Hong Zheng1, Jing Gao1, Shuli Man2, Jingze Zhang3, Zhaoxiang Jin4, Wenyuan Gao5. 1. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. 2. College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: msl@tust.edu.cn. 3. Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin 300309, China. 4. Tianjin Lerentang Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd., Tianjin 300380, China. 5. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
Abstract
BACKGROUND: Aquilariae Lignum Resinatum as a traditional Chinese medicine is used in prescription for treatment of gastrointestinal diseases. Phytochemical investigations show that there are many anti-ulcer and anti-inflammatory ingredients in A. agallocha methanol extract (AEE). However, scarce data is available about the constituents absorbed into the blood, activity and mechanisms of AEE on intestinal mucositis. HYPOTHESIS/ PURPOSE: To analyze the bioactive constituents of AEE absorbed in the blood, and further explore the potential mechanisms of the protection against chemotherapy-induced intestinal mucositis. METHODS: The serum pharmacochemistry using UHPLC-Q-TOF/MS was performed to screen the bioactive compounds of AEE absorbed in serum. The intestinal mucositis was induced by 5-Fuorouracil (5-Fu) and treated with AEE. The severity of intestinal mucositis was evaluated based on body weight, food-intake and diarrhea. Furthermore, the mechanism of AEE was investigated involved in the pathogenesis of mucositis on repairing injury of intestinal mucosa, immune functions, and inflammatory response. RESULTS: Altogether, 11 components were identified or tentatively characterized in dosed plasma. In pharmacodynamics study, intestinal mucositis caused by 5-Fu was effectively attenuated after AEE treatment. AEE treatment improved food-intake and injury of the intestinal mucosa, relieved body weight loss and severe diarrhea through up-regulating expression of proliferating cell nuclear antigen (PCNA) and inhibiting the levels of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in ileum segments. CONCLUSIONS: AEE protected against 5-Fu-induced intestinal mucositis (IM) in mice through mechanisms that involved in promoting the enterocyte proliferative activity, maintaining the integrity of tight junction proteins, inhibiting oxidative stress and ameliorating the inflammatory disturbances. Accordingly, A. agallocha may be a promising therapeutic candidate used for the prevention of IM during cancer chemotherapy.
BACKGROUND: Aquilariae Lignum Resinatum as a traditional Chinese medicine is used in prescription for treatment of gastrointestinal diseases. Phytochemical investigations show that there are many anti-ulcer and anti-inflammatory ingredients in A. agallocha methanol extract (AEE). However, scarce data is available about the constituents absorbed into the blood, activity and mechanisms of AEE on intestinal mucositis. HYPOTHESIS/ PURPOSE: To analyze the bioactive constituents of AEE absorbed in the blood, and further explore the potential mechanisms of the protection against chemotherapy-induced intestinal mucositis. METHODS: The serum pharmacochemistry using UHPLC-Q-TOF/MS was performed to screen the bioactive compounds of AEE absorbed in serum. The intestinal mucositis was induced by 5-Fuorouracil (5-Fu) and treated with AEE. The severity of intestinal mucositis was evaluated based on body weight, food-intake and diarrhea. Furthermore, the mechanism of AEE was investigated involved in the pathogenesis of mucositis on repairing injury of intestinal mucosa, immune functions, and inflammatory response. RESULTS: Altogether, 11 components were identified or tentatively characterized in dosed plasma. In pharmacodynamics study, intestinal mucositis caused by 5-Fu was effectively attenuated after AEE treatment. AEE treatment improved food-intake and injury of the intestinal mucosa, relieved body weight loss and severe diarrhea through up-regulating expression of proliferating cell nuclear antigen (PCNA) and inhibiting the levels of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in ileum segments. CONCLUSIONS: AEE protected against 5-Fu-induced intestinal mucositis (IM) in mice through mechanisms that involved in promoting the enterocyte proliferative activity, maintaining the integrity of tight junction proteins, inhibiting oxidative stress and ameliorating the inflammatory disturbances. Accordingly, A. agallocha may be a promising therapeutic candidate used for the prevention of IM during cancer chemotherapy.