The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease

Hindawi Journal of Diabetes Research Volume 2019, Article ID 2697672, 14 pages https://doi.org/10.1155/2019/2697672 Review Article The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease Zhenzhen Lu , Yifei Zhong, Wangyi Liu, Ling Xiang, and Yueyi Deng The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China Correspondence should be addressed to Yueyi Deng; Received 30 March 2019; Revised 25 July 2019; Accepted 7 August 2019; Published 25 August 2019 Academic Editor: Akira Sugawara Copyright © 2019 Zhenzhen Lu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of endstage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD. 1. Introduction Diabetic kidney disease (DKD) refers to kidney damage caused by diabetes, based on the appearance of proteinuria in diabetic patients. Clinically, the differential diagnosis of diabetic nephropathy and nondiabetic nephropathy mainly depends on the history of diabetes, screening of urinary protein, retinopathy and neuropathy, and so on. When it is difficult to diagnose, it depends on kidney biopsies. Epidemiological studies have shown that global burden of diabetes now affects more than 425 million people. If nothing is done, the number of people with diabetes worldwide will rise to 629 million in 2045 [1]. With the prevalence in diabetes, the incidence of DKD is growing rapidly. About 30%-40% of diabetic patients develop DKD, and one third of the patients further progress to end-stage renal disease (ESRD), which brings enormous economic burden for our society [2, 3]. DKD is divided into five stages according to Mogensen criteria by the course of DKD, pathological changes, the degree of proteinuria, and renal dysfunction. Persistent albuminuria and renal injury are well-established clinical signature and risk factors of renal lesions, which cause glomerulosclerosis and subsequent interstitial fibrosis [4]. Early medical research has shown that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), the first-line treatment for DKD, can reduce proteinuria and have a certain effect on delaying the progress of renal dysfunction [5]. However, the side effects of ACEI/ARB, such as dry cough, hypotension, hyperkalemia, and angioedema, limit the application of these drugs. Evidence-based medical studies have shown that these agents have not significantly reduced DKD vascular event rate and mortality [6]. Some promising therapies addressing novel targets, such as incretin-based therapies glucagon-like peptide-1 (GLP-1) receptor antagonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, might improve albuminuria in type 2 diabetes, 2 Journal of Diabetes Research Hyperglycemia Hyperlipidemia Hypertension Abnormalities of hemodynamics Diabetes CHM Molecular mechanism Cellular mechanism Gene mechanism Metabolism mechanism Insulin resistance Podocyte injury mechregulation anism The of miRNA m echaregulation nism The of metabolism Inflammation response Mesangial cell proliferation ECM accumulation Endothelial cell dysfunction Oxidative stress EMT of tubuloepithelial cells DKD Figure 1: Traditional Chinese medicine treatment of diabetic nephropathy from molecular, cellular, and gene levels. Abbreviations: ECM: extracellular matrix; EMT: epithelial-mesenchymal transition. while effects on clinically relevant kidney outcomeshile effects on clinically relevant kidney outcomes are still under evaluation [7]. Several large-scale trials focused on sodiumglucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) have reported favorable effects on the primary endpoint, a composite of myocardial infarction, stroke, and cardiovascular death of people who have type 2 diabetes [8, 9]. Recently, CREDENCE clinical trials, a double-blind, randomized trial, demonstrated that patents in the canagliflozin group have a lower risk of the primary composite outcome of end-stage kidney disease, doubling of the serum creatinine level or death from renal or cardiovascular causes than in the placebo group with a median follow-up of 2.62 years [10]. However, adverse events associated with SGLT2 inhibitors include genital mycotic infections, urinary tract infection, hypoglycemia, diabetic ketoacidosis, hypotension, acute kidney injury, fractures, and amputations [11]. It is of great urgency to search for safe and effective therapies for DKD. A systematic review and meta-analysis reported that traditional Chinese medicine (TCM) had a great beneficial effect on the reduction of urinary albumin creatinine ratio and proteinuria [12]. TCM has formed a unique system to diagnose and cure illness which incorporates Chinese herbal medicine (CHM), acupuncture, moxibustion, massage (tui na), and exercise (qi gong). CHM is composed by the principle of “Jun Chen Zuo Shi,” which can achieve the purpose of improving efficacy and reducing toxicity. This combination of compounds is a synergistic effect rather than a simple additional effect. CHM can be also administered in various forms, such as patent medicine, injection, and single-herb extract. In order to clarify the modern theoretical basis and molecular mechanisms of CHM compound and their extractions, great (...truncated)