Effect of Jiawei Huangqi Guizhi decoction (加味黄芪桂枝汤) on the expression of gastrin content and phosphatidylinositol 3-kinase/ protein kinase B/mechanistic target of rapamycin complex 2 signalling pathways in rats with chronic atrophic gastritis

doi:10.19852/j.cnki.jtcm.2025.04.007

Abstract

Abstract:

OBJECTIVE: To investigate the effects of Jiawei Huangqi Guizhi decoction (加味黄芪桂枝汤) on chronic atrophic gastritis (CAG) in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/ mechanistic target of rapamycin complex 2 (PI3K/Akt/ mTORC2) signaling pathway.

METHODS: CAG was induced in rats and treated with high-, medium-, or low-dose Jiawei Huangqi Guizhi decoction. Gastric histopathology was observed by hematoxylin and eosin staining. Serum levels of gastrin, PI3K, Akt, and mTORC2 were detected by enzyme-linked immunosorbent assay. Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.

RESULTS: The decoction alleviated gastric mucosal injury, reduced inflammation, and restored epithelial structure. It regulated PI3K, Akt, and mTORC2 expression at both mRNA and protein levels.

CONCLUSION: Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/mTORC2 signaling pathway.

Key words: gastrins, PI3K, Akt, mechanistic target of rapamycin complex 2, signal transduction, pathology, Jiawei Huangqi Guizhi decoction

ZHOU Xia, LIANG Kaiqing, CHEN Weigang, CAO Yong, DUO Hongdong, LI Qiangbin, AN Yun. Effect of Jiawei Huangqi Guizhi decoction (加味黄芪桂枝汤) on the expression of gastrin content and phosphatidylinositol 3-kinase/ protein kinase B/mechanistic target of rapamycin complex 2 signalling pathways in rats with chronic atrophic gastritis[J]. Journal of Traditional Chinese Medicine, 2025, 45(4): 770-776.

Figures/Tables 5

Figure 1 Effects of Jiawei Huangqi Guizhi decoction on gastric histopathology in rats with chronic atrophic gastritis. A: gross anatomy of gastric tissues in different groups; B: HE-stained gastric pathological sections. Magnification: × 100, × 200. A1, B1: NC group; A2, B2: MC group; A3, B3: AC group; A4, B4: HH group; A5, B5: HM group; A6, B6: HL group. NC group: normal rats without modeling or treatment (n = 10); MC group: rats with CAG induced by MNNG, without treatment (n = 10); AC group: CAG rats treated with folic acid (5 mg·kg-1·d-1, gavage, n = 10); HH group: CAG rats treated with high-dose Jiawei Huangqi Guizhi decoction (28 g/kg crude drug, gavage, n = 10); HM group: medium-dose group (14 g/kg crude drug, gavage, n = 10); HL group: low-dose group (7 g/kg crude drug, gavage, n = 10). All interventions were administered by gavage, once daily, 5 d per week for 6 weeks. HE: hematoxylin and eosin; MNNG: methylnitronitrosoguanidine; CAG: chronic atrophic gastritis.

Table 1 Effect of Huangqi Guizhi decoction on pathological changes of rat stomach tissue ($\bar{x} \pm s$, n = 5)

Group	n	Gross pathological changes	Pathological changes under microscope
NC	5	0.0±0.0	0.0±0.0
MC	5	3.0±0.5^a	7.8±0.7^a
AC	5	1.6±0.3^b	2.8±2.2^b
HH	5	1.5±0.6^b	3.6±1.9^b
HM	5	1.4±0.5^b	2.6±2.1^b
HL	5	1.5±0.5^b	3.8±1.7^b

Figure 2 Comparison of serum expression levels of GC, PI3K, Akt and mTORC2 in CAG rats A-D: serum levels of GC (A), PI3K (B), Akt (C) and mTORC2 (D) in different groups after 6-week treatment. NC group: normal rats without modeling or treatment (n = 10); MC group: rats with chronic atrophic gastritis (CAG) induced by MNNG, without treatment (n = 10); AC group: CAG rats treated with folic acid (5 mg·kg-1·d-1, gavage, n = 10); HH group: CAG rats treated with high-dose Jiawei Huangqi Guizhi decoction (28 g/kg crude drug, gavage, n = 10); HM group: medium-dose group (14 g/kg crude drug, gavage, n = 10); HL group: low-dose group (7 g/kg crude drug, gavage, n = 10). All interventions were administered by gavage, once daily, 5 days per week for 6 weeks. GC: gastric corticosterone; Pi3K: phosphatidylinositol 3-kinase; Akt: protein kinase B; mTORC2: mechanistic target of rapamycin complex 2; CAG: chronic atrophic gastritis. Data are expressed as mean ± standard deviation (n = 10 per group). Statistical significance was determined by one-way analysis of variance. aP < 0.01, compared with the model group.

Figure 3 Comparison of PI3K, Akt and mTORC2 mRNA expression levels in gastric mucosa of CAG rats. A-C: relative mRNA expression levels of PI3K (A), Akt (B), and mTORC2 (C) in each group after 6-week treatment. NC group: normal rats without modeling or treatment (n = 10); MC group: rats with chronic atrophic gastritis (CAG) induced by MNNG, without treatment (n = 10); AC group: CAG rats treated with folic acid (5 mg·kg-1·d-1, gavage, n = 10); HH group: CAG rats treated with high-dose Jiawei Huangqi Guizhi decoction (28 g/kg crude drug, gavage, n = 10); HM group: medium-dose group (14 g/kg crude drug, gavage, n = 10); HL group: low-dose group (7 g/kg crude drug, gavage, n = 10). All interventions were administered by gavage, once daily, 5 d per week for 6 weeks. GC: gastric corticosterone; Pi3K: phosphatidylinositol 3-kinase; Akt: protein kinase B; mTORC2: mechanistic target of rapamycin complex 2; CAG: chronic atrophic gastritis. Data are expressed as mean ± standard deviation (n = 10 per group). Statistical significance was determined by one-way analysis of variance. aP < 0.01; bP < 0.05, compared with the model group.

Figure 4 Effect of Jiawei Huangqi Guizhi decoction on the protein expression levels of PI3K/Akt/mTORC2 pathway-related targets in gastric mucosa of CAG rats A: Western blot analysis of PI3K, p-PI3K, Akt, p-Akt and mTORC2 in different groups; B1-B5: quantitative analysis of protein levels of PI3K (B1), p-PI3K (B2), Akt (B3), p-Akt (B4) and mTORC2 (B5), normalized to GAPDH. NC group: normal rats without modeling or treatment (n = 10); MC group: rats with CAG induced by MNNG, without treatment (n = 10); AC group: CAG rats treated with folic acid (5 mg·kg-1·d-1, gavage, n = 10); HH group: CAG rats treated with high-dose Jiawei Huangqi Guizhi decoction (28 g/kg crude drug, gavage, n = 10); HM group: medium-dose group (14 g/kg crude drug, gavage, n = 10); HL group: low-dose group (7 g/kg crude drug, gavage, n = 10). All interventions were administered by gavage, once daily, 5 d per week for 6 weeks. Pi3K: phosphatidylinositol 3-kinase; p-Pi3K: phosphorylated phosphatidylinositol 3-kinase; Akt: protein kinase B; p-Akt: phosphorylated protein kinase B; mTORC2: mechanistic target of rapamycin complex 2s; GADPH: glyceraldehyde-3-phosphate dehydrogenase; CAG: chronic atrophic gastritis. Data are expressed as mean ± standard deviation (n = 10 per group). Statistical significance was determined by one-way analysis of variance. aP < 0.01; bP < 0.05, compared with the model group.

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