptosis, ↑caspase-3, PARP, ↓IKKβ, NF-κBB | ||
| In vitro | LLC | ↓Cell viability, invasion, migration, ↑E-cadherin ↓p-mTOR, p-S6K1, Snai1 | Niu et al., (2015) | |
| In vivo | LLC transplant | ↓Tumor growth, lung metastasis | Niu et al., (2015) | |
| In vitro | A549, H460, H292, H1299, H1975 | ↓Cell viability, EMT, ZEB1, Bcl-2 PI3K/Akt/mTOR, ↓Colony formation, N-cadherin, cyclin D1/CDK4, migration, invasion, ↑E-cadherin, G2/M phase arrest, apoptosis, caspase-3, Bax | Zhou et al. (2019) | |
| In vivo | H460 xenograft | ↓Tumor growth, Ki-67, PI3K/Akt/mTOR | Zhou et al. (2019) | |
| In vitro | A549 | ↓Cell migration, G2/M phase arrest, ↑apoptosis, ↑caspase-3/7, ↑caspase-9, ↑PARP cleavage, ↓Mcl-1, ↓p-mTOR, ↓p-4EBP1C | Break et al., (2018) | |
| Melanoma | In vitro | A375 | ↓Cell viability, invasion, ↑apoptosis, caspase-3, ↑PARP | Berning et al. (2019) |
| Myeloma | In vitro | RPMI 8226, U266, ARH-77, RPMI 8226 | ↓Cell proliferation ↑ Apoptosis, caspase-3, PARP, ↓Bcl-2, Bcl-xL, ↓ survivin, XIAP, cIAP-1, cIAP-2, NF-κB/p65, ↓IKK, IKKβ, p-IκBα, ICAM-1, COX-2, VEGF | Qin et al. (2012) |
| NPC | In vitro | HK1 | ↓Cell migration, G2/M phase arrest, ↑apoptosis, ↑caspase-3/7, ↑caspase-9, ↑PARP cleavage, ↓Mcl-1, ↓p-mTOR, ↓p-4EBP1C | Break et al., (2018) |
| Ovarian Cancer | In vitro | SKOV3 | ↓Cell viability, VEGF, HIF-1α, HIF-2α, ↓p-mTOR, p-S6K1 | Xue et al., (2016) |
| In vitro | SKOV3 | ↓p-Raptor, mTORC1, p-S6K1, Lamp2 | Shi et al. (2018a) | |
| In vitro | SKOV3 | ↓Glycolysis, HK, LDH, ↑autophagy, LC3-II, ↑LAMP1, ↓p-S6K1, p-mTOR, HK2, ↑p-AMPK | Shi et al. (2018b) | |
| In vitro | SKOV3 | ↓Cell viability, ↑autophagy, ↑LC3-II, ↑apoptosis, ↑caspase-3, PARP, ↓Raptor, mTOR, S6K1 | Shi et al. (2018c) | |
| In vitro | SKOV3, A2780 SKOV3 | ↓Cell viability, colony formation ↑G2/M phase arrest, ↓XIAP, survivin, Bcl-2, ↓mTOR, p70S6K | Niu et al. (2018) | |
| In vitro | SKOV3 | ↓Cell viability, S6 kinase 1, TNF-α, IL-6, NF-κB | Chen et al. (2018b) | |
| PC | In vitro | DU145, LNCaP | ↓STAT3, JAK2, ↓cell proliferation, ↑apoptosis ↑caspase-3, -8, -9, PARP, ↓Bcl-xl, Bcl-2, Survivin, ↓ XIAP, VEGF, COX2, MMP9, Cyclin D1, CDK4, ↓Cyclin E, CDK2, ↓migration, invasion, ↑metastasis | Zhang et al. (2017) |
| In silico | ↓STAT3, SH2 domain | Zhang et al. (2017) | ||
| In vitro | PC-3 | ↓Cell growth, ↑apoptosis, ↓NF-κB1 | Pascoal et al., (2014) | |
| CVD | In vivo | Mesenteric arteries | ↑CDR; ↓PIC, SCE, TCR | Wang et al., (2001) |
| In vivo | Rat tail artery myocytes | ↑ KCa1.1, ↓ICa(L), IBa(L), Cav1.2 | Fusi et al. (2010) | |
| In vivo | DOX-induced cardiotoxicity | ↑Nrf2, HO1, NAD(P), (NQO1), GCLM, SOD, GSH, CAT, ↓MDA, ROS, Caspase-3, NF-κB | Qi et al. (2020) | |
| In vitro | H2C9 | ↓4E-BP1, S6, mTOR-Raptor | You et al. (2018) | |
| In vivo | LPS treated C57 mice | ↓Contractile defects, apoptosis, oxidative stress, ↓LPS induced Nrf2 signaling, inflammation, NK-κB | Tan et al. (2020) | |
| Diabetes | In vivo | FEIR SD rats | ↑ISI, ↓VSMC, VT, mTOR, HOMA-IR ↓4E-BP1, p-P70S6K1 | Liao et al., (2010) |
| Gastritis | In vitro | EtOH/HCl induced gastric ulcer | ↑LOOH, oxidative stress, SOD ↓ GSH | de Oliveria Cabral et al. (2017) |
| HI | In vitro | weight hanging method | ↑NO, eNOS expression; ↓iNOS, ↓NF-κB, TNF-α, ↓Bcl-2, | Atef et al. (2017) |
| ID | In vitro | RAW264.7 | ↓TNF-α, IL-6, IL-1β, NF-κB, NO, PGE2, iNOS,COX-2 mRNAs, IL-1β mRNA, ROS | Kim et al. (2010) |
| In vitro | HT-29, LS174T, RAW264.7 | ↓NF-κB, LPS, MAPK | Ren et al. (2015) | |
| In vivo | DSS induced colitis | ↓iNOS, COX-2, MCP-1, TNF-α, IL-6, IL-15, NF-κB, MAPK, TLR4 | Ren et al. (2015) | |
| In vitro | BMDMs, PBMCs | ↓caspase-1, IL-1β, NLRP3 | Wang et al. (2019b) | |
| In vivo | LPS induced septic shock | ↓ NLRP3, caspase-1, IL-1β | Wang et al. (2019b) | |
| Arthritis | In vitro | CFA Induced Cells | ↓TNF-α, IL-1β, IL-6 | Voon et al., (2017) |
| Pathological Pain/Nociceptive | In vitro | MG63, RAW264.7 | ↑IκB; ↓Tgase-2, COX-2, p65,NF-κB | Park et al. (2014) |
| In vivo | CIC | ↓WR, COX-2, Tgase-2 | Park et al. (2014) | |
| In silico | HEK293 | ↓TRPA1 | Wang et al. (2016) | |
| In vivo | ACIAWR Model FIPL Model, Hot Plate Test GIPL Model | ↓capsaicin-induced nociception | Ping et al. (2018) | |
| Ulcerative colitis | In vivo | acetic acid induced | ↓MPO, iNOS, NF-κB, TNFα, MDA, COX-2, caspase-3 | Ali et al. (2017) |
| Nephrotoxicity | In vivo | cis induced nephrotoxicity | ↓caspase-3, ↓Bax/Bcl-2, NOX-1, IL-1β, TNF-α, NF-κB, iNOS, MCP-1, ICAM | El-Naga (2014) |
| Neuropathic Pain | In vitro | PCI2 | ↑Nrf2, HO-1, NQO1, Trx1, TrxR1, GCLC, GCLM; ↓LDH, caspase-3, ROS | Peng et al. (2017) |
| Sjögren's Syndrome | ex vivo | BMCI-pSS | ↓TNF-a, IL-6, NO, iNOS, NF-қB | Benchabane et al. (2018) |
Notations.
ADimethyl cardamonin or 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC).
BCardamonin analogs 4,4′-dihydroxylchalcone (DHC) and 4,4′-dihydroxy2′-methoxychalcone (DHMC).
CCardamonin analog Compound 19.
Abbreviations: AAI Model = acetic acid-induced model; AE = Antihyperalgesic Effects; ALDH1 = aldehyde dehydrogenase 1; AP = activator prostratin; AOM = Azoxymethane; ATG5 = Autophagy related 5; AWR Model = abdominal writhing response model; BAG6 = BCL2-Associated Athanogene 6; BCL2L13 = BCL2-like 13 (apoptosis facilitator); BMCI-PSS = blood mononuclear cells isolated from pSS patients; BMDMs = bone-marrow-derived macrophages; BRAT1 = BRCA1-associated ATM activator 1; CA= Cold Allodynia; CAT = catalase; Cca = Cell Cycle Arrest; CCA = cardiac contractile abnormality; CCC = cancer cell migration; CCF = cancer cell colony formation; CCI = chronic constriction injury; CCP = cell cycle progression; CDK 4 = cyclin dependent kinase 4; CDR=Concentration dependent relaxation; CFA = complete Freund's adjuvant; CIC= Carrageenan-induced cells; CIS=Cisplatin; c-JNK = c-Jun N-terminal kinase; COX-2 = cyclooxygenase-2; CRC= Colorectal Cancer, CVD= Cardiovascular Diseases; cyt-C = cytochrome; DAP = Death Aassociated Protein; DDIT3 = DNA-Damage Inducible Transcript; DDIT4 = DNA-Damage-inducible Transcript 4; DSS = dextran sulfate sodium; DMC = dimethyl cardamonin; FEIR = fructose-enriched insulin resistant; FIPL Model = Formalin-Induced Paw Licking Model; FOXO3a = Forkhead box O3; 5-FU = 5-fluorouracil; G2/M CCA = G2 phase cell cycle arrest; GCLM = glutamate-cysteine ligase modifier subunit; GIPL model = glutamate-induced paw licking model; GSH = glutathione; HCC= Hepatocellular Carcinoma; HO1 = heme oxygenase-1; HI=Hepatic ischemia;; HOMA-HSP=High shock proteins; IR: = homeostasis model assessment for insulin resistance; ID=Inflammatory Diseases; IL = interlukin; iNOS = inducible nitric oxide synthase; ISI=Insulin Sensitivity Index; JNKs = Jun N-terminal kinases; LAPE = lactic acid production and efflux; LOOH = lipidhydroperoxide, LIDCS = LPS-induced defect in cardiomyocyte shortening; LPS = lipopolysaccharide; MA = Mechanical Allodynia; MAPK = mitogen-activated protein kinase; MCD = Myocardial Contractile Dysfunction; MCP-1 = monocyte chemoattractant protein 1; MD = mitochondrial depolarization; MDA = malondialdehyde; MMP = matrix metalloproteinases; MOP = mitochondrial oxidative Phosphorylation; MPO = Myeloperoxidase; NAC=N-acetyl-cysteine; NC=Nuclear Condensation; NF-κB = Nuclear Factor kappa B; NO=Nitric Oxide; NLRP3 = NOD-LRR- and pyrin domain containing protein 3; NPC= Nasopharyngial carcinoma; NQO1 = NAD(P)H:quinone oxidoreductase 1; Nrf2 = nuclear factor erythroid-2 related factor 2; NT = nuclear translocation; OBTF 4 = octamer-binding transcription factor4; OS= Oxidative Stress; TSP50 = testes-specific protease 50;; p-Akt = phosphorylated-Akt; p-4EBP1 = phosphorylated 4E binding protein 1; PBMCs = human peripheral blood mononuclear cells; PC=Prostate Cancer; PGE2 = prostaglandin E2; PIC = phenylephrine induced contraction; PKB = protein kinase B; p-mTOR = phosphorylated-mTOR; pSS = Primary Sj€ogren's syndrome; PVT1 = Plasmacytoma Varient Translocation 1; ROS = Reactive Oxygen Species; SCE=Sustained Contraction by Endothelin I; SOD = superoxide dismutase; Tgase-2 = .transglutaminase-2; S6K1 = S6 kinase 1 TH = Thermal Hyperalgesia; TMBIM4 = transmembrane BAX inhibitor motif containing 4; TNF-α = tumor necrosis factor-α;; TLR4 = toll-like receptor 4 signaling; TRPA1 = transient receptor potential ankyrin 1; TxB2 = thromboxane B2; UC=Ulcerative Colitis; VEGF= Vascular Endothelial Growth Factor; VSMC = vascular smooth muscle cells; VT = vascular thickening; WR=Writhing Response.