. 2021 Jul 1;12:685002. doi: 10.3389/fphar.2021.685002

TABLE 2.

CMFs for anti-CRC and corresponding mechanisms.

CMF name	Composition	Cell lines/model	Dose	Detail	Mechanism	Ref
Fu Fang Yi Liu Yin formula	Astragali Radix, Ganoderma lucidum, semen armeniacae amarum, H. diffusa Willd., Aconiti Lateralis Radix Praeparata, Glycyrrhiza glabra Linn., Radix Panacis Quinquefolii, and Platycodi Radix	HCT 116 cells	3–15 mg/ml	In vitro	Inhibit cell proliferation and induce apoptosis and block cell at G₀/G₁ phase. In vivo, inhibit tumor growth	Dong et al. (2020)
		SW 480 cells	3–15 mg/ml	In vitro
		BALB/c mice	2.4 mg/g	In vivo
Yi Fu Zi Bai Jiang San	Semen coicis, monkshood, and Herba Patriniae	HCT 116 cells	15.625–62.5 μg/ml	In vitro	Block tumor initiation and progression, increase immune function, regulate gut flora, alter cell growth, and reduce phosphorylation of β-catenin	Sui et al. (2020)
		MC 38 cells	15.625–62.5 μg/ml	In vitro
		C57BL/6 J mice	3.825–15.3 g/kg	In vivo
Astragalus atractylodes mixture	Astragalus membranaceus, Atractylodes macrocephala, Actinidia arguta, Curcuma aromatica, Benincasa hispida, and Ficus pumila.	HCT 116 cells	0.5–16 mg/ml	In vitro	Inhibit hypoxia-induced ROS generation, migration and VM formation, as well as HIF-1 alpha and MMP2 expression	Zong et al. (2020)
Astragalus atractylodes mixture		LoVo cells	0.5–16 mg/ml	In vitro		Zong et al. (2020)
Xiang Sha Liu Jun Zi decoction	Radix Codonopsis, rhizoma Atractylodis macrocephalae, radix glycyrrhizae, Poria, Pericarpium citri reticulatae, Pinellia tuber, Radix Aucklandiae, and Fructus Amomi	Patients with stage III or IV CRC	Unknown	In vivo	Unknown	Hong et al. (2020)
Wu Mei Wan	Fructus Mume, rhizoma coptidis, Herba Asari Mandshurici, Ramulus Cinnamomi, Radix Ginseng, Radix Aconiti Lateralis Preparata, Pericarpium Zanthoxyli Bungeani, Rhizoma Zingiberis, Cortex Phellodendri Amurensis, and Radix Angelicae Sinensis	C57BL/6 J mice	5.8 g/kg	In vivo	Improve the survival rate and attenuate symptoms, reduce proliferation of tumor cells, decrease the expression of p65, IL-6, and p-STAT3, decrease Bacteroidetes, and increase Firmicutes	Jiang et al. (2020)
Zuo Jin Wan	Coptis chinensis Franch. and Evodia ruticarpa	HCT 116 cells	100–300 µM	In vitro	Induce apoptosis through the PI3K-Akt signaling pathway	Huang et al. (2020b)
Zuo Jin Wan	Coptis chinensis Franch. and Evodia ruticarpa	HT 29 cells	100–300 µM	In vitro	Induce apoptosis through the PI3K-Akt signaling pathway	Huang et al. (2020b)
Zuo Jin Wan	Coptis chinensis Franch. and Evodia ruticarpa	SW 403 cell	25–800 μg/ml	In vitro	Increase G₁ arrest in cell cycle, induce apoptosis, suppress cell migration and invasion, and decrease the expression of 5-HTR1D and β-catenin	Pan et al. (2017)
Compound sophorae decoction	Sophora flavescens and Sanguisorba officinalis, Indigo naturalis, Bletilla striata, Panax notoginseng, and Glycyrrhiza uralensis	C57BL/6 J mice	0.1614 g	In vivo	Execute UCRCC-inhibitory activity by counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy	Deng et al. (2019)
Qing Jie Fu Zheng granules	Scutellaria barbata, malt, Hedyotis diffusa, and Astragalus mongholicus	HCT 8 cells	0.5–2 mg/ml	In vitro	Inhibit proliferation and induce apoptosis by suppressing the PI3K/AKT and ERK pathways	Yang et al. (2019a)
Qing Jie Fu Zheng granules		HCT 116 cells	0.5–2 mg/ml	In vitro		Yang et al. (2019a)
Si Jun Zi decoction	Codonopsis pilosula, Poria cocos, Atractylodes macrocephala, and radix liquiritiae	Balb/c mice	45 g/kg	In vivo	Increase survival rate and reduce liver metastasis, elevate plasma GM-CSF level, and increase the number of macrophages but not neutrophils in the spleen	Zhou et al. (2019a)
Chang Wei Qing	Astragalus membranaceus, Atractylodes macrocephala, Codonopsis pilosula, Akebia quinata, Polyporus umbellatus, Coix seed, Vitis quinquangularis Rehder, and Sargentodoxa cuneata	C57BL/6 J mice	5, 10 mg/kg	In vivo	Restore colon length, decrease tumor number and size, reduce colitis score, suppress expansion of F. prausnitzii population, and inhibit activity of beta-glucuronidase and leakage of d-lactose and endotoxin	Wan et al. (2019)
Su Yang decoction	Broccoli and green cabbage	HT 29 cells	10–200 μg/ml	In vitro	Inhibit colon cancer cell proliferation and induce G₁ phase arrest and induce the cleavage of poly (ADP-ribose) polymerase, tumor necrosis factor superfamily member 10, X-linked inhibitor of apoptosis	Ge et al. (2019)
		LS 174-T cells	10–200 μg/ml	In vitro
		CRL-1790 cells	10–200 μg/ml	In vitro
Jian Pi Jie Du decoction	Astragalus membranaceusceus, Panax quinquefolius, Atractylodes macrocephala, Poria cocos, Coix seed, Smilax china, Hedyotis diffusa, Sculellaria barbata, Paris polyphylla, Actinidia argut, and gGlycyrrhiza uralensis Fisch.	HCT116 cells	0.3125–2.5 mg/ml	In vitro	Inhibit viability and proliferation, induce apoptosis, suppress migration, invasion, and angiogenesis by inhibiting the mTOR/HIF-1α/VEGF signaling pathway, decrease the CD34 and VEGF, and downregulate the mTOR/HIF-1α/VEGF pathway	Peng et al. (2018)
		HT29 cells	0.3125–2.5 mg/ml	In vitro
		LoVo cells	0.3125–2.5 mg/	In vitro
		SW48 cells	0.3125–2.5 mg/ml	In vitro
Tian Xian liquid	Radix Ginseng, Cordyceps, Radix Astragali, Radix Glycyrrhizae, rhizoma, margarita, Fructus lycii, Ganoderma lucidum, Fructus ligustri lucidi, and Herba Scutellariae barbatae	HT29 cells	0.625–5% (v/v	In vitro	Inhibit proliferation, upregulate the p21 mRNA and protein, downregulate G₁ phase cell cycle protein, cyclin D1 mRNA and protein, and reverse multidrug resistance	Leigh et al. (2017)
Tian Xian liquid		Nude mice	200 µl	In vivo		Leigh et al. (2017)
Yi Ai Fang	Astragalus membranaceus, Atractylis ovate, Actinidia arguta, Curcuma zedoaria, and Benincasa hispida	BABL/c mice HCT 116 cells	8–32 mg/kg	In vivo	Restrain the formation of vasculogenic mimicry through the HIF-1α/EMT pathway, inhibit growth of the xenografted tumors, enhance expression of E-cd and claudin-4, and decrease the expression of HIF-1α and VIM	Hou et al. (2016)
Yi Ai Fang		BABL/c mice HCT 116 cells	25–200 μg/ml	In vitro		Hou et al. (2016)
Huang Qin decoction	Scutellaria baicalensis Georgi., Paeonia lactiflora Pall., Glycyrrhiza uralensis Fisch., and Ziziphus jujuba Mill.	C57BL/6 mice	9.1 g/kg	In vivo	Inhibit AOM/DSS-induced CRC and the production of inflammatory cytokines and increase antioxidant capacity both in chronic DSS- and AOM/DSS-treated mice	Chen et al. (2016)
Shen Ling Bai Zhu San	Radix et rRhizoma gGinseng, Poria, Rhizoma Atractylodis Macrocephalae, semen Lablab Album, Rhizoma Dioscoreae, Radix et Rhizoma Glycyrrhizae, Plumula nelumbinis, Fructus Amomi, semen coicis, and Radix Platycodonis	C57BL/6 J mice	3.64–14.56 g/kg	In vivo	Supress colitis-associated CRC through the inhibition of EMT and myeloid-derived suppressor infiltration	Lin et al. (2015)
		SW480 cells	6–16 mg/ml	In vitro
		HCT116 cells	6–16 mg/ml	In vitro
Jian Pi Hua Yu decoction	Atractylodes macrocephala Koidz., Euphorbia humifusa Willd., Salvia miltiorrhiza Bunge., Paris polyphylla Sm., Curcuma phaeocaulis Val., Scutellaria barbata D. Don., and Artemisia capillaris Thunb.	SW480 cells	0.25–8 mg/ml	In vitro	Decrease viability, induce G₀/g₁-phase cell cycle arrest and induce apoptosis, enhance the expression of p27, cleaved PARP, cleaved caspase-3, and bax, and decrease the levels of PARP, caspase-3, Bcl-2, CDK2, CDK4, CDK6, cyclin D1, cyclin D2, cyclin D3, and cyclin E1	Xi et al. (2015)
Yi Qi Fu Sheng formula	Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Radix liquiritiae, Myristica fragrans, and Fructus Akebiae	HCT-116 cells	50–250 mg/ml 200–800 mg/kg	In vitro	Inhibit migration/invasion of CRC by inhibiting the activation of ERK/MAPK signaling pathways	Deng et al. (2013b)
Yi Qi Fu Sheng formula		Athymic mice	50–250 mg/ml 200–800 mg/kg	In vivo		Deng et al. (2013b)
Jian Pi Jie Du recipe	Radix Astragal, Rhizoma Atractylodis macrocephala, wild grapevines, Fructus Akebia, Salvia chinensis Benth., and Evodia rutaecarpa	LoVo cells	12.5–400 μg/ml	In vitro	Inhibit invasive and migratory and reduce the transcriptional activities of EMT-associated factors snail and E-cadherin. In vivo, inhibit liver and lung metastasis of orthotopic CRC, prolonging the survival time	Liu et al. (2017b)
Jian Pi Jie Du recipe		Nude mice	250–1,000 mg/kg	In vivo		Liu et al. (2017b)
Huang Lian Jie Du decoction	Coptis chinensis Franch., Phellodendron amurense Rupr., Gardenia jasminoides J. Ellis, and Scutellaria baicalensis Georgi.	Athymic mice	50–200 mg/kg	In vivo	Promote renewal of the intestinal cell wall, induce presentation of CD44-postive cells, initiate the expression of stemness-associated genes, elevate transcriptional products of the downstream Wnt signaling of CD44, and reduce diarrhea and intestinal damage	Chan et al. (2020)
Xiao Ai Jie Du decoction	Hedyotis diffusa and Codonopsis pilosa, Sophora flavescens, and Zingiber officinale	Patients who fulfill the criteria	Unknown	In vivo	Unknown	Zhou et al. (2019c)
BP10A	Descurainiae sophia semen and Peucedani praeruptorum radix	HCT-116 cells KM12SM cells	6.25–25 μg/ml 25–200 μg/ml	In vitro	Delay tumor growth and enhance the antitumor activity of each anticancer drug and delay tumor growth	Kim et al. (2019b)
BP10A		HCT-116 cells KM12SM cells	6.25–25 μg/ml 25–200 μg/ml	In vitro		Kim et al. (2019b)
Ge Gen Qin Lian decoction	Radix Puerariae, Scutellariae radix, Coptidis Rhizoma, and liquorice	BALB/c mice	300–7500 mg/kg	In vivo	Enrich related intestinal microorganisms, increase the proportion of CD8⁺ T cells in peripheral blood and tumor tissues, increase the expression of IFN-γ, downregulate PD-1, and increase IL-2 levels	Lv et al. (2019)
Zhi Zhen Fang formula	Radix Astragali, fFructus ligustri lucidi, semen coicis, Salvia chinensis, Vitis quinquangularis Rehd., Actinidia arguta, and Cyperus rotundus L.	HCT-116 cells HCT-8 cells	25–1,600 μg/ml	In vitro	Enhance the sensitivity of chemotherapeutic drugs and induce apoptosis, inhibit the hedgehog pathway, inhibit tumor growth, and reduce Gli1 levels	Sui et al. (2017)
		Athymic mice	25–1,600 μg/ml	In vitro
		Athymic mice	13.27–53.08 g/kg	In vivo
Teng Long Bu Zhong Tang	Actinidia chinensis, Solanum nigrum, Duchesnea indica, Atractylodes macrocephala Koidz., Poria cocos, Coix seed, mistletoe, and Scutellaria barbata	BALB/c mice	22.5, 30 mg/kg	In vivo	Inhibit cancer cell growth, elicite apoptosis, and downregulate XIAP and survivin, induce cell senescence, and enhance anticancer effects of 5-Fu	Deng et al. (2013a)
Wei Chang An	Pseudostellaria heterophylla Pax., Atractylodes macrocephala Koidz., Poria cocos Wolf., Glycyrrhiza uralensis Fisch., Sargentodoxa cuneata, and Prunella vulgaris L.	HCT-116 cells	3–9%	In vitro	Reduce the rate of metastasis, decrease the expression of β-catenin and MMP-7, and reduce nuclear translocation of β-catenin	Tao et al. (2015)