Pharmacology Research Lab, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh 160014, India.
Pharmacology Research Lab, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh 160014, India; Food and Nutritional Biotechnology Division, National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab 140306, India; ICMR-National Institute of Occupational Health (NIOH), Ahmedabad 380016, India.
Life Sci. 2020 Apr 15;247:117442. doi: 10.1016/j.lfs.2020.117442. Epub 2020 Feb 17.
Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.
瞬时受体电位香草酸型 1（TRPV1）通道是代谢紊乱的新兴治疗靶点。黄连素是 TRPV1 的调节剂，已被证明具有抗肥胖和抗糖尿病作用。本研究旨在探讨黄连素通过 TRPV1 通道对奥氮平引起的下丘脑食欲控制、炎症和代谢异常的保护作用。将雌性 BALB/c 小鼠（18-23g）用奥氮平（6mg/kg，po）处理 6 周以诱导代谢改变，而黄连素（100 和 200mg/kg，po）和二甲双胍（100mg/kg，po）分别作为试验和标准干预措施。每周评估饲料和水的摄入量、体温和体重，第 1 周和第 6 周结束时测量运动。通过生化方法评估血清葡萄糖和脂质谱，通过 ELISA 评估其他血清生物标志物。使用 qPCR 定量下丘脑的 mRNA 表达。奥氮平处理显著增加了摄食量、体重增加、肥胖指数，而降低了体温和运动活动，这些都被黄连素处理所逆转。黄连素处理降低了血清 ghrelin 和 leptin 水平，以及奥氮平处理小鼠下丘脑食欲肽、炎症标志物和 ghrelin 受体的 mRNA 表达减少。奥氮平处理增加了下丘脑 TRPV1/TRPV3 的表达，而黄连素处理则显著降低了这种表达。我们的结果表明，黄连素通过 TRPV1/TRPV3 的调节，减轻了奥氮平引起的小鼠代谢异常。因此，在精神科患者中补充黄连素可能是一种预防措施，可以减少抗精神病药物的代谢不良反应。
