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

Table 2 In vitro and in vivo protective effects of active components of Chinese herbal medicine on gastric precancerous lesions and gastric cancer

Pathological stages	Effect	No.	Ref.	Active component	Animal/cells	Pathways/targets
Gastric precancerous lesions (GPL)	Anti-proliferation inducing apoptosis	c1	Wang et al[37], 2021	Erianin	GES-1 cell	HRAS-PI3K-Akt↓; p-Gsk3β, MDM2, p21, CyclinD1↓
		c2	Zhu et al[38], 2021	Epigallocatechin gallate	Male Wistar rats, PLGC model	PI3K/Akt/mTOR↓; PTEN↑; PI3K, Akt, mTOR↓
		c3	Zeng et al[33], 2021	Ginsenoside Rb1	Sprague-Dawley rats, PLGC model	β-catenin/TCF4↓; c-myc, cyclin, Birc5↓
		c4	Lv et al[131], 2022	Ginsenoside Rg3	Male Sprague-Dawley rats, PLGC model GPL cell	TIGAR, G6PDH, NADP, GSH↓; ROS↑
	Anti-inflammatory	c5	Liu et al[50], 2020	Calycosin	Male (SD) rats, PLGC model	Integrinβ1/NF-κB/DARPP-32; Integrinβ1, NF-κB, DARPP-32↑; STAT3↓
	Anti-angiogenesis	c5	Liu et al[50], 2020	Calycosin	Male (SD) rats, PLGC model	Integrinβ1/NF-κB/DARPP-32; Integrinβ1, NF-κB, DARPP-32↑; STAT3↓
		c6	Gao et al[58], 2022	Atractylenolide III	Female SD rats, Gastric Precancerous, Lesions Model	HIF-1α, VEGF-A, DLL4↓
		c4	Zeng et al[120], 2022	Ginsenoside Rg3	Male Sprague Dawley rats, PLGC modelAGS cell, HGC-27 cell	GLUT1, GLUT4↓
	Inhibit glycolysis	c4	Liu et al[63], 2020	Ginsenoside Rg3	Male Atp4a/ C57Bl/6 mice, PLGC model	PI3K/Akt/mTOR↓; PI3K/Akt/miRNA-21↓; PI3K, AKT, mTOR, HIF-1α, miRNA-21↓; caspase-3↑
		c7	Zhang et al[65], 2018	Astragaloside IV	Male Sprague-Dawley rats, PLGC model	LDHA, MCT1, MCT4, HIF-1α, CD147, TIGAR↓; miRNA-34a, p53↑
	Improvement of EMT	C8	Liao et al[68], 2023	Gallic acid	GES-1 cell, MC cells	Wnt/β-catenin↓
	Induce autophagy	c7	Cai et al[44], 2018	Astragaloside IV	Sprague Dawley rats, PLGC model	Bcl-2/Bax, p53, Beclin1, p62, ATG5, ATG12↓; caspase3↑
GC	Anti-proliferation inducing apoptosis	c9	Xu et al[74], 2021	Naringin	SNU-1 cell, GES-1 cell	PI3K/Akt↓; PI3K, Akt, Bcl-2↓; caspase 3, Bax↑
		c10	Yang et al[132], 2016	Epigallocatechin-3-gallate	SGC-7901 cells, Nude mouse tumour xenograft model	Wnt/β-catenin↓; GSK3b, β-catenin↓
		c11	Lee et al[75], 2018	Pectolinarigenin	AGS cell, MKN28 cell	PI3K/Akt/mTOR↓; PI3K, p-Akt, mTOR, p-p70S6K, p-4EBP1↓
		c10	Fu et al[133], 2019	Epigallocatechin-3-gallate	SGC7901 cell	VEGF, HIF-1α↓
		c12	Wang et al[77], 2020	Aloin	HGC-27 cell, BGC-823 cell	Akt/mTOR, Stat3, NF-κB↓; NOX2, ROS, Akt, mTOR, Stat3, IκBα, p65↓
		c13	Chen et al[109], 2020	Betulinic acid	BGC-823 cells, MNK45 cells	NF-κB, VASP↓
		c14	Geng et al[134], 2018	Usnic acid	BGC823 cell, SGC7901 cell	Bax, LC3-II↑; Bcl-2, p62↓
		c15	Xu et al[135], 2020	T-17	SGC-7901, AGS cell, MGC-803 cell, BGC-823 cell, NCI-N87 cell,HUVEC cell	JNK, Bcl-2↑
		c16	Liu et al[81], 2015	Ponicidin	MKN28 cell	JAK2/STAT3↓; Bcl-2, VEGF, VEGFR2, JAK2 STAT3↓; Bax, caspase-3↑
		c17	Chen et al[136], 2012	Tanshinone IIA	MKN45 cell, SGC7901 cell	cyto-c, Bax, Caspase-9↑; Bcl-2↓
		c18	Yang et al[52], 2020	Tomentosin	GCCs cell, AGS cell	IL-6, TNF-α, IL-1, IL-8, Bcl-2↓; Bax↑
		c19	Sun et al[137], 2007	Swainsonine	SGC-7901 cell, BALB/c nu/nu mice, GC model	p53, Bcl-2↓; cmyc↑
		c20	Tang et al[82], 2019	Micheliolide	AGS cell, N87 cell	IL-6, STAT3, cyclinD1, Mcl-1, MMP-2↓
		c21	Li et al[138], 2013	Andrographolide	BGC-823 cell	Bax, caspasase-3↑; Bcl-2↓
		c22	Liu et al[139], 2016	Curcumin	SGC7901 cell, GES-1 cell	c-Myc/H19↓; c-Myc, H19↓; p53↑
		c23	Lee et al[140], 2016	Quercetin	NOD/SCID mice, PLGC model SNU719 cell, MKN74 cells	p53, p21, Bax, Puma, caspase-3, caspase-9, PARP↑
		c4	Aziz et al[121], 2016	Ginsenoside Rg3	SGC-7901 cell	Caspases-3, caspase-8, caspase-9, PARP, SP1↑; HSF1, FUT4↓
		c24	Saralamma et al[141], 2015	Poncirin	AGS cells	Fasl, caspase-8, caspase-3, PARP↑
	Anti-inflammatory	c18	Yang et al[52], 2020	Tomentosin	GCCs cell, AGS cell	IL-6, TNF-α, IL-1, IL-8, Bcl-2↓; Bax↑
		c25	Tharmalingam et al[115], 2016	Piperine	AGS cell	β-catenin, IL-8↓
		c26	Su et al[53], 2019	Artemisinin	SGC-7901 cell, GES-1 cells, C57BL/6 J mice	NF-κB↓; IL-8, IL-6, TNF-α, IL-1β, COX-2, p-IκBα↓; IκBα↑
		c27	Han et al[54], 2015	Rosmarinic acid	MKN45 cell	IL-6/STAT3↓; IL-6, IL-1β, TNF-α, TNFsR-1, HIF-1α, miRNA-155-5p↓; IL-10↑
		c28	Sun and Meng[55], 2022	Scutellarin	AGS cell, albino Wistar rats, GC modelr	TNF-α, IL-1β, IL-2↓
	Anti-angiogenesis	c4	Li and Qu[89], 2019	Ginsenoside Rg3	BGC823 cell	HIF 1α, VEGF↓
	Inhibit glycolysis	C29	Wang et al[142], 2022	Licochalcone A	MKN45 cell, SGC7901cell, GES-1 cell	Akt/HK2↓; Akt, HK2↓
		C30	Chen et al[96], 2015	Baicalein	AGS cell	PTEN/Akt/HIF-1α↓; HK2, LDH-A, PDK1, Akt, HIF-1α↓; PTEN↑
		C31	Wang et al[142], 2022	Helichrysetin	MGC803 cell, HCT-8 cell	mTOR/p70S6K/c-Myc/PDHK1↓; mTOR/p70S6K, c-Myc, PDHK1↓
		C27	Han et al[54], 2015	Rosmarinic acid	MKN45 cell	IL-6/STAT3↓; IL-6, IL-1β, TNF-α, TNFsR-1, HIF-1α, miRNA-155-5p↓; IL-10↑
	Improvement of EMT	C32	Wang et al[99], 2022	Poria acid	AGS cell, MKN-28 cell	E-cadherin↑; N-cadherin, Vimentin↓
		C33	Zang et al[143], 2017	Luteolin	NCI-N87 cell, MKN28 cell, Hs-746T cell	E-cadherin↑; N-cadherin, vimentin, Snail↓
		c34	Zhou et al[108], 2019	Crocin	AGS cell, HGC-27 cell, GES-1 cell	miR-320/KLF5/HIF-1α; KLF5/HIF-1α; KLF5, HIF-1α↓; miR-320↑
		c7	Zhu and Wen, 2020[144], 2018	Astragaloside IV	BGC-823 cell, MKN-74 cell, GES-1 cell	PI3K/Akt/NF-κB↓; TGF-β1↓
	Regulate immune function	c35	Zhuang et al[105], 2020	Sophoridine	MFC cell, RAW264.7 cell	iNOS, IFN-β, IL-12α, Granzyme-B, TNF-α, Perforin↑; Arg-1, CD206, IL-10, PD-1, Tim-3, Lag-3, CCR2↓
		C36	Lu et al, 2021[104]	Oleanolic acid	MKN-45, Jurkat T cell	IL-1β/ NF-κB /TET3↓; PD-L1↓
	Induce autophagy	c11	Lee et al, 2018[75]	Pectolinarigenin	AGS cell, MKN28 cell	PI3K/Akt/mTOR↓; PI3K, p-Akt, mTOR, mTOR, p-p70S6K, p-4EBP1↓
		c14	Geng et al[134], 2018	Usnic acid	BGC823 cell, SGC7901 cell	Bax, LC3-II↑; Bcl-2, p62↓
		c15	Xu et al[135], 2020	T-17	SGC-7901, AGS, MGC-803, BGC-823, NCI-N87, HUVEC cell	JNK, Bcl-2↑
	Inhibits migration, and invasion	c12	Wang et al[77], 2020	Aloin	HGC-27 cell, BGC-823 cell	Akt/mTOR, Stat3, NF-κB↓; NOX2, ROS, Akt, mTOR, Stat3, IκBα, p65↓
		c13	Chen et al[109] , 2020	Betulinic acid	BGC-823 cells, MNK45 cells	NF-κB, VASP↓
		c34	Zhou et al[108], 2019	Crocin	AGS cell, HGC-27 cell, GES-1 cell	miR-320/KLF5/HIF-1α; KLF5/HIF-1α; KLF5, HIF-1α↓; miR-320↑
		c37	Cai et al[110], 2018	18β-glycyrrhetinic acid	SGC-7901 cell	ROS/PKC-α/ERK↓; ROS, PKC-α, ERK↓
		c30	Yan et al[111], 2015	Baicalein	SGC7901 Cell, MGC803 cell	MMP-2, mmp-9, p38↓
	Anti-Helicobacter pylori	c25	Tharmalingam et al[115], 2016	Piperine	AGS cell lines	β-catenin, IL-8↓
		c26	Su et al[53], 2019	Artemisinin	SGC-7901 cell, GES-1 cells	NF-κB↓; IL-8, IL-6, TNF-α, IL-1β, COX-2, p-IκBα↓; IκBα↑
		c28	Sun and Meng[55], 2022	Scutellarin	(AGS) cell, albino Wistar rats, GC model	TNF-α, IL-1β, IL-2↓

GPL: Gastric precancerous lesions; GC: Gastric cancer; EMT: Epithelial-mesenchymal transformation; NF-κB: Noncanonical nuclear factor-kappaB; TNF-α: Tumour necrosis factor alpha; IL: Interleukin; HIF-1α: Hypoxia-inducible factor 1α.