Habiba Esraa S, Fathelbab Mona Hassan, AbdElaziz Marwa M, El-Sayed Norhan S, Mady Marwa Mahmoud, Khamis Gehad M
Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 26. doi: 10.1007/s00210-025-04376-5.
Inflammatory bowel disease (IBD) is linked to psychiatric issues like anxiety and depression. Berberine (BER), a natural compound with anti-inflammatory and antioxidant characteristics, shows promise in managing IBD. However, its effects on inflammation-induced anxiety and the underlying mechanisms remain imprecise. This study explores BER's impact on inflammation and anxiety in a rat model of colitis, focusing on the AMPK/NURR1 axis. Acute colitis was induced in 32 male Wistar rats via intrarectal administration of 4% acetic acid (AA), followed by a 7-day treatment with oral saline, BER (50 or 100 mg/kg), or 5-aminosalicylic acid (5-ASA, 100 mg/kg). Furthermore, eight control rats received a single dose of intrarectal saline and then daily oral saline for the same duration. Colitis activity score was monitored throughout the study, and anxiety-like behavior was assessed on the seventh day. On the eighth day, colon and brain samples were collected for evaluation of the colon weight-to-length ratio and biochemical analyses of inflammatory markers, oxidative stress, apoptosis, and the expression of AMPK and NURR1. Additionally, macroscopic and microscopic examinations of the colon were conducted. BER, in a dose-dependent manner, decreased anxiety-like behaviors, improved colitis activity score, decreased weight-to-length ratio, and mitigated inflammation, oxidative stress, and apoptosis. Furthermore, BER elevated the expression of AMPK and NURR1 in colonic tissues and enhanced both the macroscopic and microscopic features of the colon. By regulating the AMPK/NURR1 axis, BER effectively lessens colitis-related inflammation and anxiety, highlighting its potential as a possible treatment for IBD-associated physical and psychosocial symptoms.
炎症性肠病（IBD）与焦虑和抑郁等精神问题有关。黄连素（BER）是一种具有抗炎和抗氧化特性的天然化合物，在治疗IBD方面显示出前景。然而，其对炎症诱导的焦虑的影响及潜在机制仍不明确。本研究探讨了BER对结肠炎大鼠模型中炎症和焦虑的影响，重点关注AMPK/NURR1轴。通过直肠内给予4%乙酸（AA）诱导32只雄性Wistar大鼠发生急性结肠炎，随后分别用口服生理盐水、BER（50或100mg/kg）或5-氨基水杨酸（5-ASA，100mg/kg）进行为期7天的治疗。此外，8只对照大鼠接受单次直肠内生理盐水注射，然后在相同时间段内每日口服生理盐水。在整个研究过程中监测结肠炎活动评分，并在第7天评估焦虑样行为。在第8天，收集结肠和脑样本，以评估结肠重量与长度之比，并对炎症标志物、氧化应激、细胞凋亡以及AMPK和NURR1的表达进行生化分析。此外，还对结肠进行了大体和显微镜检查。BER以剂量依赖的方式减少了焦虑样行为，改善了结肠炎活动评分，降低了重量与长度之比，并减轻了炎症、氧化应激和细胞凋亡。此外，BER提高了结肠组织中AMPK和NURR1的表达，并改善了结肠的大体和显微镜特征。通过调节AMPK/NURR1轴，BER有效减轻了与结肠炎相关的炎症和焦虑，突出了其作为IBD相关身体和心理社会症状潜在治疗方法的潜力。
