Chronic atrophic gastritis (CAG) is a gastric disease with pathological characteristics of abnormal glands of the gastric mucosa, mucosal muscle layer thickening, intestinal metaplasia (IM), and dysplasia (de Vries et al., 2008; Soltermann et al., 2007). CAG is considered a pivotal precancerous lesion of gastric carcinoma (Adamu et al., 2010, 2011) and ranked as the fifth most common cancer globally (Sung et al., 2021). Due to the lacking of early diagnosis and effective therapeutic drugs, most patients are already in an advanced stage when diagnosed with gastric cancer (Li et al., 2021). So, it is crucial to treat CAG timely and block the progress of IM to reduce the incidence of gastric cancer (de Vries et al., 2008; Li et al., 2017).

At present, the pathogenesis of CAG has not completely elucidated yet. Chronic infection of Helicobacter pylori (HP) (Graham and Miftahussurur, 2018) and the followed inflammation of gastric mucosa (Wang et al., 2022) were considered the most common cause of CAG. Repeated inflammatory stimulation induces gastric epithelial cells apoptosis, leading to gastric mucosa atrophy, intraepithelial neoplasia, and even gastric cancer (Gong et al., 2010). In clinical, antibiotics, proton pump inhibitors (PPI), antacids, and gastric mucosal protective drugs are the main drugs for CAG treatment. These drugs could effectively improve mucosal inflammation and alleviate symptoms such as stomachache, but long-term use of them would lead to some adverse reactions, such as multidrug resistance, renal injury, hypomagnesemia, and osteoporotic fractures (Schoenfeld and Grady, 2016), that affect tremendous the health and the life quality of patients (Ji et al., 2020).

Traditional Chinese medicines have unique advantages in treatment of chronic stomach diseases (Wei et al., 2019). It has been reported that Sijunzi decoction could inhibit inflammation and oxidative stress of gastric mucosa (Tian et al., 2019). Moluodan, a condensed pill of Chinese patent medicine, improves CAG by inhibiting inflammatory responses and regulating cell proliferation and apoptosis (Zhou et al., 2022). Zuojinwan (Wen et al., 2022), Weifuchun (Gu et al., 2020), and Sancao Tiaowei decoction (Cai et al., 2022) alleviates CAG and blocks precancerous lesions of gastric carcinoma by regulating HMGB1/NF-kB, RUNX3/TGF-beta/Smad, Hedgehog, and Wnt signaling pathway respectively. Dangshen (He et al., 2022), Codonopsis and its active fraction inulin fructan CP-A and Codonyl glycoside (Li et al., 2017) could effectively reduce gastric mucosa damage, block gastric inflammation–gastric cancer transformation by regulating cancer cells energy metabolism and Shh related signal pathway. Costunolide could also induce apoptosis of BGC-823 cells through the mitochondrial apoptosis pathway (Yan et al., 2019).

Weierning (WEN) tablet is a Chinese patent medicine that has been used to treat CAG in clinical for decades (Li et al., 1995). It is composed of Codonopsis pilosula (Franch.) Nannf. (Dangshen in Chinese), Trichosanthes kirilowii Maxim. (Tianhuafen in Chinese), Houpoea officinalis (Rehder & E.H. Wilson) N.H. Xia & C.Y. Wu (Houpo in Chinese), Dolomiaea costus (Falc.) Kasana & A.K. Pandey (Muxiang in Chinese), Pinellia ternata (Thunb.) Makino (Fabanxia in Chinese), Sepiella maindroni de Rochebrune (Haipiaoxiao in Chinese), and Strychnos nux-vomica L. (Maqianzifen in Chinese). All names of mentioned plants have been checked with www.worldfloraonline.org on October 24th, 2022. The Chinese medicinal herb Codonopsis pilosula in the prescription of WEN tablets is an edible traditional Chinese medicine with a wide range of pharmacological activities. The inulin fructan CP-A and Codonyl glycoside in Codonopsis pilosula has gastric mucosal protective and anti-inflammatory activities (Li et al., 2017; Meng et al., 2020). Trichosanthis Radix is the dried root of Trichosanthes kirilowii Maxim (Wang et al., 2018). It has a positive effect in suppressing inflammatory mediators and attenuating oxidative stress. Magnoliae officinalis has been used to treat gastrointestinal disorders, such as ulcers, in folk over hundreds of years. magnolol is the main active compound of Houpoea officinalis with excellent activities in antioxidant, anti-inflammation, anti-ulcer et al. (Yang et al., 2019). Codenolactone and dehydrocodenolactone in Dolomiaea costus (Falc.) Kasana & A.K.Pandey protect gastric mucosa by regulating oxidative stress and inhibiting NF-κB p65-mediated inflammatory response (Zheng et al., 2016). Pinellia ternata (Thunb.) Makino can inhibit the proliferation of gastric cancer cells (Feng et al., 2021). All seven Chinese medicines put together possess functions of invigorating the spleen function to eliminate dampness and regulate Qi-flowing to relieve pain. Clinical studies have confirmed that WEN significantly improves clinical symptoms and the pathological integral of CAG (Li et al., 1995). But the characteristic function, such as anti-inflammation, improving atrophy, and blocking IM, of WEN in CAG therapy and the underlying mechanisms are still unveiled.

Thus, a CAG rat model, induced by orally administrated rat with a combinate solution of 2% sodium salicylate and 30% anhydrous ethanol, with drinking freely of 0.1% ammonia and irregular fasting, was applied to illuminate the exact function or stage of WEN on CAG. The potential targets for anti -inflammation, cell apoptosis, and IM were also investigated.