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Research Progress on the Mechanisms of Berberine Protecting the Kidney in Diabetic Kidney Disease
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 45, Issue 3, Pages: 354-360(2024)
- 作者机构：
西藏民族大学，陕西 咸阳 712082
- 作者简介：
TONG Xiaopeng； E-mail： xptong@xzmu.edu.cn
- 基金信息：
DOI：10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240419.003
CLC： R392.6Published：20 May 2024，
Received：28 January 2024，
Accepted：09 April 2024
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曲柄衡,童晓鹏.小檗碱保护糖尿病肾病肾脏作用机制研究进展[J].中山大学学报（医学科学版）,2024,45(03):354-360.
QU Bingheng,TONG Xiaopeng.Research Progress on the Mechanisms of Berberine Protecting the Kidney in Diabetic Kidney Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(03):354-360.
曲柄衡,童晓鹏.小檗碱保护糖尿病肾病肾脏作用机制研究进展[J].中山大学学报（医学科学版）,2024,45(03):354-360. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240419.003.
QU Bingheng,TONG Xiaopeng.Research Progress on the Mechanisms of Berberine Protecting the Kidney in Diabetic Kidney Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(03):354-360. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240419.003.
摘要
糖尿病肾病（DKD）是指由糖尿病导致的慢性肾脏疾病，受遗传和环境因素及其相互作用的影响，是慢性肾脏病和终末期肾病的主要病因。小檗碱（BBR）是一种天然的异喹啉生物碱。近年来研究发现，BBR具有降血糖、降血脂、抗氧化、抗炎及抗纤维化作用，可以有效改善DKD的肾脏损害，其作用机制可能包括：改善糖脂代谢、减轻氧化应激、减轻炎症反应、改善肾脏纤维化、调控DNA甲基化、改善线粒体功能、调节肠道菌群，改善肠道代谢及清除功能。本文系统性综述了BBR治疗DKD的作用机制的研究现状，为未来BBR的临床应用及DKD的治疗提供参考。
Abstract
Diabetic kidney disease （DKD） is a chronic kidney disease caused by diabetes， influenced by genetic and environmental factors and their interaction. It is the primary cause of chronic kidney disease and end-stage renal disease. Recent studies have found， as a natural isoquinoline alkaloid， berberine （BBR） has hypoglycemic， hypolipidemic， antioxidant， anti-inflammatory and anti-fibrotic properties， thus protects against kidney injury in DKD. The mechanisms of action of BBR may involve improving glucolipid metabolism， reducing oxidative stress， alleviating inflammatory responses， mitigating renal fibrosis， regulating DNA methylation， promoting mitochondrial function and modulating the gut microbiota to enhance gut metabolism and clearance. This article systematically reviews the current status of research on the mechanisms of BBR in the treatment of DKD and provides reference for future clinical application of BBR in the treatment of DKD.
关键词
小檗碱糖尿病肾病肾功能改善作用机制系统综述
Keywords
berberine （BBR）diabetic kidney disease （DKD）improved renal functionmechanisms of actionsystematic review
references
中华医学会肾脏病学分会专家组. 糖尿病肾脏疾病临床诊疗中国指南［J］. 中华肾脏病杂志， 2021， 37（3）： 255-304.
Expert Group of Chinese Society of Nephrology. Chinese guidelines for diagnosis and treatment of diabetic kidney disease［J］. Chin J Nephrol， 2021， 37（3）： 255-304.
Kidney Disease： Improving Global Outcomes （KDIGO） Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease［J］. Kidney Int， 2022， 102（5S）： S1-S127.
Pavkov ME， Miyamoto Y. IDF diabetes atlas report - diabetes and kidney disease［R］. Atlanta： International Diabetes Federation， 2023.
Fox CS， Matsushita K， Woodward M， et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes： a meta-analysis［J］. Lancet， 2012， 380（9854）： 1662-1673.
Magliano DJ， Boyko EJ， Balkau B， et al. IDF diabetes atlas 10th edition［R］. Brussels： International Diabetes Federation， 2021.
Ju J， Li J， Lin Q， et al. Efficacy and safety of berberine for dyslipidaemias： a systematic review and meta-analysis of randomized clinical trials［J］. Phytomedicine， 2018， 50： 25-34.
李自云， 刘波， 庄新娟， 等. 黄连素对2型糖尿病患者血清胱抑素C及尿微量白蛋白/肌酐比值的影响［J］. 中华医学杂志， 2018， 98（46）： 3756-3761.
Li ZY， Liu B， Zhuang XJ， et al. Effects of berberine on the serum cystatin C levels and urine albumin/creatine ratio in patients with type 2 diabetes mellitus［J］. Natl Med J Chin， 2018， 98（46）： 3756-3761.
娄文娇， 郭敬， 张帆， 等. 黄连素（小檗碱）治疗早期糖尿病肾病有效性和安全性系统回顾及Meta分析［J］. 中国中西医结合肾病杂志， 2022， 23（6）： 510-513.
Lou WJ， Guo J， Zhang F， et al. Systematic review and meta-analysis of the effectiveness and safety of berberine （BBR） in the treatment of early diabetic nephropathy［J］. Chin J Integr Tradit Western Nephrol， 2022， 23（6）： 510-513.
Rauf A， Abu-Izneid T， Khalil AA， et al. Berberine as a potential anticancer agent： a comprehensive review［J］. Molecules， 2021， 26（23）： 7368.
Li Z， Wang Y， Xu Q， et al. Berberine and health outcomes： an umbrella review［J］. Phytother Res， 2023， 37（5）： 2051-2066.
Guo J， Chen H， Zhang X， et al. The effect of berberine on metabolic profiles in type 2 diabetic patients： a systematic review and meta-analysis of randomized controlled trials［J］. Oxid Med Cell Longev， 2021， 2021： 2074610.
Yang L， Yuan S， Wang R， et al. Exploring the molecular mechanism of berberine for treating diabetic nephropathy based on network pharmacology［J］. Int Immunopharmacol， 2024， 126： 111237.
Cai Y， Xin Q， Lu J， et al. A new therapeutic candidate for cardiovascular diseases： berberine［J］. Front Pharmacol， 2021， 12： 631100.
Chen P， Li Y， Xiao L. Berberine ameliorates nonalcoholic fatty liver disease by decreasing the liver lipid content via reversing the abnormal expression of MTTP and LDLR［J］. Exp Ther Med， 2021， 22（4）： 1109.
Kikkawa R， Koya D， Haneda M. Progression of diabetic nephropathy［J］. Am J Kidney Dis， 2003， 41（3 Suppl 1）： S19-21.
Wang D， Li J， Luo G， et al. Nox4 as a novel therapeutic target for diabetic vascular complications［J］. Redox Biol， 2023， 64： 102781.
Sun KX， Chen YY， Li Z， et al. Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway［J］. World J Diabetes， 2023， 14（9）： 1349-1368.
Qiu YY， Tang LQ， Wei W. Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy［J］. Mol Cell Endocrinol， 2017， 443： 89-105.
Liu WH， Hei ZQ， Nie H， et al. Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase［J］. Chin Med J （Engl）， 2008， 121（8）： 706-712.
Zhu QJ， Zhu M， Xu XX， et al. Exosomes from high glucose-treated macrophages activate glomerular mesangial cells via TGF-β1/Smad3 pathway in vivo and in vitro［J］. FASEB J， 2019， 33（8）： 9279-9290.
Sun SF， Zhao TT， Zhang HJ， et al. Renoprotective effect of berberine on type 2 diabetic nephropathy in rats［J］. Clin Exp Pharmacol Physiol， 2015， 42（6）： 662-670.
Konrad D， Somwar R， Sweeney G， et al. The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation： potential role of p38 mitogen-activated protein kinase in GLUT4 activation［J］. Diabetes， 2001， 50（6）： 1464-1471.
Zhang H， Wei J， Xue R， et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression［J］. Metabolism， 2010， 59（2）： 285-292.
Blais JE， Huang X， Zhao JV. Overall and sex-specific effect of berberine for the treatment of dyslipidemia in adults： a systematic review and meta-analysis of randomized placebo-controlled trials［J］. Drugs， 2023， 83（5）： 403-427.
Tarabra E， Giunti S， Barutta F， et al. Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes［J］. Diabetes， 2009， 58（9）： 2109-2118.
Kahn BB， Alquier T， Carling D， et al. AMP-activated protein kinase： ancient energy gauge provides clues to modern understanding of metabolism［J］. Cell Metab， 2005， 1（1）： 15-25.
Li H， Chen W， Zhou Y， et al. Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements［J］. J Lipid Res， 2009， 50（5）： 820-831.
Kong W， Wei J， Abidi P， et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins［J］. Nat Med， 2004， 10（12）： 1344-1351.
Zhang M， Liu J， Yu C， et al. Berberine regulation of cellular oxidative stress， apoptosis and autophagy by modulation of m6A mRNA methylation through targeting the Camk1db/ERK pathway in zebrafish-hepatocytes［J］. Antioxidants （Basel）， 2022， 11（12）： 2370.
Wu D， Wen W， Qi CL， et al. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin［J］. Phytomedicine， 2012， 19（8-9）： 712-718.
Dou Y， Huang R， Li Q， et al. Oxyberberine， an absorbed metabolite of berberine， possess superior hypoglycemic effect via regulating the PI3K/Akt and Nrf2 signaling pathways［J］. Biomed Pharmacother， 2021， 137： 111312.
Hsu YY， Chen CS， Wu SN， et al. Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells［J］. Eur J Pharm Sci， 2012， 46（5）： 415-425.
陈诚， 邓斌. 盐酸小檗碱介导LINC01619/miR-27a/FOXO1通路改善糖尿病肾病模型db/db小鼠内质网应激作用研究［J］. 药物评价研究， 2022， 45（7）： 1274-1281.
Chen C， Deng B. Improvement of berberine hydrochloride on endoplasmic reticulum stress by mediation of LINC01619/miR-27a/FOXO1 pathway in diabetic nephropathy model db/db mice［J］. Drug Eval Res， 2022， 45（7）： 1274-1281.
Fu Y， Wang X， Zhang L， et al. Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway in diabetic kidney disease［J］. Biochem Biophys Res Commun， 2022， 614： 63-69.
Ren G， Ding YW， Wang LL， et al. Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1［J］. Front Pharmacol， 2023， 14： 1148611.
Zhang B， Pan Y， Xu L， et al. Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3［J］. Endocrine， 2018， 62（3）： 576-587.
Reddi KK， Li H， Li W， et al. Berberine， a phytoalkaloid， inhibits inflammatory response induced by LPS through NF-Kappaβ pathway： possible involvement of the IKKα［J］. Molecules， 2021， 26（16）： 4733.
Ma Z， Zhu L， Wang S， et al. Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome［J］. Ren Fail， 2022， 44（1）： 923-932.
Lin YC， Chang YH， Yang SY， et al. Update of pathophysiology and management of diabetic kidney disease［J］. J Formos Med Assoc， 2018， 117（8）： 662-675.
Chen D， Liu Y， Chen J， et al. JAK/STAT pathway promotes the progression of diabetic kidney disease via autophagy in podocytes［J］. Eur J Pharmacol， 2021， 902： 174121.
Yu J， Wu H， Liu ZY， et al. Advanced glycation end products induce the apoptosis of and inflammation in mouse podocytes through CXCL9-mediated JAK2/STAT3 pathway activation［J］. Int J Mol Med， 2017， 40（4）： 1185-1193.
杨琳， 王蓉蓉， 郭小雨， 等. 小檗碱激活SIRT1/AMPK信号通路改善高糖诱导的系膜细胞异常增殖和自噬功能［J］. 安徽医科大学学报， 2023， 58（6）： 896-901.
Yang L， Wang RR， Guo XY， et al. Berberine activates the SIRT1/AMPK signaling pathway to improve abnormal proliferation and autophagy function of high glucose induced mesangial cells［J］. Acta Univ Med Anhui， 2023， 58（6）： 896-901.
Ni WJ， Zhou H， Ding HH， et al. Berberine ameliorates renal impairment and inhibits podocyte dysfunction by targeting the phosphatidylinositol 3-kinase-protein kinase B pathway in diabetic rats［J］. J Diabetes Investig， 2020， 11（2）： 297-306.
Li C， Guan XM， Wang RY， et al. Berberine mitigates high glucose-induced podocyte apoptosis by modulating autophagy via the mTOR/P70S6K/4EBP1 pathway［J］. Life Sci， 2020， 243： 117277.
DeFronzo RA， Reeves WB， Awad AS. Pathophysiology of diabetic kidney disease： impact of SGLT2 inhibitors［J］. Nat Rev Nephrol， 2021， 17（5）： 319-334.
Ricciardi CA， Gnudi L. Kidney disease in diabetes： from mechanisms to clinical presentation and treatment strategies［J］. Metabolism， 2021， 124： 154890.
Sheibani N. Connective tissue growth factor： a key factor among mediators of tissue fibrosis［J］. J Ophthalmic Vis Res， 2022， 17（4）： 449-452.
Liu W， Zhang X， Liu P， et al. Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury［J］. Eur J Pharmacol， 2010， 638（1-3）： 150-155.
Yang G， Zhao Z， Zhang X， et al. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice［J］. Drug Des Devel Ther， 2017， 11： 1065-1079.
Meng M， Lu M， Feng J， et al. Exosomal PPARγ derived from macrophages suppresses LPS-induced peritonitis by negative regulation of CD14/TLR4 axis［J］. Inflamm Res， 2023， 72（8）： 1567-1581.
Pironti G， Strachan RT， Abraham D， et al. Circulating exosomes induced by cardiac pressure overload contain functional angiotensin Ⅱ type 1 receptors［J］. Circulation， 2015， 131（24）： 2120-2130.
胡亚琴. 糖尿病肾病足细胞源外泌体促进系膜细胞损伤的机制及小檗碱的作用［D］. 合肥： 安徽医科大学， 2022.
Hu YQ. Mechanism by which exosomes derived from diabetic nephropathy podocyte promote mesangial cells injury and the effect of berberine［D］. Hefei： Anhui Med Univ， 2022.
Yao Y， Song Q， Hu C， et al. Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes［J］. Cardiovasc Res， 2022， 118（1）： 196-211.
Smyth LJ， Dahlström EH， Syreeni A， et al. Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease［J］. Nat Commun， 2022， 13（1）： 7891.
庞雨浓， 梁英文， 王玉刚， 等. 小檗碱通过调节PPARγ启动子甲基化对缺血再灌注脑损伤的作用（英文）［J］. J Chin Pharm Sci， 2018， 27（3）： 170-182.
Pang YN， Liang YW， Wang YG， et al. Effect of berberine against cerebral ischemia and reperfusion involving in the methylation of PPARγ promoter（English）［J］. J Chin Pharm Sci， 2018， 27（3）： 170-182.
Zhang L， Zhang Q， Liu S， et al. DNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury［J］. Kidney Int， 2017， 92（1）： 140-153.
Li L， Wang C， Yang H， et al. Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients［J］. Mol Biosyst， 2017， 13（11）： 2392-2400.
Fernandez-Marcos PJ， Auwerx J. Regulation of PGC-1α， a nodal regulator of mitochondrial biogenesis［J］. Am J Clin Nutr， 2011， 93（4）： 884S-90.
Fontecha-Barriuso M， Martin-Sanchez D， Martinez-Moreno JM， et al. The role of PGC-1α and mitochondrial biogenesis in kidney diseases［J］. Biomolecules， 2020， 10（2）： 347.
Qin X， Jiang M， Zhao Y， et al. Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis［J］. Br J Pharmacol， 2020， 177（16）： 3646-3661.
Xu J， Liu L， Gan L， et al. Berberine acts on C/EBPβ/lncRNA Gas5/miR-18a-5p loop to decrease the mitochondrial ROS generation in HK-2 cells［J］. Front Endocrinol （Lausanne）， 2021， 12： 675834..
Tian E， Wang F， Zhao L， et al. The pathogenic role of intestinal flora metabolites in diabetic nephropathy［J］. Front in Physiol， 2023， 14： 1231621.
Zhang L， Wang Z， Zhang X， et al. Alterations of the gut microbiota in patients with diabetic nephropathy［J］. Microbiol Spectr， 2022， 10（4）： e0032422.
Xu X， Gao Z， Yang F， et al. Antidiabetic effects of Gegen Qinlian decoction via the gut microbiota are attributable to its key ingredient berberine［J］. Genomics Proteomics Bioinformatics， 2020， 18（6）： 721-736.
Zhang X， Zhao Y， Zhang M， et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats［J］. PloS One， 2012， 7（8）： e42529.
Pan L， Yu H， Fu J， et al. Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota［J］. Acta Pharm Sin B， 2023， 13（4）： 1537-1553.
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