Drug Design, Development and Therapy (Jun 2020)
Gastro-Protective Effects of Calycosin Against Precancerous Lesions of Gastric Carcinoma in Rats
Abstract
Danyan Li,1 Luqing Zhao,1 Yuxin Li,1,2 Xiuhong Kang,1 Shengsheng Zhang1 1Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Shengsheng ZhangDigestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaEmail [email protected]: Gastric cancer is a leading cause of cancer death worldwide. In-depth research of precancerous lesions of gastric carcinoma (PLGC) with malignant transformation potential is a key measure to prevent the development of gastric carcinoma. Recently, calycosin has been shown to have anticancer effects in vitro and in vivo. The molecular mechanism by which calycosin affects PLGC, however, has not yet been elucidated. The purpose of this study was to evaluate the effect and mechanism of calycosin in N‐methyl‐Nʹ‐nitro‐N‐nitrosoguanidine (MNNG)-induced PLGC rats.Methods: The effects of calycosin in the gastric mucosa of rats with PLGC were evaluated using histopathology and transmission electron microscopy (TEM). For further characterization, the expression levels of integrin β 1, nuclear factor kappa B (NF-κB), p-NF-κB, DARPP-32 and signal transducer and activator of transcription 3 (STAT3) were determined by Western blot assay and immunohistochemistry.Results: Hematoxylin–eosin and high iron diamine–Alcian blue–periodic acid-Schiff (HID-AB-PAS) staining showed that intestinal metaplasia and dysplasia were significantly ameliorated in the calycosin intervention groups compared with the model group. Further, TEM results showed that calycosin intervention tempered microvascular abnormalities and cell morphology of primary and parietal cells in PLGC tissues. The results suggested that calycosin had gastro-protective effects in MNNG-induced PLGC rats. Western blot and immunohistochemistry analysis showed that the increased protein expression levels of NF-κB, p-NF-κB, DARPP-32 and STAT3 in the model group were downregulated by calycosin. The upregulation of integrin β 1 expression induced by MNNG was decreased in the calycosin groups.Conclusion: Collectively, calycosin protected against gastric mucosal injury in part via regulation of the integrin β 1/NF-κB/DARPP-32 pathway and suppressed the expression of STAT3 in PLGC. The elucidation of this effect and mechanism of calycosin in PLGC provides a potential therapeutic strategy for treatment of gastric precancerous lesions.Keywords: precancerous lesions of gastric carcinoma, calycosin, inflammation, angiogenesis, gastric mucosa protection
