Traditional Chinese medicine in the treatment of Helicobacter pylori-related gastritis: The mechanisms of signalling pathway regulations

Table 1 The effects of extracts or active ingredient from herb medicines on Helicobacter pylori-associated gastritis

Ref.	Active ingredient	Experiments of the TCM group		Related signaling pathway	Mechanisms/results	Outcome
		In vitro	In vivo
Wang et al[39], 2018	Polygonum capitatum extract	-	Rats	PI3K/AKT	↑PTEN	Polygonum capitatum prevents the release of inflammatory factors, and stimulates the proliferation of gastric mucosa cells to repair damaged tissues
					↓PI3K, AKT
Peng et al[42], 2022	Syzygium aromaticum extract	GES-1	-	PI3K/AKT, MAPK	↓p-PI3K, p-AKT, p-MAPK	The active components of syzygium aromatic extract played a therapeutic role in HPAG through the synergistic regulation of the PI3K/Akt and MAPK signalling pathways
Ma et al[54], 2020; Ma et al[96], 2021	Alpiniae Officinarum Rhizoma extract	-	Mice	MAPK	↓p-ERK1/2, P-JNK, p38MAPK, IL-8	The Alpiniae Officinarum Rhizoma extract played a therapeutic role in HPAG through regulation of the and MAPK and NF-κB signalling pathways
		GES-1	Mice	NF-κB	↓IKKβ, p-IKKα/β, NF-κBp65, p-NF-κBp65, p-IκBα, IL-8
Deng and Wan[57], 2017	Baicalin	GES-1	-	MAPK	↑Bcl-2, ↓IL-1β, p-p38 MAPK, IL-8, Bax	Baicalin markedly decreased the apoptosis of gastric mucosal epithelial cells, improved proliferation, and alleviated inflammation
Tian and Huang[60], 2019	Dandelion polysaccharide	-	Rats	MAPK	↑IL-10	Dandelion polysaccharide can reduce the inflammatory response of gastric mucosa in rats with HPAG by inhibiting the MAPK/ERK signalling pathway, so as to play a protective role in gastric mucosa
					↓p-ERK1/2, IL-6, TNF-α, PGE2, iNOS, COX-2
Jia et al[66], 2024	Ferulic acid	-	Mice	Wnt/β-catenin	↓Wnt2, β-catenin, TNF-α, IL-8	Ferulic acid can reduce H. pylori colonization and gastric mucosal inflammation through inhibitory effects of the Wnt/β-catenin signalling pathway
Liu et al[69], 2022	Patchouli alcohol	-	Mice	Wnt/β-catenin, NF-κB	↓Wnt2, β-catenin, NF-κB	Patchouli alcohol reduces the inflammatory response of gastric mucosa and prevent the epithelial-mesenchymal transition of gastric mucosal cells through the synergistic regulation of the Wnt/β-catenin and NF-κB signalling pathway
Zhang et al[83], 2015	Resveratrol	-	Mice	Nrf2/HO-1, NF-κB	↑HO-1, Nrf2	Resveratrol might play a therapeutic role in HPAG through the anti-oxidant, anti-inflammatory, regulation of the NF-κB and Nrf2/HO-1 signalling pathway
					↓MPO, LPO, IL-8, iNOS, p-IκBα
Liu et al[85], 2023	Rhein	-	Mice	Nrf2/HO-1, MAPK	↑HO-1, Nrf2	Rhein can regulate the MAPK and Nrf2/HO-1 signalling pathway to inhibit gastric inflammation of HPAG
					↓p-JNK1/2, p-p38MAPK, TNF-α, COX-2, IL-6, IL-1β, PGE2
Lu et al[95], 2021	Berberine	GES-1	Mice	NF-κB	↓TNF-α, IL-6, IL-8, COX-2, NF-κB p65, NF-κB p50, CagA	Berberine can inhibit gastric inflammation and virulence of H. pylori by inhibiting the effective activation of the NF-κB signalling pathway

TCM: Traditional Chinese medicine; ↑: Increased; ↓: Decreased; H. pylori: Helicobacter pylori; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; PTEN: Phosphatase and tensin homolog; p-PI3K: Phosphorylation of phosphatidylinositol 3-kinase; p-AKT: Phosphorylation of protein kinase B; MAPK: Mitogen-activated protein kinase; p-MAPK: Phosphorylation of mitogen-activated protein kinase; HPAG: Helicobacter pylori-associated gastritis; p-JNK: Phosphorylation of c-Jun N-terminal kinase; p-ERK1/2: Phosphorylation of extracellular signal-regulated kinase1/2; IL: Interleukin; NF-κB: Nuclear factor-kappa B; IKK: Inhibitor Kappa B kinase; p-IKK: Phosphorylation of inhibitor kappa B kinase; IκB: Inhibitor of nuclear factor-κB; p-IκB: Phosphorylation of inhibitor of nuclear factor-κB; iNOS: Inducible nitric oxide synthase; COX-2: Cyclooxygenase-2; PGE2: Prostaglandin E2; CagA: Cytotoxin-associated gene A; LPO: Lipid peroxidation; MPO: Myeloperoxidase; Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; TNF: Tumor necrosis factor; Bax: B-cell associated X protein; Bcl-2: B-cell lymphoma-2.

Table 2 The effects of herb formulas on Helicobacter pylori-associated gastritis

Ref.	Herb formulas	Ingredients	Experiments of the TCM group		Related signaling pathway	Mechanisms/results	Outcome
			In vitro	In vivo
Jiang et al[101], 2024	San-Ren decoction	Ku Xing Ren (Semen Armeniacae Amarum), Zhi Ban Xia (Pinelliae Rhizoma Praeparata), Hua Shi (Talcum), Yi Yi Ren (Semen Coicis), Tong Cao (Medulla tetrapanacis), Bai Dou Kou (Amomi Fructus Rotundus), Dan Zhu Ye (Herba Lophatheri), Hou Po (Cortex Magnoliae Officinalis)	-	Rats	AKT/NF-κB	↑IL-10, IL-4, Bcl-2	San-Ren decoction can decrease stomach epithelial cell apoptosis and regulate the Akt/NF-κB signalling pathway, which can ameliorate the inflammatory response and functional dyspepsia in HPAG
						↓Caspase-3, Bax, Akt, NF-κB p65
Wang et al[109], 2022	Wei-Fu-Chun table	Ren Shen (Radix Ginseng), Zhi Qiao (Fructus Aurantii), Xiang Cha Cai (Isodon)	-	Rats	JAK/STAT	↓IL-6, JAK, STAT, NF-κB	Wei-Fu-Chun table can inhibit the JAK/STAT signalling pathway to improve the gastric mucosal inflammation symptoms of HPAG
Yan[112], 2023; Yu et al[113], 2014	Mie-You decoction	Huang Qin (Radix Scutellariae), Pu Gong Ying (Herba Taraxaci), San Qi (Radix notoginseng), Bai Ji (Rhizoma Bletillae), Qing Pi (Pericarpium Citri Reticulatae Viride), Chen Pi (Pericarpium Citri Reticulatae), Hai Piao Xiao (Endoconcha Sepiae)	-	Mice	Nrf2/HO-1, NF-κB	↑Keap1, Nrf 2, HO-1, SOD	Mie-You decoction can inhibit the oxidative stress response and the expression of TLR4, NF-κB65 and downstream factors by interfering with TLR4/NF-κB65 signalling pathway to achieve the purpose of treating HPAG
						↓MDA, NF-κB, TLR4, TNF-α, IL-8
Zheng[114], 2019	Qilian Wendan decoction	Huang Qi (Radix Astragalie), Huang Lian (Rhizoma Coptidis), Zhi Qiao (Fructus Aurantii), Zhu Ru (Caulis Bambusae in Taenia), Zhi Ban Xia (Pinelliae Rhizoma Praeparata), Chen Pi (Pericarpium Citri Reticulatae), Fu Ling (Poria), Pu Gong Ying (Herba Taraxaci), Gan Cao (Radix Glycyrrhizae)	-	Mice	NF-κB	↓NF-κB p65, IκBα	Qilian Wendan decoction can reduce H. pylori colonization in the stomach, and improve the pathological morphological damage of HPAG
Wang et al[115], 2024	Qibei Xiaoyong decoction	Huang Qi (Radix Astragalie), Pu Gong Ying (Herba Taraxaci), Zhe Bei Mu (Bulbus Fritillariae Thunbergii), Ku Shen (Radix Sophorae flavescentis), Hai Piao Xiao (Endoconcha Sepiae), Ren Shen (Radix Ginseng), Chai Hu (Radix Bupleuri), Bai Ji (Rhizoma Bletillae), San Qi (Radix notoginseng), Huang Lian (Rhizoma Coptidis), Pu Huang (Pollen Typhae), Wu Ling Zhi (Faeces Trogopterori), Gan Cao (Radix Glycyrrhizae)	-	Human	NF-κB	↑SOD, NO	Qibei Xiaoyong decoction can significantly improve oxidative stress and inflammation caused by HPAG
						↓NF-κB, MDA, TNF-α, IL-8, MMP-9
Ye et al[118], 2015	Jinghua Weikang capsule	Tu Jing Jie (Herba Chenodii Ambrosiodis), Shui Tuan Hua (Adina pilulifera)	-	Mice	NF-κB	↓NF-кBp65	Jinghua Weikang capsule have anti-inflammatory effect on HPAG by reducing the expression level of NF-κB p65
Liu et al[119], 2021	Jianpi Qinghua decoction	Dang Shen (Radix Codonopsis), Fu Ling (Poria), Bai Zhu (Rhizoma Atractylodis Macrocephalae), Huang Lian (Rhizoma Coptidis), Da Huang (Radix et Rhizoma Rhei), Pu Gong Ying (Herba Taraxaci), Dan Shen (Radix Salviae Miltiorrhizae), Gan Cao (Radix Glycyrrhizae)	-	Rats	NF-κB	↑HSP70	Jianpi Qinghua decoction can inhibit and kill H. pylori to a certain extent, reduce the progression of inflammatory reaction, so as to reduce gastric tissue damage and protect gastric mucosa
						↓NF-кBp65
Wen et al[121], 2022	Zuo-Jin-Pill	Huang Lian (Rhizoma Coptidis), Wu Zhuyu (Rhizoma Coptidis)	GES-1	Mice	HMGB1/NF-κB	↓IL-6, MCP-1, PGE2, TNF-α, VEGF, HMGB1, JMJD2B, COX-2, NF-κB p65, MYD88, TLR4	Zuo-Jin-Pill exerts therapeutic effects on H. pylori-induced CAG by inhibiting the JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signalling pathway
Huang et al[129], 2018	Banxia Xiexin decoction	Zhi Ban Xia (Rhizoma Pinelliae), Huang Qin (Radix Scutellariae), Gan Jiang (Rhizoma Zingiberis), Ren Shen (Radix Ginseng), Huang Lian (Rhizoma Coptidis), Da Zao (Jujubae Fructus), Gan Cao (Radix Glycyrrhizae)	GES-1	-	TGF-β/Smad	↑Smad2/3, TGF-β1, p-Smad2/3	Banxia Xiexin decoction can reduce the damage of gastric mucosal epithelial cells induced by H. pylori, promote the proliferation of gastric mucosal epithelial cells
						↓Smad7, p-Smad7, LPO, IL-8, iNOS, p-IκBα
Su et al[131], 2023	Biling Weitong granule	Bi Cheng Qie (Fructus Litseae), Wu Zhu Yu (Fructus Evodiae), Xiang Fu (Rhizoma Cyperi), Chuan Lian Zi (Fructus toosendan), Yan Hu Suo (Rhizoma corydalis), Huang Lian (Rhizoma Coptidis), Da Huang (Radix et Rhizoma Rhei), Fo Shou (Fructus Citri Sarcodactylis), Xiang Yuan (Fructus Citri), Hai Piao Xiao (Endoconcha Sepiae), Wa Leng Zi (Concha Arcae)	-	Human	TGF-β/Smad	↓IL-6, TNF-α, EGF, TGF-β1	The combination of Biling Weitong granule and quadruple therapy can significantly improve the eradication rate of H. pylori, and can significantly increase the relief rate of upper abdominal pain in patients with gastric ulcer, and improve the clinical efficacy
Hui et al[137], 2023	Wei-Su granule	Zi Su Geng (Caulis Perillae), Xiang Fu (Rhizoma Cyperi), Chen Pi (Pericarpium Citri Reticulatae), Fo Shou (Fructus Citri Sarcodactylis), Xiang Yuan (Fructus Citri), Zhi Qiao (Fructus Aurantii), Ji Nei Jin (Endothelium Corneum Gigeriae Galli), Bin Lang (Semen Arecae)	-	Rats	Hippo/TAZ	↑LATS2	Wei-Su granule has great potential and specific therapeutic value in innovative drug development for HPAG
						↓TAZ

↑: Increased; ↓: Decreased; TCM: Traditional Chinese medicine; AKT: Protein kinase B; NF-κB: Nuclear factor-kappa B; IL: Interleukin; Bax: B-cell associated X protein; Bcl-2: B-cell lymphoma-2; HPAG: Helicobacter pylori-associated gastritis; JAK: c-Jun N-terminal kinase; STAT: Signal transducer and activator of transcription; Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; Keap1: Kelch-like associated protein 1; SOD: Superoxide dismutase; TLR: Toll-like receptor; MDA: Malondialdehyde; TNF: Tumor necrosis factor; IκBα: IkappaBalpha; H. pylori: Helicobacter pylori; NO: Nitric oxide; MMP-9: Matrix metalloproteinase 9; HSP70: Heat shock protein70; HMGB1: High mobility group box 1; MCP-1: Monocyte chemoattractant protein-1; PGE2: Prostaglandin E2; VEGF: Vascular endothelial growth factor; JMJD2B: Jumonji domain-containing protein2B; COX-2: Cyclooxygenase-2; CAG: Chronic atrophic gastritis; MYD88: Myeloid differentiation factor 88; Smad2/3: Small mothers against decapentaplegic homolog 2/3; LPO: Lipid peroxidation; iNOS: Inducible nitric oxide synthase; p-IκBα: Phosphorylation of IkappaBalpha; EGF: Epidermal growth factor; TAZ: Transcriptional coactivator with PDZ-binding motif; LATS2: Large tumor suppressor 2.