Medicinal Plants in the Prevention and Treatment of Colon Cancer

Table 2

(a) Efficacy of medicinal plants on colon cancer in in vivo models

Scientific name	Parts used	Model		Dose	Type of extract	Important compounds	Cellular effect	Mechanisms	References
Vitis vinifera	Seed	In vivo (murine)	Caco-2	In vivo: 400–1,000 mg/kg; In vitro: 10–25 μg/mL	Aqueous	Procyanidins	(i) Increased crypt depth and growth-inhibitory effects; (ii) Inhibited cell viability; (iii) Significantly decreased the histological damage score	Reduced MPO (myeloperoxidase) activity	[180]
	Seed	In vivo	HT-29, SW480	5 mg/kg	Aqueous	NM	NM	Decreased VEGF, TNF, MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, and MMP-13 protein expression	[181]
	Skin	In vivo	NM	7.5, 30, 60 μg/mL	Methanolic	4-Geranyloxyferulic acid	NM	NM	[30]
	Seed	In vivo (murine)	NM	0.12%	NM	Catechin, epicatechin	NM	(i) Suppressed proliferation, sphere formation, nuclear translocation of β-catenin and Wnt/β-catenin signaling; (ii) Elevated p53, Bax/Bcl-2 ratio, and cleaved PARP and mitochondrial-mediated apoptosis	[31]
Camellia sinensis	Leaf	In vivo (murine)	HT-29	In vitro: 0, 10, 30, 50 μM; In vivo: 1.5 mg per day	Aqueous	Catechin, epigallocatechin gallate	1.9-fold increase in tumor endothelial cell apoptosis	Inhibited the ERK-1 and ERK-2 activation, VEGF expression, and VEGF promoter	[182]
		In vivo (murine)	HCT116	0.5%	NM	NM	Reduced basement membrane	Inhibition of MMP-9 and VEGF secretion	[183]
		In vivo (murine)	Caco-2, HT-29	300 μM	Aqueous	Theaflavins (TF-2, TF-3, TF-1)	Induced apoptosis of human colon cancer cells	Inhibition of edema formation correlated to attenuation of COX-2 expression and promoter analysis revealed modulation of NFκB, AP-1, CREB, and/or NF-Il-6 (C/EBP)	[36]
		In vivo (murine)	HT115	25 μg/mL	Hydroethanolic	Phenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)	NM	Inhibition via reduced expression of a range of α5 & β1	[184]
Sasa quelpaertensis	Leaf	In vivo	HT-29, HCT116	0, 100, 200, 300 mg/L	Ethanolic	p-Coumaric acid, tricin	Inhibition of colony formation	(i) Nonadherent sphere formation suppressed CD133+ & CD44+ population; (ii) Downregulated expression of cancer stem cell markers	[41]
Anoectochilus	NM	In vivo	CT26	Oral dose of 50 & 10 mg/mouse per day	Aqueous	Kinsenoside	Stimulated proliferation of lymphoid tissues	Activation of phagocytosis of peritoneal macrophages	[185]
Purple-fleshed potatoes	Fruit	In vivo	Colon cancer stem cells	5.0 μg/mL	Ethanol, methanol, ethyl acetate	Anthocyanin, β-catenin, cytochrome c	Reduction in colon CSCs number and tumor incidence	(i) Increase in cytochrome c levels from p53 status and maybe mitochondria-mediated apoptosis; (ii) Suppressed levels of cytoplasmic and nuclear β-catenin	[58]
Phaseolus vulgaris	Leaf	In vivo	HT-29	Nm	Ethanolic	Polysaccharides, oligosaccharides	Induction of apoptosis and inhibit proliferation	(i) Inactivation of the retinoblastoma phosphoprotein; (ii) Induced G1 arrest; (iii) Suppression of NF-jb1; (iv) Increase in EGR1 expression	[59]
Rosmarinus officinalis L.	Leaf	In vivo	HT-29	SC-RE 30 μg/mL and CA 12.5 μg/mL	Ethanolic	Polyphenols (carnosic acid (CA) and carnosol)		(i) Activation of Nrf2 transcription factor; (ii) Activated common regulators, such as XBP1 (Xbp1) gene, SREBF1/SREBF2 (Srebp1/2), CEBPA and NR1I2 (Pxr) genes
	Leaf	In vivo (rat)	NM	NM	Ethanolic	Rosmanol and its isomers, carnosol, rosmadial, carnosic acid, and 12-methoxycarnosic acid, carnosic acid, carnosol	Interactions with the gut microbiota and by a direct effect on colonocytes with respect to the onset of cancer or its progression	NM
Wasabia japonica	Rhizomes	In vivo	COLO 205	5 mg/mL	Methanolic	6-(Methylsulfinyl)hexyl isothiocyanate	Anticolon cancer properties through the induction of apoptosis and autophagy	(i) Activation of TNF-α, Fas-L, caspases; (ii) Truncated Bid and cytochrome c; (iii) Decreased phosphorylation of Akt and Mtor; (iv) Promoted expression of microtubule-associated protein 1 light chain 3-II and AVO formation	[186]
Zingiberaceae	Rhizome	HT-29	HT-29	5 g/kg	Dichloromethanic	Turmerone	Suppressed the proliferation of HT-29 colon cancer cells	(i) LDH release; (ii) ROS generation; (iii) Collapse in mitochondrial membrane potential; (iv) Cytochrome c leakage; (v) Activation of caspase 9 and caspase 3	[187]
Panax quinquefolius	Root	In vivo (murine)	NM	30 mg/kg	Ethanolic	Ginsenosides (protopanaxadiol or protopanaxatriol)	Attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load	(i) Reduced experimental colitis; (ii) Attenuated on AOM/DSS-induced colon carcinogenesis; (iii) Proinflammatory cytokines activation; (iv) Suppressed DSS; (v) Downregulated inflammatory cytokine gene expression	[188]
Myrtaceae	Leaf	In vivo (murine)	HCT116	100 μg/mL (in vitro) 200 and 100 μg/disc (in vivo)	Methanolic	Phenolics, flavonoids, betulinic acid	Inhibition of tumor angiogenesis	(i) Inhibition of angiogenesis of tube formation on Matrigel matrix and HUVECS migration (in vitro); (ii) Decreased nutrient and oxygen supply and consequently tumor growth and tumor size (in vivo); (iii) Increased extent of tumor necrosis	[82]
Spica prunellae	Leaf	In vivo	HT-29	200 mg/mL (in vitro), 600 mg/mL (in vivo)	Ethanolic	Rosmarinic acid	Induction of apoptosis and inhibition of cell proliferation and tumor angiogenesis	(i) Induced apoptosis; (ii) Inhibited cancer cell proliferation and angiogenesis STAT3 phosphorylation; (iii) Regulated expression of Bcl-2, Bax, cyclin D1, CDK4, VEGF-A, and VEGFR-2 (in vivo)	[83]
Gymnaster koraiensis	Aerial part	In vivo (murine)	NM	500 μmol/kg	Ethanolic	Gymnasterkoreaynes B, C, E, 2,9,16-heptadecatrien-4,6-dyne-8-ol	Anti-inflammatory and cancer preventive activities	(i) Significant decrease in expression of COX-2; (ii) Increase in serum IL-6	[189]
Allium fistulosum	Edible portions	In vivo (murine)	CT26	50 mg/kg b.w.	Hot water	p-Coumaric acid, ferulic acid, sinapic acid, quercitrin, isoquercitrin, quercetol, kaempferol	Suppression of tumor growth and enhanced survival rate of test mice	(i) Decreased expression of inflammatory molecular markers; (ii) Downregulated expression of MMP-9 and ICAM; (iii) Metabolite profiling and candidate active phytochemical components	[190]
Annona squamosa Linn	Leaf	In vivo (animal)	HCT116	8.98 μg/mL	Crude ethyl acetate	Acetogenins (annoreticuin & isoannoreticuin) and alkaloids dopamine, salsolinol, and coclaurine	(i) Inhibited growth and proliferation of tumor cells	Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release, and caspases 3/7, 8, 9 activation	[191]
Eupatorium cannabinum	Aerial parts	In vivo (murine)	HT-29	25 μg/mL	Ethanolic	Pyrrolizidine alkaloids (senecionine, senkirkine, monocrotaline, echimidine)	Cytotoxicity against colon cancer cells	(i) Upregulation of p21 and downregulation of NCL, FOS, and AURKA, indicating reduced proliferation capacity; (ii) Mitotic disruption and nonapoptotic cell death via upregulation of Bcl-xL	[96]
Flacourtia indica	Aerial parts	In vivo (murine)	HCT116	500 μg/mL	Methanolic	Phenolic glucoside (flacourticin, 4-benzoylpoliothrysoside)	Antiproliferative and proapoptotic effects in HCT116 cells	Apoptosis via generation of ROS and activation of caspases (PARP)	[192]
Sorghum bicolor	The dermal layer of stalk	In vivo (murine)	HCT116 & colon cancer stem cells	>16 and 103 μg/mL	Phenolic, acetone	Apigeninidin & luteolinidin	Antiproliferative effect	(i) Target p53-dependent and p53-independent pathways	[97]
Gleditsia sinensis	Thorn	In vivo (murine)	HCT116	800 μg/mL	Aqueous	Flavonoid, lupine acid, ellagic acid glycosides	Inhibited proliferation of colon cancer	(i) Increased p53 levels; (ii) Downregulation of the checkpoint proteins, cyclin B1, Cdc2, and Cdc25c	[90]
	Thorn	In vivo (murine)	HCT116	600 μg/mL	Ethanolic	NM	Inhibitory effect on the proliferation of human colon cancer HCT116 cells	(i) Caused G2/M phase cell cycle arrest	[91]
Zingiber officinale	Rhizome	In vitro/in vivo (murine)	HCT116	5 μM	Ethanolic	6-Paradol, 6- and 10-dehydrogingerdione, 6- and 10-gingerdione, 4-, 6-, 8-, and 10-gingerdiol, 6-methylgingerdiol, zingerone, 6-hydroxyshogaol, 6-, 8-, 10-dehydroshogaol, diarylheptanoids	Inhibitory effects on the proliferation of human colon cancer cells	(i) Arrest of G0/G1 phase; (ii) Reduced DNA synthesis; (iii) Induced apoptosis	[103]
Cucumaria frondosa	The enzymatically hydrolyzed epithelium of the edible	In vivo (murine)	HCT116	<150 μg/mL	Hydroalcoholic	Monosulphated triterpenoid glycoside frondoside A, the disulphated glycoside frondoside B, the trisulphated glycoside frondoside C	(i) Inhibition at S and G2-M phase with a decrease in Cdc25c; (ii) Increase in p21WAF1/CIP	(i) Inhibition the growth of human colon; (ii) Apoptosis associated with H2AX phosphorylation and caspase 2	[105]
Rolandra fruticosa	Leaf & twigs	In vivo (murine)	HT-29	10 and 5 mg/kg/day	Methanolic	Sesquiterpene lactone (13-acetoxyrolandrolide)	Antiproliferative effect against human colon cancer cells	(i) Inhibition of the NFκB pathway, subunit p65 (RelA) and upstream mediators IKKβ and oncogenic K-ras	[106]
Cydonia oblonga Miller	Leaf & fruit	In vivo (murine)	Caco-2	250–500 μg/mL	Methanolic	Phenolic compound (flavonol and flavone heterosides, 5-O-caffeoylquinic acid)	Antiproliferative effect against human kidney and colon cancer cells	(i) Suppression of NFκB activation, activator (AP-1), mitogen-activated protein kinases, namely, PKC, (GFR)-mediated pathways; (ii) Cell cycle arrest; (iii) Induction of apoptosis, antioxidant, and anti-inflammatory effects	[107]
Sedum kamtschaticum	Aerial part	In vivo (murine)	HT-29	0–0.5 mg/mL	Methanolic	Buddlejasaponin IV	Induced apoptosis in HT-29 human colon cancer cells	(i) Induced apoptosis via mitochondrial-dependent pathway triggered by downregulation of Bcl-2 protein levels, caspase 3 activation, and subsequent PARP cleavage	[109]
Ganoderma lucidum	Caps & stalks	In vivo (murine)	HT-29	0-0.1 mg/mL	Triterpene extract (hot water) extract	Polysaccharides (mainly glucans & glycoproteins), triterpenes (ganoderic acids, ganoderic alcohols, and their derivatives)	Cytokine expression inhibited during early inflammation in colorectal carcinoma	Induced autophagy through inhibition of p38 mitogen-activated kinase and activation of farnesyl protein transferase (FPT)	[193]
Ginkgo biloba	Fruit & leaf	In vivo (murine)	HT-29	20–320 mg/L	Aqueous	Terpene lactones and flavonoid glycosides	Inhibited progression of human colon cancer cells induced HT-29 cell apoptosis	(i) Activation in caspase 3, reduction in Bcl-2 expression, and elevation in p53 expression	[112]
Rubus occidentalis	Fruit	In vivo (murine)	JB6 Cl 41	25 μg/mL	Methanolic	β-Carotene, α-carotene, ellagic acid, ferulic acid, coumaric acid	Inhibited tumor development	(i) Impaired signal transduction pathways leading to activation of AP-1 and NFB RU-ME fraction	[194]
Oryza sativa	Seed	In vivo (murine)	HT-29, SW 480, HCEC	100 μg/mL	Ethyl acetate extract	Phenolic compound (tricin, ferulic acid, caffeic acid, and methoxycinnamic acid)	Inhibited growth of human colon cancer cells	(i) Induction of apoptosis by enhanced activation of caspases 8 and 3; (ii) Decreased the number of viable SW480 and HCEC cells	[113]
Cistanche deserticola	Dried stem	In vivo (murine)	SW480	In vivo: 0.4 g/kg/day; In vitro: 100 mg/mL	Aqueous	Polysaccharides, phenylethanoid glycosides	Decreased mucosal hyperplasia and helicobacter infection	(i) Increased number of splenic macrophages and NK cells; (ii) Decreased frequency of hyperplasia and H. hepaticus infection of the intestine	[133]
Rehmannia glutinosa	NM	In vivo (male C57BL6 mice and Sprague-Dawley rats)	CT26	28 mg/kg	NM	Catalpol	(i) Inhibited proliferation, growth, and expression of angiogenic markers	(i) VEGF, VEGFR2, HIF-1α, bFGF inhibited the expressions of inflammatory factors such as IL-1β, IL-6, and IL-8	[143]
Olea europaea	Olive mill wastewater	In vivo (murine)	NM	NM	Methanolic	Hydroxytyrosol	Interferes with tumor cell growth	NM	[195]
	Leaf	In vivo (xenograft model) (murine)	HCT116, HCT8	0, 5, 10, 20, 30, 50, and 70 μg/mL	Phenolic	Oleuropein and hydroxytyrosol	NM	(i) Activation of caspases 3, 7, and 9; (ii) Decrease of mitochondrial membrane potential and cytochrome c release; (iii) Increase in intracellular Ca2+ concentration	[196]
Ginkgo biloba L.	Leaf	In vivo (rat)	NM	0.675 and 1.35 g/kg	Methanolic	Flavonoid glycosides, terpene lactones, and ginkgolic acids	(i) Suppressed tumor cell proliferation, promoted apoptosis, and mitigated inflammation	NM	[197]
Rhus trilobata Nutt.	NM	In vivo (hamster)	NM	400 mg/kg, 100 mg/kg	Aqueous	Tannic acid, gallic acid	Cytotoxic activity	NM	[54]
Annona diversifolia Saff.	NM	In vivo (mice)	SW-480	1.5, 7.5 mg/kg/day	NM	Laherradurin	Cytotoxic activity	NM	[54]
A. muricata L.	NM	In vivo (rat)	NM	250/500 mg/kg	EtOAc	A, B, and C, and cis- and trans-annomuricin-D-ones	Cytotoxic activity	NM	[54]
Plumeria acutifolia Poir.	NM	In vivo (hamster)	NM	400 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Lasianthaea podocephala (A. Gray) K. M. Becker	NM	In vivo (hamster)	NM	200 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Flourensia cernua DC.	NM	In vivo (hamster)	NM	350 mg/kg/day	Aqueous	Flavonoids, sesquiterpenoids, monoterpenoids, acetylenes, p-acetophenones, benzopyrans, benzofurans	Cytotoxic activity	NM	[54]
Ambrosia ambrosioides (Cav.) W. W. Payne	NM	In vivo (hamster)	NM	400 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Alnus jorullensis Kunth	NM	In vivo (hamster)	NM	175 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Dimorphocarpa wislizeni (Engelm.) Rollins	NM	In vivo (hamster)	NM	100 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Euphorbia pulcherrima Willd. ex Klotzsch	NM	In vivo (hamster)	NM	200 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Acalypha monostachya Cav.	NM	In vivo (hamster)	NM	400 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Crotalaria longirostrata Hook. & Arn.	NM	In vivo (hamster)	NM	400 mg/kg/day, 350 mg/kg/day	EtOH-CHCl3	NM	Cytotoxic activity	NM	[54]
Asterohyptis stellulata (Benth.) Epling	NM	In vivo (hamster)	NM	50 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Acacia constricta A. Gray	NM	In vivo (hamster)	NM	400 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Holodiscus dumosus A. Heller	NM	In vivo (hamster)	NM	350 mg/kg/day	Aqueous	NM	Cytotoxic activity	NM	[54]
Butea monosperma	Flower	In vivo (rat)	HT-29	150 mg/kg	n-Butanol extract	Isocoreopsin, butrin, and isobutrin	Free radical scavenging and anticancer activities	NM	[198]
Taraxacum spp.	Root	In vivo (xenograft murine model)	HT-29, HCT116	40 mg/kg/day	Aqueous	α-Amyrin, β-amyrin, lupeol, and taraxasterol	Induced programmed cell death	NM	[199]

NM: not mentioned.

(b) Other effects of medicinal plants in in vivo models

Scientific name	Parts used	Model		Dose	Type of extract	Important compounds	Cellular effect	Mechanisms	References
Allium sativum	Root	In vivo (murine)	NM	2.4 mL of daily	Ethanolic	Allicin, S-allylmercaptocysteine	Significantly suppressed both the size and number of colon adenomas	Enhancement of detoxifying enzymes: SAC and GST activity	[200]
Olea europaea	Fruit	In vivo	Caco-2	50 μM	Aqueous	Phenolic compounds, authentic hydroxyl tyrosol (HT)	(i) Effect of OPE and HT on CB1 associated with reduced proliferation of Caco-2 cells; (ii) Increase in CB1 expression in the colon of rats receiving dietary EVOO	Increase in Cnr1 gene expression, CB1 protein levels	[201]
		In vivo (murine)	HT115	25 μg/mL	Hydroethanolic	Phenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)	NM	Inhibition via reduced expression of a range of α5 & β1	[184]
Origanum vulgare L.	Leaf	In vivo (murine)	NM	20, 40, 60 mg·kg^−1	Aqueous	Rosmarinic acid, caffeic acid, flavonoids	Antioxidant status	(i) Increased LPO products and activity of SOD and CAT enzymes and GST and GPx activity; (ii) Antioxidant and anticarcinogenic effect	[202]
Hazelnut	Skin	In vivo	NM	The flow rate 0.21 mL/min and injection volume 9.4 μL	Aqueous	Flavan-3-ols, in monomeric and polymeric forms, and phenolic acids	(i) Decreased circulating levels of free fatty acids and triglycerides; (ii) Higher excretion of bile acid	Increase of the total antioxidant capacity of plasma	[203]
Apples and apple juice	Fruit	In vivo	NM	90 mg/L	Aqueous	Phenolic acids, flavonoids, tannins, stilbenes, curcuminoids	NM	NM	[204]
Grifola frondosa	Fruit	In vivo (murine)	HT-29	10 ng/mL	Aqueous	Phenolic compounds (pyrogallol, caffeic acid, myricetin, protocatechuic acid, etc.)	Inhibition of TNBS-induced rat colitis	(i) Induced cell cycle progression in G0/G1 phase and apoptotic death	[104]
Ruta chalepensis	Leaf	In vivo (human)	NM	250 μg/mL	Ethanolic	Rutin, gallic acid, catechin hydrate, naringin	Oxidative profile in patients with colon cancer	NM	[205]
Cannabis sativa	Dry flower & leaf	In vivo (murine)	DLD-1 and HCT116	0.3–5 μM	Methanolic	Cannabidiol, phytocannabinoids	NM	(i) Reduced cell proliferation in a CB1-sensitive and AOM-induced preneoplastic lesions and polyps; (ii) Inhibition of colorectal cancer cell proliferation via CB1and CB2 receptor activation	[121]
Melia toosendan	Fruit	In vivo (murine)	SW480, CT26	0, 10, 20, 30, 40, 50 μg/mL	Ethanolic	Triterpenoids, flavonoids, polysaccharide, limonoids	NM	(i) Inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation; (ii) Induced caspase 9 activity which further activated caspase 3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis	[123]
Smallanthus sonchifolius	Root	In vivo (murine)	NM	73.90, 150.74, 147.65, and 123.26 mg/kg	Aqueous	Fructans	NM	Reduction incidence of colon tumors expressing altered β-catenin	[206]
Punica granatum	Peel	In vivo (adult male Wistar rats)	NM	4.5 g/kg	Methanolic	Gallic acid, protocatechuic acid, cateachin, rutin, ellagic acid, punicalagin	NM	(i) Reduction in TGF-β, Bcl-2, EGF, CEA, CCSA-4, MMP-7 and in COX-2, cyclin D1, survivin content; (ii) Downregulated expression of β-catenin, K-ras, c-Myc genes	[207]
Linum usitatissimum	Seed	In vivo (male Sprague-Dawley rats)	NM	500 mg/kg	Alkaline	Secoisolariciresinol diglucoside, carbohydrates, proteins, and tannins	Reduced the serum fasting glucose levels	Significantly reduced the HbA1c, insulin levels, and proinflammatory cytokines	[208]
Diospyros kaki	Fruit	In vivo (male CD-1 mice)	NM	15 mg/kg	Hydroacetone	Polyphenol	(i) Decreased attenuation of colon length in diarrhea severity; (ii) Reduced mortality rate; (iii) Reduction of the extent of visible injury (ulcer formation) and of mucosal hemorrhage	Decreased expression of COX-2 and iNOS in the colonic tissue	[147]
Muntingia calabura	Leaf	In vivo (rat)	NM	50, 250, 500 mg/kg	Methanolic	Rutin, gallic acid, ferulic acid, and pinocembrin	Reduction of the colonic oxidative stress, increasing the antioxidants levels possibly via the synergistic action of several flavonoids	NM	[209]
Portulaca oleracea	NM	In vivo (murine)	HT-29 CSCs	2.25 μg/mL	Alcoholic	NM	Regulatory and target genes that mediate the Notch signal transduction pathway	Inhibition of expression of the Notch1 and β-catenin genes	[161]
Aloe vera	Gel	In vivo (murine)	NM	400 mg/kg/day	Gel	Polysaccharides	NM	(i) Via inhibition of the cell cycle progression; (ii) Induction of cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1; on the other hand, PAG increased the expression of caudal-related homeobox transcription factor 2	[210]
Artemisia annua Linné	Powder	In vivo (xenograft murine model)	HCT116	20, 40 mg/kg/day	Ethanolic	Phenolic compounds	NM	(i) Induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through PTEN/p53; (ii) Inhibited cell viability and increased LDH release and apoptotic bodies, caspase 3 and 7 activation, and reduced mitochondria membrane potential; (iii) Regulated cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane; (iv) Regulation of proteins	[169]
Hordeum vulgare	Powder	In vivo (xenograft murine model)	HT-29	2 g/kg and 1 g/kg	Aqueous (fermented)	β-Glucan, protein, amino acids, phenolic compounds	NM	(i) Promoted tumor apoptosis by upregulating the mRNA expression of Bax and caspase 3 and downregulating the mRNA expression of Bcl-2 and cyclin D1; (ii) Decreased mRNA expression of Bcl-2 and cyclin D1; (iii) Upregulated expressions levels of Bax and caspase 3	[211]
Dendrophthoe pentandra	Leaf	In vivo (murine)	NM	125, 250, 500 mg/kg	Ethanolic	Quercetin-3-rhamnose	NM	(i) Decreased the levels of IL-22, MPO levels, proliferation of epithelial cells; (ii) Inhibited S phase of the cell cycle; (iii) Upregulated p53 wild-type gene expression	[212]
Aquilaria crassna	Stem, bark	In vivo (murine)	HCT116	2,000 mg/kg/day; 100, 200 mg/kg	NM	Resin and essential oils	NM	NM	[213]
Berberis integerrima	NM	In vivo (murine)	NM	50 and 100 mg/kg	Hydroalcoholic	NM	NM	NM	[214]
Salix aegyptiaca	Bark	In vivo (murine)	NM	100 and 400 mg/kg	Ethanolic	Catechin, catechol, and salicin	NM	Decreased level of EGFR, nuclear β-catenin, and COX-2	[215]