Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review

Table 3 In vitro and in vivo protective effects of Chinese herbal compound on gastric precancerous lesions and gastric cancer

Pathological stages	Effect	No.	Ref.	Formulas	Main component	Animal/cells	Pathways/targets
GPL	Anti-proliferation inducing apoptosis	fa	Zeng et al[31], 2016	Weipixiao (WPX)	Radix Astragali, Radix Pseudostellariae, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhiz, Herba Hedyotis Diffusae	Male SD rats, PLGC model	Wnt/β-catenin↓; Lgr5, MMP-7, Wnt1, β-catenin↓
		fa	Zeng et al[145], 2018	Weipixiao (WPX)	Astragalus Membranaceus, Pseudostellaria Heterophylla, Atractylodis Macrocephalae, Curcuma zedoaria, Salvia Miltiorrhiza and Hedyotis Diffusa Willd	Male SD rats, PLGC model	Wnt/GSK3β; GSK3β↑; C-myc↓
		fb	Yin et al[29], 2019	Weiqi decoction (WQD)	Radix Angelicae Sinensis, Radix Astragali, Radix Codonopsis, Rhizoma Curcumae, Fructus Aurantii, Fructus Akebiae and Herba Taraxaci	Male Wistar rats, CAG with Precancerous Lesion Mode	PGE2, caspase-3↑; Ki67, HIF-1, COX-2, VEGF, VEGFR1↓
		fc	Cai et al[146], 2022	Sancao Tiaowei Decoction	Pseudostellariae Radix, stirbaked Atractylodis Macrocephalae Rhizoma inbran, Poria, Agrimoniae Herba, Taraxaci Herba, Hedyotis Diffusa Willd, Salviae Miltiorrhizae Radix Etrhizoma, Curcumae Rhizoma and Glycyrrhizae Radix Et Rhizoma	SD male rats, PLGC model	Hh signaling↓; Shh, Gli-1, Smo, cyclinD1, CDKN2A/p16INK4a, NF-κB P65↓; Ptch↑
		fd	Hao et al[147], 2022	Huazhuojiedu decoction	Artemisia capillaris Thunb, Scutellaria baicalensis Georgi, Oldenlandia diffusa Roxb, Isatis indigotica Fortune, Lobelia chinensis Lour, Pogostemon cablinBenth, Scutellaria barbata D. Don, Sophora flavescens Aiton, Coptis chinensis Franch, Gynostemma pentaphyllum Makino, and Eupatorium fortunei Turcz	Male SD rats, PLGC model	Lnc 517368↓
		fe	Xu et al[148], 2018	Xiao Tan He Wei Decoction	Radix bupleuri, processed rhizomapinelliae, poriacocos, coptischinensis, oldenlandiadiffusa, dandelion,cassia twig, rhubarb, radix paeoniae alba, radix glycyrrhizae preparata	GES-1 cell, Wistar rats, PLGC rat animal models	Bax, caspase-3↑; Bcl-2, NF-κB↓
		ff	Shen et al[149], 2008	Jinguo Weikang Capsule (JWC)	Tinospora root, trifoliate-orange Immature fruit, kaempfer dutchmanspipe root	SD rats, PLGC model	H-ras, EGFR, P53, c-myc↓
	Anti-inflammatory	fb	Yin et al[29], 2019	Weiqi decoction (WQD)	Radix Angelicae Sinensis, Radix Astragali, Radix Codonopsis, Rhizoma Curcumae, Fructus Aurantii, Fructus Akebiae, and Herba Taraxaci	Male Wistar rats, CAG with Precancerous Lesion Mode	PGE2, caspase-3↑; Ki67, HIF-1, COX-2, VEGF,VEGFR1↓
		fg	Deng et al[125], 2012	Weining granule	Radix Astragali Mongolici, Herba Hedyotdis, Rhizoma Curcumae Phaeocau, Fructus Lycii	Male Wistar rats, PLGC model	VEGF, IL-6, IgG↓; CD4+, CD4+/CD8+, IL-2↑
	Anti-angiogenesis	fb	Yin et al[29], 2019	Weiqi decoction (WQD)	Radix Angelicae Sinensis, Radix Astragali, Radix Codonopsis, Rhizoma Curcumae, Fructus Aurantii, Fructus Akebiae, and Herba Taraxaci	Male Wistar rats, CAG with Precancerous Lesion Mode	PGE2, caspase 3↑; Ki67, HIF-1, COX-2, VEGF,VEGFR1↓
		fa	Zeng et al[59], 2018	Weipixiao (WPX)	Astragalus Membranaceus, Pseudostellaria Heterophylla, Atractylodis Macrocephalae, Curcuma zedoaria, Salvia Miltiorrhiza and Hedyotis Diffusa Willd	Male SD rats, PLGC model	ERK1/CylinD1; HIF-1α, VEGF, ERK1, CylinD1↓
		fh	Wang et al[150], 2020	Jinlongshe (JLS)	Rhizoma Pinelliae, Radix, Rhizome Arisaemat, Glycyrrhizaepreparata, corium stomachiumgalli, etc.	Male SD rats, PLGC model	Apelin, CD34↓
	Protecting gastric mucosa	fi	Yi et al[151], 2022	Elian granules	Curcumae Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Angelicae Sinensis, Diels, Coptidis Rhizoma, Hedyotis Diffusa, Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Poria	Male SD rats, PLGC model	MAPK; JNK, p38↑
		fj	Wang et al[32], 2020	WeiFuChun (WFC)	Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides H. Hara, and fried Fructus Aurantii	Male SD rats, PLGC model	MAPK; VEGF, FOXO4, AKT, TP53, FAS, MAPK8, MAPK11, MAPK14↓
	Inhibit glycolysis	fa	Cai et al[64], 2019	Weipixiao (WPX)	Astragalus, Radix Pseudostellariae, Atractylodes macrocephala, Salvia miltiorrhiza Bge, Oldenlandia diffusa(Willd.)Roxb	Male SD rats, PLGC model	miRNA-34a/PI3K/AKT/Mtor; LDHA, CD147, MCT4, PI3K, AKT, mTOR, HIF-1α, miRNA-34a↓
		fk	Liu et al[152], 2019	Weipiling (WPL)	Hedysarum multijugum Maxim, Pseudostellaria heterophylla Pax, Atractylodes macrocephala Koidz, Poria cocos Wolf, Panax notoginseng F.H. Chen, Curcuma zedoaria, Roscoe,Hedyotis diffusa Willd,Hericium erinaceus Pers	Male Atp4a-/-C57Bl/6 mice	mTOR/HIF-1α↓; CDX2, MUC2, ki-67, PTEN and p53, mTOR, HIF-1a, AMPK↓; TSC1, TSC2↑
	Improvement of EMT	fl	Li et al[69], 2022	Manpixiao decoction	Heterophylla falsestarwort root, root of red rooted salvia, drug solomonseal, common perilla stem, largehead atractylodes rhizome, corydalis ambigua, japanese apricot fruit, citron, rose, villous amomum fruit, spreading hedyotis herb, liquorice	Wistar male rats, PLGC model	EGFR-PI3K-AKT↓; EGFR, β-catenin, N-cadherin protein↓
GC	Anti-proliferation inducing apoptosis	fm	He et al[76], 2020	Weifufang	Astragalus, Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Nutgrass Galingale Rhizome, Radix Curcumae, Sappan Wood, Rhizoma Curcumae, Zaoxiu Paris Root Rhizoma Paridis, Barbed Skullcap Herb, Ligustrum lucidum, South Dodder Seed, Oldenlandia, Liquorice Root, Chicken’s Gizzard-membrane, fry malt, and fry Rice-grain Sprout	BALB/c-nu nude mice, BGC-823 cell, Nude mice with xenografts	PTEN↑
		fn	Fang et al[153], 2021	Huosu Yangwei (HSYW)	Huoxiang, Zisugeng, Baizhu, Zhike, Doukou, Foshou, Wumei, Shengjiang, Dazao, Gancao, Huangqi, Dihuang, Mudanpi, Tianhuafen, Danggui, Chuanxiong, Ezhu, Gouqizi, Huanglian, Dangsheng, and Pugongying	Male Balb/c mice, PLGC model	DNAJB4, CALD1, AKR1C1, CST1, CASP1, PREX1, SOCS3, PRDM1
		fo	Yuan et al[154], 2020	Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction	Radix astragali, Radix codonopsis pilosulae, Rhizoma Sparganiiand Rhizoma Curcumae	HGC-27 cells ,THP-1 cell, MFC cell	PI3Kγ, NF-κB, AKT, p-C/EBPβ, IL-10↓; IL-1β, TNF-α, IL-12p↑
		fg	Deng et al[92], 2019	Weining granule	Radix Astragali Mongolici and Herba Hedyotdis Rhizoma Curcumae Phaeocaulis,Fructus Lycii	Male Wistar rats, PLGC model	Bcl-2, VEGF↓; caspase-3, PTEN↑
	Anti-inflammatory	fp	Li et al[155], 2021	Guiqi Baizhu prescription	Astragali radix, Atractylodis macrocephalae, Angelicae,Paeoniae radix alba, Pericarpium citri reticulatae, Rhubarb, Glycyrrhizae	MKN-45 cell, SGC-7901 cell, BGC-823 cell, GES-1cell	HER2, PD-L1↑
	Anti-angiogenesis	fg	Deng et al[92], 2019	Weining granule	Radix Astragali Mongolici and Herba Hedyotdis Rhizoma Curcumae Phaeocaulis, Fructus Lycii	Male Wistar rats, PLGC model	Bcl-2, VEGF↓; caspase-3, PTEN↑
	Improvement of EMT	fq	Liu et al[100], 2020	Babao Dan	Natural bezoar, snake gall, antelope horn, pearl, musk, and Panax notoginseng	AGS cell, MGC803 cell	TGF-b/Smad↓; TGF-b1, p-Smad2/3↓
		fo	Yuan et al[154], 2020	Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction	Radix astragali, Radix codonopsis pilosulae, Rhizoma Sparganiiand Rhizoma Curcumae	HGC-27 cells, THP-1 cell, MFC cell	PI3Kγ, NF-κB, AKT, p-C/EBPβ, IL-10↓; IL-1β, TNF-α, IL-12p↑
	Inhibits migration, and invasion	fr	Chen et al[112], 2018	Yangzheng Sanjie Decoction (YZSJD)	Astragali Radix, Scutellariae Barbatae, Herba, Arisaematis Rhizoma Preparatum, Citri Sarcodactylis, Fructus, Cremastrae Pseudobulbus and Curcumae Longae, Rhizoma	MKN-45 cell	EGFR, miR-7↑

SD: Sprague Dawley; GPL: Gastric precancerous lesions; GC: Gastric cancer; EMT: Epithelial-mesenchymal transformation; NF-κB: Noncanonical nuclear factor-kappa B.