Adjuvant role of traditional Chinese medicine in postoperative gastric cancer

Table 3 Effects and specific mechanisms of single herbs and their ingredients for the treatment of gastric cancer

Herb	Active component/extract	Functions	Clinical stage	Experimental model	Effect	Specific mechanism	Ref.
Peel and pulp of citrus grandis, citrus paradise and orange (Zhike, Chenpi)	Naringin	Anti-tumor	GC	In vitro (MGC803 and MKN45 GC cells). In vivo (BALB/c female nude mice)	Block the cell-cycle of GC cells	Induce cancer cell apoptosis, and inhibit the epithelial mesenchymal transition process by inhibiting the PI3K-AKT/Zeb1 pathway	[66]
Poria cocos (Fuling)	Pachymic acid	Anti-tumor	GC	In vitro (SGC-7901, AGS, and GES-1). In vivo (BALB/c nude mice)	Ferroptosis in GC cells	Suppressing the PDGFRB-mediated PI3K/AKT pathway	[67]
	Poria acid			In vitro (AGS and MKN-28)	Inhibit the invasion and metastasis of GC cells	Inhibit the EMT process and expressions of metastasis-related proteins matrix metalloproteinase in GC cells	[68]
Cimicifugae Rhizoma (Shengma)	Cimifugin	Anti-tumor	GC	In vitro (MKN28)	Inhibits GC cell proliferation, invasion, and migration	Interacts with AKR1C2, MAOB and PDE2A to modulate various metabolic pathways	[69]
the roots of Plumbago zeylanica (Banlangen)	Plumbagin	Anti-tumor	GC	In vitro (SGC-7901 cells)	Inhibits cell apoptosis in human GC cells	Suppressed the expression of BAX, BCL-2, pro-caspase-3, and cleaved-caspase-3; restrained the expression and phosphorylation of STAT3 and decreased the phosphorylation of AKT1	[70]
Eremias multiocellata	N/A	Removing blood stasis, eliminating nodules	Cisplatin-resistant GC	In vitro (MKN45/DDP). In vivo (BALB/c nude mice)	Reversing DDP resistance and increasing the sensitivity of gastric cancer drug-resistant cells to DDP	Regulating the NF-κB/Snail signaling pathway, PI3K/AKT/mTOR signaling pathway, and the expression of drug resistance-related proteins and genes	[112]
Salvia miltiorrhiza Bunge (Danshen)	Diterpenoid tanshinones	Activating blood circulation and removing blood stasis	GC	In vitro (SGC-7901, HUVECs). In vivo (BALB/c-nu nude mice)	Inhibit tumor growth and angiogenesis	Affecting the expression of the angiogenic factor VEGF through the PI3K/AKT/mTOR pathway	[73]
Celastrus orbiculatus Thunb (Leigongteng)	Triptonoterpene	Anti-metastasis, anti-tumor	Advanced GC	In vitro (BGC-823, MKN-28)	Inhibit the migration and invasion of GC cells	Inhibit the changes in EMT-related and invasion and metastasis-related proteins	[71]
				In vitro (BGC-823 and AGS). In vivo (nude mice)	Inhibit the metastasis and EMT of GC cells	Inhibited the remodeling of the actin skeleton of gastriccancer cells by promoting the degradation of CFL1	[72]
Trametes robiniophila Murr. (Huaier)	Huaier n-butanol extract	Anti-metastasis, anti-tumor	Advanced GC	In vitro (GES-1, MGC803, MKN74, AZ-521, and MKN28). In vivo (nude mice)	Inhibits GC growth and hepatic metastasis	Inhibiting the syntenin/STAT3 signaling pathway and reversing EMT	[76]
Rhizoma coptidis (Chaihu)	Berberine	Anti-inflammatory, anti-tumor	Advanced GC	In vitro (MKN-45 and HGC-27 and GES-1). In vivo (male BALB/C nude mice)	Inhibits GC cell proliferation	Modulating the signaling pathways related to IL-6/JAK2/STAT3	[77]
Paeonia suffruticosa Andr. (Mudanpi)	Paeonol	Anti-tumor, anti-inflammation, immune regulation	Apatinib-resistant GC	In vitro (BGC-823 and MGC-80). In vivo (female BALB/C nude mice)	Inhibit the malignancy of Apatinib-resistant GC cells	Regulating the LINC00665/miR-665/MAPK1 axis	[81]
Brucea javanica (Yadanzi)	Brusatol	Antitumor	Advanced GC	In vitro (SGC-7901)	Suppress GC cell proliferation, migration, invasion, and EMT formation	Inhibit LPS-induced EMT via the deactivation of the PI3K/AKT/NF-кB signaling pathway	[83]
Curcuma (wenyujin)	β-Elemene	Anti-metastasis, anti-tumor	Multidrug resistant GC	In vitro (SGC7901, SGC7901/ADR). In vivo (male BALB/C nude mice)	Inhibits the metastasis of multidrug resistant GC cells	Modulating the miR-1323/Cbl-b/EGFR signaling axis	[86]
Highly toxic beetles of the family Meloidae	Cantharidin	Anti-metastasis, anti-tumor	Advanced GC	In vitro (MGC803 and BGC823)	Suppress GC cell growth and migration/invasion	Inhibited the activation of the PI3K/AKT signaling pathway by downregulating CCAT1 targeting	[89]
Arachis hypogaea Linn. and Vitis vinifera Linn.	Resveratrol	Anti-metastasis, anti-tumor	Advanced GC	In vitro (SGC7901, BGC823 and GES1)	Suppress the invasion and migration of human GC cells	Inhibition of MALAT1-mediated epithelial-to-mesenchymal transition	[92]
			Interleukin-6 induced GC metastasis	In vitro (SGC-7901). In vivo (male NOD/SCID mice)	Prevent the IL-6 induced GC metastasis	Block the IL-6 induced invasion through the blocking of Raf-MAPK signaling pathway	[93]
Radix Angelica Sinensis (danggui)	N-butylidenephthalide	Anti-metastasis, anti-tumor	Advanced GC	In vitro (AGS, NCI-N87 and TSGH-9201). In vivo (NOD-SCID mice)	Inhibit proliferation and induces mitochondrial-dependent apoptosis in GC cells	Activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in GC cells	[94]
Venenum Bufonis (Chan Su)	Bufalin	Anti-invasion, anti-metastasis	Advanced GC	In vitro (AGS). In vivo (male BALB/c mice)	Arrests GC invasion and metastasis	Down-regulation of the Wnt/β-catenin signaling pathway, followed by the inhibition of ASCL2 expression and EMT	[95]
Ginseng	Ginsenoside Rg3	Anti-metastasis, anti-tumor	Metastatic GC	In vitro (NUGC-4). In vivo (female BALB/c mice)	Inhibite tumor growth and reduced lymphatic metastasis	Suppress expression of VEGF-C, VEGF-D and VEGFR-3	[96]

GC: Gastric cancer; GPL: Gastric precancerous lesions; STAT3: Signal transducer and activator of transcription 3; AKT: Protein kinase B; DDP: Cisplatin; VEGF: Vascular endothelial growth factor; HUVEC: Human umbilical vein endothelial cell; EMT: Epidermal mesenchymal transition; LPS: Lipopolysaccharide; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; ASCL2: Achaete-scute-like 2; PI3K: Phosphoinositide 3-kinase; Zeb1: Zinc finger E-box-binding homeobox 1; PDGFRB: Platelet-derived growth factor receptor beta; AKR1C2: Aldo-keto reductase family 1 member C2; MAOB: Monoamine oxidase B; PDE2A: Phosphodiesterase 2A; AX: Axin; BCL-2: B-cell lymphoma 2; STAT3: Signal transducer and activator of transcription 3; NF-κB: Nuclear factor kappa B; Snail: Snail family transcriptional repressor 1; mTOR: Mechanistic target of rapamycin; VEGF: Vascular endothelial growth factor; CFL1: Cofilin-1; IL-6: Interleukin-6; JAK2: Janus kinase 2; MAPK1: Mitogen-activated protein kinase 1; Cbl-b: Casitas B-lineage lymphoma b; EGFR: Epidermal growth factor receptor; CCAT1: Colon cancer-associated transcript 1; REDD1: Regulated in development and DNA damage responses 1.