Integrating network pharmacology and experimental verification to explore the mucosal protective effect of Chimonanthus nitens Oliv. Leaf Granule on ulcerative colitis

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease mainly located in the rectum and colon. The exact cause of UC remains unclear, though it is likely multifactorial involving genetic, immunological, and environmental factors (Du and Ha, 2020). One factor that has become increasingly linked to the pathogenesis of UC is oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants that can lead to tissue damage (Wang et al., 2016). Elevated levels of ROS and weakened antioxidant defenses have been observed in the intestines of UC patients, suggesting oxidative stress contributes to colonic injury and intestinal inflammation (Aviello and Knaus, 2017; Tian et al., 2017). Therefore, Modulating the redox state by inhibiting oxidative stress therefore represents a promising therapeutic approach for UC (Ashique et al., 2023).

Chimonanthus nitens Oliv. Leaf Granule (COG), which has been in clinical use for many years, is developed by China Jiangxi Youmei Pharmaceutical Co., Ltd., and is mainly made from the dried leaves of a plant called Chimonanthus nitens Oliv. (CO) (name standardized from http://www.worldfloraonline.org). As a medicine and tea, it was formally included in the Pharmacopoeia of the people's Republic of China (1977) and Chinese Materia Medica. Due to the effect of dispel wind and release the exterior (‘Qu Feng Jie Biao’ in Chinese), clear heat and eliminate toxins (‘Qing Re Jie Du’ in Chinese) (Wu et al., 2021), COG can treat influenza (Zhou, 2016), hand-foot-and-mouth disease (Qiu and Zhou, 2015), and upper respiratory tract infection (Ding et al., 2020). Some studies have shown that COG has a wide range of pharmacological effects, such as anti-inflammatory (Liu et al., 2013; Sun et al., 2017; Wan et al., 2021), immunomodulatory (Huang et al., 2020), and antioxidant effects (Chen et al., 2017; Ye et al., 2020). Inspired by the viewpoint of "The lungs and large intestine are interior-exteriorly related" in the TCM theory, we preliminarily verified the therapeutic effect of COG on acute ulcerative colitis in our previous study (Huang et al., 2022), but the mechanism of its treatment of UC still leaves a lot to be explored. In this study, we combined network pharmacology with in vitro and in vivo experiments to investigate the mechanism of COG protecting intestinal mucosa for the treatment of chronic UC mice. The findings may support COG as a new natural therapy for inhibiting oxidative damage and reducing the severity of UC.

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