Shenzhuo formulation ameliorates diabetic nephropathy by regulating cytochrome P450-mediated arachidonic acid metabolism  

作　　者：Zhong-Yong Zhang Yu-Ming Wang Ning Wang Yuan-Song Wang Hui Zhang Duo Wang Li-Xin Wang Huan-Tian Cui Wei-Bo Wen Shu-Quan Lv Yong-Jun Cao 

机构地区：[1]Department of Endocrinology,Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine,Cangzhou 061012,Hebei Province,China [2]College of Integrative Chinese and Western Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China [3]The First School of Clinical Medicine,Yunnan University of Chinese Medicine,Kunming 650500,Yunnan Province,China [4]North China University of Science and Technology,Tangshan 063000,Hebei Province,China [5]Department of Endocrinology,Nantong Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Nantong 226000,Jiangsu Province,China

出　　处：《World Journal of Diabetes》2025年第5期331-345,共15页世界糖尿病杂志(英文)

基　　金：Supported by the Natural Science Foundation of Hebei Province Beijing-Tianjin-Hebei Basic Research Special Program,No.H2020110287;Key Laboratory for Diabetic Kidney Disease Syndrome and Treatment of the Traditional Chinese Medicine Administration of Hebei Province,No.7[2024];Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio,No.3[2024];Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications,No.SZX2020015;Jiangsu Province Chinese Medicine Science and Technology Development Program Project,No.YB2020065.

摘　　要：BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved rena

关 键 词：Diabetic nephropathy Shenzhuo formulation TRANSCRIPTOMIC METABOLOMIC Cytochrome P450 Arachidonic acid metabolic INFLAMMATORY Oxidative stress 

分 类 号：R285[医药卫生—中药学]