Stepaniuk Anna, Sztolsztener Klaudia, Konstantynowicz-Nowicka Karolina, Harasim-Symbor Ewa, Bielawiec Patrycja, Chabowski Adrian
Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
Int J Mol Sci. 2025 Mar 28;26(7):3114. doi: 10.3390/ijms26073114.
The inflammatory state is a significant factor associated with diabetic kidney disease (DKD), making it one of the significant causes of chronic kidney disease. Despite the availability of data, there is a lack of targeted treatment strategies for diabetes-related kidney disorders. The aim of our study was to determine the impact of cannabigerol (CBG) on lipid precursors for inflammatory mediators during DKD development. A six-week experiment was conducted on male Wistar rats fed standard (Control) or high-fat high-sucrose (HFHS) diets. For the last 14 days of the experiment (5th and 6th weeks), half of the rats from the Control and HFHS groups intragastrically received CBG solution. Gas-liquid chromatography (GLC) was used to measure the activities of n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolic pathways and the concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in selected lipid fractions. Immunoblotting was performed to assess the expression of proteins involved in the regulation of the inflammatory state. A multiplex immunoassay kit was used to determine kidney toxicity biomarker levels. Our results revealed that CBG administration to rats fed an HFHS diet decreased n-6 PUFA biosynthetic pathway activity in phospholipid (PL) and triacylglycerol (TAG) and increased n-3 PUFA biosynthetic pathway activity in TAG and free fatty acid (FFA). We also observed a reduction in the AA concentration in PL, FFA, and diacylglycerol (DAG). CBG supplementation reduced the level of kidney damage biomarkers, such as osteopontin (OPN). Our observations confirm that CBG has potential anti-inflammatory properties and may be successfully used for further research to seek targeted therapies of inflammatory disorders, including diabetic kidney disease progression.
炎症状态是与糖尿病肾病（DKD）相关的一个重要因素，使其成为慢性肾病的主要病因之一。尽管有相关数据，但针对糖尿病相关肾脏疾病缺乏有针对性的治疗策略。我们研究的目的是确定大麻二酚（CBG）在DKD发展过程中对炎症介质脂质前体的影响。对喂食标准（对照）或高脂高糖（HFHS）饮食的雄性Wistar大鼠进行了为期六周的实验。在实验的最后14天（第5周和第6周），来自对照和HFHS组的一半大鼠通过胃内给予CBG溶液。采用气液色谱法（GLC）测量n-6和n-3多不饱和脂肪酸（PUFA）代谢途径的活性以及选定脂质组分中花生四烯酸（AA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的浓度。进行免疫印迹以评估参与炎症状态调节的蛋白质的表达。使用多重免疫分析试剂盒测定肾脏毒性生物标志物水平。我们的结果显示，对喂食HFHS饮食的大鼠给予CBG可降低磷脂（PL）和三酰甘油（TAG）中n-6 PUFA生物合成途径的活性，并增加TAG和游离脂肪酸（FFA）中n-3 PUFA生物合成途径的活性。我们还观察到PL、FFA和二酰甘油（DAG）中AA浓度的降低。补充CBG降低了肾脏损伤生物标志物的水平，如骨桥蛋白（OPN）。我们的观察结果证实，CBG具有潜在的抗炎特性，可能成功用于进一步研究，以寻求针对炎症性疾病（包括糖尿病肾病进展）的靶向治疗方法。
