Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway

Abstract

Aim. Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats. Methods. Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry. Results. Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment. Conclusion. WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway.

A Systematic Review of the Mechanisms Underlying Treatment of Gastric Precancerous Lesions by Traditional Chinese Medicine

“…It is used for GPL treatment and fortifies the spleen, removes blood stasis, and harmonizes the stomach [67]. Experimental studies have shown that Weiqi decoction had an inhibitory effect on gastric inflammation by reducing COX-2 and increasing PGE2 in chronic atrophy gastritis rats with precancerous lesions [39]. Among the decoctions, herbs such as Radix Angelicae Sinensis [68], Radix Astragali [69], Radix Codonopsis [70], and Rhizoma Curcumae [71] were reported to exert anti-inflammatory effects by modulating the release of inflammatory mediators, which indicated that attenuating the inflammatory injury is a key mechanism of Weiqi decoction in the treatment of GPL.…”

“…Caspase-3 and Ki67 are considered apoptosis and proliferative cell markers in tumor formation, respectively [82,83]. A recent study showed that the Weiqi decoction introduced above could enhance the protein expression of cleaved caspase-3 and decrease the protein expression of Ki67 in pyloric gastric mucosa in GPL rats, indicating that this decoction could regulate the imbalance of proliferation and apoptosis [39]. Ginkgo biloba is an ancient herb that has been used for thousands of years in China.…”

“…Activated HIF-1α in tumor cells can increase the expression and activity of glycolytic enzymes, including GLUT1 and HK2, to accelerate the glycolytic rate [103]. Chinese medicine prescriptions such as Weipixiao formula and Weiqi decoction have been proven to attenuate GPL by suppressing levels of HIF-1α [16,39], suggesting their potential antiglycolytic function.…”

A Network Pharmacology Approach to Determine the Mechanisms of Action of Shuangshen Granules in Suppressing Pancreatic Cancer Precursor Lesions

“…It has several bene ts such as its satisfactory curative effects, and its low prevalence of side effects and cost, and has been gradually accepted by the public both in China and internationally [9][10][11][12][13]. Studies have shown that Chinese herbal compounds can regulate cell apoptosis via multiple pathways [14], can reduce the angiogenesis response of rats with precursor lesions, alleviate microvascular abnormalities [15] and regulate blood ow disorders which can delay, block, or reverse the development of precursor lesions [16]. This demonstrates the bene ts of TCM and highlights the great potential of Chinese herbal compounds for the treatment and prevention of diseases.…”

The effect of the fortifying the spleen, clearing heat, activating blood method on chronic atrophic gastritis: a real-world study

“…Compared to chemical drugs, traditional Chinese medicine (TCM) has a unique advantage in the treatment of CAG and produces no serious side effects [16] . For example, Weiqi Decoction attenuated CAG with precancerous lesions by regulating the disturbed gastric mucosal blood flow and the HIF-1 signaling pathway [17] . Tian G et al [18] adopted immune repertoire sequencing techniques to evaluate the effect of Modified Sijunzi Decoction for treating CAG.…”