Design, synthesis and evaluation of a baicalin and berberine hybrid compound as therapeutic agent for ulcerative colitis
BIOORGANIC & MEDICINAL CHEMISTRY
Authors: Jia, Dan; Dou, Yonghui; Li, Ziwen; Zhou, Xinxin; Gao, Ying; Chen, Keji; Cong, Weihong; Ma, Min; Wu, Zhengzhi; Li, Weimin
Abstract
Structural modification of active natural compounds which were originated from Traditional Chinese Medicine (TCM) have showed great advantages in the development of new drugs. In TCM, "Huangqin - Huanglian" is a classic "medicine couple" that has been used to treat intestinal diseases for thousands of years, while baicalin and berberine are the major active compounds of Huangqin and Huanglian respectively. Based on this "medicine couple", we designed and synthesized a new baicalin and berberine hybrid compound (BBH). Its molecular structure was confirmed by spectroscopy. The antibacterial activity of BBH was detected in vitro. Results indicated that the new hybrid compound exhibited the best antibacterial activity for proteobacteria as compared with its original synthetic materials (baicalin and berberine). In vivo, the effect of BBH on ulcerative colitis was also investigated. BBH treatment significantly ameliorated the disease symptoms and prevented the colon damage of ulcerative colitis. Furthermore, BBH showed a significant anti-inflammatory effect through regulating activities of SOD, MPO and expressions of pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in colon tissue. Data also suggested that BBH was more superior than baicalin and berberine in ameliorating colonic damage. This indicated that the new hybrid compound BBH showed enhanced efficacy in treating ulcerative colitis.
Effect of penehyclidine hydrochloride on IL-6, TNF-alpha, HIF-1 alpha and oxidative stress in lung tissue of young rats with acute lung injury
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
Authors: Shu, Jihong; Fang, Zhenjiao; Xiong, Xinjun
Abstract
Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), hypoxia inducible factor-1 alpha (HIF-1 alpha), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats. Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-alpha and HIF-1 alpha were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining. Results: The lung tissue levels of IL-6, TNF-alpha and HIF-1 alpha were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05). Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-alpha and HIF-1 alpha in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this