Subscribe to RSS
Download PDF
DOI: 10.1055/a-2432-2732
Preclinical Evidence of Mulberry Leaf Polysaccharides on Diabetic Kidney Disease: a Systematic Review and Meta-Analysis
This research was funded by the Project of Medical and Health Technology Platform of Zhejiang Province, grant numbers 2022RC004 and 2023KY434.
Abstract
Mulberry leaf polysaccharides (MLPs) have a variety of biological activities. Preliminary scattered evidence of preclinical studies have reported their potenzial effects on diabetic kidney disease (DKD). Here, we intended to assess the preclinical evidence of MLPs and explore their potenzial mechanisms on DKD, offering a scientific reference for the therapeutic use of MLPs. The study has been registered under the CRD42022309117 registration number at PROSPERO. Comprehensive search was conducted across eight databases from their establishment till January 2024, and eight studies with 270 animals were included in the meta-analysis. The primary outcome measurements in the MLP group, including serum creatinine (Scr) (P = 0.0005), blood urea nitrogen (BUN) (P = 0.02), 24-hour urinary protein (UP) (P = 0.001), and urinary microalbumin (UAlb) (P < 0.0001), were significantly reduced compared to the control group. Additionally, MLP treatment was significantly correlated with fasting blood glucose (FBG), total cholesterol (TC), protein expression of TGF-β1, CTGF mRNA, and the kidney index (all P values < 0.05) and delayed the progression of local pathological changes in the kidney. Subgroup analysis revealed significant species differences in the efficacy of MLPs. Also, it showed that the dosage of streptozotocin potenzially affected the Scr and UAlb results, while the duration of MLP treatment influenced UAlb results. MLPs may exert potenzial renal protection by delaying renal fibrosis, inhibiting inflammatory reactions, suppressing the growth hormone–insulin-like growth factor–insulin-like growth factor binding protein axis, and regulating the insulin receptor pathway. In summary, MLPs have multifaceted renal protective effects, suggesting their potenzial for treating DKD.
Keywords
mulberry leaf polysaccharides - DKD - meta-analysis - systematic review - renal protection - Moraceae - MorusSupporting Information
- Supporting Information
The literature search strategy, sensitivity analyses, and subgroup analysis are available as Supporting Information.
Publication History
Received: 02 June 2024
Accepted after revision: 27 September 2024
Accepted Manuscript online:
02 October 2024
Article published online:
28 October 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Wen CP, Chang CH, Tsai MK, Lee JH, Lu PJ, Tsai SP, Wen C, Chen CH, Kao CW, Tsao CK, Wu X. Diabetes with early kidney involvement may shorten life expectancy by 16 years. Kidney Int 2017; 92: 388-396
- 2 ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA. on behalf of the American Diabetes A. 11. Chronic kidney disease and risk management: Standards of care in diabetes-2023. Diabetes Care 2023; 46: S191-S202
- 3 Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms of diabetic kidney disease. J Clin Invest 2014; 124: 2333-2340
- 4 Qu L, Liang X, Tian G, Zhang G, Wu Q, Huang X, Cui Y, Liu Y, Shen Z, Xiao C, Qin Y, Miao H, Zhang Y, Li Z, Ye S, Zhang X, Yang J, Cao G, Li Y, Yang G, Hu J, Wang X, Li Z, Li Y, Zhang X, Zhang G, Chen L, Hua W, Yu M, Lu C, Zhang X, Jiang H. Efficacy and safety of mulberry twig alkaloids tablet for the treatment of type 2 diabetes: A multicenter, randomized, double-blind, double-dummy, and parallel controlled clinical trial. Diabetes Care 2021; 44: 1324-1333
- 5 Li R, Zhou J, Zhang X, Zhang T, Wang J, Zhang M, He C, Chen H. Isolation, structural characterization and cholesterol-lowering effects of a novel polysaccharide from mulberry (Morus alba L.) leaf. Ind Crops Prod 2023; 202: 117010
- 6 Wang F, Li J, Jiang Y. Polysaccharides from mulberry leaf in relation to their antioxidant activity and antibacterial ability. J Food Process Eng 2010; 33: 39-50
- 7 Yang S, Li Y, Jia D, Yao K, Liu W. The synergy of Box-Behnken designs on the optimization of polysaccharide extraction from mulberry leaves. Ind Crops Prod 2017; 99: 70-78
- 8 Thirugnanasambandham K, Sivakumar V, Maran JP. Microwave-assisted extraction of polysaccharides from mulberry leaves. Int J Biol Macromol 2015; 72: 1-5
- 9 Ying Z, Han X, Li J. Ultrasound-assisted extraction of polysaccharides from mulberry leaves. Food Chem 2011; 127: 1273-1279
- 10 Zhang DY, Wan Y, Xu JY, Wu GH, Li L, Yao XH. Ultrasound extraction of polysaccharides from mulberry leaves and their effect on enhancing antioxidant activity. Carbohydr Polym 2016; 137: 473-479
- 11 Chen X, Sheng Z, Qiu S, Yang H, Jia J, Wang J, Jiang C. Purification, characterization and in vitro and in vivo immune enhancement of polysaccharides from mulberry leaves. PLoS One 2019; 14: e0208611
- 12 Yuan Q, Xie Y, Wang W, Yan Y, Ye H, Jabbar S, Zeng X. Extraction optimization, characterization and antioxidant activity in vitro of polysaccharides from mulberry (Morus alba L.) leaves. Carbohydr Polym 2015; 128: 52-62
- 13 Xia W, Liu SQ, Zhang WQ, Luo GA. Structural features of a pectic polysaccharide from mulberry leaves. J Asian Nat Prod Res 2008; 10: 857-865
- 14 Wang H, Huang G. Extraction, purification, structural modification, activities and application of polysaccharides from different parts of mulberry. Food Funct 2024; 15: 3939-3958
- 15 Chen R, Zhou X, Deng Q, Yang M, Li S, Zhang Q, Sun Y, Chen H. Extraction, structural characterization and biological activities of polysaccharides from mulberry leaves: A review. Int J Biol Macromol 2024; 257: 128669
- 16 van Luijk J, Leenaars M, Hooijmans C, Wever K, de Vries R, Ritskes-Hoitinga M. Towards evidence-based translational research: the pros and cons of conducting systematic reviews of animal studies. ALTEX 2013; 30: 256-257
- 17 Wu SJ. Mulberry leaf polysaccharides suppress renal fibrosis. Int J Biol Macromol 2019; 124: 1090-1093
- 18 Zhang LW. Improvement Effect and Mechanism of Mulberry Leaf Active Components on Diabetes and Liver and Kidney Injury Complicated [dissertation]. Nanjing: Nanjing University of Chinese Medicine; 2019
- 19 Zhang Z, Li L, Li ZK, Wu F, Hang BY, Cai BY, Weng ZF, Zhao L, Ding CF, Du YG. Effect and mechanism of mulberry leaf polysaccharide on type 1 diabetic nephropathy in rats. Natl Med J Chin 2018; 98: 1792-1796
- 20 Zhang YW, Xue JT, Li Q, Han ZX, Liu HF. Protective effects and mechanism of mulberry leaf polysaccharide on diabetic nephropathy rats. Chin Arch Tradit Chin Med 2016; 34: 1381-1383
- 21 Huang LJ, Du YG, Sun ZJ, Zhou HM, Lv B, Shen CL, Zhao XM. Effects of mulberry leaf flavonoids and polysaccharides on serum tumor necrosis factor-α, C-reactive protein content and renal function in diabetic rats. Chin J Gerontol 2016; 36: 4703-4705
- 22 Chen JQ, Lin SJ, Zheng N. Effects of polysaccharides from mulberry leaves on diabetic nephropathy in mice. Chin J Hosp Pharm 2016; 36: 806-809
- 23 Song TJ, Li Q, Xue JT, Han ZX, Liu HF, Wang GY. Effect of mulberry leaf polysaccharide on CTGF expression in kidney of DN rats. Food Nutr Chin 2014; 20: 73-75
- 24 Liu HF, Han ZX, Nie Y, Jin LY, Wang GY, Yue H, Li Q, Xue JT, Shen MS. Effect of mulberry leaf polysaccharide on renal fibrosis in diabetic nephropathy rats. Chin J Gerontol 2014; 14: 3959-3960
- 25 Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, Agrawal YO. Challenges and issues with streptozotocin-induced diabetes – A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact 2016; 244: 49-63
- 26 Skyler JS. Microvascular complications. Retinopathy and nephropathy. Endocrinol Metab Clin North Am 2001; 30: 833-856
- 27 Liu CG, Ma YP, Zhang XJ. Effects of mulberry leaf polysaccharide on oxidative stress in pancreatic β-cells of type 2 diabetic rats. Eur Rev Med Pharmacol Sci 2017; 21: 2482-2488
- 28 Feng L, Chen C, Xiong X, Wang X, Li X, Kuang Q, Wei X, Gao L, Niu X, Li Q, Yang J, Li L, Luo P. PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-β1/Smad2/3 signaling pathways. Ecotoxicol Environ Saf 2024; 273: 116102
- 29 Wang L, Wang HL, Liu TT, Lan HY. TGF-Beta as a master regulator of diabetic nephropathy. Int J Mol Sci 2021; 22: 7881
- 30 Sun Y, Ge J, Shao F, Ren Z, Huang Z, Ding Z, Dong L, Chen J, Zhang J, Zang Y. Long noncoding RNA AI662270 promotes kidney fibrosis through enhancing METTL3-mediated m(6) A modification of CTGF mRNA. FASEB J 2023; 37: e23071
- 31 Oda Y, Nishi H, Nangaku M. Role of inflammation in progression of chronic kidney disease in type 2 diabetes mellitus: Clinical implications. Semin Nephrol 2023; 43: 151431
- 32 Oh Y. The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities. Kidney Res Clin Pract 2012; 31: 26-37
- 33 Mohebi R, Liu Y, Hansen MK, Yavin Y, Sattar N, Pollock CA, Butler J, Jardine M, Masson S, Heerspink HJL, Januzzi jr. JL. Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: An analysis from the CREDENCE trial. Cardiovasc Diabetol 2023; 22: 176
- 34 Ren C, Zhang Y, Cui W, Lu G, Wang Y, Gao H, Huang L, Mu Z. A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin. Int J Biol Macromol 2015; 72: 951-959
- 35 Liu HF, Ren YH, Song TJ, Han ZX. Effect of mulberry leaves polysaccharides on gene expression of resistin in type 2 diabetes mellitus rats. Food Nutr Chin 2012; 18: 67-68
- 36 Han ZX, Xue JT, Li Q, Song TJ, Wang GY, Liu HF. Effect of MLP on expression of AdipoR1 in diabetic nephropathy rats. Food Nutr Chin 2014; 20: 74-75
- 37 Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLEʼs risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43
- 38 Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage 2012; 20: 256-260
- 39 Franco A, Malhotra N, Simonovits G. Social science. Publication bias in the social sciences: Unlocking the file drawer. Science 2014; 345: 1502-1505
- 40 Brosius 3rd FC, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, Harris RC, Kakoki M, Kretzler M, Leiter EH, Levi M, McIndoe RA, Sharma K, Smithies O, Susztak K, Takahashi N, Takahashi T. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2009; 20: 2503-2512
- 41 Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023). Cochrane, 2023. Accessed February 2024 at http://www.training.cochrane.org/handbook