Abstract
Background Paeonia extract mixture HT074 is a standardized multiherbal mixture comprising extracts from Inula britannica flowers and Paeonia lactiflora roots, which are used to treat digestive disorders in traditional Korean medicine. This study was focused on elucidating the underlying mechanisms of the gastroprotective effects of HT074 in different gastric ulcer models. Methods Gastric lesions were induced in rats by an HCl/EtOH solution, water immersion-restraint stress (WIRS), and indomethacin. Gastric secretions were studied in pylorus-ligated rats, while mucus secretions were assessed by measuring alcian blue-binding capacity of mucus in the rat model of HCl/EtOH-induced gastric ulcer. Additionally, the involvement of nitric oxide (NO) and sulfhydryl compounds in HT074-mediated mucosal protection was elucidated using their inhibitors, i.e., N G-nitro- L-arginine methyl ester hydrochloride (L-NAME) and N-ethylmaleimide (NEM), respectively. Furthermore, the effects on indomethacin-induced cell death and prostaglandin E2 (PGE2) levels were assessed in AGS cells. Results Oral administration of HT074 significantly decreased gastric lesions induced by HCl/EtOH, WIRS, and indomethacin. Furthermore, it significantly decreased the volume, acidity, and total acidity of gastric juice in pylorus-ligated rats and increased the alcian blue-stained gastric mucus in HCl/EtOH-induced gastric ulcer in rats. Pretreatment with NEM abolished the gastroprotective effects of HT074, while L-NAME did not. In AGS cells, HT074 significantly reduced indomethacin-induced cell death and increased the PGE2 levels. Conclusions These findings suggest that HT074 has gastroprotective effects against various ulcerogens, including HCl/EtOH, immersion stress, and NSAIDs. These effects are attributed to the inhibition of gastric secretions and preservation of the gastric mucosal barrier by increased mucus production, which is partially mediated through endogenous sulfhydryl compounds and PGE2. Based on these findings, we propose that HT074 may be a promising therapeutic agent for gastritis and gastric ulcer.
Highlights
Gastric ulcer is one of the most prevalent chronic diseases of the gastrointestinal tract [1, 2]
A gastric ulcer occurs as a result of the imbalance between the aggressive factors in the gastric system, including gastric acids or pepsin, and the protective factors, such as mucus secretion, prostaglandins, sulfhydryl compounds, nitric oxide, and antioxidants [7]
The results of this study are consistent with previous studies that reported carbenoxolone to protect the gastric mucosa by acting on nitric oxide (NO) and SH compounds [77, 78]. These results suggest that sulfhydryl compounds are involved in the gastroprotective effects of HT074, whereas gastroprotection by HT074 is independent of NO
Summary
Gastric ulcer is one of the most prevalent chronic diseases of the gastrointestinal tract [1, 2]. Typical treatments for gastric ulcers are acid suppressant drugs, such as type-2 histamine receptor antagonists and proton pump inhibitors [2], but they have some adverse effects. Because gastric acid is only one of the many ulcerogenic factors, new treatments need to focus on other protective factors [10]. For this reason, mucosal protective agents with relatively low side effect can be a good alternative [11]. Medicinal herbs have been used as an alternative therapeutic source for the treatment of gastric ulcers [12]. The involvement of nitric oxide (NO) and sulfhydryl compounds in HT074-mediated mucosal protection was elucidated using their inhibitors, i.e., NG-
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